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Frontal lobe dysfunction in Parkinson's disease. The cortical focus of neostriatal outflow
Abstract
This study investigates the hypothesis that, as a consequence of Parkinson's disease, disturbed caudate outflow will lead to deficits in cognitive functions dependent upon the integrity of the prefrontal cortex, the cortical focus of caudatofugal signals. Since Parkinson's disease also involves lesions in extra-striatal midbrain cells which reduce the extrinsic supply of dopamine to this cortical region, such functions are at double risk. Forty nondemented parkinsonian patients were drawn from a pool of 100 consecutive patients and matched with 40 normal control subjects according to age, education, IQ, and sex. All patients were quantitatively rated on neurological indices of disease. Neuropsychological assessment of the patient and normal groups included tests of general intelligence, psychomotor skills, memory, visuospatial and executive functions. No global cognitive decline was observed in the parkinsonian group. Moreover, memory and visuospatial abilities were generally intact. A small cluster of deficits emerged, interpreted as reflecting impairment in the ability to spontaneously generate efficient strategies when relying on self-directed task-specific planning. In addition, several tests thought to be sensitive to frontal lobe function distinguished patients with symptoms strongly lateralized to the right versus left side of the body. Deficits in strategic planning were later investigated in relation to severity of disease and to patient attributes including IQ and age, both of which were relevant to performance on specific tasks. Results were compared with previous investigations in parkinsonian patients and discussed from the perspective of both animal and human studies involving damage to the cerebral cortex and basal ganglia. As the prefrontal cortex is thought to play a crucial role in self-directed behavioural planning, the validity of an outflow model in predicting the consequences of caudate nucleus dysfunction was supported.
... The failures of Parkinson's disease (PD) patients without dementia to learn and retain information necessary to perform explicit verbal memory tasks have been reported frequently (Buytenhuijs et al., 1994;Cooper, Sagar, Jordan, Harvey, & Sullivan, 1991;Daum et al., 1995;Gabrieli, Singh, Stebbins, & Goetz, 1996;Levin, Llabre, & Weiner, 1989;Taylor, Saint-Cyr, & Lang, 1986). However, the cognitive characteristics of the memory deficits shown by PD patients remain somewhat elusive. ...
... Furthermore, similarities between the cognitive patterns shown by PD and frontal lobe patients (Gabrieli et al., 1996;Levin et al., 1989;Taylor, Saint-Cyr, & Lang, 1986 have been interpreted as evidence that PD patients' impairment on memory and learning tasks results from a basic lack of strategy in self-directed planning (Bondi, Kaszniak, Bayles, & Vance, 1993;Stamm et al., 1993) and set shifting when the information that drives behavior comes from internal rather than external sources (Fimm, Bartl, Zimmermann, & Wallesch, 1994 (Breen, 1993;Buytenhuijs et al., 1994;Gabrieli et al., 1996;Taylor et al., 1986). According to the frontal hypothesis, PD patients fail on tasks requiring spontaneous organization of learned material and, similar to frontal lobe patients, improve (Gershberg & Shimamura, 1995) or even succeed (Daum et al., 1995;Hirst & Volpe, 1988) when the material is already explicitly structured. ...
... Furthermore, similarities between the cognitive patterns shown by PD and frontal lobe patients (Gabrieli et al., 1996;Levin et al., 1989;Taylor, Saint-Cyr, & Lang, 1986 have been interpreted as evidence that PD patients' impairment on memory and learning tasks results from a basic lack of strategy in self-directed planning (Bondi, Kaszniak, Bayles, & Vance, 1993;Stamm et al., 1993) and set shifting when the information that drives behavior comes from internal rather than external sources (Fimm, Bartl, Zimmermann, & Wallesch, 1994 (Breen, 1993;Buytenhuijs et al., 1994;Gabrieli et al., 1996;Taylor et al., 1986). According to the frontal hypothesis, PD patients fail on tasks requiring spontaneous organization of learned material and, similar to frontal lobe patients, improve (Gershberg & Shimamura, 1995) or even succeed (Daum et al., 1995;Hirst & Volpe, 1988) when the material is already explicitly structured. ...
Word-list learning was studied in patients with Parkinson's disease (PD) and normal control (NC) participants by means of the selective-reminding procedure of H. Buschke and P. A. Fuld (1974) in 3 learning conditions using semantically unrelated items; semantically related items, whose implicit categorical structure had to be spontaneously guessed; and semantically related items, whose explicit categorical structure was known in advance. The PD patients displayed poor learning in all 3 conditions. To identify the functional locus of the PD patients' deficits, the authors performed a stochastic Markov chain analysis, which allowed individual measurements of encoding, retrieval, and category clustering abilities. PD patients were never significantly impaired in encoding word engrams; their impairment was confined to automatic and intentional retrieval and to the ability to benefit from explicit semantic clues.
... lNTRODUCTION Considered for over a century and a half (fîrst dcscribed 1 , 10 1817, by James Parkinson in his "Essay on Shaking Palsy") an exclusively motor dis1urbance 2 , Parkinson 's disease 3 seems lO be accom paniedas it has become more and more obvious in the recent years (4,5,13) by minute psychobehavioral dysfunctions, e.g., visuospatial impairmem, loss of explicit and especially implicit memory, and impairment of auention and executive functions ( 10). ...
... Severa! patients (13) showed much significant impairments of p � rformances _ for visuospatial tasks accompamed by a minor alteration of executive functions. The opposite pattern was encountered în � ther 19 patients. ...
... The results of the present study support severa! findirngs on the pathological invol vement of s , ubcortical-cortical circuits in Parkinson's disease (4,5,13). Moreover, based on a classical double dissociation, they suggest the disjunction of the subcor tical-frontal disturbances from the subcor tical-parietal ones. ...
It was recently proven that the lesions of basal ganglia are accompanied by specific impairments in memory (visuospatioan organization and execution). In the present study the performance of a group of 43 non-demented and non-depressive patients with Parkinson's disease on a mini-battery of visuospatial and executive tests was compared with that of a control group of 25 patients. Results show that in some patients impairment in performance on the two types of tests seem to be independent from the other, suggesting a distinct etiological involvement of subcortical-cortical circuits.
... For example, non-demented PD patients exhibit impaired free recall (spontaneous retrieval) but benefit substantially from cueing, demonstrating that externally triggered retrieval is intact (Costa et al., 2014;Lees and Smith, 1983). Recognition memory is also intact at this stage (Lees and Smith, 1983;Taylor et al., 1986) although there is some debate about this (Whittington et al., 2000). Overall, this indicates that in PD memories are encoded and stored, but not independently retrieved. ...
... However, such hypo-activation was only present during task phases that specifically required co-activation with the striatum in controls, indicating that striatal dysfunction was the determining factor in executive impairment in PD rather than frontal dysfunction. Both the globus pallidus internus (GPi) and caudate are heavily affected by dopaminergic degeneration in PD (Taylor et al., 1986), and PET studies have specifically implicated dysfunction of these two structures in interruption of normal processing in the fronto-striatal network. For example, PD patients demonstrating executive impairments on tasks involving planning (Owen et al., 1998) or random number generation (Dirnberger et al., 2005) show significantly altered outflow activity from the pallidum to the frontal cortices. ...
The Lewy body dementias, Parkinson’s disease dementia and dementia with Lewy bodies, are two of the most common causes of dementia worldwide, and share both a common clinical phenotype and underlying pathology. Despite their growing economic and societal disease burden, there are currently only a small number of limited symptomatic therapies available, while modern approaches to develop disease modifying biologic agents have so far produced little tangible effect. There is growing recognition of the need to explore alternative treatment avenues, and the success of deep brain stimulation (DBS) in modulating aberrant neural network processing to relieve symptoms in other neuropsychiatric diseases raises the possibility that this might be achievable in Lewy body dementias. The nucleus basalis of Meynert (NBM) provides the major source of ascending cholinergic innervation to the cortex, and is proposed to be a key node in multiple distributed cognitive networks. The nucleus degenerates significantly in Lewy body dementias, which correlates closely with the severity of cognitive decline. It is therefore proposed that deep brain stimulation to the NBM may be able to modulate cholinergic transmission to cortex, and thereby impact directly upon dementia symptoms. In this thesis I will present preliminary evidence from two experimental clinical trials of deep brain stimulation to the NBM in Lewy body dementias. I will present data showing that this invasive neurosurgical procedure is both safe and well tolerated in patients with advanced dementia, and that low frequency stimulation may be associated with improvements in both memory functions and neuropsychiatric symptomatology. Furthermore, I will present results from the first direct electrophysiological recordings from human NBM in vivo, showing that activity in the nucleus may reflect levels of sustained attention. Finally, I evaluate the overall clinical impact of this novel therapeutic approach in Lewy body dementias, and discuss how our electrophysiological findings may relate to this, and how they contribute to our existing understanding of the physiological function of NBM.
... Different subcomponents of executive functions have been reported to be impaired in PD patients, including planning, problem-solving, working memory, verbal fluency, set-shifting, and inhibitory control (McKinlay et al., 2010). Increasing evidence shows that individuals with PD, compared with age-matched controls, perform poorly on standardized neuropsychological tests used for clinical assessment of executive functions (EFs), such as the Wisconsin Card Sorting Test (Berg, 1948;Grant and Berg, 1948), the Stroop Color and Word Test (Stroop, 1935), the Trail Making Test (Reitan, 1958) and the Tower of Hanoi or Tower of London (Cooper et al., 1992;Taylor and Saint-Cyr, 1995;Taylor et al., 1986). Since EFs play a crucial role in ensuring optimal functioning and goal achievement in everyday life, their impairment can significantly impact patients with PD and their caregivers. ...
... It has been known that AD and PD alter the morphology and functionality of the cortex areas. For three decades, it has been known that PD leads to dysfunctionality in frontal lobe that is related to cognitive behavior and decision-making [8]. AD causes synapse loss in the frontal cortex [9] and asymmetry in the temporal lobe [10]. ...
Two of the most prevalent central neuron system disorders are Alzheimer (AD) and Parkinson’s disease (PD). Interestingly, despite their differences in both pathological and molecular basis of the diseases, they exhibit some degrees of similarities. Here, we have conducted a comparative systems-level analysis study for these diseases. Cohort cortex samples from healthy control cases and AD/PD patients were obtained, then we have applied weighted gene co-expression network analysis (WGCNA). Network analysis identified key modules of genes related to each of these diseases. Gene ontology enrichment of the modules showed the involvement of both disease-specific and shared biological processes, including chemical synaptic transmission, nervous system development, and immune responses that are involved in both AD and PD. Surprisingly, the expression patterns for the gene members of the shared modules were strikingly identical. Additionally, we have identified a set of novel genes, including INPP4A, CREG2, ABI3, MYO1F, NAPB, NXN, DOCK6, CPSF6, and IKZF1. While these genes are implicated in either AD or PD modules as shown in Table 2, their potential functional relevance to both diseases warrants further investigation. In conclusion, besides unveiling the presence of high molecular level similarities between AD and PD, for the first time, several novel genes have been proposed that can open a new opportunity for diagnostic or treatment applications.
... Thus, it is possible that the habit learning deficit exhibited by these patients is due to the relatively diffuse damage caused by the disease process. Cognitive deficits associated with PD and HD include impaired executive functions (Flowers & Robertson, 1985;Lees & Smith, 1983;Taylor, Saint-Cyr, & Lang, 1986) and visuospatial abnormalities unrelated to motor deficits (Boller et al., 1984;Hovestadt, de Jong, & Meerwaldt, 1987;Villardita, Smirni, le Pira, Zappala, & Nicoletti, 1982). As a result, it is possible that nonspecific damage to neocortical structures contributed to the habit learning deficit seen in PD and HD patients. ...
Habit learning refers to the incremental implicit learning of associations. Patients with Alzheimer's disease (AD) exhibit deficits in explicit memory and in conceptual implicit memory tasks that rely on the cortical areas damaged in AD. The authors tested patients with AD and controls on a probabilistic classification task in which participants implicitly acquire cue-outcome associations. Both groups showed evidence of learning across 50 trials, and performance did not differ significantly between the groups. In contrast, patients with AD exhibited a profound impairment in explicit memory for the testing episode. These results are consistent with the idea that habit learning relies on subcortical structures, including the basal ganglia, and is independent of the medial temporal and cortical areas damaged in AD.
... The number of perseverative responses, reflected by 1and 2-back errors, was similar for patients and controls. This finding is consistent with those from a growing number of studies indicating that an increased tendency to perseverate is not observed in nondemented Parkinson's patients (Massman, Delis, Butters, Levin, & Salmon, 1990;Owen et al., 1993;Taylor, Saint-Cyr, & Lang, 1986). In comparison, an increased tendency to perseverate is seen in patients with PD who possess global cognitive impairments indicating the presence of dementia (Beatty & Monson, 1990;Sagar, Sullivan, Cooper, & Jordan, 1991). ...
The factors contributing to the working memory deficit observed in older adults and individuals with Parkinson's disease on the Self-Ordered Pointing Task were examined in 2 experiments. A detailed analysis of the error data revealed that errors tended to be clustered toward the end of a trial and that this effect was somewhat independent of set size. This pattern was proposed to result from a monitoring deficit where individuals failed to maintain an integrated representation of how far they had proceeded in the trial, an interpretation consistent with animal work byM. Petrides (1995) .
... Individuals with Parkinson's disease (PD) exhibit a task-dependent deficit in verbal explicit memory [5][6][7][8][9][10]. Within word-list learning tests, this deficit typically occurs when words have to be freely recalled, and not during the recognition phase [10,11]. ...
Background:
Learning is a long-term memory process, influenced by working memory control processes, including recognition of semantic properties of items by which subjects generate a semantic structure of engrams.
Objectives:
The aim of the study is to investigate the verbal learning strategies of individuals with Parkinson's disease (PD).
Method:
Thirty individuals with idiopathic PD and healthy control (HC) subjects were tested with a multi-trial word list learning, under two conditions: without cue and then with an explicit cue suggesting the categories in the list, respectively.
Results:
In comparison to HC subjects, individuals with PD recalled fewer words and achieved a reduced number of categorical clusters; the strategical cue did not improve their performance.
Conclusion:
This suggests, besides a difficulty in identifying the correct learning strategy, a deficit in working memory, which undermines the strategy implementation.
... The timed test offers some quantitative measure of the speed of cognitive processing (reduced in PD). PD patients are impaired in tasks requiring the spontaneous elaboration, maintenance and change of cognitive strategies (Bowen et al., 1975;Matison et al., 1982;Weingartner et al., 1984;Flowers and Robertson, 1985;Taylor et al., 1986;Gotham et al., 1988). The short story test as a test of working memory (a recognized subcategory of executive function) (Baddeley, 1992;D'Esposito et al., 1995) was impaired in the PD subjects. ...
Background
Parkinson’s disease (PD) is a chronic neurodegenerative disorder complicated by cognitive dysfunctions which are associated with increased caregiver burden, pressure on community health facilities, and mortality in affected patients. Most of the data concerning cognitive dysfunctions in PD are from studies conducted in Europe and North America, but there is paucity of data from Sub-Saharan Africa.
Objective
The objective of this study is to determine the frequency, pattern and predictors of cognitive impairments amongst patients with Parkinson’s disease.
Materials and methods
This was a cross sectional case control study carried out at a tertiary health facility in South-south Nigeria. Participants with PD were consecutively recruited from the neurology outpatient clinics. Demographic and disease-specific data were obtained with the use of a pre-tested questionnaire. Cognitive performance of thirty patients with PD were compared with thirty demographically matched controls using the Community Screening Instrument for Dementia (CSID). CSID was already validated among Nigerians.
Results
The frequency of cognitive impairment using the CSID was 50% for PD patients (3.3% for controls). Poor cognitive performance was observed across several cognitive domains including language, executive dysfunction, psychomotor speed, and constructional apraxia among PD patients. The independent predictors of the overall cognitive impairment in patients with PD determined by logistic regression analysis include recall deficiency (p = 0.007), impairment with naming (p = 0.044), apraxia (p = 0.003), Hoen&Yahr staging (p = 0.046), UPDRS score (p = 0.015) and age at presentation (p = 0.014).
Conclusion
Cognitive impairments occur more frequently in patients with PD compared to controls. This study also demonstrated the predictive role of severity of disease based on Hoehn &Yahr staging and UPDRS score, and presence of recall deficiency, poor naming ability and apraxia.
... It has been known that AD and PD alter the morphology and functionality of the cortex areas. For three decades, it has been known that PD leads to dysfunctionality in frontal lobe that is related to cognitive behavior and decision-making (TAYLOR et al. 1986). AD causes synapse loss in the frontal cortex (DeKosky and Scheff 1990) and asymmetry in the temporal lobe (Geroldi et al. 2000). ...
Background: Two of the most prevalent central neuron system disorders are Alzheimer (AD) and Parkinson’s disease (PD). Interestingly, despite their differences in both pathological and molecular basis of the diseases, they exhibit some degrees of similarities. Here, we have conducted a comparative systems-level analysis study for these diseases. Cohort cortex samples from healthy control cases and AD/PD patients were obtained, then we have applied weighted gene co-expression network analysis (WGCNA).
Results: Network analysis identified key modules of genes related to each of these diseases. Gene ontology enrichment of the modules showed the involvement of both disease-specific and shared biological processes, including chemical synaptic transmission, nervous system development, and immune responses that are involved in both AD and PD. Surprisingly, the expression patterns for the gene members of the shared modules were strikingly identical. Additionally, we have introduced a handful of novel genes, including INPP4A, CREG2, ABI3, MYO1F, NAPB, NXN, DOCK6, CPSF6, and IKZF1, with potential functionality in both diseases; AD and PD.
Conclusions: In conclusion, besides unveiling the presence of high molecular level similarities between AD and PD, for the first time, several novel genes have been proposed that can open a new opportunity for diagnostic or treatment applications.
... With regard to the influence of clinical status on DD, we are aware that PD patients can be affected by impulse control disorders, which can lead to several abnormal behaviours such us pathological gambling, binge eating, hypersexual disorder, compulsive buying (See [51], for a review), which are known to be related to a steeper DD [111]. As impulse control refers to the prefrontal neural network [14] one might link the steeper DD of PD (in the "off medication" condition) to their prefrontal lobe disfunction [123,7]. However, this does not mean to exclude the role of the limbic-subcortical system, which is known to play a role in DD by driving immediate reward seeking [17], which is abnormal in PD [106]. ...
Delay discounting refers to the depreciation of the value of a reward as a function of
the time it takes to obtain it. Growing evidence shows altered delay discounting in
several pathological conditions, including neurological disorders. Here, we conducted
a systematic review and meta-analysis of the published literature on delay discounting
(DD) in Parkinson’s Disease (PD). We found steeper DD in patients with PD, compared
to healthy controls, both in “on” and “off” dopaminergic medication. This pattern was
unaffected by the presence of impulse control disorders. Moreover, we found steeper
DD in “on medication” compared to “off medication” condition. These results confirm
altered DD in PD and suggest an independent influence of the dopaminergic
medication and the clinical condition itself on it.
... It is also believed that the working memory deficit in PD is primarily associated with impaired executive functions localized in the dorsolateral prefrontal cortex (DLPFC) (Taylor et al., 1986;Morris et al., 1988;Gabrieli et al., 1996;West et al., 1998). This is explained by a decrease in the dopamine concentration in DLPFC due to degeneration of dopaminergic neurons of the substantia nigra and the ventral region of the tegmentum, disruption of the normal interaction between direct and indirect connections between the cortex, basal nuclei and the thalamus, as well as impaired functioning of neuroplasticity mechanisms (Owen, 2004;Leh et al., 2010). ...
Decrease in cognitive function is one of the most common causes of poor life quality and early disability in patients with Parkinson’s disease (PD). Existing methods of treatment are aimed at both correction of motor and non-motor symptoms. Methods of adjuvant therapy (or complementary therapy) for maintaining cognitive functions in patients with PD are of interest. A promising subject of research in this regard is the method of transcranial electric current stimulation (tES). Here we reviewed the current understanding of the pathogenesis of cognitive impairment in PD and of the effects of transcranial direct current stimulation and transcranial alternating current stimulation on the cognitive function of patients with PD-MCI (Parkinson’s Disease–Mild Cognitive Impairment).
... La MP est la deuxième pathologie neurodégénérative la plus commune (Hughes et al., 1992;Chaudhuri et al., 2011) (Taylor et al.., 1986;Hornykiewicz & Kish, 1987;Hughes et al., 1992;Jankovic, 2008;Wolters, 2009;Chaudhuri et al., 2011). Les autres symptômes de la MP sont rassemblés sous le terme « symptômes nonmoteurs », comprenant des troubles cognitifs et neuropsychiatriques (lesquels seraient principalement la conséquence de la désafférentation du cortex frontal en raison de l'atteinte des boucles sous-corticofrontales (Wolters, 2009)), mais également des symptômes sensoriels (anosmie, agueusie, douleurs et paresthésies), une dysautonomie, une perte de poids et des troubles du sommeil (Hughes et al., 1992;Jankovic, 2008;Chaudhuri et al., 2011). ...
La cognition sociale regroupe plusieurs capacités, comme la reconnaissance des émotions faciales (REF), la Théorie de l’Esprit (TDE) et l’empathie. Celles-ci sont sévèrement altérées dans la variante comportementale de la Dégénérescence Fronto-Temporale (DFT-c) et plus légèrement dans la Maladie d’Alzheimer (MA) et la Maladie de Parkinson (MP), avec pour conséquences des troubles du comportement (TDC), désinhibition et apathie en particulier, qui conduisent à l’épuisement de l’aidant familial. Dans ces trois maladies une diminution des capacités top-down et une modification des capacités bottom-up de guidage de l’attention lors de la recherche d’informations visuelles sont aussi observées. Or, la REF, la TDE et l’empathie s’appuient sur la détection visuelle d’indices sociaux, sur le visage en particulier. Enfin, de nombreux chevauchements existent entre les structures, les faisceaux et les réseaux cérébraux impliqués dans la cognition sociale et dans l’exploration visuelle.
A travers trois études expérimentales, cette thèse a pour premier objectif de mettre en évidence que l’atteinte de la cognition sociale dans la DFT-c, la MA et la MP, et les TDC qui en découlent, sont liés à une modification des stratégies d’exploration visuelle. L’objectif secondaire est de montrer qu’une remédiation des stratégies d’observation des visages exprimant une émotion chez les personnes atteintes de maladie neurodégénératives permet une amélioration de la REF, entraine une diminution des TDC et un allègement du fardeau de leurs aidants familiaux.
Nos résultats confirment le triple lien entre stratégies de regard, cognition sociale et TDC. Les difficultés de REF sont associées à une perturbation des mécanismes d’orientation de l’attention sur les régions saillantes du visage liées à chaque émotion. Dans la DFT-c l’altération de ces mécanismes est sévère, le pattern d’exploration des visages exprimant une émotion étant similaire à celui d’un visage neutre. Pour la MA et la MP, cela concerne une perte d’attractivité de la région des yeux et une capture attentionnelle accrue de la région de la bouche. La TDE quant à elle est principalement impactée par une altération des stratégies top-down de recherche d’indices visuels permettant de prendre la perspective d’autrui et d’inférer ses états mentaux. Là aussi c’est dans la DFT-c que le pattern d’observation est le plus perturbé, avec une perte de stratégies d’observations et une insensibilité aux informations données qui conduisent à une prise de perspective d’autrui décalée dans le temps. Ces types d’observations de scènes sociales sont corrélés à la production de TDC. Enfin, la remédiation de la REF menée auprès d’un groupe MA montre que l’amélioration des performances est conjointe à une modification des stratégies d’observation des visages, avec une observation plus importante de la région des yeux, et entraîne une diminution des TDC et du fardeau de l’aidant.
Nos résultats suggèrent donc une forte participation des mécanismes attentionnels dans le déficit de cognition sociale dans les maladies neurodégénératives. Par conséquent une prise en charge des TDC axée sur une remédiation des stratégies de recherche d’indices visuels sociaux semble être une piste intéressante afin de prévenir l’épuisement de l’aidant familial et de retarder l’institutionnalisation.
... Despite the well-described link between PD and frontal lobe dysfunction, we found no association between executive domain items on the MOCA and caregiver-reported aggression. 35,36 In PD, this form of cognitive impairment can lead to a loss of emotional detection and decreased empathy, which can translate to higher caregiver burden. 36 Detection of these cognitive and metacognitive deficits can be challenging for even experienced clinicians and is likely underrecognized in patients who do not otherwise meet the threshold for a diagnosis of dementia. ...
Objective
To estimate the point prevalence and cumulative incidence of caregiver-reported aggressive behaviors amongst people living with advanced Parkinson’s disease and related disorders (PDRD) and secondarily examine variables associated with aggression.
Methods
Caregivers from a clinical trial of outpatient palliative care for PDRD were surveyed about patient aggression at baseline and every three months over 12 months. Baseline responses were used for point prevalence. Cumulative incidence was calculated using responses from caregivers with no reported baseline aggression and available data at all other timepoints. Measures of disease severity, quality of life, mood and caregiver burden were included in correlation and relative risk models, adjusting for age, sex, and diagnosis.
Results
Of 170 caregivers, 31 (18.2%) reported physical aggression and 18 (10.6%) reported sexual aggression. 12-month cumulative incidence for physical and sexual aggression were 21.1% (23/109) and 16.0% (19/119) respectively. Physical aggression cumulative incidence was associated with patient depression (r=0.37), patient-perceived quality of life (r= -0.26), caregiver burden (r=0.26), caregiver-perceived patient quality of life (r= -0.26), and caregiver anxiety (r=0.20). Age, sex, cognitive impairment and dementia were not associated with aggression. No variables were associated with cumulative sexual aggression.
Conclusion
There was a high prevalence and incidence of aggression in our PDRD cohort. This is an understudied issue in PDRD and our findings highlight the need for increased awareness among neurologists. Providers should consider assessing for aggression when discussing neuropsychiatric symptoms or screening for caregiver burden. Future research should examine the relationship between aggression and patient and caregiver health outcomes.
... Previous studies [14,15,16] that evaluated the difference in cognitive functions between the healthy elderly and Parkinson's disease patients without dementia reported that cognitive issues of Parkinson's disease patients were mainly associated with frontal lobe dysfunction. Cooper et al. (1991) [17] reported that Parkinson's disease patients had difficulty in processing information due to frontal lobe dysfunction and they could show impaired performance or inappropriate behaviors for the situation due to decline concentration. ...
As the number of Parkinson's disease patients increases in the elderly population, it has become a critical issue to understand the early characteristics of Parkinson's disease and to detect Parkinson's disease as soon as possible during normal aging. This study minimized the imbalance issue by employing Synthetic Minority Over-sampling Technique (SMOTE), developed eight Support Vector Machine (SVM) models for predicting Parkinson's disease using different kernel types {(C-SVM or Nu-SVM)×(Gaussian kernel, linear, polynomial, or sigmoid algorithm)}, and compared the accuracy, sensitivity, and specificity of the developed models. This study evaluated 76 senior citizens with Parkinson's disease (32 males and 44 females) and 285 healthy senior citizens without Parkinson's disease (148 males and 137 females). The analysis results showed that the liner kernel-based Nu-SVM had the highest sensitivity (62.0%), specificity (81.6%), and overall accuracy (71.3%). The major negative relationship factors of the Parkinson's disease prediction model were MMSE-K, Stroop Test, Rey Complex Figure Test (RCFT), verbal memory test, ADL, IADL, 70 years old or older, middle school graduation or below, and women. When the influence of variables was compared using "functional weight", RCFT was identified as the most influential variable in the model for distinguishing Parkinson's disease from healthy elderly. The results of this study implied that developing a prediction model by using linear kernel-based Nu-SVM would be more accurate than other kernel-based SVM models for handling imbalanced disease data.
... Investigaciones llevadas a cabo en las últimas décadas revelaron que los trastornos cognitivos forman parte de la sintomatología clínica de la enfermedad. Los mismos pueden presentarse en diferentes grados, mientras que en algunos pacientes se observa un deterioro más generalizado acompañado de un cuadro demencial, en otros sólo se observa una sintomatología específica (Pirazzolo, Hansch & Mortiner, 1982;Lieberman, Dziatolowski, Kupersmith, Serby, Goodgold, Koreim et al, 1982;Elizan, Sroka, Maker, Smith &Yahr, 1986;Taylor, Saint-Cyr & Lang, 1986;Ostrosky-Solis, 2000). A nivel mundial afecta a 1 de cada 100 personas mayores de 60 años (OMS) y en Argentina se calcula que 60.000 personas padecen esta enfermedad (Estimación ACEPTAR, 2006). ...
La preocupación ambiental se conceptualiza a partir de una estructura de cuatro dimensiones: apatía hacia el medio ambiente;
antropocentrismo; conectividad con la naturaleza y afinidad emocional hacia la naturaleza. Por su parte, las competencias socioemocionales representan un conjunto de conocimientos, capacidades, y actitudes necesarias para comprender, expresar y regular
de forma apropiada los fenómenos emocionales. Este trabajo se
propuso evaluar la preocupación ambiental y las competencias socio-emocionales en adultos mayores que participaban de un taller
en el Centro Cultural Rector Ricardo Rojas, en la Ciudad Autónoma
de Buenos Aires, al inicio y final del mismo; en el marco de un
programa de extensión universitaria. La muestra estuvo conformada por 32 Adultos Mayores, 98 % mujeres, de 61 a 83 años (M =
73; SD = 5). Se administraron la Escala de Preocupación Ambiental
(Amérigo, Aragonés & García, 2012; Adaptación Argentina: Cassullo,
2015) y el Inventario de Competencias Socio-emocionales (ICSE;
Mikulic, 2013). Se encontró que los Adultos mayores expresaron
mayor Afinidad Emocional y Conectividad, luego de haber participado del taller; así como también, mayor optimismo, asertividad y Comunicación Expresiva. Los resultados encontrados son promisorios
respecto de la conformación de espacios significativos positivos en
nuestro contexto, que permiten trabajar con adultos mayores desde
la integración de la Psicología Ambiental y Positiva.
... Investigaciones llevadas a cabo en las últimas décadas revelaron que los trastornos cognitivos forman parte de la sintomatología clínica de la enfermedad. Los mismos pueden presentarse en diferentes grados, mientras que en algunos pacientes se observa un deterioro más generalizado acompañado de un cuadro demencial, en otros sólo se observa una sintomatología específica (Pirazzolo, Hansch & Mortiner, 1982;Lieberman, Dziatolowski, Kupersmith, Serby, Goodgold, Koreim et al, 1982;Elizan, Sroka, Maker, Smith &Yahr, 1986;Taylor, Saint-Cyr & Lang, 1986;Ostrosky-Solis, 2000). A nivel mundial afecta a 1 de cada 100 personas mayores de 60 años (OMS) y en Argentina se calcula que 60.000 personas padecen esta enfermedad (Estimación ACEPTAR, 2006). ...
La Psicología Ambiental analiza la interacción entre las personas
y el ambiente entendiéndolo como todo lo que las rodea desde un
carácter sociofísico, tanto natural como construido (Aragonés y
Amérigo, 2010). La preocupación ambiental se entiende como el
interés que los sujetos presentan por el cuidado ambiental (Amérigo, 2006). Se conoce que habitar en lugares vulnerables genera
un impacto negativo en la salud (Prüss-Üstün y Corvalán, 2006).
A consecuencia resulta relevante conocer cómo se manifiesta la
preocupación ambiental en los estudiantes universitarios, futuros
profesionales en ejercicio. La orientación de la formación se vincula con los intereses. Los estudiantes de Psicología centran su
formación en la salud mental de las personas, mientras que los de
Arquitectura en la construcción y acondicionamiento de espacios
que las personas habitan. El objetivo de la presente es comparar
la preocupación ambiental entre estudiantes de Psicología (n=50)
y de Arquitectura (n=50).Se administró la escala de Preocupación
Ambiental (Amérigo, Aragonés y García, 2012; Adaptación Argentina: Cassullo, Caballero, Favara, Colombo y Rusca, 2015) en ambas
poblaciones. Los resultados hallados se relacionan con los obtenidos en estudiantes de Psicología (Cassullo et al., 2015), importante
para la planificación de intervenciones basadas en datos empíricos.
... In line with this, one previous study reported that longer ISIs degraded frequency discriminatory ability, or acuity, in listeners with and without Alzheimer's disease and that discriminatory ability was more affected by longer ISIs in individuals with Alzheimer's disease compared to individuals without Alzheimer's disease (Pekkonen et al., 1994). Given that Alzheimer's disease and PD both affect cognition via the prefrontal cortex (DeKosky & Scheff, 1990;Gotham et al., 1988;Taylor et al., 1986), experimental ISIs could similarly have a greater effect on pitch perception measures in PD compared to individuals without PD. When examining loudness discrimination under increasing memory load conditions in individuals with and without PD, one study reported reduced discriminatory ability for both groups, but no significant interaction of group and task (Richardson & Sussman, 2019). ...
Purpose
Given the role of auditory perception in voice production, studies have investigated whether impairments in auditory perception may underlie the noted disruptions in speech in Parkinson's disease (PD). Studies of loudness perception in PD show impairments in the perception of self-generated speech, but not external tones. Studies of pitch perception in PD have only examined external tones, but these studies differed in terms of the interstimulus intervals (ISIs) that were used, did not examine the impact of cognition, and report conflicting results. To clarify pitch perception in PD, this work investigated perception of self-generated vocal pitch, controlling for cognition and ISI.
Method
A total of 30 individuals with and without PD completed (a) hearing threshold testing, (b) the Montreal Cognitive Assessment, and (c) an adaptive just-noticeable-difference paradigm under two separate ISIs (100 ms and 1,000 ms) to assess acuity to self-generated vocal pitch.
Results
There was no significant difference in acuity between individuals with and without PD. Both groups demonstrated significantly worse acuity for longer compared to shorter ISIs. Montreal Cognitive Assessment scores were not a significant predictor of acuity.
Conclusions
The results suggest that acuity to self-generated vocal pitch does not differ between individuals with and without PD.
... Patients with AD typically present with poor primacy and normal recency effect [10,11], and a reduced primacy effect at MCI stage has further been shown to be predictive for the development of AD dementia [12]. However, SPE in PD have scarcely been explored and only inconsistent results were reported [13,14]. ...
Objective:
The first (primacy region) and last (recency region) items of a word list are generally better memorized than items from the middle region. The recency effect depends on short-term memory (STM) and the primacy effect on long-term memory (LTM), where verbal information is transferred from STM into LTM by maintenance rehearsal. We compared the serial position effects (SPE) between patients with mild cognitive impairment (MCI) due to Parkinson's disease (PD), i.e., PD-MCI, and patients with MCI due to Alzheimer's disease (AD-MCI), and evaluated the influence of SPE and frontostriatal deficits on verbal memory recall.
Methods:
Four similar groups of subjects participated in the study: 26 PD-MCI patients, 26 cognitively normal patients with PD (PD-CN), 26 AD-MCI patients, and 26 normal controls (NC). Verbal episodic memory, verbal span, attentional capacity, executive functions, and verbal working memory performance were assessed. Measures for primacy and recency regions were defined at the first trial of a 16-items word list. Hierarchical regression models were used to investigate the contribution of frontostriatal deficits beyond SPE on verbal memory recall performance ("long-delay free recall") in PD and AD patients.
Results:
Primacy effects were significantly diminished in both PD-MCI and AD-MCI patients relative to NC and PD-CN (all p < 0.01). Compared to PD-MCI patients, AD-MCI patients exhibited significantly worse "delayed-recall 'savings'." Reduced primacy effect was predictive for decreased recall performance in PD and AD. The conducted hierarchical regression model revealed that in PD, but not in AD patients, performance of attention and executive function significantly increased the prediction of free recalled words.
Conclusions:
Reduced recall performance is likely due to impaired transition of newly learned material from STM into LTM in AD and in PD. Whereas AD-MCI patients suffer from a storage deficit, the similarly reduced recall performance found in patients with PD-MCI may additionally be related to deficient attentional and executive capacity.
... The FIT circuit is responsible for decision-making (Gleichgerrcht et al. 2010), an extremely complex human behavior involving stimulus encoding, action selection, and expected reward (Gleichgerrcht et al. 2010). Accumulating evidence suggests that the FIT circuit is affected in brain neurodegenerative diseases such as frontotemporal dementia, Parkinson disease, and Alzheimer's disease (Taylor et al. 1986;Rahman et al. 1999;Torralva et al. 2000). Importantly, Mann et al. (1989) and Cauffman et al. (2010) showed that young adolescents had impairment in decisionmaking as compared with older individuals, suggesting that developmental differences affect decision-making performance, particularly under situations of emotional engagement and uncertain outcome. ...
Accumulating neuroimaging evidence shows that age estimation obtained from brain connectomics reflects the level of brain maturation along with neural development. It is well known that autism spectrum disorder (ASD) alters neurodevelopmental trajectories of brain connectomics, but the precise relationship between chronological age (ChA) and brain connectome age (BCA) during development in ASD has not been addressed. This study uses neuroimaging data collected from 50 individuals with ASD and 47 age- and gender-matched typically developing controls (TDCs; age range: 5-18 years). Both functional and structural connectomics were assessed using resting-state functional magnetic resonance imaging and diffusion tensor imaging data from the Autism Brain Imaging Data Exchange repository. For each participant, BCA was estimated from structure-function connectomics through linear support vector regression. We found that BCA matched well with ChA in TDC children and adolescents, but not in ASD. In particular, our findings revealed that individuals with ASD exhibited accelerated brain maturation in youth, followed by a delay of brain development starting at preadolescence. Our results highlight the critical role of BCA in understanding aberrant developmental trajectories in ASD and provide the new insights into the pathophysiological mechanisms of this disorder.
... Este procesamiento de información exterior no solo es generado por una sola área cortical en mamíferos, sino que es orquestado por un patrón de actividades abarcando varios campos corticales como las áreas sensoriales, de memoria y motoras; dentro de estos campos la corteza prefontral (PFC) probablemente juega el papel más importante monitoreando y organizando los patrones de actividad corticales para las respuestas dirigidas hacia un objetivo (Gomez, 2005). Las funciones del PFC fueron estudiadas en relación con lo denominado como "función ejecutiva", un conjunto de funciones cognitivas que subyacen a la habilidad de generar estrategias eficientes espontáneas cuando se trata de la planeación ante situaciones específicas (Taylor, et al., 1986) (Para mayor detalle, capítulo 2). . ...
... ). Estas alteraciones pueden presentarse en diferentes grados, mientras que en algunos pacientes se observa un deterioro más generalizado acompañado de un cuadro demencial, en otros sólo se observa una sintomatología específica(Pirazzolo, Hansch & Mortiner, 1982; Liberman, Dziatolowski, Kupersmith, Serby, Goodgold, Koreim et al, 1982; Elizan, Sroka, Maker, Smith & Yahr, 1986;Taylor, Saint-Cyr & Lang, 1986; Ostrosky-Solis, 2000, Chade, 2008. Es una de las más comunes enfermedades neurodegenerativas progresivas. ...
The aim of this project is to explore Subjective Temporary in young
people - 18 to 26 years old - from the city of Buenos Aires. The research is intended to know the subjective representation of <>. The
design of the research is non-experimental, cross sectional study
and correlation study. The sample - 110 young people - is intentional and non-probabilistic. People were asked to answer a questionnaire of socio-demographic data and the questionnaire of Subjective Temporary which was made specifically for this research. It
includes opened and closed questions. A quantitative analysis of the
answers was made with descriptive and inference statistics processes. Discussion about the results is provided. Among the most
significant ones we found that young people consider that distant
past means between 1 and 5 years behind; and far future means
between 5 and 10 years. This conclusion confirms the idea that
young people have a preference for present time, without the opportunity to think of long term periods of time.
Keywords: Time - Subjective temporary - Youth
... La Enfermedad de Parkinson (EP) es una patología degenerativa, altamente prevalente, caracterizada por temblor, rigidez, bradicinesia e inestabilidad postural (Calne, Snow y Lee, 1992). Es una patología progresiva con degeneración del sistema dopaminérgico nigro-estriatal (Dubois y Pillon, 1996), con depósitos de cuerpos de Lewy y neuritas distróficas (Lippa et al., 2007), que afecta principalmente los ganglios basales y consecuentemente la vía talámica ventral anterior y medial dorsal con proyecciones al lóbulo frontal (Taylor, Saint-Cyr y Lang, 1986). Con respecto a las alteraciones cognitivas, y en consecuencia a la disfunción en proyecciones frontales, se han observado alteraciones en funciones ejecutivas (Perfetti et al., 2010;Petrova et al., 2010), específicamente en atención sostenida (Alonso- Prieto, 2003;Chaná et al., 2013), memoria de trabajo (Lewis et al., 2003), planificación y flexibilidad cognitiva (Cools et al., 2001). ...
La Enfermedad de Parkinson (EP) es una patología progresiva con degeneración del sistema dopaminérgico nigro-estriatal con disfunción de proyecciones frontales que genera alteraciones en funciones ejecutivas. Esta condición debería afectar particularmente la capacidad de evocar unidades léxicas y recuperarlas desde la memoria de largo plazo; no obstante, si bien se cuenta con datos acerca de este comportamiento, aún es necesario determinar qué subcomponentes del lenguaje se ven afectados a fin de comprender con mayor especificidad tanto la patología como su manifestación lingüística. En este marco, el objetivo del presente estudio consistió en describir el rendimiento en tareas de fluidez verbal de tipo fonológica, morfosintáctica, semántica y sus combinaciones en participantes con enfermedad de Parkinson (EP). Para ello, se realizó un estudio transversal con 42 sujetos, agrupados en Adulto Mayor Sano (AMS; n = 23) y Adulto Mayor Diagnosticado con EP (EP; n = 19). Cada sujeto realizó un total de 15 tareas de fluidez verbal en las que debió evocar la mayor cantidad de unidades léxicas en 60 segundos, las que fueron, además, medidas en intervalos de 15 segundos. Los resultados permitieron observar diferencias estadísticamente significativas en las subtareas de tipo fonológica de fonema excluido, categoría gramatical, relaciones semánticas y de combinación campo léxico y fonema inicial. Estos datos parecen indicar que los sujetos con EP muestran un rendimiento significativamente inferior en tareas que exigen alto control inhibitorio, dado que las subtareas que combinan niveles de la lengua implican evocación e inhibición.
... Though DA deficiency of the nigrostriatal pathway accounts for the major motor symptoms of PD, however, PD patients also exhibit impairments in learning and memory, executive function, and visuospatial function, and these cognitive impairments are associated with PFC lesions [53][54][55]. Working memory deficits are important aspects of the cognitive impairment in PD, particularly in the early stages of PD pathogenesis [22][23][24]. Since MPTP model has also been reported to successfully mimic the working memory deficit and other cognitive impairments in PD [36,[56][57][58][59]. ...
Parkinson's disease (PD) is a common neurodegenerative disease, featured by motor deficits and non-motor symptoms such as cognitive impairment, and malfunction of gamma-aminobutyric acid (GABA) mediated inhibitory transmission plays an important role in PD pathogenesis. The ginsenoside Rb1 molecule, a major constituent of the extract from the Ginseng root, has been demonstrated to ameliorate motor deficits and prevent dopaminergic neuron death in PD. However, whether Rb1 can regulate GABAergic transmission in PD-associated deficits and its underlying mechanisms are still unclear. In this study, we explored the effects of Rb1 on the GABAergic synaptic transmission in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. We demonstrated that Rb1 can bind with GABAARα1 and increase its expression in the SH-SY5Y cells and in the prefrontal cortex (PFC) of MPTP model in vitro and in vivo. Furthermore, Rb1 can promote prefrontal cortical GABA level and GABAergic transmission in MPTP-treated mice. We also revealed that Rb1 may suppress presynaptic GABABR1 to enhance GABA release and GABAA receptor-mediated inhibitory transmission. In addition, Rb1 attenuated MPTP-induced dysfunctional gait dynamic and cognitive impairment, and this neuroprotective mechanism possibly involved regulating prefrontal cortical GABAergic transmission. Thus, Rb1 may serve as a potential drug candidate for the treatment of PD.
... MCI can be observed in prodromal and manifest PD affecting around 20% of patients at the time of diagnosis (Muslimovic et al. 2005;Aarsland et al. 2009a) and displays a major risk factor for the progression to PD dementia (PDD) (Hoogland et al. 2017;Hobson and Meara 2015;Pedersen et al. 2017). Cognitive impairment most commonly affects executive functions, resulting in a 'dysexecutive syndrome' resembling that seen in patients with frontal lobe damage (Owen et al. 1993(Owen et al. , 1995Taylor et al. 1986;Muslimovic et al. 2005;Rowe et al. 2002). The pathophysiology of MCI and dementia in PD is heterogeneous and involves a combination and synergism of distinct pathological changes. ...
Neurodegeneration of the nigrostriatal dopaminergic system and concurrent dopamine (DA) deficiency in the basal ganglia represent core features of Parkinson’s disease (PD). Despite the central role of DA in the pathogenesis of PD, dopaminergic systems outside of the midbrain have not been systematically investigated for Lewy body pathology or neurodegeneration. Dopaminergic neurons show a surprisingly rich neurobiological diversity, suggesting that there is not one general type of dopaminergic neuron, but rather a spectrum of different dopaminergic phenotypes. This heterogeneity on the cellular level could account for the observed differences in susceptibility of the dopaminergic systems to the PD disease process. In this review, we will summarize the long history from the first description of PD to the rationally derived DA replacement therapy, describe the basal neuroanatomical and neuropathological features of the different dopaminergic systems in health and PD, explore how neuroimaging techniques broadened our view of the dysfunctional dopaminergic systems in PD and discuss how dopaminergic replacement therapy ameliorates the classical motor symptoms but simultaneously induces a new set of hyperdopaminergic symptoms.
... whereas the other one involves implicit learning and probabilistic classification (Jackson, Jackson, Harrison, Henderson & Kennard, 1995;Ashby, Noble, Filoteo, Waldron & Ell, 2003;Maddox, Ashby & Bohil, 2003). Evidence has suggested that patients with PD showed inability to plan motor tasks and mental inflexibility (Taylor, Saint-Cyr & Lang, 1986;Brown & Marsden, 1998;Berardelli, Accornero, Argenta, Meco & Manfredi, 1986). Such impairment in executive functions may be viewed as deficits in behaviours that are based on updating information continuously, which is potentially caused by dopamine degeneration (Nieoullon, 2002). ...
The general aim of the present PhD thesis is to investigate the effects of two common treatments of Parkinson’s disease (PD), dopamine medication and deep brain stimulation (DBS) of the subthalamic nucleus (STN), on executive functions (EFs) including the abilities of shifting, updating and inhibition in patients relative to age-matched healthy controls. The thesis consisted of four studies. Study 1 examined the acute effect of dopamine medication on PD patients who had been previously diagnosed with impulsive control disorders (ICDs) using a moving dots paradigm to assess their abilities of context monitoring. Study 2 created predictive models using behavioural data from the previous studies to build classification predictive models, to demonstrate that behavioural patterns on a moving dots task could potentially be used as a screening tool in predicting vulnerability to develop ICDs in PD patients. Study 3 examined the acute effects of STN DBS on task switching using a moving dots paradigm in PD patients. Study 4 investigated the acute effects of STN DBS on reprogramming actions when encountering surprising events, using a probabilistic reaction time (RT) task. It was hypothesised that for both treatments, being ON states would induce impaired executive functions that lead to faster RTs and more incorrect responses in PD patients, due to the ‘dopamine overdose hypothesis’ and the DBS interrupting the role of the STN in inhibitory control. In summary, the acute manipulation of both treatments did not render significantly negative effects on PD patients behaviourally. However, PD patients still showed certain difference on task performance compared to age-matched healthy controls, which may shed lights on the role of basal ganglia in basic abilities of EFs. Furthermore, the behavioural patterns on tasks involving core aspects of EFs may potentially be used to predict the onset of ICDs, which provides benefits to clinical purpose.
... ). Estas alteraciones pueden presentarse en diferentes grados, mientras que en algunos pacientes se observa un deterioro más generalizado acompañado de un cuadro demencial, en otros sólo se observa una sintomatología específica(Pirazzolo, Hansch & Mortiner, 1982; Liberman, Dziatolowski, Kupersmith, Serby, Goodgold, Koreim et al, 1982; Elizan, Sroka, Maker, Smith & Yahr, 1986;Taylor, Saint-Cyr & Lang, 1986; Ostrosky-Solis, 2000, Chade, 2008. Es una de las más comunes enfermedades neurodegenerativas progresivas. ...
El presente trabajo está orientado a explorar la Temporalidad Subjetiva en jóvenes de 18 a 25 años de zonas urbanas de Buenos Aires. Se quiere conocer cuál es su representación subjetiva de la noción . Se utiliza un diseño no-experimental, transversal, correlacional con una muestra de tipo no probabilística intencional. La muestra está compuesta por 110 jóvenes de 18 a 26 años de ambos sexos. Se administró un cuestionario de datos socio-demográficos y un cuestionario construido para evaluar Temporalidad Subjetiva con preguntas cerradas y abiertas. Se llevó a cabo un análisis cuantitativo de los datos y se aplicaron técnicas de estadística descriptiva e inferencial. Se formaron 4 categorías de análisis: pasado reciente, pasado lejano, futuro cercano, futuro lejano, y se analizaron las respuestas en función a las mismas. También se analizó la cualidad de los hechos pasados mencionados. Entre los resultados más significativos, hallamos que la mayoría de los jóvenes considera que Pasado Lejano implica entre 1 a 5 años atrás; y el Futuro Lejano implica entre 5 a 10 años. Esto nos ratifica la idea de que los jóvenes tienen una preeminencia de orientación al presente, sin poder pensar en períodos largos de tiempo ni poder proyectarse a largo plazo.
In the realm of contemporary medical research, the extraction of pivotal attributes associated with Parkinson's disease (PD) from intricate Magnetic Resonance Imaging (MRI) data characterized by multifaceted dimensions and non-linearity stands as a formidable challenge in the pursuit of realizing automated diagnostic support. To address this issue, an approach is introduced, denoted as the Deep Frequency-Channel Attention Factorization (Deep FCAF), designed to address the complexities inherent to the neurodegenerative ailment of Parkinson's. The Deep FCAF amalgamates three key elements: (1) the inherent capacity for non-linear processing exhibited by neural networks, (2) the inherent capability of the attention mechanism to capture global interdependencies, and (3) the underpinning principles of tensor decomposition within the order of multi-dimensional data structures. The experiments conducted on the identification of PD underscore the efficacy of Deep FCAF in assimilating structural and non-linear factor matrices, consequently leading to an improved classification performance. Notably, the elucidation of functional connectivity based on the acquired factor matrices align with previous scholarly investigations. The mathematical formulations, derived from the MRI data, facilitate the measurement of the dynamic mechanism inherent in the MRI data.
This article describes a neuropsychological theory of motor skill learning that is based on the idea that learning grows directly out of motor control processes. Three motor control processes may be tuned to specific tasks, thereby improving performance: selecting spatial targets for movement, sequencing these targets, and transforming them into muscle commands. These processes operate outside of awareness. A 4th, conscious process can improve performance in either of 2 ways: by selecting more effective goals of what should be changed in the environment or by selecting and sequencing spatial targets. The theory accounts for patterns of impairment of motor skill learning in patient populations and for learning-related changes in activity in functional imaging studies. It also makes a number of predictions about the purely cognitive, including accounts of mental practice, the representation of motor skill, and the interaction of conscious and unconscious processes in motor skill learning.
Introduction:
Parkinson's disease (PD) is a severe neurodegenerative disease that affects millions of people. Early diagnosis is important to facilitate prompt interventions to slow down disease progression. However, accurate PD diagnosis can be challenging, especially in the early disease stages. The aim of this work was to develop and evaluate a robust explainable deep learning model for PD classification trained from one of the largest collections of T1-weighted magnetic resonance imaging datasets.
Materials and methods:
A total of 2,041 T1-weighted MRI datasets from 13 different studies were collected, including 1,024 datasets from PD patients and 1,017 datasets from age- and sex-matched healthy controls (HC). The datasets were skull stripped, resampled to isotropic resolution, bias field corrected, and non-linearly registered to the MNI PD25 atlas. The Jacobian maps derived from the deformation fields together with basic clinical parameters were used to train a state-of-the-art convolutional neural network (CNN) to classify PD and HC subjects. Saliency maps were generated to display the brain regions contributing the most to the classification task as a means of explainable artificial intelligence.
Results:
The CNN model was trained using an 85%/5%/10% train/validation/test split stratified by diagnosis, sex, and study. The model achieved an accuracy of 79.3%, precision of 80.2%, specificity of 81.3%, sensitivity of 77.7%, and AUC-ROC of 0.87 on the test set while performing similarly on an independent test set. Saliency maps computed for the test set data highlighted frontotemporal regions, the orbital-frontal cortex, and multiple deep gray matter structures as most important.
Conclusion:
The developed CNN model, trained on a large heterogenous database, was able to differentiate PD patients from HC subjects with high accuracy with clinically feasible classification explanations. Future research should aim to investigate the combination of multiple imaging modalities with deep learning and on validating these results in a prospective trial as a clinical decision support system.
Parkinson's disease (PD) is commonly treated with dopaminergic medication, which enhances some, while impairing other cognitive functions. It can even contribute to impulse control disorder and addiction. We describe the history of research supporting the dopamine overdose hypothesis, which accounts for the large within-patient variability in dopaminergic medication effects across different tasks by referring to the spatially non-uniform pattern of dopamine depletion in dorsal versus ventral striatum. However, there is tremendous variability in dopaminergic medication effects not just within patients across distinct tasks, but also across different patients. In the second part of this chapter we review recent studies addressing the large individual variability in the negative side effects of dopaminergic medication on functions that implicate dopamine, such as value-based learning and choice. These studies begin to unravel the mechanisms of dopamine overdosing, thus revising the strict version of the overdose hypothesis. For example, the work shows that the canonical boosting of reward-versus punishment-based choice by medication is greater in patients with depression and a non-tremor phenotype, which both implicate, among other pathology, more rather than less severe dysregulation of the mesolimbic dopamine system. Future longitudinal cohort studies are needed to identify how to optimally combine different clinical, personality, cognitive, neural, genetic and molecular predictors of detrimental medication effects in order to account for as much of the relevant variability as possible. This will provide a useful tool for precision neurology, allowing individual and contextual tailoring of (the dose of) dopaminergic medication in order to maximize its cognitive benefits, yet minimize its side effects.
While cognitive dysfunction in Parkinson's disease (PD) is increasingly recognized as a progressive symptom of the underlying neurodegenerative disease, our understanding of the functional and structural anatomic changes underlying these cognitive changes remains incomplete. Like the motor system, research point to a complex interplay between multiple parallel yet interconnected networks or circuits that are affected in PD and give rise to cognitive symptomatology. These circuits are most often studied in the context of disorders of executive function, and tightly linke to frontal lobe dysfunction. While the tasks employed vary across studies and it is often unclear whether differences in anatomy and function are causal or compensatory, the literature points to several key circuits that seem to be uniquely impaired in PD patients with cognitive dysfunction. This chapter reviews four of these circuits including the frontostriatal, frontoparietal, mesocortical, and noradrenergic circuits. By gaining a better understanding of the functional neuroanatomy of these circuits, we begin to develop a more comprehensive and unifed picture of how they to account for the pathophysiology of cognitive dysfunction in PD.
The operation of the central nervous system (CNS) has been a mystery until recently when its structures are being linked to activity and/or pathologies. The drugs that influence the CNS were seen as spiritual manipulators, and often times they were used to invite the spirit into the human body. Researches have proven that these myths are unfounded and have provided explanations for the observed effect of the agents on the brain and human behavior. Most of the agents used to influence the brain in prescience ages were derived from plants. These actions of plant-related substances were termed as mystical. Science has unraveled the causes of the actions of plants on the CNS. The substances in plants that influence the brain are the biomolecules it contained. This chapter examines these biomolecules and their effects and mechanism of action. The biomolecules could produce stimulant, depressive, antidepressant, cognitive, toxic, and dependence effect on the brain. Substances like caffeine, cocaine, tobacco, ergot, opioids, etc., have been well studied to obtain an explanation for their effects on the brain and behavior. This review also revealed that biomolecules that influence the CNS does so by: acting as an agonist or antagonist at receptor sites, releasing neurotransmitters, inhibiting enzymes that are involved in neurotransmitter physiology, altering intracellular enzyme or protein levels, altering ion level in the brain, interacting with gamma aminobutyric acid receptors at different sites, or acting as precursor/false precursor for the synthesis of neurotransmitters. These effects could be beneficial or harmful to the human body. Some may result in the amelioration of disease or cure of CNS disease conditions. The beneficial effects of herbal biomolecules are indeed enormous and have contributed to the advancement of CNS science and the quantity of life of human race.
Objective
To investigate the neural correlates of impaired self-awareness of cognitive deficits (IACd) in nondemented patients with Parkinson’s disease (PD)
Methods
This cross-sectional study enrolled 153 drug-naïve and nondemented PD patients who underwent brain magnetic resonance imaging, dopamine transporter (DAT) positron emission tomography, detailed neuropsychological testing, and Cognitive Complaint Interview at baseline. Based on the presence of mild cognitive impairment (MCI) and subjective cognitive complaints, we grouped patients into those with IACd (PD-IACd+, n = 33), normal recognition of cognitive function (PD-NCf, n = 82), or underestimation of cognitive function (PD-UCf, n = 38). We compared cortical thickness, white matter (WM) integrity, DAT availability, and cognitive function between the groups.
Results
The prevalence of IACd was 21.6% in drug-naïve patients with PD. The PD-IACd+ group had a lower z-score in the Stroop color reading test than the other groups. Patients in the PD-IACd+ group had WM disintegrity, especially in the genu of the corpus callosum and anterior limb of the internal capsule, compared to those without IACd, while cortical thickness or striatal DAT availability was comparable regardless of the presence of IACd. Among patients with MCI, those with IACd had more severe WM disintegrity than those without IACd.
Conclusion
Structural connectivity between and from the frontal lobes is closely associated with self-awareness of cognitive deficits in PD. Evaluating frontal structural connectivity from the early stages of PD will be important in assessing the actual cognitive and daily life performance of patients with PD.
Background: Most research in genomics of Parkinson's disease (PD) has been done in subjects of European ancestry, leading to sampling bias and leaving Latin American populations underrepresented. We sought to clinically characterize PD patients of Costa Rican origin and to sequence familial PD and atypical parkinsonism-associated genes in cases and controls.
Methods: We enrolled 118 PD patients with 97 unrelated controls. Collected information included demographics, exposure to risk and protective factors, and motor and cognitive assessments. We sequenced coding and untranslated regions in familial PD and atypical parkinsonism-associated genes including GBA, SNCA, VPS35, LRRK2, GCH1, PRKN, PINK1, DJ-1, VPS13C, and ATP13A2.
Results: Mean age of PD probands was 62.12 ± 13.51 years; 57.6% were male. The frequency of risk and protective factors averaged ~45%. Physical activity significantly correlated with better motor performance despite years of disease. Increased years of education were significantly associated with better cognitive function, whereas hallucinations, falls, mood disorders, and coffee consumption correlated with worse cognitive performance. We did not identify an association between tested genes and PD or any damaging homozygous or compound heterozygous variants. Rare variants in LRRK2 were nominally associated with PD; six were located between amino acids p.1620 and 1623 in the C-terminal-of-ROC (COR) domain of Lrrk2. Non-synonymous GBA variants (p.T369M, p.N370S, and p.L444P) were identified in three healthy individuals. One PD patient carried a pathogenic GCH1 variant, p.K224R.
Discussion: This is the first study that describes sociodemographics, risk factors, clinical presentation, and genetics of Costa Rican patients with PD, adding information to genomics research in a Latino population.
This study examined whether Parkinson's disease (PD¹) and schizophrenia (SCZ²) share a hypo dopaminergic dysfunction of the prefrontal cortex leading to cognitive impairments in decision processing. 24 medicated PD patients and 28 matched controls performed the Eriksen flanker two-choice reaction time (RT³) task while brain activity was measured throughout, using functional Magnetic Resonance Imaging (fMRI⁴). Results were directly compared to those of 30 SCZ patients and 30 matched controls. Significant differences between SCZ and PD were found, through directly comparing the z-score deviations from healthy controls across all behavioral measures, where only SCZ patients showed deviances from controls. Similarly a direct comparison of z-score activation deviations from controls indicated significant differences in prefrontal and cingulate cortical activation between SCZ and PD, where only SCZ patients showed hypo-activation of these areas compared to controls. The hypo-activation of the dorsolateral prefrontal cortex was related to larger RT variability (ex-Gaussian tau) in SCZ but not PD patients. Overall, the concluding evidence does not support a shared neural substrate of cognitive dysfunction, since the deficit in speeded decision processing and the related cortical hypo-activation observed in SCZ were absent in PD.
Background:
Parkinson's disease (PD) is a complex, age-related neurodegenerative disorder of largely unknown etiology. PD is strongly associated with mitochondrial respiratory dysfunction, which can lead to epigenetic dysregulation and specifically altered histone acetylation. Nevertheless, and despite the emerging role of epigenetics in age-related brain disorders, the question of whether aberrant histone acetylation is involved in PD remains unresolved.
Methods:
We studied fresh-frozen brain tissue from two independent cohorts of individuals with idiopathic PD (n = 28) and neurologically healthy controls (n = 21). We performed comprehensive immunoblotting to identify histone sites with altered acetylation levels in PD, followed by chromatin immunoprecipitation sequencing (ChIP-seq). RNA sequencing data from the same individuals was used to assess the impact of altered histone acetylation on gene expression.
Results:
Immunoblotting analyses revealed increased acetylation at several histone sites in PD, with the most prominent change observed for H3K27, a marker of active promoters and enhancers. ChIP-seq analysis further indicated that H3K27 hyperacetylation in the PD brain is a genome-wide phenomenon with a strong predilection for genes implicated in the disease, including SNCA, PARK7, PRKN and MAPT. Integration of the ChIP-seq with transcriptomic data from the same individuals revealed that the correlation between promoter H3K27 acetylation and gene expression is attenuated in PD patients, suggesting that H3K27 acetylation may be decoupled from transcription in the PD brain. Strikingly, this decoupling was most pronounced among nuclear-encoded mitochondrial genes, corroborating the notion that impaired crosstalk between the nucleus and mitochondria is involved in the pathogenesis of PD. Our findings independently replicated in the two cohorts.
Conclusions:
Our findings strongly suggest that aberrant histone acetylation and altered transcriptional regulation are involved in the pathophysiology of PD. We demonstrate that PD-associated genes are particularly prone to epigenetic dysregulation and identify novel epigenetic signatures associated with the disease.
Introduction
Although the motor signs of Parkinson’s disease (PD) are well defined, nonmotor symptoms, including higher-level language deficits, have also been shown to be frequent in patients with PD. In the present study, we used a lexical decision task (LDT) to find out whether access to the mental lexicon is impaired in patients with PD, and whether task performance is affected by bradykinesia.
Materials and Methods
Participants were 34 nondemented patients with PD, either without (off) medication (n = 16) or under optimum (on) medication (n = 18). A total of 19 age-matched control volunteers were also recruited. We recorded reaction times (RTs) to the LDT and a simple RT (control) task. In each task, stimuli were either visual or auditory. Statistical analyses consisted of repeated-measures analyses of variance and Tukey’s HSD post hoc tests.
Results
In the LDT, participants with PD both off and on medication exhibited intact access to the mental lexicon in both modalities. In the visual modality, patients off medication were just as fast as controls when identifying real words, but slower when identifying pseudowords. In the visual modality of the control task, RTs for pseudowords were significantly longer for PD patients off medication than for controls, revealing an unexpected but significant lexicality effect in patients that was not observed in the auditory modality. Performances of patients on medication did not differ from those of age-matched controls.
Discussion
Motor execution was not slowed in patients with PD either off or on medication, in comparison with controls. Regarding lexical access, patients off medication seemed to (1) have difficulty inhibiting a cognitive-linguistic process (i.e., reading) when it was not required (simple reaction time task), and (2) exhibit a specific pseudoword processing deficit in the LDT, which may have been related to impaired lateral word inhibition within the mental lexicon. These deficits seemed to be compensated by medication.
Gender differences in language can be signs of cognitive differences, but can also by themselves be the cause for such differences. Females have a slight linguistic advantage over males, but effect sizes are small, and gender explains very little of the variance seen in the normal population (1%–2%). However, males outnumber females in the lowest 10th percentile in language tests (2:1), causing males to more often be diagnosed with developmental disorders, which rely on tests of language development.
Thus, gender differences in language are negligible, if you focus on the whole population, but if you focus on language deficits, gender differences are outspoken. Differences in voice and word use can be observed among the genders, making it possible to predict gender from these measures with a high degree of certainty. A subtle finding is that women use more first person pronouns. This is also observed in depression, which is more prevalent in females, opening up a potential link. Sex chromosome trisomies are often accompanied by language deficits, but the causes for this are not known. No gender differences are observed in the linguistic symptoms of neurodegenerative disorders. Poststroke aphasia is more prevalent among women than among men, but this seems to be an age-effect. A link between the brain and gender differences in language is thus missing.
Parkinson's disease (PD) is an age-dependent neurodegenerative disorder. Besides characteristic motor symptoms, patients suffer from cognitive impairments linked to pathology in cortical areas. Due to obvious challenges in tracing the underlying molecular perturbations in human brain over time, we took advantage of a well-characterized PD rat model. Using RNA sequencing, we profiled the frontocortical transcriptome of post-mortem patient samples and aligned expression changes with perturbation patterns obtained in the model at 5 and 12 months of age reflecting a presymptomatic and symptomatic time point. Integrating cell type-specific reference data, we identified a shared expression signature between both species that pointed to oligodendrocyte-specific, myelin-associated genes. Drawing on longitudinal information from the model, their nearly identical upregulation in both species could be traced to two distinctive perturbance modes. While one mode exhibited age-independent alterations that affected genes including proteolipid protein 1 (PLP1), the other mode, impacting on genes like myelin-associated glycoprotein (MAG), was characterized by interferences of disease gene and adequate expression adaptations along aging. Our results highlight that even for a group of functionally linked genes distinct interference mechanisms may underlie disease progression that cannot be distinguished by examining the terminal point alone but instead require longitudinal interrogation of the system.
Studies on evoked responses in Parkinson's disease (PD) may be useful for elucidating the etiology and quantitative evaluation of PD. However, in previous studies, the association between evoked responses and detailed motor symptoms or cognitive functions has not been clear. This study investigated the characteristics of the visual (VEF), auditory (AEF), and somatosensory (SEF) evoked magnetic fields in patients with Parkinson's disease (PD), and the correlations between evoked fields and the patient's clinical characteristics, motor symptoms, and cognitive functions. Twenty patients with PD and 10 healthy controls (HCs) were recruited as participants. We recorded VEF, AEF, and SEF, collected clinical characteristics, performed physical examinations, and administered 10 cognitive tests. We investigated differences in the latencies of the evoked fields between patients with PD and HCs. We also evaluated the correlation of the latencies with motor symptoms and cognitive functioning. There were significant differences between the two groups in 6 of the cognitive tests, all of which suggested mild cognitive impairment in patients with PD. The latencies of the VEF N75m, P100m, N145m, AEF P50m, P100m, and SEF P60m components were greater in the patients with PD than in the HCs. The latencies mainly correlated with medication and motor symptoms, less so with cognitive tests, with some elements of the correlations remaining significant after Bonferroni correction. In conclusion, the latencies of the VEF, AEF, and SEF were greater in PD patients than in HCs and were mainly correlated with medication and motor symptoms rather than cognitive functioning. Findings from this study suggest that evoked fields may reflect basal ganglia functioning and are candidates for assessing motor symptoms or the therapeutic effects of medication in patients with PD.
Reptiles and birds are a fascinating group of animals that is most critical to understanding the evolution of vertebrate brains. Birds are the only class of vertebrates that can rival mammals with respect to their cognitive abilities. And they do so with brains that are vastly different from ours. This chapter reviews what we know about reptilian and avian brains in terms of quantitative analyses, structures, and systems. Brains evolved to produce behavior. Therefore, all anatomical and physiological information in this chapter is embedded into a functional framework.
Studies on evoked responses in Parkinson's disease (PD) may be useful for elucidating the etiology and quantitative evaluation of PD. However, in previous studies, the association between evoked responses and detailed motor symptoms or cognitive functions has not been clear. This study investigated the characteristics of the visual (VEF), auditory (AEF), and somatosensory (SEF) evoked magnetic fields in patients with Parkinson's disease (PD), and the correlations between evoked fields and the patient's clinical characteristics, motor symptoms, and cognitive functions. Twenty patients with PD and 10 healthy controls (HCs) were recruited as participants. We recorded VEF, AEF, and SEF, collected clinical characteristics, performed physical examinations, and administered 10 cognitive tests. We investigated differences in the latencies of the evoked fields between patients with PD and HCs. We also evaluated the correlation of the latencies with motor symptoms and cognitive functioning. There were significant differences between the two groups in 6 of the cognitive tests, all of which suggested mild cognitive impairment in patients with PD. The latencies of the VEF N75m, P100m, N145m, AEF P50m, P100m, and SEF P60m components were greater in the patients with PD than in the HCs. The latencies mainly correlated with medication and motor symptoms, less so with cognitive tests, with some elements of the correlations remaining significant after Bonferroni correction. In conclusion, the latencies of the VEF, AEF, and SEF were greater in PD patients than in HCs and were mainly correlated with medication and motor symptoms rather than cognitive functioning. Findings from this study suggest that evoked fields may reflect basal ganglia functioning and are candidates for assessing motor symptoms or the therapeutic effects of medication in patients with PD.
Aminopeptidase A is responsible for the hydrolysis of angiotensin II and cholecystokinin. By measuring its activity we obtain a reflection of the functional status of its endogenous substrates. Dopamine coexists with these neuropeptides in striatum and prefrontal cortex. If the content of any of them is altered, the others and the functions they are involved in would also be affected. Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) are rat models with different motor behavior and mood. We hypothesized that aminopeptidase A activity could be modified in WKY or SHR affecting the brain dopamine. The results may provide new insights for the understanding of dopamine-related disorders such as schizophrenia, depression or Parkinson's disease. To analyze the influence of unilateral depletions of dopamine on the intra- and inter-hemispheric behavior of aminopeptidase A in striatum and prefrontal cortex of WKY and SHR, aminopeptidase A activity was measured fluorometrically, using an arylamide derivative as substrate, in the left and right sides of striatum and prefrontal cortex of WKY and SHR treated with saline (control groups) or following left or right intrastriatal injections of 6-hydroxydopamine (lesioned groups). Differential asymmetrical intra- and inter-hemispheric behaviors of aminopeptidase A were observed, depending on the lesioned hemisphere, the region and the strain analyzed. Results also demonstrated differential intra and inter-hemispheric correlations between striatum and prefrontal cortex and between both regions and motor behavior depending on the side of lesion. The changes mostly involved the left hemisphere. The functions in which the aminopeptidase A activity is involved could be modified depending on whether the dopamine depletion occurs on the left or right hemisphere.
Background
The Controlled Oral Word Association Test (COWAT) evaluates frontal lobe and executive function. Therefore, it can be helpful in differentiating cognitive deficits. However, there are no studies comparing the COWAT performance according to the type and stage of cognitive impairment.
Objective
To compare performance among persons with Alzheimer’s dementia (AD), vascular dementia (VaD), and Parkinson’s disease dementia (PDD) on the COWAT according to stage of cognitive impairment.
Design
Retrospective chart review study
Settings
University Hospital Rehabilitation Psychology Center
Patients
We reviewed the medical records of 246 persons diagnosed with mild cognitive impairment (MCI) or dementia using the Diagnostic and Statistical Manual of Mental Disorder, fifth edition (DSM‐5) and Korean‐Instrumental Activities of Daily Living (K‐IADL). Persons were divided into a control group, Alzheimer groups (amnestic mild cognitive impairment (aMCI) + AD), Vascular groups (vascular mild cognitive impairment (VaMCI) + VaD), and Parkinson groups (Parkinson’s disease‐mild cognitive impairment (PD‐MCI) + PDD).
Methods
Total scores (i.e., total number of words produced in 60 seconds on the semantic and phonemic fluency tests of the COWAT) were analyzed. Secondary analysis included calculating percentage scores of words produced during each of the four 15‐second segments from the total number of words produced in each trial.
Results
All MCI groups scored significantly lower than the control group on both semantic and phonemic fluency tests. Among the dementia groups, the VaD (5.6 ± 5.1) and PDD (5.5 ± 5.5) groups’ scores were significantly lower and worse than that of the AD (11.0 ± 8.8) group on the phonemic test (p<.001).
The difference in percentage scores was most marked between the PD‐MCI (17.0 ± 2.2) and PDD (1.2 ± 3.1) groups, followed by the VaMCI (13.3 ± 1.9) and VaD (5.6 ± 1.8) groups on the latter phonemic test (p=.007).
Conclusions
The COWAT is a sensitive test of frontal‐lobe and executive function impairment in persons with MCI. Decreased verbal output in last 15‐seconds of phonemic fluency test is significantly decreased and impaired in persons with VaMCI and PDMCI compared to persons with aMCI as they progress to dementia.
Level of Evidence
III
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Individuals with Parkinson's disease (PD) have shown impaired performance on the verbal suppression component of the Haylings Sentence Completion Test (HSCT). The present study aimed to determine whether this performance related to (i) the inability to suppress a pre-potent response or (ii) difficulty in the generation of a strategy to facilitate task execution. The study adopted a novel variation of the HSCT that isolated each process and employed fMRI to examine the associated neural correlates in a comparison of individuals with PD and matched healthy controls. No significant behavioral differences were detected between these two groups. However, fMRI results revealed atypical underlying neural activity in the PD group. Controls exhibited increased activation in the left dorsolateral prefrontal cortex and striatum when generating a response independently, relative to generation when a supporting strategy was provided. The PD group demonstrated the opposite pattern of activation, in addition to greater recruitment of right hemisphere regions. This pattern of activation was postulated to be evidence of compensatory mechanisms, acting to bolster the output of frontostriatal circuits compromised by disease pathology.
The ability to inhibit a prepared emotional or motor action is difficult but critical to everyday functioning. It is well‐established that response inhibition relies on the dopaminergic system in the basal ganglia. However, response inhibition is often measured imprecisely due to a process which slows our responses and increases subsequent inhibition success known as proactive inhibition. As the role of the dopamine system in proactive inhibition is unclear, we investigated the contribution of dopaminergic genes to proactive inhibition. We operationalised proactive inhibition as slower responses after failures to inhibit a response in a Go/No‐Go paradigm and investigated its relationship to rs686/A at DRD1 (associated with increased gene expression) and rs1800497/T at DRD2 (associated with reduced D2 receptor availability). Even though our sample (N = 264) was relatively young (18‐40 years), we found that proactive inhibition improves the ability to withhold erroneous responses in older participants (P = 0.002) and those with lower fluid intelligence scores (P < 0.001), indicating that proactive inhibition is likely a naturally‐occurring compensatory mechanism. Critically, we found that a polygenic risk score consisting of the number of rs686 A and rs1800497 T alleles predicts higher engagement of proactive inhibition (P = 0.040), even after controlling for age (P = 0.011). Furthermore, age seemed to magnify these genetic effects (P < 0.001). This suggests that the extent to which proactive inhibition is engaged depends on increased dopamine D1 and decreased D2 neurotransmission. These results provide important considerations for future work investigating disorders of the dopaminergic system.
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Objective:
Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is a severe, but treatable, autoimmune disorder, characterized by autoantibodies causing hypofunction of blocking NMDA receptors leading to a unique constellation of cognitive, motor, and psychiatric symptoms. Neuropsychological and psychopathological outcome has not been fully explored, particularly in children. Aim of this study was to investigate pediatric anti-NMDAR encephalitis as a model of impairment of the complex frontal-subcortical circuits who are implicated in several of the childhood neuropsychiatric disorders.
Method:
Seven children diagnosed with anti-NMDAR encephalitis at our department underwent an evaluation of the global mental functioning before discharge, a neuropsychological and psychological/behavioral standardized examination within one month after discharge and subsequently were followed up longitudinally for mean 35 months (range 24-48 months). Collected neuropsychological data were evaluated retrospectively.
Results:
Deficits in attention, executive functions and/or visual motor functions involving executive functions were seen in all children within one month after discharge. These deficits were long lasting in about a half of the patients. In addition, four patients developed persistent psychopathological dysfunctions: difficulties to regulate their own behavior, impulsivity, hyperactivity, irritability, apathy, and obsessive-compulsive symptoms.
Conclusions:
Our data are in line with research suggesting a crucial role of the executive functions impairments in cognitive outcome disturbance of anti-NMDAR encephalitis. We found also behavioral and psychological deficits pointing to a more comprehensive framework of frontal-subcortical dysfunction, in which the NMDA mediated transmission appear to have a role, as suggested by neurobiological, pharmacological, and neuroimaging studies.
Objectives: Patients with Parkinson's disease (PD) tend to show impairment in switching, but not clustering, during semantic fluency tasks. When time limits are imposed for completing a fluency task, clustering and switching can be negatively correlated. To better understand the characteristics of clustering, verbal fluency needs to be assessed both with and without time limits. The purpose of this study was to investigate the effect of time limits on clustering performance, and to study characteristics of semantic impairment related to clustering in PD. Methods: We studied 27 PD patients and 32 normal controls (NC). We conducted a semantic fluency task and measured the total number of words, average size of clusters, number of clusters, and number of switches generated in a 1-minute time limit, also making the same measurements without a time limit. Finally, we conducted a semantic knowledge task utilizing spontaneous production, specific guiding questions, and forced-choice questions. Results: First, when there was no time limit the average size of clusters was significantly smaller in PD than in NC. Second, on the semantic knowledge task, the PD patients scored significantly lower than NC on the specific guiding questions and in total. Lastly, we found significant correlations between the average size of clusters and the scores on the semantic knowledge task in PD. Conclusion: On semantic fluency tasks, time limits for completing a task may affect clustering in PD. Also, impaired clustering in PD may be attributed to impaired retrieval of semantic knowledge rather than a deficit in semantic knowledge itself. © 2018 Korean Academy of Speech-Language Pathology and Audiology.