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Dopaminergic Contribution to the Regulation of Emotional Perception
Abstract
Dopamine (DA) acts as a key neurotransmitter in the brain. Numerous studies have shown its regulatory role in motor and cognitive function. However, the impairment of emotional processes in neurologic and psychiatric pathologies involving the dopaminergic system (Parkinson disease, schizophrenia, autism, Attention Deficit Hyperactivity Disorder, Huntington disease, frontal lobe lesions), as well as the influence that administration of dopaminergic agonists/antagonists exert on the processing of emotion, suggest a role for DA in emotional processes. Moreover, emotional processes are dependent upon a variety of structures, the majority of which form part of the limbic system and are subject to DA innervation. In reviewing the literature, the amygdala emerges as a brain structure critical for emotional processing. It may also be implicated in deficits in emotional recognition found in two major disorders where DA's implication is clear: Parkinson disease and schizophrenia. In addition, the amygdala's response to emotional tasks is likely to be altered by the administration of both agonist and antagonist dopaminergic drugs. Experimental studies reinforce the idea of a dopaminergic contribution to emotional response, as suggested by biochemical, pharmacologic, and lesion experiments. Although the implication of the dopaminergic system in emotional processing appears to be clearly documented, the contribution of specific DA receptor subtypes, or of the DA cotransmitters cholecystokinin and neurotensin, or even glutamate, is, however, still unclear. Altogether, these observations suggest that DA has, undoubtedly, a direct and/or indirect role in the full emotional process.
... Internalizing problems have been implicated in social competence (Blackman, Ostrander, & Herman, 2005;Mikami, Ransone, & Calhoun, 2011), daily functioning (Sciberras et al., 2014), and self-injury behavior risk (Kang et al., 2019;Lin, You, Wu, & Jiang, 2018). Internalizing problems may result from dysfunctional dopaminergic and serotonergic systems that play important roles in the regulation of emotion and motivation (Canli & Lesch, 2007;Salgado-Pineda, Delaveau, Blin, & Nieoullon, 2005). Fortunately, these neurotransmitter systems can be enhanced by repetitively acute bouts of exercise (for review, see Wegner et al., 2014), which have been found to increase monoamine levels (for review, see Basso & Suzuki, 2017). ...
... Individuals with internalizing disorders and children with ADHD have both been implicated in dysfunction of the dopaminergic and serotonergic systems (Canli & Lesch, 2007;Paclt et al., 2005;Salgado-Pineda et al., 2005;Volkow et al., 2011), which may modulate the effect of acute bouts of AE on FAA. Previous studies have shown that these two neuromodulators might, at least partly, explain the mechanism by which acute bouts of AE alter FAA. ...
... With respect to potential dopaminergic effects, findings from Wacker (2018) support a dopaminergic basis for frontal EEG asymmetry. However, the downstream effects of these two neurochemical factors on the frontal lobe, such as regulation of motivation and emotion (Canli & Lesch, 2007;Salgado-Pineda et al., 2005), might depend on the density of serotonergic/dopaminergic terminals and receptors (Celada, Puig, & Artigas, 2013;Schultz, Tremblay, & Hollerman, 1998). Children with ADHD exhibited less dopaminergic response to 30-minute bouts of AE compared to healthy controls, suggesting an impaired dopaminergic system (Wigal et al., 2003). ...
Background
Frontal alpha asymmetry (FAA) has been associated with the regulation of certain types of internalizing psychopathologies, and is affected by acute aerobic exercise (AE). However, no previous studies have examined the association between FAA and internalizing problems or the effects of acute exercise on FAA in children with ADHD.
Aims
This study had two objectives. First, it aimed to examine the relationship between FAA and internalizing behaviors in children with ADHD. Second, it sought to investigate the differential effects of acute AE (30 and 50 min) on FAA.
Method
Participants were assigned to one of the following three groups: 50 min of AE, 30 min of AE, and a control group. Resting electroencephalogram (EEG) data were recorded before and after their respective treatments. EEG data from 43 participants were analyzed to investigate the association between pre-test FAA and internalizing problems as assessed by Child Behavior Checklist scores. Additionally, EEG data from 46 participants were analyzed to examine the effects of acute AE on post-test FAA while controlling for pre-test FAA.
Results
Pre-test FAA was found to be significantly negatively associated with internalizing problems, with both hemispheres contributing to this association. Regarding the effects of acute exercise, the 50-minute AE group had highest post-test FAA, reflected by the increased relative left-side frontal activity.
Conclusions
These findings suggest that FAA is a biological marker of internalizing symptoms in children with ADHD, and a 50-minute session of AE can effectively modulate FAA.
... There are likely many such factors, but one potential neurobiological moderator, salient because it is linked to all aforementioned factors, involves dopaminergic function. Child maltreatment influences dopaminergic function (e.g., Galvin et al., 1991;Meaney, Brake, & Gratton, 2002), and dopamine has a critical impact on brain structures implicated in emotion regulation (Wager, Davidson, Hughes, Lindquist, & Ochsner, 2008) such as the prefrontal cortex, striatum, and amygdala (Salgado-Pineda, Delaveau, Blin, & Nieoullon, 2005). On reviewing the literature on dopamine and an array of psychiatric disorders, Salgado-Pineda et al. (2005) concluded, "DA has, undoubtedly, a direct and/or indirect role in the full emotional process" (p. ...
... Child maltreatment influences dopaminergic function (e.g., Galvin et al., 1991;Meaney, Brake, & Gratton, 2002), and dopamine has a critical impact on brain structures implicated in emotion regulation (Wager, Davidson, Hughes, Lindquist, & Ochsner, 2008) such as the prefrontal cortex, striatum, and amygdala (Salgado-Pineda, Delaveau, Blin, & Nieoullon, 2005). On reviewing the literature on dopamine and an array of psychiatric disorders, Salgado-Pineda et al. (2005) concluded, "DA has, undoubtedly, a direct and/or indirect role in the full emotional process" (p. 228). ...
... Specifically, infants with more DRD2, SLC6A3, and COMT plasticity alleles (A1, 10-repeat, and valine alleles, respectively), relative to infants with fewer plasticity alleles, are expected to engage in independent regulatory strategies for Villani et al. greater durations of time (i.e., rely less on the mother for regulation) if the mother has a history of greater, as opposed to lower, maltreatment. These specific genes were selected based on the aforementioned associations with correlates of emotion regulation, and the role of dopamine within emotion regulation (Salgado-Pineda et al., 2005). This study does not specifically differentiate between diathesis-stress, differential susceptibility, and vantage sensitivity models of Gene  Environment (GÂE) interaction (Roisman et al., 2012) given that maternal maltreatment history does not equate to infants' direct rearing environment. ...
Although infants less than 18 months old are capable of engaging in self-regulatory behavior (e.g., avoidance, withdrawal, and orienting to other aspects of their environment), the use of self-regulatory strategies at this age (as opposed to relying on caregivers) is associated with elevated behavioral and physiological distress. This study investigated infant dopamine-related genotypes (dopamine receptor D2 [ DRD2 ], dopamine transporter solute carrier family C6, member 4 [ SLC6A3 ], and catechol- O -methyltransferase [ COMT ]) as they interact with maternal self-reported history of maltreatment to predict observed infant independent emotion regulation behavior. A community sample ( N = 193) of mother–infant dyads participated in a toy frustration challenge at infant age 15 months, and infant emotion regulation behavior was coded. Buccal cells were collected for genotyping. Maternal maltreatment history significantly interacted with infant SLC6A3 and COMT genotypes, such that infants with more 10-repeat and valine alleles of SLC6A3 and COMT, respectively, relative to infants with fewer or no 10-repeat and valine alleles, utilized more independent (i.e., maladaptive) regulatory behavior if mother reported a more extensive maltreatment history, as opposed to less. The findings indicate that child genetic factors moderate the intergenerational impact of maternal maltreatment history. The results are discussed in terms of potential mechanism of Gene × Environment interaction.
... A considerable amount of data from brain lesions, neural recordings, and neuroimaging studies demonstrates that mesencephalic regions and other brainstem regions participate in emotion generation and regulation [7][8][9]. For instance, the ventral tegmental area (VTA)/substantia nigra (SNG) complex exerts an important modulatory function of autonomic, emotional, and motivational responses through ascending dopaminergic nigrostriatal and mesocorticolimbic pathways [10,11]. In addition, the periaqueductal grey (PAG), a mesencephalic region strongly involved in fear responses [12], would also mediate emotional behavior through stimulus salience processing [5,13]. ...
... Neurofunctional accounts of the AI, besides indicating its relevance for the assessment and integration of high level interoceptive inferences and physiological homeostatic signals [96], proposed its specific role in error-based learning of emotional states [99]. In this context, ascending dopaminergic prediction error signals [100,101] would be highly relevant for emotion regulation [10]. The extensive dopaminergic innervations [102] and high density of D1 dopamine receptors of the agranular insular cortex [103] can support regulation of emotion through the analysis of primary and secondary mappings of interoceptive signals. ...
Increasing evidence shows that the generation and regulation of affective responses is associated with activity of large brain networks that also include phylogenetically older regions in the brainstem. Mesencephalic regions not only control autonomic responses but also participate in the modulation of autonomic, emotional, and motivational responses. The specific contribution of the midbrain to emotion regulation in humans remains elusive. Neuroimaging studies grounding on appraisal models of emotion emphasize a major role of prefrontal cortex in modulating emotion-related cortical and subcortical regions but usually neglect the contribution of the midbrain and other brainstem regions. Here, the role of mesolimbic and mesocortical networks in core affect generation and regulation was explored during emotion regulation guided by real-time fMRI feedback of the anterior insula activity. The fMRI and functional connectivity analysis revealed that the upper midbrain significantly contributes to emotion regulation in humans. Moreover, differential functional interactions between the dopaminergic mesocorticolimbic system and frontoparietal networks mediate up and down emotion regulatory processes. Finally, these findings further indicate the potential of real-time fMRI feedback approach in guiding core affect regulation.
... There is substantial support for the role of dopamine in emotion recognition ( Salgado-Pineda et al., 2005 ), mainly by animal and human studies manipulating dopamine agonists and antagonists ( Péron et al., 2012 ). The involvement of dopamine in emotion processing is expected since most of the brain regions implicated in emotion are targeted by the mesolimbic and mesocortical dopaminergic pathways. ...
... Notably, accuracy of matching emotional stimuli was not associated with cognitive function. The results are consistent with the proposed role of dopamine in emotion recognition ( Salgado-Pineda et al., 2005 ). However, there have been previous conflicting findings regarding the influence of dopaminergic medication on behavior in emotional face processing. ...
Emotional and cognitive impairments in Parkinson's disease (PD) are prevalent, hamper interpersonal relations and reduce quality of life. It is however unclear to what extent these domains interplay in PD-related deficits and how they are influenced by dopaminergic availability. This study examined the effect of cognitive impairment and dopaminergic medication on neural and behavioral mechanisms of facial emotion recognition in PD patients. PD patients on and off dopaminergic medication and matched healthy controls underwent an emotional face matching task during functional MRI. In addition, a comprehensive neuropsychological evaluation of cognitive function was conducted. Increased BOLD response to emotional faces was found in the visual cortex of PD patients relative to controls irrespective of cognitive function and medication status. Administration of dopaminergic medication in PD patients resulted in restored behavioral accuracy for emotional faces relative to controls and decreased retrosplenial cortex BOLD response to emotion relative to off-medication state. Furthermore, cognitive impairment in PD patients was associated with reduced behavioral accuracy for non-emotional stimuli and predicted BOLD response to emotion in the anterior and posterior cingulate cortices, depending on medication status. Findings of aberrant visual and retrosplenial BOLD response to emotion are suggested to stem from altered attentional and/or emotion-driven modulation from subcortical and higher cortical regions. Our results indicate neural disruptions and behavioral deficits in emotion processing in PD patients that are dependent on dopaminergic availability and independent of cognitive function. Our findings highlight the importance of dopaminergic treatment not only for the motor symptoms but also the emotional disturbances in PD.
... Emotion regulation may also serve as a mediating pathway through which DRD4 affects maternal sensitivity. Prior research has demonstrated that dopamine and dopamine-related genes play important roles in self-regulation (Cómbita, Voelker, Abundis-Gutierrez, Pozuelos, & Rueda, 2017) and emotional processes (Salgado-Pineda, Delaveau, Blin, & Nieoullon, 2005). Numerous studies have examined the role of DRD4 in self-regulation, largely focusing on cognitive and attentional self-regulation in clinical samples of children with attention-deficit/hyperactivity disorder and yielding inconsistent findings regarding main effects of DRD4 on self-regulation (e.g., Johnson et al., 2008;Langley et al., 2004). ...
... Future research is warranted to examine this possibility. This indirect pathway is also consistent with the view that genes involved in the dopamine system are related to self-regulation and emotional processes (Cómbita et al., 2017;Salgado-Pineda et al., 2005) and play an important role in maternal behavior (Bridgett et al., 2015;Numan, 2010). It appears that mothers with the DRD4 long allele have greater difficulty regulating their emotions, which undermines their ability to respond sensitively to their infants' needs. ...
We examined whether and how the dopamine receptor D4 (DRD4) interacts with adverse life events to predict maternal sensitivity directly and indirectly via emotion regulation. The sample included 209 (106 European American, 103 African American) mothers and their children (52% female). Sensitive maternal behavior was rated and aggregated across five stress-free and stress-inducing tasks when children were about 2 years old, when mothers also retrospectively reported on their adverse life experiences and transitions throughout childhood from birth to age 20. When children were about 1 year old, mothers reported on their difficulties with emotion regulation. Results from path analysis indicated that mothers who carried the long allele of DRD4 and experienced more adverse life events were less sensitive in interactions with their children. These mothers were also more likely to have difficulties with emotion regulation, which in turn predicted lower maternal sensitivity. These effects were significant above and beyond the effects of maternal education, coherence of mind, race, or infants’ DRD4 genotype, and did not vary for African American and European American mothers. Results suggest that genetic predispositions modify the effects of maternal experience of adverse life events on maternal sensitivity and that emotion regulation serves as one mechanism by which genetic factors and gene–environment interactions affect maternal behavior.
... contains supplementary material, which is available to authorized users. others depends on the PFC (Forbes and Grafman 2010) and DA transmission, as this process has been shown to be affected in Parkinson's patients and DA treatments in them (Salgado-Pineda et al. 2005;Sprengelmeyer et al. 2003). ...
... Although the roles of mesocortical DA transmission in the PFC for cognitive functions in nonsocial domains have been extensively studies (Arnsten 1997;Robbins 2000;Seamans and Yang 2004), its roles on social cognition have remained elusive. That DA is involved in recognition of emotional expressions of faces has been reported in studies with Parkinson's patients under therapeutic treatments with Ldopa (Salgado-Pineda et al. 2005;Sprengelmeyer et al. 2003). We have also recently shown that DA regulates visual attention preference to social over nonsocial stimuli, but through distinct mechanisms with D1 and D2 receptor signaling (Yamaguchi et al. 2017a). ...
Rationale:
Dopamine (DA) is a neurotransmitter whose roles have been suggested in various aspects of brain functions. Recent studies in rodents have reported its roles in social function. However, how DA is involved in social information processing in primates has largely remained unclear.
Objectives:
We investigated prefrontal cortical (PFC) activities associated with social vs. nonsocial visual stimulus processing.
Methods:
Near-infrared spectroscopy (NIRS) was applied to Japanese macaques, along with pharmacological manipulations of DA transmission, while they were gazing at social and nonsocial visual stimuli.
Results:
Oxygenated (oxy-Hb) and deoxygenated (deoxy-Hb) hemoglobin changes as well as functional connectivity based on such Hb changes within the PFC network which were distinct between social and nonsocial stimuli were observed. Administration of both D1 and D2 receptor antagonists affected the Hb changes associated with social stimuli, whereas D1, but not D2, receptor antagonist affected the Hb changes associated with nonsocial stimuli.
Conclusions:
These results suggest that mesocortical DA transmission in the PFC plays significant roles in social information processing, which involves both D1 and D2 receptor activation, in nonhuman primates. However, D1 and D2 receptor signaling in the PFC mediates different aspects of social vs. nonsocial information processing.
... Impairment of the fronto-subcortical circuits mediating limbic functions is considered as the main substratum of emotional dysfunctions in PD (Assogna et al., 2008;Gray & Tickle-Degnen, 2010;Péron, Dondaine, et al., 2011;Salgado-Pineda et al., 2005). However, an interesting parallel hypothesis comes from the embodied simulation theory. ...
... importante de perturbations des relations sociales. En effet, la dénervation dopaminergique, davantage mésocorticolimbique que nigrostriatale (Salgado-Pineda,Delaveau, Blin, & Nieoullon, 2005), participe activement à l'altération des processus émotionnels(Dondaine & Péron, 2012;Péron, Dondaine, Le Jeune, Grandjean, & Vérin, 2011;Sotgiu & Rusconi, 2013). Par conséquent, les patients parkinsoniens présentent des difficultés pour exprimer et reconnaître les émotions qu'elles soient portées par la voix(Schröder, Nikolova, & Dengler, 2010) ou véhiculées sur le visage(Assogna, Pontieri, Caltagirone, & Spalletta, 2008). ...
La maladie de Parkinson est une affection neurodégénérative principalement associée à la dégénérescence progressive des neurones dopaminergiques du mésencéphale provoquant un dysfonctionnement des noyaux gris centraux. En parallèle de symptômes moteurs bien connus, cette affection entraîne également l’émergence de déficits émotionnels impactant en outre l’expression et la reconnaissance des émotions. Ici, se pose la question d’un déficit de reconnaissance des émotions faciales chez les patients parkinsoniens lié au moins en partie aux troubles moteurs. En effet, selon les théories de simulation des émotions, copier les émotions de l’autre nous permettrait de mieux les reconnaître. Ce serait le rôle du mimétisme facial. Automatique et inconscient, ce phénomène est caractérisé par des réactions musculaires congruentes à l’émotion exprimée par autrui. Dans ce contexte, une perturbation des capacités motrices pourrait conduire à une altération des capacités de reconnaissance des émotions. Or, l’un des symptômes moteurs les plus fréquents dans la maladie de Parkinson, l’amimie faciale, consiste en une perte de la mobilité des muscles du visage. Ainsi, nous avons examiné l’efficience du mimétisme facial dans la maladie de Parkinson, son influence sur la qualité du processus de reconnaissance des émotions, ainsi que l’effet du traitement dopaminergique antiparkinsonien sur ces processus. Pour cela, nous avons développé un paradigme permettant l’évaluation simultanée des capacités de reconnaissance et de mimétisme (corrugator supercilii, zygomaticus major et orbicularis oculi) d’émotions exprimées sur des visages dynamiques (joie, colère, neutre). Cette expérience a été proposée à un groupe de patients parkinsoniens comparé à un groupe de sujets sains témoins. Nos résultats supportent l’hypothèse selon laquelle le déficit de reconnaissance des émotions chez le patient parkinsonien pourrait résulter d’un système « bruité » au sein duquel le mimétisme facial participerait. Cependant, l’altération du mimétisme facial dans la maladie de Parkinson et son influence sur la reconnaissance des émotions dépendraient des muscles impliqués dans l’expression à reconnaître. En effet, ce serait davantage le relâchement du corrugateur plutôt que les contractions du zygomatique ou de l’orbiculaire de l’œil qui nous aiderait à bien reconnaître les expressions de joie. D’un autre côté, rien ne nous permet ici de confirmer l’influence du mimétisme facial sur la reconnaissance des expressions de colère. Enfin, nous avons proposé cette expérience à des patients en condition de traitement habituel et après une interruption temporaire de traitement. Les résultats préliminaires de cette étude apportent des éléments en faveur d’un effet bénéfique du traitement dopaminergique tant sur la reconnaissance des émotions que sur les capacités de mimétisme. L’hypothèse d’un effet bénéfique dit « périphérique » sur la reconnaissance des émotions par restauration du mimétisme facial reste à tester à ce jour. Nous discutons l’ensemble de ces résultats selon les conceptions récentes sur le rôle des noyaux gris centraux et sous l’angle de l’hypothèse de feedback facial.
... This aspect is linked to hedonic processes associated with pleasure and reward (16) regulated in the brain reward system. Gene polymorphisms related to the reward system such as the Dopamine Receptor 2 (DRD2/ANKK1) gene and Catechol-O-methyltransferase (COMT) seem to influence appetitive traits, by promoting hedonic food consumption and reducing satiety control (17). The A1 allele from the DRD2/ANKK1 TaqIA1 (rs1800497) polymorphism contributes to decreased DRD2 receptor density and increases L-DOPA activity, impairing the reward system. ...
Introduction
Appetitive traits are influenced by the interplay between genetic and environmental factors. This study aimed to explore the relationship between gene polymorphisms involved in the regulation of energy balance and food reward and appetitive traits in young Mexican subjects.
Methods
This cross-sectional study involved 118 university freshman undergraduates who completed the Adult Eating Behaviour Questionnaire for Spanish speakers (AEBQ-Esp) to assess their appetitive traits. A real-time PCR system was employed to determine gene polymorphisms involved in energy balance (LEP rs7799039, MC4R rs17782313, FTO rs9939609, GHRL rs696217), and reward system (DRD2/ANKK1 Taq1A rs1800497 and COMT rs4680).
Results
The mean age of participants was 20.14 ± 3.95 years, 71.2% were women and their mean BMI was 23.52 ± 4.05 kg/m². COMT Met allele carriers presented a significantly higher “Emotional overeating” mean score than Val allele carriers (2.63 ± 0.70 vs. 2.23 ± 0.70, p = 0.028). The MC4R CC + CT genotype correlated positively with “Emotional overeating” (Phi = 0.308, p = 0.01). The COMT MetMet+MetVal genotype correlated with higher “Emotional overeating” (r = 0.257, p = 0.028; Phi = 0.249, p = 0.033). The protective genotype FTO TT correlated positively with “Emotional undereating” (Phi = 0.298, p = 0.012). Carriers of the risk genotype MC4R CC + CT presented a higher risk of “Emotional overeating” than TT carriers (OR = 2.4, 95% CI 1.3–4.8, p = 0.034). Carriers of the risk genotype COMT MetMet+MetVal (OR = 3.4, 95% CI 1.1–10.3, p = 0.033), were associated with a higher risk of “Emotional overeating” than ValVal carriers. The protective FTO genotype TT was associated with “Emotional undereating” (OR = 1.8, 95% CI 1.1–9.1, p = 0.014).
Discussion
The study found a relationship between the protective genotypes of FTO TT and “Emotional undereating” and risk genotypes of COMT Met/Met+Met/Val and MC4R CC + CT with “Emotional overeating.” These genetic factors may increase weight gain by enhancing hedonic food consumption and reducing satiety control. Future studies should focus on replication studies in ethnically diverse young adults and life stages to explore the relationship between polymorphisms and appetitive traits and weight. This will help tailor personalized nutrigenetic strategies to counteract disordered eating patterns leading to obesity and associated co-morbidities.
... Conversely, in individuals with schizophrenia, FER ability was found to improve using typical (Hempel et al, 2010) or atypical (Behere et al, 2009) neuroleptics. All types of neuroleptics affect dopamine regulation in the mesocorticolimbic system, which might lead to better regulation of amygdala activity and emotion regulation (Salgado-Pineda et al, 2005). ...
Background:
Facial emotion recognition (FER) is commonly impaired in individuals with neurodegenerative disease (NDD). This impairment has been linked to an increase in behavioral disorders and caregiver burden.
Objective:
To identify interventions targeting the improvement of FER ability in individuals with NDD and investigate the magnitude of the efficacy of the interventions. We also wanted to explore the duration of the effects of the intervention and their possible impacts on behavioral and psychological symptoms of dementia and caregiver burden.
Method:
We included 15 studies with 604 individuals who had been diagnosed with NDD. The identified interventions were categorized into three types of approach (cognitive, neurostimulation, and pharmacological) as well as a combined approach (neurostimulation with pharmacological).
Results:
The three types of approaches pooled together had a significant large effect size for FER ability improvement (standard mean difference: 1.21, 95% CI = 0.11, 2.31, z = 2.15, P = 0.03). The improvement lasted post intervention, in tandem with a decrease in behavioral disorders and caregiver burden.
Conclusion:
A combination of different approaches for FER ability improvement may be beneficial for individuals with NDD and their caregivers.
... . DA neurons are the main source of dopamine in the mammalian central nervous system (CNS) (Chinta and Andersen, 2005). They are essential for voluntary movement, cognition, emotion, working memory, and reward pathways (Bromberg-Martin et al., 2010;Chinta and Andersen, 2005;Groves, 1983;McNamara et al., 2014;Salgado-Pineda et al., 2005). As a result, insufficient dopamine levels lead not only to profoundly disabling motor symptoms, but also to mood changes and memory loss (Chinta and Andersen, 2005). ...
Parkinson's disease (PD) is a neurodegenerative disorder characterized by selective loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) region of the midbrain. The loss of neurons results in a subsequent reduction of dopamine in the striatum, which underlies the core motor symptoms of PD. To date, there are no effective treatments to stop, slow, or reverse the pathological progression of dopaminergic neurodegeneration. This unfortunate predicament is because of the current early stages in understanding the biological targets and pathways involved in PD pathogenesis. Ion channels have become emerging targets for new therapeutic development for PD due to their essential roles in neuronal function and neuroinflammation. Potassium channels are the most prominent ion channel family and have been shown to be critically important in PD pathology because of their roles in modulating neuronal excitability, neurotransmitter release, synaptic transmission, and neuroinflammation. In this review, members of the subfamilies of voltage-gated K+ channels, inward rectifying K+ channels, and Ca2+-activated potassium channels are described. Evidence of the role of these channels in PD aetiology is discussed together with the latest views on related pathological mechanisms and their potential as biological targets for developing neuroprotective drugs for PD. Significance Statement Parkinson's disease (PD) is the second most common neurodegenerative disorder, featuring progressive degeneration of dopaminergic neurons in the midbrain. It is a multifactorial disease involving multiple risk factors and complex pathobiological mechanisms. Mounting evidence suggests that ion channels play vital roles in the pathogenesis and progression of PD by regulating neuronal excitability and immune cell function. Therefore, they have become "hot" biological targets for PD, as demonstrated by multiple clinical trials of drug candidates targeting ion channels for PD therapy.
... But decades of endeavor particularly in relation to D2 receptor function has failed to produce new efficacious treatments. The role of dopaminergic function in emotional regulation and its contribution to impaired emotional processing in substance dependence is unclear (40). Acute stress is known to increase dopamine release in the accumbens and prefrontal cortex (41), which may negatively impact addicted individuals with compromised dopaminergic function and/or negative affect (42). ...
Introduction
Negative affective states contribute to the chronic-relapsing nature of addiction. Mesolimbic dopamine D3 receptors are well placed to modulate emotion and are dysregulated in substance dependence. Selective antagonists might restore dopaminergic hypofunction, thus representing a potential treatment target. We investigated the effects of selective D3 antagonist, GSK598809, on the neural response to negative emotional processing in substance dependent individuals and healthy controls.
Methodology
Functional MRI BOLD response was assessed during an evocative image task, 2 h following acute administration of GSK598809 (60 mg) or placebo in a multi-site, double-blind, pseudo-randomised, cross-over design. Abstinent drug dependent individuals (DD, n = 36) comprising alcohol-only (AO, n = 19) and cocaine-alcohol polydrug (PD, n = 17) groups, and matched controls (n = 32) were presented with aversive and neutral images in a block design (contrast of interest: aversive > neutral). Whole-brain mixed-effects and a priori ROI analyses tested for group and drug effects, with identical models exploring subgroup effects.
Results
No group differences in task-related BOLD signal were identified between DD and controls. However, subgroup analysis revealed greater amygdala/insular BOLD signal in PD compared with AO groups. Following drug administration, GSK598809 increased BOLD response across HC and DD groups in thalamus, caudate, putamen, and pallidum, and reduced BOLD response in insular and opercular cortices relative to placebo. Multivariate analyses in a priori ROIs revealed differential effects of D3 antagonism according to subgroup in substantia nigra; GSK598809 increased BOLD response in AO and decreased response in PD groups.
Conclusion
Acute GSK598809 modulates the BOLD response to aversive image processing, providing evidence that D3 antagonism may impact emotional regulation. Enhanced BOLD response within D3-rich mesolimbic regions is consistent with its pharmacology and with attenuation of substance-related hypodopaminergic function. However, the lack of group differences in task-related BOLD response and the non-specific effect of GSK598809 between groups makes it difficult to ascertain whether D3 antagonism is likely to be normalising or restorative in our abstinent populations. The suggestion of differential D3 modulation between AO and PD subgroups is intriguing, raising the possibility of divergent treatment responses. Further study is needed to determine whether D3 antagonism should be recommended as a treatment target in substance dependence.
... Moreover, regular exercise has been shown to improve dopamine receptor availability over time (12). Dr. Pilar Salgado-Pineda, researcher at the Spanish Lab FIDMAG Hermanas Hospitalarias Research Foundation, suggests that dopamine is directly connected to emotional responses (13). ...
Countless strategies in the broader field of social emotional learning have been shown to benefit individuals and organizations alike. Capacities like empathy can improve interactions and have been recommended as a necessary skill. Such psychological capacities are heavily influenced by physiological states. Research supporting this alignment continues to grow. This article examines the role of emotional granularity in empathy, and the impact of exercise on that process. All components of an organization’s environment should be deliberately crafted. Individuals and organizations hoping to improve social emotional learning should also uphold healthy standards for sleep, nutrition, and exercise. It would be a costly mistake to misunderstand the connection of body and mind. Performance, and public health at large, depend on it.
... The midbrain DA neurons in mammals are sub-grouped into VTA and SN (Adinoff, 2004;Gardner & Ashby, 2000;Poulin et al., 2014;Salgado-Pineda et al., 2005;van Domburg & ten Donkelaar, 1991). While VTA DAergic system drives the mesolimbic reward pathway (Beier et al., 2015;Halbout et al., 2019;Keiflin et al., 2019), SN provides major contribution to the nigrostriatal pathway to control motor coordination (Hodge & Butcher, 1980;Le et al., 2015;Lynd-Balta & Haber, 1994). ...
Calcium-binding proteins (CBPs) regulate neuronal function in midbrain dopamine (DA)-ergic neurons in mammals by buffering and sensing the intracellular Ca2+ , and vesicular release. In birds, the equivalent set of neurons are important in song learning, directed singing, courtship, and energy balance, yet the status of CBPs in these neurons is unknown. Herein, for the first time, we probe the nature of CBPs, namely, Calbindin-, Calretinin-, Parvalbumin-, and Secretagogin-expressing DA neurons in the ventral tegmental area (VTA) and substantia nigra (SN) in the midbrain of zebra finch, Taeniopygia guttata. qRT-PCR analysis of ventral midbrain tissue fragment revealed higher Calbindin- and Calretinin-mRNA levels compared to Parvalbumin and Secretagogin. Application of immunofluorescence showed CBP-immunoreactive (-i) neurons in VTA (anterior [VTAa], mid [VTAm], caudal [VTAc]), SN (compacta [SNc], and reticulata [SNr]). Compared to VTAa, higher Calbindin- and Parvalbumin-immunoreactivity (-ir), and lower Calretinin-ir were observed in VTAm and VTAc. Secretagogin-ir was highly localized to VTAa. In SN, Calbindin- and Calretinin-ir were higher in SNc, SNr was Parvalbumin enriched, and Secretagogin-ir was not detected. Weak, moderate, and intense tyrosine hydroxylase (TH)-i VTA neurons were demarcated as subtypes 1, 2, and 3, respectively. While subtype 1 TH-i neurons were neither Calbindin- nor Calretinin-i, ∼80 and ∼65% subtype 2 and ∼30 and ∼45% subtype 3 TH-i neurons co-expressed Calbindin and Calretinin, respectively. All TH-i neuronal subtypes co-expressed Parvalbumin with reciprocal relationship with TH-ir. We suggest that the CBPs may determine VTA DA neuronal heterogeneity and differentially regulate their activity in T. guttata.
... This animal model of dopamine signaling may be used to address the great challenges presented by many dopamine-related neurological and psychiatric disorders, including PD, schizophrenia and attention deficit hyperactivity disorder [9,50,51]. For example, levodopa (L-DOPA) and dopamine agonists are medications commonly used to treat PD patients with reduced dopamine release resulting from the degeneration of dopaminergic neurons [52][53][54]. ...
When animals are faced with food depletion, food search-associated locomotion is crucial for their survival. Although food search-associated locomotion is known to be regulated by dopamine, it has yet to investigate the potential molecular mechanisms governing the regulation of genes involved in dopamine metabolism (e.g., cat-1, cat-2) and related behavioral disorders. During the studies of the pheromone ascaroside, a signal of starvation stress in C. elegans, we identified R02D3.7, renamed rcat-1 (regulator of cat genes-1), which had previously been shown to bind to regulatory sequences of both cat-1 and cat-2 genes. It was found that RCAT-1 (R02D3.7) is expressed in dopaminergic neurons and functions as a novel negative transcriptional regulator for cat-1 and cat-2 genes. When a food source becomes depleted, the null mutant, rcat-1(ok1745), exhibited an increased frequency of high-angled turns and intensified area restricted search behavior compared to the wild-type animals. Moreover, rcat-1(ok1745) also showed defects in state-dependent olfactory adaptation and basal slowing response, suggesting that the mutants are deficient in either sensing food or locomotion toward food. However, rcat-1(ok1745) has normal cuticular structures and locomotion genes. The discovery of rcat-1 not only identifies a new subtype of dopamine-related behaviors but also provides a potential therapeutic target in Parkinson’s disease.
... Dopaminergic signaling is fundamental to a number of neurobiological processes that are required for cognition [1][2][3], emotion [4], movement [5], and reward [3,[6][7][8]. Dopamine signaling is mediated through G protein coupled receptors, D1, D2, D3, D4, and D5, that are categorized into two subfamilies, D1-like and D2-like, based on their structure and function [9][10][11][12]. ...
Dopamine is an important neurotransmitter that plays a key role in neuropsychiatric illness. Sex differences in dopaminergic signaling have been acknowledged for decades and have been linked to sex-specific heterogeneity in both dopamine-related behaviours as well as in various neuropsychiatric disorders. However, the overall number of studies that have evaluated sex differences in dopamine signaling, both in health and in these disorders, is low. This review will bring together what is known regarding sex differences in innate dopamine receptor expression and function, as well as highlight the known sex-specific roles of dopamine in addiction, depression, anxiety, schizophrenia, and attention deficit hyperactivity disorder. Due to differences in prognosis, diagnosis, and symptomatology between male and female subjects in disorders that involve dopamine signaling, or in responses that utilize pharmacological interventions that target dopamine receptors, understanding the fundamental sex differences in dopamine receptors is of vital importance for the personalization of therapeutic treatment strategies.
... In addition to positive symptoms, serotonin and dopamine are thought to be involved in the improvement of SC and possible contributes to the improvement of emotional perception and social functioning, in particular, through the facilitating effect of serotonin antagonism on dopamine release in the prefrontal cortex [21,108]. Furthermore, the role of dopamine regulation in the mesocorticolimbic system mediated by second-generation antipsychotics could act as an emotional manager over the amygdala [109], this could explain the efficacy of SGAs compared to first generation antipsychotics on SC [110]. ...
Cognitive impairment is currently considered a core feature of schizophrenia (SZ) and is gaining attention as a fundamental therapeutic target. Standard treatment for SZ involves the use of antipsychotics that are successfully used to control positive symptoms and disorganized behaviour. However, it is still unclear whether they are effective on social cognition (SC) impairment. Furthermore, different medications are currently being studied to improve SC in patients with SZ. A literature search on this topic was conducted using the PubMed database. All kinds of publications (i.e., reviews, original contributions and case reports) written in English and published in the last 15 years were included. The aim of our literature review is to draw a picture of the current state of the pharmacological treatment of SC impairment in SZ.
... The decrease in the hypothalamic level of serotonin after the fluoxetine administration at a dose of 25 mg/kg may be explained by the fact that the latter reduces the expression of gene encoding tryptophan hydroxylase-2, which is responsible for the synthesis of 5-HT in the brain [20]. In the frontal cortex of the ST rats, however, administration of fluoxetine induced the tendency for 5-HT to increase, which was accompanied by significant decrease in DA that is involved in the control of anxiety [24] and regulation of motor activity as well [25]. ...
Background:
The seizures, triggered by a loud sound in laboratory animals, are associated with the imbalance of the brain monoamines. Serotonin (5-HT) is regarded as one of the principal neurotransmitters to be involved in regulation of wide variety of physiological and psychological processes. Among the drugs that affect 5-HT synaptic transmission, the leading role is given to selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine.
Aim:
The aim of the study is to investigate the effects of fluoxetine on seizures in Wistar rats with high susceptibility to audiogenic stress.
Methods:
The study was performed on male Wistar rats. Before the experiments, the animals were tested for susceptibility to audiogenic seizures by exposure to a sound of 90-110 dB for 2 min in the soundproof box. The difference between congenital susceptibility to seizures served as a basis for dividing animals into two groups: Seizure-susceptible (SS) and seizure-tolerant (ST) rats. One hour before the experiment, the experimental animals were orally administered with fluoxetine, while the control rats were treated with distilled water. The effect of fluoxetine on the level of the biogenic amines in different regions of the brain was determined by enzyme-linked immunosorbent assay (ELISA).
Results:
It has been shown that in 100% of the cases, the control SS rats, exposed to audiogenic stimulus, exhibited wild running around in circles and jumping as some of the signs of seizure responses that evolved into tonic-clonic seizures in 70% of the cases. As regards the experimental SS animals: Only in 60% of the cases (P<0.05), they exhibited wild running and flinch, which did not evolve into the tonic-clonic phase.
Conclusion:
Decreased manifestation of seizures in the experimental SS rats under acute administration of fluoxetine may be explained by highly distinctive repertoire and spatial distribution of 5-HT receptors in their brain structures in comparison to the ST rats.
Relevance for patients:
The study of the monoaminergic mechanisms of seizure generation is of practical importance due to the existence of pharmacological agents, which selectively affect the activity of the monoaminergic systems of the brain, as well as the metabolism of the monoamines synthesized by them.
... The presence of FERD in disorders like Parkinsonism, Huntington's disease, thalamic stroke and also psychiatric disorder like schizophrenia suggests the involvement of basal ganglia, limbic system and dopaminergic system in emotion perception. [49] Functional MRI studies have demonstrated under activation of amygdala & hippocampus [35] and prefrontal cortex [50] in response to fear in schizophrenia patients. ...
... In this study, we concentrated on negative emotional salience for two reasons. First, PD shows a progressive and chronic degeneration of the nigrostriatal and mesocorticolimbic dopaminergic systems (Braak et al., 2005;Wu et al., 2012) and an impaired dopaminergic pathway of emotional processing (Badgaiyan, 2010;Laviolette, 2007;Salgado-Pineda et al., 2005). PD patients therefore show a wide range of emotional processing deficits (see recent reviews: (Moonen et al., 2017;Péron et al., 2012)), mainly linked to n abnormalities in predominantly ventral regions of the affective neurocircuitry. ...
Objective
Current research does not provide a clear explanation for why some patients with Parkinson’s Disease (PD) develop psychotic symptoms. The ‘aberrant salience hypothesis’ of psychosis has been influential and proposes that dopaminergic dysregulation leads to inappropriate attribution of salience to irrelevant/non-informative stimuli, facilitating the formation of hallucinations and delusions. The aim of this study is to investigate whether non-motivational salience is altered in PD patients and possibly linked to the development of psychotic symptoms.
Methods
We investigated salience processing in 14 PD patients with psychotic symptoms, 23 PD patients without psychotic symptoms and 19 healthy controls. All patients were on dopaminergic medication for their PD. We examined emotional salience using a visual oddball fMRI paradigm that has been used to investigate early stages of schizophrenia spectrum psychosis, controlling for resting cerebral blood flow as assessed with arterial spin labelling fMRI.
Results
We found significant differences between patient groups in brain responses to emotional salience. PD patients with psychotic symptoms had enhanced brain responses in the striatum, dopaminergic midbrain, hippocampus and amygdala compared to patients without psychotic symptoms. PD patients with psychotic symptoms showed significant correlations between the levels of dopaminergic drugs they were taking and BOLD signalling, as well as psychotic symptom scores.
Conclusion
Our study suggests that enhanced signalling in the striatum, dopaminergic midbrain, the hippocampus and amygdala is associated with the development of psychotic symptoms in PD, in line with that proposed in the ‘aberrant salience hypothesis’ of psychosis in schizophrenia.
... It can be observed that substance use disorder and dependence may relate to changes in this system [4]. Shaping and maintaining both the control of emotional behavior and processing of emotions seemed to be directly conditioned by dopaminergic transmission [5]. One of the dopamine receptors, D2, is active in this process [6]. ...
Development of an addiction is conditioned by many factors. The dopaminergic system has been shown to be the key element in this process. In this paper, we analyzed the influence of dopamine receptor 2 polymorphism rs1076560 in two groups—polysubstance-dependent male patients (n = 299) and the controls matched for age (n = 301). In both groups, we applied the same questionnaires for testing—Mini-international neuropsychiatric interview, the NEO Five-Factor Inventory, and the State–Trait Anxiety Inventory. The real-time PCR method was used for genotyping. When we compared the controls with the case group subjects, we observed significantly higher scores in the second group on both the state and trait scales of anxiety, as well as on the Neuroticism and Openness scales of the NEO-FFI; and lower scores on the scales of Extraversion and Agreeability of the NEO-FFI. The model 2×3 factorial ANOVA of the addicted subjects and controls was performed, and the DRD2 rs1076560 variant interaction was found for the anxiety state and trait scales, and for the NEO-FFI Neuroticism scale. The observed associations allow noticing that analysis of psychological factors in combination with genetic data opens new possibilities in addiction research.
... The resulting progressive loss of nigrostriatal dopamine signaling is the main cause of the cardinal motor symptoms of PD, such as bradykinesia, rigidity and resting tremor (3). Besides, emotional and cognitive disturbances, contributing to the non-motor symptoms of PD, are based on the dysregulation of cortical circuits, which are partly dependent on the midbrain dopamine system (4)(5)(6)(7). ...
Parkinson's disease (PD) is a neurodegenerative disorder characterized by protein inclusions mostly composed of aggregated forms of α-synuclein (α-Syn) and by the progressive degeneration of midbrain dopaminergic neurons (mDANs), resulting in motor symptoms. While other brain regions also undergo pathologic changes in PD, the relevance of α-Syn aggregation for the preferential loss of mDANs in PD pathology is not completely understood yet. To elucidate the mechanisms of the brain region-specific neuronal vulnerability in PD, we modelled human PD using human induced pluripotent stem cells (iPSCs) from familial PD cases with a duplication (Dupl) of the α-Syn gene (SNCA) locus. Human iPSCs from PD Dupl patients and a control individual were differentiated into mDANs and cortical projection neurons (CPNs). SNCA dosage increase did not influence differentiation efficiency of mDANs and CPNs. However, elevated α-Syn pathology, as revealed by enhanced α-Syn insolubility and phosphorylation, was determined in PD-derived mDANs compared to PD CPNs. PD-derived mDANs exhibited higher levels of reactive oxygen species and protein nitration levels compared to CPNs, which might underlie elevated α-Syn pathology observed in mDANs. Finally, increased neuronal death was observed in PD-derived mDANs compared to PD CPNs and to control mDANs and CPNs. Our results reveal, for the first time, a higher α-Syn pathology, oxidative stress level, and neuronal death rate in human PD mDANs compared to PD CPNs from the same patient. The finding implies the contribution of pathogenic α-Syn, probably induced by oxidative stress, to selective vulnerability of substantia nigra dopaminergic neurons in human PD.
... There were indices of upregulated transporter expression within each transmitter system, and significantly higher SERT/ DAT co-expression, in SAD patients in brain regions involved in fear and reward processing. Significant statistical interactions between the transporters, indicating increased SERT/DAT co-expression in SAD relative to HC, were prominent in the amygdala, a structure heavily implicated in fear and anxiety [53,54] strongly influenced both by serotonin [55] and dopamine [56]. This was also noted in the putamen which is involved in reinforcement learning [57] and may be structurally enlarged in SAD [58]. ...
Serotonin and dopamine are putatively involved in the etiology and treatment of anxiety disorders, but positron emission tomography (PET) studies probing the two neurotransmitters in the same individuals are lacking. The aim of this multitracer PET study was to evaluate the regional expression and co-expression of the transporter proteins for serotonin (SERT) and dopamine (DAT) in patients with social anxiety disorder (SAD). Voxel-wise binding potentials (BPND) for SERT and DAT were determined in 27 patients with SAD and 43 age- and sex-matched healthy controls, using the radioligands [¹¹C]DASB (3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile) and [¹¹C]PE2I (N-(3-iodopro-2E-enyl)-2beta-carbomethoxy-3beta-(4′-methylphenyl)nortropane). Results showed that, within transmitter systems, SAD patients exhibited higher SERT binding in the nucleus accumbens while DAT availability in the amygdala, hippocampus, and putamen correlated positively with symptom severity. At a more lenient statistical threshold, SERT and DAT BPND were also higher in other striatal and limbic regions in patients, and correlated with symptom severity, whereas no brain region showed higher binding in healthy controls. Moreover, SERT/DAT co-expression was significantly higher in SAD patients in the amygdala, nucleus accumbens, caudate, putamen, and posterior ventral thalamus, while lower co-expression was noted in the dorsomedial thalamus. Follow-up logistic regression analysis confirmed that SAD diagnosis was significantly predicted by the statistical interaction between SERT and DAT availability, in the amygdala, putamen, and dorsomedial thalamus. Thus, SAD was associated with mainly increased expression and co-expression of the transporters for serotonin and dopamine in fear and reward-related brain regions. Resultant monoamine dysregulation may underlie SAD symptomatology and constitute a target for treatment.
... Adolescence coincides with a particularly sensitive maturation period for the dopaminergic system (Chambers et al., 2003;Casey et al., 2008;Ernst et al., 2009;Novick et al., 2011;Sinclair et al., 2014;Fuhrmann et al., 2015;Niwa et al., 2016). Dopamine (DA) is a catecholamine neurotransmitter important for modulation of eating (Rolls et al., 1974;Yoshida et al., 1992;Volkow et al., 2003;Davis et al., 2009), motor activity (Andén et al., 1973;Baldo et al., 2002;Gallardo et al., 2014;Robertson et al., 2015;Felger and Treadway, 2016), emotion (Herman et al., 1982;Salgado-Pineda et al., 2005;Kienast et al., 2008;Belujon and Grace, 2015), impulsivity (Gaalen et al., 2006;Buckholtz et al., 2010;Pine et al., 2010;Dalley and Robbins, 2017), and reward (Nestler and Carlezon, 2006;Johnson and Kenny, 2010;Eshel et al., 2016). Eating disorders, particularly AN and bulimia nervosa, are characterized by drastic changes in eating and/or activity behaviors that, when sufficiently rewarding to the individual's desired outcome (e.g., dramatic weight loss), can lead to compulsive engagement in such behavior despite severe deterioration in health or lifestyle. ...
Eating disorders such as anorexia typically emerge during adolescence, are characterized by engagement in compulsive and detrimental behaviors, and are often comorbid with neuropsychiatric disorders and drug abuse. No effective treatments exist. Moreover, anorexia lacks adolescent animal models, contributing to a poor understanding of underlying age-specific neurophysiological disruptions. To evaluate the contribution of dopaminergic signaling to the emergence of anorexia-related behaviors during the vulnerable adolescent period, we applied an established adult activity-based anorexia (ABA) paradigm (food restriction plus unlimited exercise access for 4 to 5 days) to adult and adolescent rats of both sexes. At the end of the paradigm, measures of plasma volume, blood hormone levels, dopamine transporter (DAT) expression and function, acute cocaine-induced locomotion, and brain water weight were taken. Adolescents were dramatically more affected by the ABA paradigm than adults in all measures. In vivo chronoamperometry and cocaine locomotor responses revealed sex-specific changes in adolescent DAT function after ABA that were independent of DAT expression differences. Hematocrit, insulin, ghrelin, and corticosterone levels did not resemble shifts typically observed in patients with anorexia, though decreases in leptin levels aligned with human reports. These findings are the first to suggest that food restriction in conjunction with excessive exercise sex-dependently and age-specifically modulate DAT functional plasticity during adolescence. The adolescent vulnerability to this relatively short manipulation, combined with blood measures, evidence need for an optimized age-appropriate ABA paradigm with greater face and predictive validity for the study of the pathophysiology and treatment of anorexia.
SIGNIFICANCE STATEMENT
Adolescent rats exhibit a distinctive, sex-specific plasticity in dopamine transporter function and cocaine response after food restriction and exercise access; this plasticity is both absent in adults and not attributable to changes in dopamine transporter expression levels. These novel findings may help explain sex differences in vulnerability to eating disorders and drug abuse during adolescence.
... De plus, il a été montré que l'administration de la D-amphétamine, durant la visualisation de stimuli aversifs, augmentait la réponse amygdalienne(Hariri et al., 2002). De façon plus générale, la dopamine semble moduler le traitement et la régulation de l'expression émotionnelle de stimulations positives et négatives(Salgado-Pineda, Delaveau, Blin, & Nieoullon, 2005). Aussi nous avons émis l'hypothèse que cette variabilité, exprimée à travers une intensification de l'expérience émotionnelle puisse être liée à une atteinte de la voie cortico-méso-limbique et des noyaux de la base en particulier.Notre deuxième étude avait pour but d'explorer justement les sous-bassements neuro-anatomiques de la variabilité de l'expérience émotionnelle observée chez nos patientes. ...
Les troubles émotionnels sont considérés comme fréquents dans la sclérose en plaque (SEP) et ont été généralement étudiés par la reconnaissance des émotions faciales. En revanche, l’expérience émotionnelle a été très peu analysée dans la SEP, et ses corrélats neuro-anatomiques jamais explorés. De plus, l’intrication des difficultés émotionnelles avec d’autres variables cliniques reste mal comprise, notamment l’alexithymie, qui est fréquente dans cette pathologie et qui est susceptible de modifier le traitement émotionnel.Le but de cette étude est de préciser les difficultés émotionnelles dans la SEP, dans ses composantes de reconnaissance et d’expérience émotionnelle positive et négative. II s’agit également d’explorer les corrélats neuro-fonctionnels de l’expérience émotionnelle dans la SEP en général, et chez des patientes atteintes de SEP alexithymique versus non alexithymique en particulier. Une première étude nous a permis de confirmer l’atteinte de la capacité à reconnaitre les émotions faciales dans un groupe de patientes SEP et ceci de façon plus marquée pour les émotions négatives. Cette étude a aussi mis en avant une expérience émotionnelle très variable chez nos patientes avec une intensification du vécu subjectif plaisant et déplaisant. A travers une deuxième étude en imagerie par résonance magnétique fonctionnelle (IRMf), nous avons montré que cette variabilité de l’expérience émotionnelle était sous-tendue par une grande hétérogénéité des réponses hémodynamiques de nos patientes au niveau de structures cérébrales connues pour leur implication dans la construction du ressenti subjectif plaisant et déplaisant. Des analyses complémentaires en imagerie de diffusion soutiennent l’idée que ces anomalies fonctionnelles soient liées à une atteinte structurelle notamment au niveau des boucles limbiques et des structures fronto-insulaires qui forment le réseau de saillance. Une troisième étude a mis en avant un effet spécifique de l’alexithymie dans les activations cérébrales fonctionnelles des émotions positives, notamment de l’insula, tandis que les émotions négatives semblent être influencées par la maladie et l’alexithymie comorbide. Les analyses en imagerie de diffusion s’avèrent, pour leur part, indépendantes du statut alexithymique. Ainsi les troubles émotionnels dans la SEP concernent tant la capacité à reconnaitre les émotions chez l’autre qu’une modification de leur propre expérience émotionnelle positive et négative. L’alexithymie, dont la comorbidité est fréquente dans la SEP, accentue la présence de tels troubles au même titre que le phénomène lésionnel inhérent à la SEP. Considérant l’implication que de tels troubles peuvent avoir pour les patients et leur entourage familial, social et professionnel, il semble important de prendre en compte ces aspects pour une meilleure prise en charge de cette pathologie.
... Psychiatric syndromes such as schizophrenia and major depressive disorder are characterized by emotional incompetence, due to a hypo activity of both prefrontal regions [11,12] and amygdalae [13,14]. Even dopaminergic systems seem to co-participate in decreasing facial expression recognition ability [15], as patients with Parkinson's disease [16] and schizophrenia [17] are at high risk for this condition [18]. ...
Friedreich’s ataxia (FRDA) is an autosomal recessive disease presenting with ataxia, corticospinal signs, peripheral neuropathy, and cardiac abnormalities. Little effort has been made to understand the psychological and emotional burden of the disease. The aim of our study was to measure patients’ ability to recognize emotions using visual and non-verbal auditory hints, and to correlate this ability with psychological, neuropsychological, and neurological variables. We included 20 patients with FRDA, and 20 age, sex, and education matched healthy controls (HC). We measured emotion recognition using the Geneva Emotion Recognition Test (GERT). Neuropsychological status was assessed measuring memory, executive functions, and prosopagnosia. Psychological tests were Patient Health Questionnaire-9 (PHQ-9), State Trait Anxiety Inventory–state/−trait (STAI-S/−T), and Structured Clinical Interview for DSM Disorders II. FRDA patients scored worse at the global assessment and showed impaired immediate visuospatial memory and executive functions. Patients presented lower STAI-S scores, and similar scores at the STAI-T, and PHQ-9 as compared to HC. Three patients were identified with personality disorders. Emotion recognition was impaired in FRDA with 29% reduction at the total GERT score (95% CI − 44.8%, − 12.6%; p < 0.001; Cohen’s d = 1.2). Variables associated with poor GERT scores were the 10/36 spatial recall test, the Ray Auditory Verbal Learning Test, the Montreal Cognitive Assessment, and the STAI-T (R² = 0.906; p < 0.001). FRDA patients have impaired emotion recognition that may be secondary to neuropsychological impairment. Depression and anxiety were not higher in FRDA as compared to HC and should not be considered as part of the disease.
... Studies proposed that these changes are linked to an imbalance in basal ganglia dopamine availability. This imbalance affects circuit connections to regions related to cognitive and emotional functions, like prefrontal cortex, amygdala, hippocampus, and ventral tegmental area, among other regions [68][69][70][71]. Importantly, similar to the evaluation of oral movements, cotreatment with PAS did not alter reserpineinduced memory deficit. ...
Passiflora cincinnata Masters is a Brazilian native species of passionflower. This genus is known in the American continent folk medicine for its diuretic and analgesic properties. Nevertheless, few studies investigated possible biological effects of P. cincinnata extracts. Further, evidence of antioxidant actions encourages the investigation of possible neuroprotective effects in animal models of neurodegenerative diseases. This study investigates the effect of the P. cincinnata ethanolic extract (PAS) on mice submitted to a progressive model of Parkinson’s disease (PD) induced by reserpine. Male (6-month-old) mice received reserpine (0.1 mg/kg, s.c.), every other day, for 40 days, with or without a concomitant treatment with daily injections of PAS (25 mg/kg, i.p.). Catalepsy, open field, oral movements, and plus-maze discriminative avoidance evaluations were performed across treatment, and immunohistochemistry for tyrosine hydroxylase was conducted at the end. The results showed that PAS treatment delayed the onset of motor impairments and prevented the occurrence of increased catalepsy behavior in the premotor phase. However, PAS administration did not modify reserpine-induced cognitive impairments. Moreover, PAS prevented the decrease in tyrosine hydroxylase immunostaining in the substantia nigra pars compacta (SNpc) induced by reserpine. Taken together, our results suggested that PAS exerted a neuroprotective effect in a progressive model of PD.
... In humans, the DDC gene encodes DDC, an enzyme that catalyzes the decarboxylation of 5-hydroxytryptophan to serotonin and L-DOPA to dopamine (Sumi-Ichinose et al., 1992). Given that this gene is involved in both the dopaminergic pathway and the serotonergic pathway, two pathways that play critical roles in emotional processing (Salgado-Pineda et al., 2005;Alcaro et al., 2007;Merens et al., 2007;Cools et al., 2008;Harmer, 2008;Badgaiyan et al., 2009), this gene may contribute to a series of processes involved in affective processing. For example, SNPbased association studies demonstrated that the DDC gene is associated with emotional dysregulation such as anxiety (Costas et al., 2010) and bipolar disorder (Børglum et al., 2003). ...
The framing effect refers the tendency to be risk-averse when options are presented positively but be risk-seeking when the same options are presented negatively during decision-making. This effect has been found to be modulated by the serotonin transporter gene (SLC6A4) and the catechol-o-methyltransferase gene (COMT) polymorphisms, which are on the dopaminergic and serotonergic pathways and which are associated with affective processing. The current study aimed to identify new genetic variations of genes on dopaminergic and serotonergic pathways that may contribute to individual differences in the susceptibility to framing. Using genome-wide association (GWA) data and the gene-based principal components regression (PCReg) method, we examined genetic variations of 26 genes on the pathways in 1317 Chinese Han participants. Consistent with previous studies, we found that the genetic variations of the SLC6A4 gene and the COMT gene were associated with the framing effect. More importantly, we demonstrated that the genetic variations of the aromatic-L-amino-acid decarboxylase (DDC) gene, which is involved in the synthesis of both dopamine and serotonin, contributed to individual differences in the susceptibility to framing. Our findings shed light on the understanding of the genetic basis of affective decision-making.
... 22 Childhood adversity has documented effects on the mesolimbic systems involved in processing substance use reinforcement, systems that also play critical roles in emotion processing and regulation. 23 Existing vulnerabilities in these emotion regulation pathways may interact with substance use, compounding its effects. 21 We thus hypothesize that substance use will have a particularly robust effect on depressive symptoms when young men have been exposed to adverse childhood experiences. ...
Background and objectives:
Depressive symptoms have been identified as an important consequence of substance use. Both heavy drinking and marijuana use have acute and short-term effects on systems that regulate emotion, increasing the potential for substance use to induce problems with negative affect and irritability. We investigated the effects of alcohol and marijuana use on depressive symptoms among a sample of young Black men. We also tested the stress sensitization hypothesis that exposure to adverse childhood experiences would amplify the influence of substance use on men's depressive symptoms.
Methods:
Hypotheses were tested with 505 rural Black men who, at ages 19-22 years, provided data on their substance use, adverse childhood experiences, and depressive symptoms; they provided data again 18 months later.
Results:
Substance use forecasted increases in depressive symptoms; cross-lagged analyses yielded no evidence for the inverse path, depressive symptoms increasing substance use. The impact of substance use on depressive symptoms was amplified among young Black men who were exposed to adverse childhood experiences. Substance use did not significantly predict depressive symptoms when adversity was low.
Discussion and conclusions:
Our findings suggest that, during young adulthood, substance use increases depressive symptoms among Black men who were exposed to childhood adversity. Because childhood adversity disproportionately affects Black men, these findings inform future cross-group research designed to investigate racial disparities in the consequences of substance use.
Scientific significance:
Depressive symptoms may be understood as an effect as well as a cause of substance use, particularly among vulnerable young Black men. (Am J Addict 2017;XX:1-7).
... Impairments in emotional processes are also evident in other psychiatric conditions 59-61 as well as in neurological disorders which involve the dopaminergic system. 62 For example, in patients with Parkinson's disease emotion recognition deficits were found to be associated with decreased amygdala activation. 63 In addition, the amygdala's response to emotional tasks has been shown to be altered by the administration of dopaminergic drugs. ...
Problems in the perception of emotional material, in particular deficits in the recognition of negative stimuli, have been demonstrated in schizophrenia including in first-episode samples. However, it is largely unknown if emotion recognition impairment is present in people with subthreshold psychotic symptoms. Here, we examined the capacity to recognize facially expressed emotion and affective prosody in 79 individuals at ultra high-risk for psychosis, 30 clinically stable individuals with first-episode schizophrenia assessed as outpatients during the early recovery phase of illness, and 30 unaffected healthy control subjects. We compared (1) scores for a combined fear-sadness aggregate index across face and voice modalities, (2) summary scores of specific emotions across modalities, and (3) scores for specific emotions for each sensory modality. Findings supported deficits in recognition of fear and sadness across both modalities for the clinical groups (the ultra high-risk and first-episode group) as compared with the healthy controls. Furthermore, planned contrasts indicated that compared with the healthy control subjects, both clinical groups had a significant deficit for fear and sadness recognition in faces and for anger recognition in voices. Specific impairments in emotion recognition may be apparent in people at clinical high-risk for schizophrenia before the full expression of psychotic illness. The results suggest a trait deficit and an involvement of the amygdala in the pathology of ultra high-risk states.
... Since the pioneering work by Olds and Milner (Olds and Milner 1954), the mesolimbic dopamine (DA) pathway, consisting of the ventral tegmental area (VTA), and DA neuron projections into the ventral striatum, have been demonstrated to play a critical role in reward processing (Phillips et al. 2008;Schultz 2013). In addition, extensive studies have revealed that mesocortical DA innervations in the prefrontal cortex (PFC) is also involved in multiple facets of cognitive and affective functions (Goldman-Rakic et al. 2000;Klanker et al. 2013;Robbins 2000;Salgado-Pineda et al. 2005). In addition to cognitive and affective functions, emerging evidence suggests that DA is also significantly involved in social functions (Skuse and Gallagher 2009). ...
RationaleDopamine (DA) plays a central role in reward processing. Accumulating evidence suggests that social interaction and social stimuli have rewarding properties that activate the DA reward circuits. However, few studies have attempted to investigate how DA is involved in the processing of social stimuli. Objectives
In this study, we investigated the effects of pharmacological manipulations of DA D1 and D2 receptors on social vs. nonsocial visual attention preference in macaques. Methods
Japanese macaques were subjected to behavioral tests in which visual attention toward social (monkey faces with and without affective expressions) and nonsocial stimuli was examined, with D1 and D2 antagonist administration. ResultsThe macaques exhibited significantly longer durations of gazing toward the images with social cues than did those with nonsocial cues. Both D1 and D2 antagonist administration decreased duration of gazing toward the social images with and without affective valences. In addition, although D1 antagonist administration increased the duration of gazing toward the nonsocial images, D2 antagonism had no effect. Conclusions
These results suggest that both D1 and D2 receptors may have roles in the processing of social signals but through separate mechanisms.
... In spite of elevated dopamine activity, KO mice showed increased mechanical nociceptive sensitivity. Dopamine is known to contribute to mood regulation [14,15]. A number of studies reported that mood alteration and pain are reciprocally associated [16][17][18]. ...
Nociception is one of the most complex senses that is affected not only by external stimulation but also internal conditions. Previous studies have suggested that circadian rhythm is important in modulating nociception. REV-ERBα knock-out (KO) mice have disrupted circadian rhythm and altered mood-related phenotypes. In this study, we examined the role of REV-ERBα in inflammatory nociception. We found that the nociceptive sensitivity of KO mice was partially enhanced in mechanical nociception. However, this partial alteration was independent of the circadian rhythm. Taken together, deletion of REV-ERBα induced a mild change in mechanical nociceptive sensitivity but this alteration was not dependent on the circadian rhythm.
... In healthy humans, music listening induces endogenous dopamine release in the nucleus accumbens at peak emotional arousal (Salimpoor et al., 2011). Second, human and animal studies indicated that dopamine neurotransmission is crucially involved in emotion processing and behavior (Gendreau et al., 1998;Hariri et al., 2002;Tessitore et al., 2002;Salgado-Pineda et al., 2005). Third, convergent evidence in humans suggests that dopamine is involved in the regulation of mood. ...
Sounds, like music and noise, are capable of reliably affecting individuals' mood and emotions. However, these effects are highly variable across individuals. A putative source of variability is genetic background. Here we explored the interaction between a functional polymorphism of the dopamine D2 receptor gene (DRD2 rs1076560, G>T, previously associated with the relative expression of D2S/L isoforms) and sound environment on mood and emotion-related brain activity. Thirty-eight healthy subjects were genotyped for DRD2 rs1076560 (G/G=26; G/T=12) and underwent functional magnetic resonance imaging (fMRI) during performance of an implicit emotion-processing task while listening to music or noise. Individual variation in mood induction was assessed before and after the task. Results showed mood improvement after music exposure in DRD2 GG subjects and mood deterioration after noise exposure in GT subjects. Moreover, the music as opposed to noise environment, decreased the striatal activity of GT subjects as well as the prefrontal activity of GG subjects while processing emotional faces. These findings suggest that genetic variability of dopamine receptors affects sound environment modulations of mood and emotion processing.
Millions of people suffer from dopamine‐related disorders spanning disturbances in movement, cognition and emotion. These changes are often attributed to changes in striatal dopamine function. Thus, understanding how dopamine signalling in the striatum and basal ganglia shapes human behaviour is fundamental to advancing the treatment of affected patients. Dopaminergic neurons innervate large‐scale brain networks, and accordingly, many different roles for dopamine signals have been proposed, such as invigoration of movement and tracking of reward contingencies. The canonical circuit architecture of cortico‐striatal loops sparks the question, of whether dopamine signals in the basal ganglia serve an overarching computational principle. Such a holistic understanding of dopamine functioning could provide new insights into symptom generation in psychiatry to neurology. Here, we review the perspective that dopamine could bidirectionally control neural population dynamics, increasing or decreasing their strength and likelihood to reoccur in the future, a process previously termed neural reinforcement . We outline how the basal ganglia pathways could drive strengthening and weakening of circuit dynamics and discuss the implication of this hypothesis on the understanding of motor signs of Parkinson's disease (PD), the most frequent dopaminergic disorder. We propose that loss of dopamine in PD may lead to a pathological brain state where repetition of neural activity leads to weakening and instability, possibly explanatory for the fact that movement in PD deteriorates with repetition. Finally, we speculate on how therapeutic interventions such as deep brain stimulation may be able to reinstate reinforcement signals and thereby improve treatment strategies for PD in the future.
Millions of people suffer from dopamine-related disorders spanning disturbances in movement, cognition and emotion, often attributed to changes in striatal dopamine function. Understanding how dopamine signaling in the striatum and basal ganglia shapes human behavior is fundamental to advancing the treatment of affected patients. Dopaminergic neurons innervate large scale brain networks and many different roles for dopamine signals have been proposed, such as invigoration of movement and tracking of reward contingencies. The canonical circuit architecture of cortico-striatal loops sparks the question, whether dopamine signals in the basal ganglia serve an overarching computational principle which could provide new insights into symptom generation in psychiatry to neurology. Here, we review the perspective that dopamine could bidirectionally control neural population dynamics, increasing, or decreasing their strength and likelihood to reoccur in the future, a process previously termed neural reinforcement. We outline how the basal ganglia pathways could drive strengthening and weakening of circuit dynamics and discuss the implication of this hypothesis on the understanding of motor signs of Parkinson’s disease (PD), the most frequent dopaminergic disorder. We propose that loss of dopamine in PD may lead to a pathological brain state where repetition of neural activity leads to weakening and instability, possibly explanatory for the fact that movement in PD deteriorates with repetition, as defined by the sequence effect or decrement of movement. Finally, we speculate on how therapeutic interventions such as deep brain stimulation (DBS) may be able to reinstate reinforcement signals and thereby improve treatment strategies of PD in the future.
The aim of this study is to examine patients with restless legs syndrome (RLS) in terms of difficulty in emotion regulation and insomnia. A total of 52 patients with RLS and 57 healthy volunteers were enrolled. Difficulties in Emotion Regulation Scale Short Form (DERS-16), Insomnia Severity Index (ISI), Hospital Anxiety and Depression Scale (HADS), and International Restless Legs Syndrome rating scale were applied to participants. The mean age was 34.00 ± 8.27 years in patients and 31.70 ± 9.12 years in control. The scores of DERS-16, ISI, HADS-A, and HADS-D were significantly higher in the patients than the controls (p = 0.000). The DERS-16 total score showed a significant correlation with age (r = 0.404, p = 0.003), ISI (r = 0.281, p = 0.043), IRLS score (r = 0.422, p = 0.002), HADS-A (r = 0.409, p = 0.003), and HADS-D (r = 0.416, p = 0.002). The factors (age, gender, ferritin, ISI, and IRLS scores) that may be associated with the DERS-16 total scores were assessed with stepwise regression analysis. It was seen that the IRLSs variable had the most ability and could predict 45% (β = 0.625, p < 0.001, ∆R2 = 0.450) of difficulty in emotion regulation. In addition, the variable of insomnia could predict difficulty in emotion regulation by 17% (β = 0.097, p = 0.001, ∆R2 = 0.170). Patients with RLS may experience more emotion regulation difficulties than healthy controls. RLS severity and insomnia may be factors affecting emotion regulation difficulties in patients with RLS. According to our knowledge and our literature review, this finding seems to be the first report in the literature.
Background:
Extensive evidence has suggested functional connections between co-occurring visuomotor and social cognitive deficits in neuropsychiatric disorders; however, such association has not been studied in bipolar disorder (BD). We aimed to investigate the relationship between visuomotor coordination and social cognition in the euthymic stage of BD (euBD). Given the shared neurobiological underpinnings involving the dopaminergic system and corticostriatal circuitry, we hypothesized a positive correlation between social cognition and visuomotor coordination in euBD patients.
Methods:
40 euBD patients and 59 healthy control (HC) participants underwent evaluation of social (Diagnostic Analysis of Nonverbal Accuracy 2-Taiwan version (DANVA-2-TW)), non-social cognitive function and visuomotor coordination. A subgroup of participants completed single-photon emission computed tomography for striatal dopamine transporter (DAT) availability assessment.
Results:
EuBD patients showed impaired nonverbal emotion recognition (ps ≤ 0.033) and poorer visuomotor coordination (ps < 0.003) compared to HC, with a positive correlation between these two abilities (r = 0.55, p < 0.01). However, after considering potential confounding factors, instead of visuomotor coordination, striatal DAT availability was a unique predictor of emotion recognition accuracy in euBD (beta = 0.33, p = 0.001).
Conclusion:
Our study result supported a functional association between social cognition and visuomotor coordination in euBD, with striatal dopaminergic dysfunction emerged as a crucial contributing factor in their interrelation.
The work is aimed at describing the relationship between the genes COMT, DRD4, 5HT2A, MAOA with the success of facial expression recognition. These genes play an important role in various emotional and cognitive processes. At the same time, hereditary aspects of recognition of facial expressions, in contrast to sociocultural ones, have not been studied enough to date. The study involved 87 healthy students of Russian universities (20.4 ± 2.6 years). DNA analysis was carried out with the determination of genotypes by the polymorphic loci of the genes rs4680 COMT, rs6313 5HT2A (HTR2A), rs1800955 DRD4, VNTR MAOA (RSMU, Rostov-on-Don). The participants of the study were asked to distinguish emotional facial expressions in photographs taken from the MMI, KDEF, Rafd, WSEFEP image databases. The obtained results indicate the following differences in the success of facial expression recognition: carriers of the Val/Val genotype of the COMT gene significantly better recognize the emotions of surprise (H=7.7, df=2, p=0.02), fear (H=10.5, df=2, p=0.005), sadness (H=11.2, df=2, p=0.004); carriers of the heterozygous C/T genotype of the DRD4 gene significantly better recognize facial expression of disgust (H=9.1, df=2, p=0.01). No relationship was found between the MAOA gene genotypes and the success of emotion recognition.
La désinhibition est un trouble présent dans plusieurs pathologies neurodégénératives, telles que la démence fronto-temporale de type comportemental (DFTc), et constitue une source de stress majeur dans la vie quotidienne des patients et de leurs aidants. Dans une revue de la littérature, nous avons décrit les troubles de l’inhibition dans les démences, en détaillant les tests permettant de les évaluer, leurs manifestations et les corrélats neuronaux associés. Il s’avère que l’étiologie et les substrats neuronaux de la désinhibition restent mal élucidés, particulièrement pour la désinhibition comportementale. Ce symptôme neuropsychiatrique est classiquement évalué comme une unique composante sur la base de questionnaires renseignés par les aidants. Cette pratique soulève des interrogations méthodologiques concernant le manque d’objectivité, de validité écologique, et de spécificité de ces outils, pouvant expliquer la diversité de corrélats neuronaux retrouvés dans la littérature. Dans ce contexte, nous avons exploré les troubles de l’inhibition comportementale chez les patients DFTc en distinguant trois sous-catégories de désinhibition – la compulsivité, l’impulsivité et la désinhibition sociale – en combinant trois approches : une étude comportementale éthologique en situation écologique, un bilan neuropsychologique et de l’imagerie structurelle. Dans un premier temps, nous avons décrit la manifestation de ces troubles et les déficits neuropsychologiques associés, avant de proposer des pistes de prise en charge non pharmacologique d’après leur contexte d’occurrence. Nous avons ensuite souligné la possibilité de distinguer différents profils clinico-anatomiques de patients DFTc sur la base des observations comportementales de la désinhibition. Enfin, nous avons mis en évidence des réseaux neuronaux distincts sous-tendant la compulsivité et la désinhibition sociale. Ces résultats sont prometteurs pour la détection et la prise en charge de la désinhibition en pratique clinique, contribuant à mieux stratifier les patients pour les essais thérapeutiques à venir. L’investigation de ces troubles dans d’autres pathologies, telles que la maladie d’Alzheimer, permettrait de surcroît d’affiner les diagnostics différentiels sur la base de la désinhibition et d’améliorer ainsi la prise en charge de ces patients.
Can exercise change the way we engage with the world? Many have noted the link between exercise and affect. In a previous study, we found that a 20- minute round of exercise improved participant scores in the self-reported areas of mood, focus, and wakefulness (Davis, 2022). This was especially compelling when compared with sedentary peers, who reported drops in those same areas after 20 minutes of sitting.
Theoretically, if a low-cost intervention like exercise can improve affect, then there would be reason to consider incorporating it in all sorts of arenas – namely, schools and businesses. Improvements in mood would surely allow students and employees to interact with their peers and work differently, and (hopefully) achieve enhanced outcomes.
Improvements in wearable technologies like the brain-sensing FocusCalm headband have allowed us to continue this research with greater depth. During late summer and fall of 2021, we attempted to replicate those previous studies – this time, instead of collecting self-reports, the FocusCalm technology allowed us to collect electroencephalogram (EEG) feedback.
Previous studies have demonstrated that sleep deprivation results in a negativity bias, especially in the context of impaired response inhibition. In the present study we investigated spontaneous eye blink rate (EBR), a correlate of dopamine function, as a mediator of the relationship between subjective sleepiness and impulsivity toward negative stimuli on a Go/NoGo task. Participants rated their sleepiness on a number of measures including the Epworth Sleepiness Scale (ESS), the Karolinska Sleepiness Scale (KSS) and subscales of the Chronic Sleep Reduction Questionnaire (CSRQ). The findings revealed that EBR mediated the relationship between sleepiness as measured by the Karolinska Sleepiness Scale (KSS) and commission errors on negatively valanced stimuli. These findings suggest that reduced inhibition in responding to negative stimuli can be found as a function of subjective sleepiness and that changes in dopamine function may be one contributing factor explaining this relationship.
Nociception alterations are frequent non-motor symptoms of the prodromal phase of Parkinson’s disease (PD). The period for the onset of symptoms and the pathophysiological mechanisms underlying these alterations remain unclear. We investigated the course of nociception alterations in a progressive model of parkinsonism induced by reserpine (RES) in rats. Male Wistar rats (6-7 months) received 5 or 10 subcutaneous injections of RES (0.1 mg/kg) or vehicle daily for 20 days. Motor evaluation and nociceptive assessment were performed throughout the treatment. At the end of the treatment rats were euthanized, the brains removed and processed for immunohistochemical analysis (TH and c-Fos). The RES-treated rats exhibited an increased nociceptive response to mechanical and chemical stimulation in the electronic von Frey and formalin tests, respectively. Moreover, these alterations preceded the motor impairment observed in the catalepsy test. In addition, the RES treatment reduced the TH-immunoreactivity in the ventral tegmental area (VTA) and increased the c-Fos expression in the ventral-lateral periaqueductal gray (vlPAG), rostral ventral medulla (RVM) and dorsal raphe nucleus (DRN) after noxious stimuli induced by formalin. Taken together, our results reinforce that nociceptive changes are one of the early signs of PD and monoamine depletion in basal ganglia can be involved in the abnormal processing of nociceptive information in PD.
Experiments on rats were carried out to study the effects of fragmentation of visual navigation signals on search behavior in a radial maze with asymmetrical food reinforcement. The dopaminergic system of the brain was found to have an important role in impairments to the animals’ invariant perception of significant sensory objects on removal of one of two adjacent extramaze navigation cues and in determining the location of the largest reinforcement in the maze. The basis of these impairments was found to be deficit of associative memory between the remaining and the remote cues. Possible animal modeling of impairments to sensory perception in neurological diseases due to dysfunction of the dopaminergic system of the brain is assessed.
Animal and Human behaviour suggests that it is ultimately an expression of events guided by the nervous system. As decision-making neurological processes became increasingly concentrated in the centralized brain over evolutionary time, behaviour became essentially an expression of brain's response to information coming to it from inside and outside the body. Human emotions guide and direct behaviour. They dominate us in such a way that there is no solution. If a person has no emotions, he becomes crippled in terms of life. An emotion is a strong feeling associated with some instincts or biological drives. In addition to the above, emotions have some more specific characteristics-they bring psychological and physiological changes. Emotions are short-lived experiences that produce coordinated changes in people's thoughts, actions and physiological responses. During emotions, specific action tendencies infuse both mind and body, simultaneously narrowing individual action urges (flight in fear, attack in anger) by mobilizing appropriate bodily support for those specific actions. Human emotions are classified into Negative (Fear, Anger, Depression, Anxiety, Envy, Shame etc.) and Positive (Love, Appreciation, Happiness, Hope, Confidence, Patience, Trust etc.) emotions. The primary emotions are anger, fear, pleasure, sadness, and disgust. Positive emotions are often characterized by a relative lack of autonomic reactivity. They broaden the scopes of attention, cognition, and action widening the array of precepts, thoughts and actions presently in mind. The positive emotion of pleasure may facilitate injective, exploratory, sexual or novel-seeking behaviour. Negative emotions such as anger and fear may promote avoidance or defensive behaviour.
Clinically, Hereditary Tyrosinemia type I (HTI) is especially characterized by severe liver dysfunction in early life. However, recurrent neurological crises are another main finding in these patients when they are treated with a tyrosine and phenylalanine restricted diet only. This is caused by the accumulation of δ-aminolevulinic acid due to the inhibitory effect of succinylacetone on the enzyme that metabolizes δ-aminolevulinic acid. Due to the biochemical and clinical resemblance of these neurological crises and acute intermittent porphyria, this group of symptoms in HTI patients is mostly called porphyria-like-syndrome. The neurological crises in HTI patients disappeared after the introduction of treatment with 2-(2 nitro-4-3 trifluoro-methylbenzoyl)-1, 3-cyclohexanedione (NTBC). However, if NTBC treatment is stopped for a while, severe neurological dysfunction will reappear.
Chapter 5 describes the Research Domain Criteria (RDoC) framework as it pertains to emotion regulation, an in-progress research framework mapping psychological constructs onto discrete units of analysis (genes, molecules, cells, brain circuits, physiology, behavior, and self-report). It accommodates contemporary and developing emotion frameworks such as the Bradley-Lang Model and Gross-Ochsner Extended Process Model (EPM), while supplementing the clinically valuable, categorical account of psychological disorders featured in the Diagnostic and Statistical Manual of Mental Disorders (DSM). The RDoC has three objectives: Describing how psychological constructs are implemented mechanistically (biologically), increasing the explanatory ability as to why a biological system or neurobiological structure works, and increasing the predictive validity of pathological phenomena. This multi-componential research framework involves interdisciplinary collaboration to uncover new avenues for exploring the etiology, maintenance, and intervention to address one of the field’s greatest challenges: the effective treatment of emotion dysregulation.
Why do certain factors seem to be related to desistance and not others? Why do some people desist earlier than others? Just why is it that marriage is associated with a change in life-course trajectories? After all the research that has focused on desistance, finding correlates, and uncovering narratives associated with behavioral change, researchers have yet to figure out why (or if) marriage causally impacts crime. This chapter focuses on theories and perspectives developed in criminology to explain desistance from crime. As will be seen, researchers (in social and biological sciences) have developed a plethora of explanations in order to better understand what desistance is and why it happens. For ease of presentation, Rocque discusses the theories in six categories: (1) pure age; (2) cognitive or neurological; (3) rational choice; (4) personality or psychosocial; (5) identity/cognitive transformation; and (6) social process theories.
Neurotransmitter release is regulated by various proteins of the active zone in the presynaptic nerve terminals. Dopamine (DA) is an essential neurotransmitter associated with the pathophysiology of diverse behavioral and mental illness such as schizophrenia and drug addiction. We measured synaptosomal DA release of knockout (KO) mice which lacked major genes related to neurotransmitter release. Synaptosomal DA uptake and release were performed and measured using [^3H]-DA and superfusion experiments. 3 of the 17 KO mice exhibited altered DA release compared to their littermate controls. In Rim1{\alpha} KO, [^3H]-DA release evoked by membrane depolarization significantly decreased. Both basal (physiological buffer-evoked) and membrane depolarization-evoked DA release significantly decreased in dopaminergic conditional KO of Rim1{\alpha}{\beta}. Dopaminergic conditional KO of neurexin3 demonstrated a significant increase of membrane depolarization-evoked DA release. These data explain the similarities and distinctions between DA and other classical neurotransmitters such as glutamate and GABA (\gamma-aminobutyric acid) release. In conclusion, Rim1{\alpha} and neurexin3 may be important regulators of presynaptic DA release and related to disorders of the nervous system.
Si bien se ha estudiado el vínculo entre los trastornos de estado de ánimo y el consumo de alcohol, tanto en humanos como en animales, todavía no es del todo claro cómo se da esta relación, y menos aún durante la adolescencia. La administración de reserpina, un depletor de monoaminas, es un modelo ampliamente utilizado en roedores adultos para inducir comportamientos asociados a depresión, pero se desconoce su utilidad en otras etapas del desarrollo. En este trabajo validamos este modelo en ratas adolescentes y posteriormente estudiamos el consumo de alcohol en estos animales, así como su modulación por antidepresivos. En el experimento1 se administró reserpina (0.0 o 1.0mg/kg, durante 4días, IP) a ratas Wistar machos de 30días. El consumo de alcohol fue evaluado luego de observar comportamientos asociados a depresión e indagar indicadores neuroendocrinos de esta patología. En el experimento2 los animales recibieron reserpina, seguida por el antidepresivo fluoxetina (0.0 o 10.0mg/kg, durante 4días, IG), y luego se evaluó el consumo de alcohol. Los resultados mostraron que la reserpina aumentó significativamente los comportamientos asociados a depresión y alteró los niveles de dopamina en la corteza insular y de hormonas tiroideas en sangre. En la prueba de consumo de alcohol los animales deprimidos, pero no los controles, mostraron un incremento en el consumo a través de los días. El segundo experimento replicó parcialmente este perfil, y no se observó un efecto significativo del antidepresivo en el consumo de alcohol. Los resultados indican que la reserpina es útil para modelar en ratas adolescentes comportamientos asociados a depresión. Se encontró una relación entre este estado y el consumo de alcohol, que no se pudo revertir con antidepresivos.
The involvement of dopamine neurotransmission in behavioral responses to novelty is suggested by reports that reward is related to increased dopamine activity, that dopamine modulates exploratory behavior in animals, and that Parkinson's disease patients report diminished responses to novelty. Some studies have reported that polymorphisms of the human dopamine D4 receptor (D4R) gene are associated with personality inventory measures of the trait called “novelty-seeking”. To explore a potential role for the D4R in behavioral responses to novelty, we evaluated D4R-knock-out (D4R−/−) and wild-type (D4R+/+) mice in three approach–avoidance paradigms: the open field, emergence, and novel object tests. These three paradigms differ in the degree to which they elicit approach, or exploratory behavior, and avoidance, or anxiety-related behavior. Thus, we used these three tests to determine whether the D4R primarily influences the exploratory or the anxious component of responses to approach–avoidance conflicts. D4R−/− mice were significantly less behaviorally responsive to novelty than D4R+/+ mice in all three tests. The largest phenotypic differences were observed in the novel object test, which maximizes approach behavior, and the smallest phenotypic differences were found in the open field test, which maximizes avoidance behavior. Hence, D4R−/− mice exhibit reductions in behavioral responses to novelty, reflecting a decrease in novelty-related exploration.
Recent research has found a discrepancy between schizophrenic patients' outward expression of emotion and their reported emotional experience. In this study, which attempts to replicate and extend the findings of previous studies, participants with and without schizophrenia viewed emotional film clips while their facial expressions were videotaped and skin conductance was recorded. Participants also reported their subjective experience of emotion following each film. Those with schizophrenia were less facially expressive than controls during the emotional films and reported experiencing as much positive and negative emotion, replicating previous findings. Additionally, schizophrenic patients exhibited greater skin conductance reactivity to all films than controls. These findings suggest a disjunction among emotional response domains for schizophrenic patients; alternative explanations for the findings are considered as well as suggestions for future research.
A model is proposed for integrating the neural and cognitive aspects of the positive symptoms of acute schizophrenia, using evidence from postmortem neuropathology and neurochemistry, clinical and preclinical studies of dopaminergic neurotransmission, anatomical connections between the limbic system and basal ganglia, attentional and other cognitive abnormalities underlying the positive symptoms of schizophrenia, specific animal models of some of these abnormalities, and previous attempts to model the cognitive functions of the septohippocampal system and the motor functions of the basal ganglia. Anatomically, the model emphasises the projections from the septohippocampal system, via the subiculum, and the amygdala to nucleus accumbens, and their interaction with the ascending dopaminergic projection to the accumbens. Psychologically, the model emphasises a failure in acute schizophrenia to integrate stored memories of past regularities of perceptual input with ongoing motor programs in the control of current perception. A number of recent experiments that offer support for the model are briefly described, including anatomical studies of limbic-striatal connections, studies in the rat of the effects of damage to these connections, and of the effects of amphetamine and neuroleptics, on the partial reinforcement extinction effect, latent inhibition and the Kamin blocking effect; and studies of the latter two phenomena in acute and chronic schizophrenics.
Dopamine D1 receptors are expressed in the hippocampus and prefrontal cortex, suggesting a role in cognition. Dopamine D1 receptor-deficient mice (D1−/−) were used to investigate the role of this receptor in spatial learning and memory. Using the Morris water maze, mice were trained to locate a hidden platform. Subsequently, the platform was removed from the maze and mice were scored for the percentage of time spent in the target quadrant and the number of crossings through the target position. D1−/− mice had significantly longer escape latencies compared to wild-type (D1+/+) and heterozygous (D1+/−) littermates and showed absence of spatial bias during the probe trials. In a visually cued task, D1−/− mice performed better than on the hidden platform trials, but maintained slightly higher escape latencies than D1+/+ and D1+/− mice. Naive D1−/− mice exposed only to the cued task eventually acquired identical escape latencies as the D1+/+ and D1+/− mice. Sensorimotor reflexes, locomotor activity, spontaneous alternation and contextual learning were not different among the groups. These results indicate that D1−/− mice have a deficit in spatial learning without visual or motor impairment, suggesting that dopamine D1 receptors are involved in at least one form of the cognitive processes.
Face perception and emotion recognition were investigated in a group of people with Huntington's disease and matched controls. In conventional tasks intended to explore the perception of age, sex, unfamiliar face identity (Benton test) and gaze direction from the face, the Huntington's disease group showed a borderline impairment of gaze direction perception and were significantly impaired on unfamiliar face matching. With a separate set of tasks using computerinterpolated (‘morphed’) facial images, people with Huntington's disease were markedly impaired at discriminating anger from fear, but experienced less difficulty with continua varying from male to female, between familiar identities, and from happiness to sadness. In a further test of recognition of facial expressions of basic emotions from the Ekman and Friesen (1976) series, interpolated images were created for six continua that lay around the perimeter of an emotion hexagon (happiness-surprise; surprise—fear; fear—sadness; sadness—disgust; disgust—anger; anger—happiness). In deciding which emotion these morphed images were most like, people with Huntington's disease again showed deficits in the recognition of anger and fear, and an especially severe problem with disgust, which was recognized only at chance level. A follow-up study with tests of facially and vocally expressed emotions confirmed that the recognition of disgust was markedly poor for the Huntington's disease group, still being no better than chance level. Questionnaires were also used to examine self-assessed emotion, but did not show such striking problems. Taken together, these data reveal severe impairments of emotion recognition in Huntington's disease, and show that the recognition of some emotions is more impaired than others. The possibility that certain basic emotions may have dedicated neural substrates needs to be seriously considered; among these, disgust is a prime candidate.
The emotional responses of schizophrenic, depressed, and normal subjects and whether differences in the emotional responding of these groups depended on how emotional responses were elicited or measured were examined. Twenty-three blunted and 20 nonblunted schizophrenics, 17 unipolar depressed subjects, and 20 normal subjects were exposed to a series of affect-eliciting stimuli. The stimuli varied in valence (positive vs. negative) and in level of cognitive demand. Subjects reported their subjective experiences, and their facial expressions were videotaped. Blunted schizophrenics were the least facially expressive, although their reported subjective experiences did not differ from those of the other groups. The nonblunted schizophrenics were more responsive than the depressed subjects to the positive stimuli, although the two groups did not differ in their clinical ratings of affective flatness.
Dopamine receptors belong to the family of G protein-coupled receptors. On the basis of the homology between these receptors, three different dopamine receptors (D1, D2, D3) have been cloned. Dopamine receptors are primary targets for drugs used in the treatment of psychomotor disorders such as Parkinson's disease and schizophrenia. In the management of socially withdrawn and treatment-resistant schizophrenics, clozapine is one of the most favoured antipsychotics because it does not cause tardive dyskinesia. Clozapine, however, has dissociation constants for binding to D2 and D3 that are 4 to 30 times the therapeutic free concentration of clozapine in plasma water. This observation suggests the existence of other types of dopamine receptors which are more sensitive to clozapine. Here we report the cloning of a gene that encodes such a receptor (D4). The D4 receptor gene has high homology to the human dopamine D2 and D3 receptor genes. The pharmacological characteristics of this receptor resembles that of the D2 and D3 receptors, but its affinity for clozapine is one order of magnitude higher. Recognition and characterization of this clozapine neuroleptic site may prove useful in the design of new types of drugs.
A dopamine receptor has been characterized which differs in its pharmacology and signalling system from the D1 or D2 receptor and represents both an autoreceptor and a postsynaptic receptor. The D3 receptor is localized to limbic areas of the brain, which are associated with cognitive, emotional and endocrine functions. It seems to mediate some of the effects of antipsychotic drugs and drugs used against Parkinson's disease, that were previously thought to interact only with D2 receptors.
The distribution of mRNA coding for the D2 dopamine receptor was studied in the rat brain by in situ hybridization. A cDNA probe corresponding to the putative third cytosolic loop and sixth and seventh transmembrane domains of the rat D2 receptor was used to generate an 35S-labeled riboprobe to hybridize to D2 receptor mRNA. D2 mRNA was found both in dopamine projection fields and in regions associated with dopamine-containing cell bodies, suggesting both postsynaptic and presynaptic autoreceptor localization. Highest concentrations of D2 mRNA were found in neostriatum, olfactory tubercle, substantia nigra, ventral tegmental area, and the nucleus accumbens. This distribution is consistent with those reported with D2 receptor autoradiography.
Locomotor activity was automatically recorded in a circular corridor in rats treated with 6-hydroxydopamine in the ventral tegmental area (VTA), septum and frontal cortex. Control and experimental groups showed similar hyperlocomotor responses in the novel apparatus lasting 3 h. Circadian changes are described. VTA lesions resulted in increased dark activity and a large response to apomorphine compared to other lesion and control groups. Septal lesions did not affect locomotion. The frontal group showed a small increase of locomotion after apomorphine treatment that might reflect increased receptor sensitivity in cortical or subcortical areas. Together with correlations between motor activity and cortical levels of dopamine and noradrenaline these results are interpreted to support a role for dopamine, noradrenaline and the frontal cortex in modulating locomotion which is primarily mediated by VTA-accumbens-dopamine activity.
Synopsis
The CNS maintains a fundamental distinction between actions elicited by external stimuli and actions elicited by internal goals (acts of will). As a result the intact organism can monitor centrally three aspects of its own actions: (1) the action appropriate to current external stimulation (stimulus intention or meaning); (2) the action appropriate to current goals (willed intention); and (3) the action which was actually selected (corollary discharge). In Type I (acute) schizophrenic patients, intentions of will lead to actions, but these willed intentions are not monitored correctly. This apparent discrepancy between will and action gives rise to experiential (1st rank) positive symptoms (e.g. delusions of control and passivity). In Type II (chronic) patients, intentions of will are no longer properly formed and so actions are rarely elicited via this route. This gives rise to behavioural negative signs (e.g. poverty of speech).
The behaviour of Type II schizophrenics has surface similarities to that shown by patients with Parkinson's disease and patients with frontal lobe lesions in that all three types of patient show a relative deficit of actions elicited by willed intentions. Dopamine blocking drugs reduce positive symptoms in Type I patients precisely because they induce Parkinsonism, i.e. reduce the likelihood of actions being initiated by willed intentions. This in turn reduces the likelihood that actions will occur for which the patient had no awareness of his intention to act.
Dopaminergic neuronal pathways arise from mesencephalic nuclei and project axons to the striatum, cortex, limbic system and hypothalamus. Through these pathways dopamine affects many physiological functions, such as the control of coordinated movement and hormone secretion. Here we have studied the physiological involvement of the dopamine D2 receptors in dopaminergic transmission, using homologous recombination to generate D2-receptor-deficient mice. Absence of D2 receptors leads to animals that are akinetic and bradykinetic in behavioural tests, and which show significantly reduced spontaneous movements. This phenotype presents analogies with symptoms characteristic of Parkinson's disease. Our study shows that D2 receptors have a key role in the dopaminergic control of nervous function. These mice have therapeutic potential as a model for investigating and correcting dysfunctions of the dopaminergic system.
The amygdala appears to play an essential role in many aspects of emotional information processing and behavior. Studies over the past year have begun to clarify the anatomical organization of the amygdala and the contribution of its individual subregions to emotional functions, especially emotional learning and memory. Researchers can now point to plausible circuits involved in the transmission of sensory inputs into the amygdala, between amygdaloid subregions, and to efferent targets in cortical and subcortical regions, for specific emotional learning and memory processes.
Unexpected stimuli that are behaviourally significant have the capacity to elicit a short-latency, short-duration burst of firing in mesencephalic dopaminergic neurones. An influential interpretation of the experimental data that characterize this response proposes that dopaminergic neurones have a crucial role in reinforcement learning because they signal error in the prediction of future reward. In this article we propose a different functional role for this ‘short-latency dopamine response’ in the mechanisms that underlie associative learning. We suggest that the initial burst of dopaminergic-neurone firing could represent an essential component in the process of switching attentional and behavioural selections to unexpected, behaviourally important stimuli. This switching response could be a crucial prerequisite for associative learning and might be part of a general short-latency response that is mediated by catecholamines and prepares the organism for an appropriate reaction to biologically significant events. Any act which in a given situation produces satisfaction becomes associated with that situation so that when the situation recurs the act is more likely than before to recur also. E.L. Thorndike (1911) .
The recent enthusiasm among clinicians for the so-called 'atypical antipsychotics' has both improved treatment for schizophrenic patients and provided a welcome stimulus for basic research on antipsychotic mechanisms. Even the newer drugs have shortcomings, and research is underway aimed at identifying novel agents with greater efficacy and safety. Much of this effort is directed towards compounds which, in addition to blocking dopamine receptors, also act on other neurotransmitter receptors such as 5-HT(2), 5-HT(1A) and alpha(2)-adrenergic receptors. However, there is also a large amount of scientific activity seeking to discover and develop selective dopamine receptor subtype antagonists (including compounds which specifically block D(3) or D(4) receptors) or drugs that specifically target the dopamine autoreceptor. Finally, a number of drug development programmes are searching for non-dopaminergic antipsychotics. Drugs that do not have affinity for dopamine receptors but act through neurotensin, sigma or cannabinoid CB, receptors or glutamatergic mechanisms are currently being evaluated. If any of these agents prove to have clinical efficacy this may lead to a third generation of antipsychotics. It is likely, however, that the mechanisms of action of such drugs will nevertheless imply the intimate involvement of dopaminergic pathways. (C) 2000 Lippincott Williams & Wilkins.
Objective - The selective deficit of recognition of disgust expression in Huntington's disease (HD) and HD gene carrier strongly suggested the possibility that basal ganglia is involved in disgust processing. To further tested this hypothesis, we test the perception of emotional expressions in patients with symptomatic Wilson's disease (WD), another basal ganglia disease resulted from abnormal copper metabolism. Methods - We developed a six basic emotional morphed face continuum (30 morphed emotional faces across happy-surprise-fear-sad-disgust-anger-happy). Participants were required to label each of these morphs in 5 trails to measure the ability of different emotion processing. The performances of 32 cases of WD were compared with 20 age- and education-matched normal controls. Results - On the group level, although significantly impaired in fear, disgust and anger (correct identification scores: 12.8 ± 3.6; 9.1 ± 4.7; 14.9 ± 4.3, P < 0.05; P < 0.001; P < 0.05 respectively compared with normal controls), WD manifested deferentially severe deficit in disgust processing (score in disgust significantly worse than that of fear and anger P < 0.001). Conclusion - The differentially severe deficit of disgust in WD supported that basal ganglia might play an important role on disgust processing. Combined with selective deficit of fear processing in cases with bilateral amygdala or bilateral cingulate gyrus lesions, the result here represented the double dissociation, which in turn suggested that certain different basic emotion could have distinct neural substrates.
What roles do mesolimbic and neostriatal dopamine systems play in reward? Do they mediate the hedonic impact of rewarding stimuli? Do they mediate hedonic reward learning and associative prediction? Our review of the literature, together with results of a new study of residual reward capacity after dopamine depletion, indicates the answer to both questions is 'no'. Rather, dopamine systems may mediate the incentive salience of rewards, modulating their motivational value in a manner separable from hedonia and reward learning. In a study of the consequences of dopamine loss, rats were depleted of dopamine in the nucleus accumbens and neostriatum by up to 99% using 6-hydroxydopamine. In a series of experiments, we applied the 'taste reactivity' measure of affective reactions (gapes, etc.) to assess the capacity of dopamine-depleted rats for: 1) normal affect (hedonic and aversive reactions), 2) modulation of hedonic affect by associative learning (taste aversion conditioning), and 3) hedonic enhancement of affect by non-dopaminergic pharmacological manipulation of palatability (benzodiazepine administration). We found normal hedonic reaction patterns to sucrose vs. quinine, normal learning of new hedonic stimulus values (a change in palatability based on predictive relations), and normal pharmacological hedonic enhancement of palatability. We discuss these results in the context of hypotheses and data concerning the role of dopamine in reward. We review neurochemical, electrophysiological, and other behavioral evidence. We conclude that dopamine systems are not needed either to mediate the hedonic pleasure of reinforcers or to mediate predictive associations involved in hedonic reward learning. We conclude instead that dopamine may be more important to incentive salience attributions to the neural representations of reward-related stimuli. Incentive salience, we suggest, is a distinct component of motivation and reward. In other words, dopamine systems are necessary for 'wanting' incentives, but not for 'liking' them or for learning new 'likes' and 'dislikes'.
Les patients schizophrènes, outre des signes positifs (délires, hallucinations) et négatifs (retrait, anhédonie), présentent des perturbations du champ émotionnel qui recouvrent des modifications à la fois quantitatives (émoussement) et qualitatives (discordance). La kétamine, dérivé de la phencyclidine, est un antagoniste non compétitif des récepteurs N-méthyl-D-aspartate (NMDA) aux acides aminés excitateurs. Chez le volontaire sain, son administration induit des signes positifs (illusions perceptives...), négatifs (déficit émotionnel, anergie, apragmatisme...) et cognitifs (troubles mnésiques et persévératifs) qui rappellent ceux observés chez le patient schizophrène. Afin de déterminer si la kétamine induit également des troubles émotionnels, 12 sujets sains ont été inclus dans un essai contrôlé randomisé en double aveugle de kétamine (0,5 mg kg–1 h–1) contre placebo. L’évaluation comportait des échelles de symptomatologie positive et négative (SAPS, SANS, BPRS), des échelles analogiques visuelles de vigilance et humeur, des questionnaires (ARCI et POMS) ainsi qu’un questionnaire (DES d’Izard) rempli au décours de la présentation de 6 extraits de films induisant chacun une émotion différenciée : peur, joie, tristesse, colère, dégoût et un état neutre. L’administration de faible dose de kétamine a induit un trouble de l’attention, un déficit émotionnel associé à des symptômes positifs et négatifs. Les données récentes sur la pharmacologie de la kétamine permettent de proposer des hypothèses relatives aux systèmes de neurotransmission et régions cérébrales impliquées dans les effets observés.
Bilateral lesions in the anteromedian neocortex or the associated part of the neostriatum were found to abolish spontaneous alternation in male albino rats; removal of the suprarhinal strip did not. The classical deficit of spatial choice following frontal lobe injury, therefore, is considered not to be an artifact of the learning paradigm; it can be extended to include nonconditioned behavior. Furthermore, the impairment is not restricted to food-reinforced or massed responses. The response-guiding role of the frontal lobe is of such wide generality in the laboratory that it can be expected to operate in the S's usual environment as well. (31 ref) (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Traditional approaches to the study of human cognition considered emotion as a distinct process that could be studied independently. Initial investigations of the neuroscience of emotion supported this distinction by identifying brain structures, such as the amygdala, that appeared to be specialized for emotion. However, recent studies indicate that the amygdala interacts extensively with brain systems linked to cognition and awareness, suggesting a means for the interaction of emotion and cognition. Cognition and awareness can influence the amygdala through the verbal communication of emotion information or the cognitive control of emotional responses. The amygdala can influence cognition and awareness by altering the retention of memory with arousal and facilitating attention and perception. Evidence from cognitive neuroscience suggests that in order to understand the neural systems of cognition, a consideration of its interaction with emotion is necessary. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Reports an error in "Experienced emotion and affect recognition in adult attention-deficit hyperactivity disorder" by Lisa J. Rapport, Sara L. Friedman, Angela Tzelepis and Amy Van Voorhis (
Neuropsychology, 2002[Jan], Vol 16[1], 102-110). On Page 102, in the byline and in the author note, and on page 109 in the Rapport et al. (2001) reference, Sara Friedman's middle initial incorrectly reads "L." Her correct middle initial is "R." (The following abstract of the original article appeared in record
2002-00339-011.) Emotional competence and deficits that may disrupt interpersonal interactions were evaluated in 28 adults with attention-deficit hyperactivity disorder (ADHD) and 28 demographically equivalent controls. Participants completed tasks assessing affect recognition and experienced emotional intensity. Adults with ADHD performed worse in affect recognition than did adults without the disorder; however, the impairment was unrelated to gross perceptual processes, fundamental abilities in facial recognition, or attentional aspects of affect perception. Moreover, intensity of experienced emotion moderated affect recognition: Among controls, experienced emotion facilitated affect recognition. Among adults with ADHD, who reported significantly greater intensity, experienced emotion was inversely related to affect recognition. Results are consistent with theories of ADHD as a deficit in behavioral inhibition; yet, results may merely reflect a constellation of deficits associated with the disorder. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Family, twin, and adoption studies have documented a strong genetic basis for ADHD/HKD, but these studies do not identify specific genes linked to the disorder. Molecular genetic studies can identify allelic variations of specific genes that are functionally associated with ADHD/HKD, and dopamine genes have been the initial candidates based on the site of action of the stimulants drugs, which for a half century have provided the primary pharmacological treatment for ADHD/HKD. Two candidate dopamine genes have been investigated and reported to be associated with ADHD/HKD: the dopamine transporter (DAT1) gene [Cook et al., American Journal of Human Genetics 1995;56:993–998, Gill et al., Molecular Psychiatry 1997;2:311–313] and the dopamine receptor D4 (DRD4) gene [LaHoste et al., Molecular Psychiatry 1996;1:121–124; Smalley et al., 1998;3:427–430; Swanson et al., Molecular Psychiatry 1998;3:38–41]. Speculative hypotheses [Swanson and Castellanos, NIH Consensus Development Conference: Diagnosis and Treatment of Attention Deficit Hyperactivity Disorder, November 1998. p. 37–42] have suggested that specific alleles of these dopamine genes may alter dopamine transmission in the neural networks implicated in ADHD/HKD (e.g. that the 10-repeat allele of the DAT1 gene may be associated with hyperactive re-uptake of dopamine or that the 7-repeat allele of the DRD4 gene may be associated with a subsensitive postsynaptic receptor). These and other variants of the dopamine hypothesis of ADHD will be discussed.
Graham (1975) demonstrated that a weak prestimulus could effectively inhibit or facilitate the eyeblink component of the startle reflex in humans, depending on the temporal duration of the prestimulus. This study had three goals: 1) to replicate the findings of Graham, 2) to establish the reliability of this phenomenon by a test-retest comparison, and 3) to compare the eyeblink reflex response of normal subjects with schizophrenic subjects. Seven prestimulus durations of continuous tone (from 0 to 2000 msec) were presented to 20 normal subjects and the results confirmed that maximal inhibition of eyeblink amplitude occurred in the 120 msec prestimulus condition. Increased amplitude occurred nonsignificantly when the prestimulus lasted for 2000 msec. On retest, 14 normal subjects showed a significant degree of reliability. When 20 normal subjects were compared to 12 schizophrenic subjects, significant differences in eyeblink response were found for blink amplitude and latency in the 60 msec prestimulus condition. This change is consistent with information processing “overload” theories of sensory overstimulation in schizophrenia. The blink reflex is a rather stable phenomenon and is probably altered in schizophrenia and/or by antipsychotic medication.
Recent brain imaging studies in Huntington’s disease (HD) and normal aging suggest a relationship between central dopaminergic neurotransmission and cognitive performance. Results demonstrate substantial losses in dopamine (DA) function in both HD and aging. Moreover, HD patients and older adults show deficits across multiple cognitive domains, including episodic memory, speed of processing, and executive functioning. Although few studies are available at present, there is converging evidence that multiple measures of pre- and postsynaptic DA biochemistry are (a) highly interrelated, and (b) strongly associated with the cognitive deficits that accompany HD and aging. There is also emerging evidence that DA neurotransmission influences cognitive performance independent of HD or age. In general, the research reviewed in this article indicates that the nigrostriatal DA system is an important component of a frontostriatal circuitry that is critically involved in cognitive functioning.
Les récents développemets des techniques d’imagerie cérébrale telles que la Tomographie par Emission de Positons (TEP) et
l’Imagerie par Résonance Magnétique fonctionnelle (IRMf), ont permis aux chercheurs de déterminer plus en détail la neuroanatomie
fonctionnelle des réponses émotionnelles. Ces travaux s’inscrivent dans le domaine nouveau des “neurosciences des affects”.
Cet article propose une revue des études menées sur les structures cérébrales impliquées dans le traitement des expressions
faciales émotionnelles d’une part, et dans la réponse émotionnelle induite expérimentalement d’autre part. L’implication des
résultats et les rôles des structures ainsi mises en évidence sont discutés.
Recent developments in functional imaging techniques, such as Positron Emission Tomography (PET) and functional Magnetic Resonance
Imaging (fMRI), allow us to more precisely characterize the functional neuroanatomy mediating emotional responding. This corpus
of studies is part of a new field of research labelled Affective Neuroscience. This paper reviews the studies investigating
the neural substrates implicated in the processing of facial expressions and those implicated in the production of experimentally
induced emotional responses. The implications of the results and the role of the cerebral structures that have been identified
are discussed.
Neuroimaging research has shown localised brain activation to different facial expressions. This, along with the finding that schizophrenia patients perform poorly in their recognition of negative emotions, has raised the suggestion that patients display an emotion specific impairment. We propose that this asymmetry in performance reflects task difficulty grada-tions, rather than aberrant processing in neural pathways subserving recognition of specific emotions. A neural network model is presented, which classifies facial expressions on the basis of measurements derived from human faces. After training, the network showed an accuracy pattern closely resembling that of healthy subjects. Lesioning of the network led to an overall decrease in the network's discriminant capacity, with the greatest accuracy decrease to fear, disgust and anger stimuli. This implies that the differential pattern of impairment in schizophrenia patients can be explained without having to postulate impair-ment of specific processing modules for negative emotion recognition. © 2001 Elsevier Science B.V. All rights reserved.
Significant progress has been made in our understanding of the neural substrates of emotion and its disorders. Neuroimaging methods have been used to characterize the circuitry underlying disorders of emotion. Particular emphasis has been placed on the prefrontal cortex, anterior cingulate, parietal cortex, and the amygdala as critical components of the circuitry that may be dysfunctional in both depression and anxiety.
What roles do mesolimbic and neostriatal dopamine systems play in reward? Do they mediate the hedonic impact of rewarding stimuli? Do they mediate hedonic reward learning and associative prediction? Our review of the literature, together with results of a new study of residual reward capacity after dopamine depletion, indicates the answer to both questions is `no'. Rather, dopamine systems may mediate the incentive salience of rewards, modulating their motivational value in a manner separable from hedonia and reward learning. In a study of the consequences of dopamine loss, rats were depleted of dopamine in the nucleus accumbens and neostriatum by up to 99% using 6-hydroxydopamine. In a series of experiments, we applied the `taste reactivity' measure of affective reactions (gapes, etc.) to assess the capacity of dopamine-depleted rats for: 1) normal affect (hedonic and aversive reactions), 2) modulation of hedonic affect by associative learning (taste aversion conditioning), and 3) hedonic enhancement of affect by non-dopaminergic pharmacological manipulation of palatability (benzodiazepine administration). We found normal hedonic reaction patterns to sucrose vs. quinine, normal learning of new hedonic stimulus values (a change in palatability based on predictive relations), and normal pharmacological hedonic enhancement of palatability. We discuss these results in the context of hypotheses and data concerning the role of dopamine in reward. We review neurochemical, electrophysiological, and other behavioral evidence. We conclude that dopamine systems are not needed either to mediate the hedonic pleasure of reinforcers or to mediate predictive associations involved in hedonic reward learning. We conclude instead that dopamine may be more important to incentive salience attributions to the neural representations of reward-related stimuli. Incentive salience, we suggest, is a distinct component of motivation and reward. In other words, dopamine systems are necessary for `wanting' incentives, but not for `liking' them or for learning new `likes' and `dislikes'.
The distribution of the messenger RNA encoding the dopamine D5 receptor was determined in the rat brain by in situ hybridization. Using [35S]-labelled riboprobes to either the rat or human D5 receptor, this mRNA was localized to the hippocampus and the parafascicular nucleus of the thalamus. This mRNA could not be visualized in the more traditional brain regions associated with dopaminergic cell bodies or projection fields. This unusual distribution suggests a novel function in the brain for this subtype of the dopamine receptor.
Dihydroxyphenylacetic acid (DOPAC) and dopamine (DA) levels were estimated in the frontal cortex, the nucleus accumbens and the striatum of the rat after electrolytical lesion of the dorsal raphe nucleus. The efficiency of this lesion was tested by measuring the decline in serotonin (5-HT) levels in the striatum. 5-HT levels were reduced by 90% when compared to those of sham-operated rats 11 days after the lesion. As revealed both by the increase in DOPAC levels and in the DOPAC/DA ratio, the rate of DA utilization was markedly increased in the nucleus accumbens, slightly enhanced in the striatum and in contrast remained unaffected in the frontal cerebral cortex 4 days after the lesion. Changes in DOPAC levels in the nucleus accumbens were also seen 11 and 30 days after the lesion but they were less pronounced than those observed at 4 days. These results suggest that neurons originating from the dorsal raphe and projecting to the ventro-tegmental area are regulating the activity of the meso-nucleus accumbens dopaminergic neurons but not that of the meso-cortical dopaminergic neurons.
IT is now well established that an important system of dopaminergic (DA)
neurones innervates various parts of the cerebral cortex in the rat and
other species1-3. In contrast to noradrenergic (NA) terminals
which are widely distributed in this structure, the DA terminals are
mainly confined to deep layers, particularly in the frontal, the
cingular and the entorhinal areas4,5. The results of lesion
studies demonstrated that the terminal endings in the frontal cortex
originate from the A10 group of DA cell bodies localised in the
mesencephalon6-8. This group also contains the cell bodies of
the classical mesolimbic DA system projecting to the tuberculum
olfactorium, the nucleus accumbens, the nucleus of the stria terminalis,
and the amydgala9. The DA terminals found in the cingulate
and entorhinal areas of cortex may originate mainly from the A9 group of
DA neurones6-8. This group gives rise to the well known
nigrostriatal DA system which is implicated in extrapyramidal processes.
Its degeneration is in part responsible for some of the symptoms seen in
Parkinsonian patients. Little is yet known about the functions of the
mesocortical and mesolimbic DA pathways. Electrocoagulation or
6-hydroxydopamine (6-OHDA)-induced lesions of the ventral tegmental
area, containing the A10 group, produce a syndrome characterised by
``locomotor hyperactivity, serious impairment in tests requiring
inhibition of a previously learned response, facilitation of approach
learning and of active avoidance and hypoemotivity''10,11.
Various workers have suggested that the antipsychotic effects of
neuroleptics are in part related to the blockade of postsynaptic DA
receptors localised in areas innervated by the mesolimbic and
mesocortical DA systems12,13. It seems important to establish
whether neurones of these two DA systems correspond to an homogeneous
population of cells with similar functional characteristics. We have
therefore explored this problem in the rat by examining the reactivity
of the mesocortical and mesolimbic DA pathways as well as that of
nigrostriatal DA system to stress induced by electric foot shocks. Our
results suggest that the mesocortical DA system is selectively activated
by this stress.
The ways in which information about faces is represented and stored in the temporal lobe visual areas of primates, as shown by recordings from single neurons in macaques, are considered. Some neurons that respond primarily to faces are found in the cortex in the anterior part of the superior temporal sulcus (in which neurons are especially likely to be tuned to facial expression and to face movement involved in gesture), and in the TE areas more ventrally forming the inferior temporal gyrus (in which neurons are more likely to have responses related to the identity of faces). Quantitative studies of the responses of the neurons that respond differently to the faces of different individuals show that information about the identity of the individual is represented by the responses of a population of neurons, that is, ensemble encoding rather than 'grandmother cell' encoding is used. It is argued that this type of tuning is a delicate compromise between very fine tuning, which has the advantage of low interference in neuronal network operations but the disadvantage of losing the useful properties (such as generalization, completion and graceful degradation) of storage in neuronal networks, and broad tuning, which has the advantage of allowing these properties of neuronal networks to be realized but the disadvantage of leading to interference between the different memories stored in an associative network. There is evidence that the responses of some of these neurons are altered by experience so that new stimuli become incorporated in the network. It is shown that the representation that is built in temporal cortical areas shows considerable invariance for size, contrast, spatial frequency and translation. Thus the representation is in a form which is particularly useful for storage and as an output from the visual system. It is also shown that one of the representations that is built is object based, which is suitable for recognition and as an input to associative memory, and that another is viewer centred, which is appropriate for conveying information about gesture. Ways are considered in which such cortical representations might be built by competitive self-organization aided by back projections in the multi-stage cortical processing hierarchy which has convergence from stage to stage.
This series of experiments compared isolation-reared and socially reared rats for their locomotor activity, behavioural stereotypy, and monoamine function both postmortem and in vivo using intracerebral dialysis. In Experiment 1, isolates showed an altered time course of locomotor activity following d-amphetamine sulphate (AMPH) administration (0.5, 2.0, 3.0, or 5.0 mg/kg, SC). Isolation-reared rats also showed increased sensitivity to the sedative effects of a low dose of apomorphine hydrochloride (0.1 mg/kg) but did not differ from social controls following higher doses of the drug (0.5, 1.5, or 3.0 mg/kg, SC). Isolates showed a decrease in the intensity of apomorphine-induced stereotyped behaviours but no change in stereotypy induced by AMPH. In Experiment 2, isolates had higher postmortem dopamine (DA) concentrations and an altered asymmetry in DA function in the medial prefrontal cortex (PFC) but not in the nucleus accumbens (NAC) or caudate putamen (CPu). Isolated rats also had a lower 5-hydroxyindoleacetic acid (5-HIAA)/5-hydroxytryptamine (5-HT) ratio in the NAC (but not in the PFC or CPu) compared to controls. Experiment 3 used intracerebral dialysis to examine monoamine function in vivo following isolation rearing. Isolates showed greater increases in extracellular DA and greater decreases in DOPAC in response to 2 mg/kg AMPH SC in both the NAC and CPu. There were no apparent differences in the perfusate concentrations of either dopamine (DA), dihydroxyphenylacetic acid (DOPAC), or homovanillic acid (HVA) prior to drug administration. However, consistent with the results of Experiment 2, isolates had a reduced basal perfusate concentration of 5-HIAA from the NAC but not from the CPu. Experiment 4 measured postsynaptic DA function in CPu tissue slices following isolation. Isolation rearing did not affect cAMP accumulation in response to stimulation of D1 DA receptors by DA (0, 2.7, 9, or 30 microM). In addition, isolation rearing did not affect the coupling between D1 and D2 receptors, as measured by the increase in cAMP accumulation with 1 microM 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1 H-3-benzazepin (SK&F 38393) and its reduction by 10 microM quinperole hydrochloride (LY 171555). These results are discussed in terms of the possible relationship between these neurochemical findings and the behavioural disturbances following isolation rearing of rats.
Twenty-three acute schizophrenics, 21 acute major depressives (Research Diagnostic Criteria), and 15 normal controls participated in a study on facial expression and emotional face recognition. Under clinical conditions, spontaneous facial expression was assessed according to the affective flattening section of the Scale for the Assessment of Negative Symptoms. Under experimental laboratory conditions involuntary (emotion-eliciting interview) and voluntary facial expression (imitation and simulation of six basic emotions) were recorded on videotape, from which a raterbased analysis of intensity or correctness of facial activity was obtained. Emotional face recognition was also assessed under experimental conditions using the same stimulus material. All subjects were assessed twice (within 4 weeks), controlling for change of the psychopathological status in the patient groups. In schizophrenics, neuroleptic drug influence was controlled by random allocation to treatment with either haloperidol or perazine. The main findings were that schizophrenics and depressives are characterized by different quantitative, qualitative, and temporal patterns of affect-related dysfunctions. In particular, schizophrenics demonstrated a trait-like deficit in affect recognition and in their spontaneous and voluntary facial activity, irrespective of medication, drug type and dosage, or extrapyramidal side-effects. In depressives a stable deficit could be demonstrated only in their involuntary expression under emotion-eliciting interview conditions, whereas in the postacute phase a reduction in their voluntary expression became apparent. Differences in patterns of affect-related behavioral deficits may reflect dysfunctions in different underlying psychobiological systems.
Groups of rats with 6-hydroxydopamine (6-OHDA) lesions of either the medial prefrontal cortex (PFC), nucleus accumbens (NAC), or caudate putamen (CPu) were given daily tests for locomotor activity in photocell cages while food deprived. Two separate groups of NAC-lesioned rats were prepared with either large [NACT (90% NAC dopamine depletion)] or partial [NACP (67% NAC dopamine depletion)] lesions. NACT rats were spontaneously hypoactive whereas NACP rats were hyperactive compared with sham-operated controls. PFC-lesioned rats were also hyperactive compared to their respective controls. Spontaneous locomotor activity in CPu-lesioned rats did not differ from shams. When daily food supplements were paired with the photocell cages, all subjects developed a conditioned locomotor response. During the first few days of conditioning, the response to this conditioning procedure was markedly greater in the NACP group whereas the response in the NACT group was unaffected initially and actually enhanced during the latter days of testing. The locomotor response to the conditioning procedure was unaffected in either the PFC- or CPu-lesioned groups. Both the NACT and NACP lesions attenuated the locomotor response to 1.5 mg/kg d-amphetamine sulphate IP, and the NACT group showed a supersensitive response to 0.1 mg/kg apomorphine HCl SC. PFC or CPu 6-OHDA lesions did not alter the response to either drug. These results differentiate the role of PFC, NAC, and CPu dopamine in spontaneous, conditioned, and drug-induced locomotor activity and further implicate dopaminergic mechanisms of the NAC in the magnitude of the behavioural response to incentive stimuli.
The data reviewed here are compatible with the hypothesis that telencephalic dopamine activity is elicited by motivationally significant stimuli which in turn creates a neural state in which animals are more prepared to respond to significant stimuli in the environment. This analysis may be viewed as extensions of both the sensorimotor hypothesis, which depicts dopamine as potentiating the ability of stimuli to elicit responses (Clody and Carlton, 1980; Marshall et al., 1974; White, 1986) and of the incentive motivational hypothesis, which emphasizes the importance of dopamine in responding to stimuli that serve as signals of biologically significant events (Blackburn et al., 1989a; Crow, 1973; Mogenson and Phillips, 1976). In addition, we have sought to emphasize that not all responses are equally dependent upon the integrity of forebrain dopamine activity. Some responses, such as ingestion of standard foods by hungry animals, copulation, and escape, are relatively impervious to dopamine disruption. Further, once other behaviours, such as avoidance or appetitive operant responses, have been acquired, they can be maintained at an initially high rate despite perturbation of dopamine systems, although performance deteriorates with repeated testing. This analysis has emerged from the joint consideration of how both appetitive and defensive behaviours are influenced by dopamine antagonists, along with an examination of dopamine release during sequences of behaviour. The data reviewed suggest that dopamine is involved in fundamental psychological processes through which environmental stimuli come to exert control over certain aspects of behaviour. In the future, as knowledge in this field advances, there will have to be an integration of the literature on dopamine and motivation with the literature on dopamine and motor systems. We expect that dopamine release will be seen as a mechanism by which important environmental cues, of innate or learned significance, lead to a general enhancement of motor skeletal responses directed towards distal cues. We conclude with a caveat: Caution must be exercised when attempting to infer a general role of any neurotransmitter in motivated behaviour based on the study of a limited number of motivational systems. Although neurotransmitter pathways may figure prominently in the control of certain behaviours, it is incorrect to think of neurotransmitters as having a single role in behaviour. However, when comparative analyses reveal a common thread among different motivational systems, as is becoming apparent for the general role of mesotelencephalic dopamine pathways in behaviour, then the goal of generating coherent and comprehensive theory concerning a neurotransmitter's function in behaviour will begin to be realised.(ABSTRACT TRUNCATED AT 400 WORDS)
The amygdala appears to play an essential role in many aspects of emotional information processing and behavior. Studies over the past year have begun to clarify the anatomical organization of the amygdala and the contribution of its individual subregions to emotional functions, especially emotional learning and memory. Researchers can now point to plausible circuits involved in the transmission of sensory inputs into the amygdala, between amygdaloid subregions, and to efferent targets in cortical and subcortical regions, for specific emotional learning and memory processes.
Audiovisual tapes of emotional situations were shown to 34 schizophrenics and 15 controls who were asked to rate the emotional content of the scenes using an adjective check-list. The schizophrenic patients failed to detect the dominant character of the scenes, and perceived the opposite emotions to those perceived by the controls. Such deviant responses were not related to paranoid symptoms, flattened affect, formal thought disorder, general level of morbidity, or duration of in-patient stay.
It has been widely demonstrated that schizophrenic patients show a broad range of deficits in interpersonal skills. Recently,
considerable attention has been focused on the ability of these patients to decode affective cues. This article reviews findings
about facial-affect recognition in schizophrenia. While the literature on this topic is extensive, many investigations have
suffered from significant methodological shortcomings. Strategies to resolve these shortcomings are presented. Possible relationships
between problems of affect recognition and other symptoms that characterize schizophrenia are discussed. Neurological mechanisms
of facial-affect recognition are reviewed and related to data on lateralized neurological impairment in schizophrenia. Suggestions
for future research emphasize careful consideration of affect-recognition deficits in relation to other parameters of schizophrenia.
Twenty patients admitted for minor or moderate closed-head injury were studied to investigate the relationship between magnetic resonance imaging (MRI) and neurobehavioral sequelae. The MRI scans demonstrated 44 more intracranial lesions than did concurrent computerized tomography (CT) scans in 17 patients (85%); most of these lesions were located in the frontal and temporal regions. Estimates of lesion volume based on MRI were frequently greater than with CT; however, MRI disclosed no additional lesions that required surgical evacuation. Neuropsychological assessment during the initial hospitalization revealed deficits in frontal lobe functioning and memory that were related to the size and localization of the lesions as defined by MRI. Follow-up MRI and neuropsychological testing at 1 month (13 cases) and 3 months (six cases) disclosed marked reduction of lesion size paralleled by improvement in cognition and memory. These findings encourage further investigation of the prognostic utility of MRI for the clinical management and rehabilitation of mild or moderate head injury.
A GABAergic nucleus accumbens-ventral pallidum projection is believed to serve as the critical first-order accumbens efferent pathway underlying the behavioral expression of mesolimbic dopamine (DA) activity in the rat. In a series of experiments, we studied the effects of lesions of several ventral pallidal efferent terminal regions on the rat locomotor response to apomorphine following 6-hydroxydopamine denervation of the nucleus accumbens. Lesions of the dorsomedial nucleus of the thalamus (DMT), but not the medial prefrontal cortex or the predunculopontine nucleus, significantly depressed the 'supersensitive' locomotor response to apomorphine. Lesions of the DMT did not depress baseline locomotion, but did diminish the locomotor activation produced by intracerebral injection of the gamma-aminobutyric acid antagonist picrotoxin into the ventral pallidum. These results suggest that accumbens-pallidothalamic circuitry plays a crucial role in translating the effects of mesolimbic DA activity to lower motor circuitry responsible for locomotor behavior in the rat.
The performance of schizophrenic inpatients (N = 14), depressed inpatients (N = 15), and normal hospital employees (N = 15), all females, was compared on Izard's (1971) test of emotion recognition. Subjects were required to match photographs of facial expressions of emotion with the correct label for the emotion. The average numbers of errors of four types were examined: Positive or neutral emotions mislabelled as other positive or neutral emotions; positive or neutral emotions mislabelled as negative; negative emotions mislabelled as positive or neutral; and negative emotions mislabelled as other negative emotions. The principal findings were (1) the schizophrenics were less accurate than normals, but they were not less accurate than the depressives, nor were they less accurate on negative than positive or neutral emotions; (2) the depressives did not display any form of negative bias in emotion recognition; and (3) both groups of inpatients were less accurate than normals when they labelled an emotion as positive or neutral, but not when they labelled it as negative. Implications of the results for the etiology and maintenance of schizophrenia and depression were noted.
Forty depressives, 48 schizophrenics and 105 non-patient controls were asked to judge the mutual similarities amongst six different facial affects depicted in photographs. Inter-stimulus distances suggest two dimensions of affect operative in controls: pleasantness-unpleasantness and arousal-non-arousal. Depressives' judgements correspond to the former dimension whilst schizophrenics' judgements correspond to the latter.
A clinical, morphological and neurochemical correlative study in patients with Parkinson's syndrome and Huntington's chorea is reported. In the former group of patients, 69 brains were examined morphologically and 28 biochemically; in the latter group, 4 brains were examined morphologically and 14 biochemically. The results were as follows: (1) The main morphological alteration common to all forms of Parkinsonism was damage to the substantia nigra with a loss of the melanin-containing nerve cells in the zona compacta; the degree and pattern of this cell loss varied in a manner characteristic of the different forms of Parkinsonism. (2) Neurochemically, Parkinson's syndrome was characterized by a decrease in the concentrations of dopamine (DA) and its metabolite homovanillic acid (HVA) in the striatum (caudate nucleus and putamen) and pallidum. (3) A satisfactory positive correlation could be established between the degree of cell loss in the zona compacta of the substantia nigra and the disturbance of DA metabolism in the nuclei of the basal ganglia. (4) The nosological classification of Parkinson's syndrome (based on clinical and morphological criteria) into 3 main groups, viz. postencephalitic, idiopathic and “arteriosclerotic”-senile, was supported by distinct, though not in all cases statistically significant, differences in the degree of disturbance of striatal DA metabolism. (5) In general, mild Parkinsonism, just manifest clinically, was associated with a disproportionately high degree of striatal DA deficiency. From this it was concluded that: (a) clinically manifest Parkinsonism represents the late, “decompensated”, stage of a disease characterized by a progressive striatal DA deficiency; and (b) the striatum can compensate functionally for lower degrees of DA deficiency. (6) Positive correlations could be established, within a certain range, between the severity of individual Parkinsonian symptoms (especially akinesia and tremor) and (a) the degree, and also the site, of the disturbance of DA metabolism within the nuclei of the basal ganglia; and (b) the sensitivity of the patients to levodopa's acute anti-akinesia effect. The latter observation was interpreted as suggesting that in Parkinsonism there exists a supersensitivity (probably of the “denervation type”) of striatal receptors to DA. (7) Based on the correlations, levodopa therapy can be regarded as a specific, though probably predominantly symptomatic, treatment of the main extrapyramidal symptoms of Parkinson's syndrome. (8) In Huntington's chorea the concentrations of DA and HVA in the putamen, pallidum and substantia nigra showed no significant deviation from control values; however in the caudate nucleus there was a small but statistically significant reduction in the levels of these compounds (9). The possible functional significance of the observed correlations for the pathophysiology of disorders of the basal ganglia such as the diseases of Parkinson and Huntington is discussed.