Figure - available from: Frontiers in Behavioral Neuroscience
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Model of a human mind’s representation (inwards/outwards). The horizontal axis refers to “cognitive” dimension, whereas the vertical axis refers to “emotional” dimension with stronger motivational accent. We assume that these two axes can create a mental representation of human mind, that can be focused outwards or inwards, forming four domains: self, ToM, empathy and hedonic evaluation.
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Schizophrenia is a complex neuropsychiatric disorder with variable symptomatology, traditionally divided into positive and negative symptoms, and cognitive deficits. However, the etiology of this disorder has yet to be fully understood. Recent findings suggest that alteration of the basic sense of self-awareness may be an essential distortion of sc...
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Context:
The aim of this study was to determine the experimental evidence of treatment/intervention programs for deficits in social skills, attention, and behavioral disorder in children and adolescents with attention deficit hyperactivity disorder (ADHD).
Evidence acquisition:
Meta-analysis procedures were employed to investigate whether childr...
Citations
... functional connectivity (FC) is associated with cognitive impairments in SZ and BP patients (20,21). ...
Schizophrenia (SZ) and bipolar disorder (BP) patients share overlapping and distinct neurocognitive deficits. Neuroimaging of these patients and postmortem gene expression analyses suggest that compromised cingulate gyrus GABA-ergic interneurons may contribute to cognitive impairments in SZ and BP. Therefore, we investigated potential gene expression signatures for SZ and BP using interneuron cell-type specific markers including glutamic acid decarboxylase (GAD67), parvalbumin (PV), somatostatin (SST), and vasoactive intestinal peptide (VIP) within cingulate Brodmann areas (BA). We report reduced GAD67 mRNA in anterior midcingulate cortex (aMCC) of SZ and BP subjects with BA24c being most dysregulated across disorders, demonstrating reduced PV (SZ), SST (BP), and VIP mRNA (SZ and BP). Dorsal posterior cingulate (dPCC) displayed decreased SST (BP) whereas retrosplenial cortex (RSC) showed reduced PV (SZ and BP) and SST mRNA (BP). Our results show shared and unique transcription signatures of two disorders in specific cingulate gyrus regions and cell types. SZ and BP show a similar profile of aMCC gene expression reductions suggesting subregional dysregulation within areas associated with error/action monitoring and the saliency network. In dPCC/RSC, transcriptional changes are associated with disease-specific gene/subregion signatures, possibly underlying differential effects on allocation of attentional resources and visuospatial memory processing unique to each disorder.
... With a lifetime risk of approximately 1%, individuals with schizophrenia face an average reduction in lifespan of 14.5 years 4 . Abnormal functional connectivity in various brain regions has been observed in schizophrenia through the utilization of restingstate functional magnetic resonance imaging (rs-fMRI) [5][6][7][8] , indicating that schizophrenia is a pervasive dysconnectivity disorder [9][10][11][12] . ...
Schizophrenia is a mental health disorder characterized by functional dysconnectivity. Eigenvector centrality mapping (ECM) has been employed to investigate alterations in functional connectivity in schizophrenia, yet the results lack consistency, and the genetic mechanisms underlying these changes remain unclear. In this study, whole-brain voxel-wise ECM analyses were conducted on resting-state functional magnetic resonance imaging data. A cohort of 91 patients with schizophrenia and 91 matched healthy controls were included during the discovery stage. Additionally, in the replication stage, 153 individuals with schizophrenia and 182 healthy individuals participated. Subsequently, a comprehensive analysis was performed using an independent transcriptional database derived from six postmortem healthy adult brains to explore potential genetic factors influencing the observed functional dysconnectivity, and to investigate the roles of identified genes in neural processes and pathways. The results revealed significant and reliable alterations in the ECM across multiple brain regions in schizophrenia. Specifically, there was a significant decrease in ECM in the bilateral superior and middle temporal gyrus, and an increase in the bilateral thalamus in both the discovery and replication stages. Furthermore, transcriptional analysis revealed 420 genes whose expression patterns were related to changes in ECM, and these genes were enriched mainly in biological processes associated with synaptic signaling and transmission. Together, this study enhances our knowledge of the neural processes and pathways involved in schizophrenia, shedding light on the genetic factors that may be linked to functional dysconnectivity in this disorder.
... The MOG is critical component of the initial phase of visual processing, serving as a fundamental element in the recognition of objects, differentiation of motion, and understanding of space (Palejwala et al., 2020). On the other hand, perception and response to visual stimuli are dependent on the CAL (Lalli et al., 2006), which is consti- (Nekovarova et al., 2014). Internally-focused cognitions, including autobiographical memory retrieval, rely on the PCC (Summerfield et al., 2009). ...
Auditory verbal hallucinations (AVH) are distinctive clinical manifestations of schizophrenia. While low‐frequency repetitive transcranial magnetic stimulation (rTMS) has demonstrated potential in mitigating AVH, the precise mechanisms by which it operates remain obscure. This study aimed to investigate alternations in structural connectivity and functional connectivity (SC‐FC) coupling among schizophrenia patients with AVH prior to and following treatment with 1 Hz rTMS that specifically targets the left temporoparietal junction. Initially, patients exhibited significantly reduced macroscopic whole brain level SC‐FC coupling compared to healthy controls. Notably, SC‐FC coupling increased significantly across multiple networks, including the somatomotor, dorsal attention, ventral attention, frontoparietal control, and default mode networks, following rTMS treatment. Significant alternations in SC‐FC coupling were noted in critical nodes comprising the somatomotor network and the default mode network, such as the precentral gyrus and the ventromedial prefrontal cortex, respectively. The alternations in SC‐FC coupling exhibited a correlation with the amelioration of clinical symptom. The results of our study illuminate the intricate relationship between white matter structures and neuronal activity in patients who are receiving low‐frequency rTMS. This advances our understanding of the foundational mechanisms underlying rTMS treatment for AVH.
... Con ayuda de estudios imagenológicos funcionales, se han descrito 3 redes neuronales que participan en organizar la respuesta neurocognitiva: La red ejecutiva central (conformada por la corteza prefrontal dorsolateral y parietal posterior) que se activa cuando predomina la atención hacia el exterior en tareas cognitivamente demandantes, la red neuronal por defecto (conformada por la corteza medial prefrontal y cingulado posterior) que se activa en reposo mental o en tareas enfocadas interiormente (por ejemplo al divagar) y la red de saliencia (conformada por el cingulado anterior y la ínsula anterior), que media la selección de estímulos salientes externos e internos. Esta última sería la encargada de promover que predomine la activación de una y desactivación de la otra, de manera alternante (Sridharan, Levitin & Menon, 2008;Menon & Uddin, 2010;Nekovarova et al., 2014;Ramírez-Mejía et al., 2023). Más adelante nos referiremos a la ínsula con más detalle y su rol en la esquizofrenia. ...
... Ya desde hace varios años existe evidencia que sustenta la hipótesis dopaminérgica de los síntomas psicóticos positivos Kapur, 2003;Ramirez-Mejía et al., 2023;Mishara et al., 2023;Burns & Marder, 2023). Complementando estos hallazgos, hoy en día también se ha descubierto que el caso de los síntomas psicóticos positivos también habría una disfunción de la triple red mencionada previamente (Nekovarova et al., 2014;Supekar et al., 2019;Buckner et al., 2013;Vinogradov et al., 2022). Revisemos este asunto a continuación. ...
Introducción: La popularización del reduccionismo neurobiológico en psicopatología conlleva la idea de que la esquizofrenia puede entenderse simplemente como el producto de alteraciones en el funcionamiento cerebral. Por otro lado, y criticando esta tradición, el enfoque fenomenológico propone que la esquizofrenia debería entenderse como un trastorno del yo. Si bien ambas tradiciones son relevantes en la actualidad, creemos que una comprensión completa del fenómeno psicótico envuelve una integración de ambas. Objetivo: Este artículo plantea que la hipótesis de la saliencia aberrante es un buen candidato para unificar la tradición fenomenológica y la neuropsiquiátrica en el estudio de la esquizofrenia. Procedimiento: Luego de examinar la hipótesis en cuestión en profundidad, exploramos la forma en que podría explicar algunos de los síntomas positivos de la esquizofrenia de forma consistente con sus descripciones fenomenológicas. Conclusiones: Finalmente, se ofrecen algunas consideraciones generales respecto de las consecuencias de nuestro análisis para el campo de la psicopatología.
... Conversely, aberrant salience processing may underlie motivational disturbances (Yuen et al. 2014). In humans, dysfunction and/or hyperactivity of the SN are implicated in psychiatric disorders (Goodkind et al. 2015;Peters et al. 2016), such as depression (Brakowski et al. 2017;Yuen et al. 2014), schizophrenia (Manoliu et al. 2014;Nekovarova et al. 2014), PTSD (Akiki et al. 2017;O'Doherty et al. 2015), and traumatic brain injury (Sharp et al. 2014;Scheibel 2017). Therefore, we propose that normalization of respiratory properties using breathing manipulation, e.g., rhythmic inhalation and exhalation in synchronization with sensory detection and motor responses, could be a target in mental health care to reduce or eliminate symptoms in patients with stress responses and neuropsychiatric disorders. ...
Breathing is a natural daily action that one cannot do without, and it sensitively and intensely changes under various situations. What if this essential act of breathing can impact our overall well-being? Recent studies have demonstrated that breathing oscillations couple with higher brain functions, i.e., perception, motor actions, and cognition. Moreover, the timing of breathing, a phase transition from exhalation to inhalation, modulates specific cortical activity and accuracy in cognitive tasks. To determine possible respiratory roles in attentional and memory processes and functional neural networks, we discussed how breathing interacts with the brain that are measured by electrophysiology and functional neuro-imaging: (i) respiration-dependent modulation of mental health and cognition; (ii) respiratory rhythm generation and respiratory pontomedullary networks in the brainstem; (iii) respiration-dependent effects on specific brainstem regions and functional neural networks (e.g., glutamatergic Pre-Bötzinger complex neurons, GABAergic parafacial neurons, adrenergic C1 neurons, parabrachial nucleus, locus coeruleus, temporoparietal junction, default-mode network, ventral attention network, and cingulo-opercular salience network); and (iv) a potential application of breathing manipulation in mental health care. These outlines and considerations of "brain-breath" interactions lead to a better understanding of the interoceptive and cognitive mechanisms that underlie brain-body interactions in health conditions and in stress-related and neuropsychiatric disorders.
... Similar findings have also emerged within neurodevelopmental disorders such as Autism and ADHD [70,71], mood disorders such as depression [72], and dissociative disorders [73], where derealization in particular has been associated with increased insula activation [73] and decreased DMN and FPN connectivity [74]. Furthermore, fMRI imaging research indicates hyperactive insula function causally underlies diminished connectivity between the DMN and FPN in schizophrenia patients, whilst hypoactive insula function enhances DMN and FPN inter-connectivity [75,76]. Specifically, a hyperactive anterior insula may suppress switching between these networks, leading to excessive self-reflection and enhanced awareness of self-signals which were previously filtered out of consciousness. ...
The concept of anomalous self-experience, also termed Self-Disorder, has attracted both clinical and research interest, as empirical studies suggest such experiences specifically aggregate in and are a core feature of schizophrenia spectrum disorders. A comprehensive neurophenomenological understanding of Self-Disorder may improve diagnostic and therapeutic practice. This systematic review aims to evaluate anatomical, physiological, and neurocognitive correlates of Self-Disorder (SD), considered a core feature of Schizophrenia Spectrum Disorders (SSDs), towards developing a neurophenomenological understanding. A search of the PubMed database retrieved 285 articles, which were evaluated for inclusion using PRISMA guidelines. Non-experimental studies, studies with no validated measure of Self-Disorder, or those with no physiological variable were excluded. In total, 21 articles were included in the review. Findings may be interpreted in the context of triple-network theory and support a core dysfunction of signal integration within two anatomical components of the Salience Network (SN), the anterior insula and dorsal anterior cingulate cortex, which may mediate connectivity across both the Default Mode Network (DMN) and Fronto-Parietal Network (FPN). We propose a theoretical Triple-Network Model of Self-Disorder characterized by increased connectivity between the Salience Network (SN) and the DMN, increased connectivity between the SN and FPN, decreased connectivity between the DMN and FPN, and increased connectivity within both the DMN and FPN. We go on to describe translational opportunities for clinical practice and provide suggestions for future research.
... The abnormalities observed in dlPFC and ACC areas are consistent with the functional deficits observed in the cognitive test scores. Studies from [85,86] show that the functional networks to which dlPFC and ACC belong, the central executive network and salience network, play critical roles in connecting heterogeneous symptoms of psychiatric disorders with the pathophysiological mechanism. This confirms the significant group differences observed from the PANSS scores, which are shown in Table 4. ...
The identification of homogeneous subgroups of patients with psychiatric disorders can play an important role in achieving personalized medicine and is essential to provide insights for understanding neuropsychological mechanisms of various mental disorders. The functional connectivity profiles obtained from functional magnetic resonance imaging (fMRI) data have been shown to be unique to each individual, similar to fingerprints; however, their use in characterizing psychiatric disorders in a clinically useful way is still being studied. In this work, we propose a framework that makes use of functional activity maps for subgroup identification using the Gershgorin disc theorem. The proposed pipeline is designed to analyze a large-scale multi-subject fMRI dataset with a fully data-driven method, a new constrained independent component analysis algorithm based on entropy bound minimization (c-EBM), followed by an eigenspectrum analysis approach. A set of resting-state network (RSN) templates is generated from an independent dataset and used as constraints for c-EBM. The constraints present a foundation for subgroup identification by establishing a connection across the subjects and aligning subject-wise separate ICA analyses. The proposed pipeline was applied to a dataset comprising 464 psychiatric patients and discovered meaningful subgroups. Subjects within the identified subgroups share similar activation patterns in certain brain areas. The identified subgroups show significant group differences in multiple meaningful brain areas including dorsolateral prefrontal cortex and anterior cingulate cortex. Three sets of cognitive test scores were used to verify the identified subgroups, and most of them showed significant differences across subgroups, which provides further confirmation of the identified subgroups. In summary, this work represents an important step forward in using neuroimaging data to characterize mental disorders.
... Knowledge of underlying DMN neurophysiology is critical for understanding its dynamic functional properties and relationship to behavior and for designing network-based treatment regimens for neuropsychiatric and neurological disorders (1,3,4). In particular, computational analyses of causal dynamics in human fMRI data have suggested that behavioral activation of the anterior insular cortex (AI), a key node of the salience network (SN), is implicated in the causal deactivation of the DMN (9,(22)(23)(24). However, its neurophysiological basis remains unknown (25). ...
... Crucially, analysis of dynamic causal interactions between these regions using neuronal GCaMP recordings revealed inhibitory causal outflow from the AI to the RSC, Cg, and PrL, providing a more precise circuit mechanism underlying neuronal antagonism between AI and RSC, Cg, and PrL. Together, these findings identify key aspects of the hierarchical intrinsic functional organization of the rodent DMN at the neuronal level and suggest that the widely documented AI-DMN antagonistic relationship in the human brain (3,9,(22)(23)(24) also exists in the rat brain. Given the wide range of cellular manipulation and recording techniques available in rodent species, our findings open a vast avenue for further investigations of large-scale brain networks, including the DMN and SN. ...
... Our analysis further revealed that the AI exhibits both dynamic coupling (States 1, 2, and 5) with, and decoupling (States 3 and 4) from, the RSC, Cg, and PrL. This dynamic decoupling of the AI from these DMN nodes is similar to what has been observed in human fMRI (3,9,(22)(23)(24). Notably, examination of functional connectivity associated with the most likely transition path (Fig. 4E) revealed a consistent cyclical pattern of changes, in which the AI-PrL GCaMP signal synchronization was out of phase from all other pairs of regions (Fig. 4H). ...
The default mode network (DMN) is critical for self-referential mental processes, and its dysfunction is implicated in many neuropsychiatric disorders. However, the neurophysiological properties and task-based functional organization of the rodent DMN are poorly understood, limiting its translational utility. Here, we combine fiber photometry with functional magnetic resonance imaging (fMRI) and computational modeling to characterize dynamics of putative rat DMN nodes and their interactions with the anterior insular cortex (AI) of the salience network. Our analysis revealed neuronal activity changes in AI and DMN nodes preceding fMRI-derived DMN activations and cyclical transitions between brain network states. Furthermore, we demonstrate that salient oddball stimuli suppress the DMN and enhance AI neuronal activity and that the AI causally inhibits the retrosplenial cortex, a prominent DMN node. These findings elucidate the neurophysiological foundations of the rodent DMN, its spatiotemporal dynamical properties, and modulation by salient stimuli, paving the way for future translational studies.
... The observed increases in gamma resting state activity are hypothesized to constitute an increased background 'noise' [23]. The underlying generators of oscillatory activity at rest are theorized to act as hubs of dynamically organized functional networks that execute distinct tasks [36,39], of which three networks exhibit marked irregularities in schizophrenia [40,41]. The triple network model of schizophrenia comprises the normally anticorrelated default mode network (DMN, i.e., self-referential autobiographical functions) and central executive network (CEN, i.e., attention and processing of exogenous stimuli), as well as the salience network (SN). ...
NMDA-receptor hypofunction is increasingly considered to be an important pathomechanism in schizophrenia. However, to date, it has not been possible to identify patients with relevant NMDA-receptor hypofunction who would respond to glutamatergic treatments. Preclinical models, such as the ketamine model, could help identify biomarkers related to NMDA-receptor function that respond to glutamatergic modulation, for example, via activation of the glycine-binding site. We, therefore, aimed to investigate the effects of opposing modulation of the NMDA receptor on gamma activity (30–100 Hz) at rest, the genesis of which appears to be highly dependent on NMDA receptors. The effects of subanesthetic doses of S-ketamine and pretreatment with glycine on gamma activity at rest were examined in twenty-five healthy male participants using 64-channel electroencephalography. Psychometric scores were assessed using the PANSS and the 5D-ASC. While S-ketamine significantly increased psychometric scores and gamma activity at the scalp and in the source space, pretreatment with glycine did not significantly attenuate any of these effects when controlled for multiple comparisons. Our results question whether increased gamma activity at rest constitutes a suitable biomarker for the target engagement of glutamatergic drugs in the preclinical ketamine model. They might further point to a differential role of NMDA receptors in gamma activity generation.
... Considering the suggested importance of the modulating role of the SN within triple networks, 1,8,18 we performed mediation analysis to determine whether the SN plays a key role in the triple-network dysconnectivity of the patients. Based on previous studies indicating alterations in SN, CEN, and DMN connectivity in chronic schizophrenia patients, [2][3][4][5][6][7][8] we hypothesized triple-network dysfunctionality in both FEP patients and individuals at CHR for psychosis. In addition, considering the crucial role of the SN in the triple-network model, 1,8,9,18 we expected that SN interconnectivity among the networks would act as a mediator. ...
... 8,34 The relationships between triplenetwork dysfunction and psychotic symptoms reported in those patients support the triple-network dysfunction theory of psychotic disorders. 2,4,5 In this study, we used the high-order ICA method to assess the inconsistencies across the previous triple-network studies on FEP patients that utilized a priori ROI methods; with our approach, we found that there was dysfunctional connectivity between the three networks of the triple-network model in FEP patients. However, unlike the current study results, a previous study by Anhøj et al. 17 that utilized high-order ICA reported no significant dysconnectivity between the triple networks in FEP patients. ...
Objective:
In the triple-network model, the salience network (SN) plays a crucial role in switching between the default-mode network (DMN) and the central executive network (CEN). Aberrant patterns of triple-network connectivity have been reported in schizophrenia patients, while findings have been less consistent for patients in the early stages of psychotic disorders. Thus, the present study examined the connectivity among the SN, DMN, and CEN in first-episode psychosis (FEP) patients and individuals at clinical high risk (CHR) for psychosis.
Methods:
Thirty-nine patients with FEP, 78 patients with CHR for psychosis, and 110 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging. We compared the SN, DMN, and CEN connectivity patterns of the three groups. The role of the SN in networks with significant connectivity differences was examined by mediation analysis.
Results:
FEP patients showed lower SN-DMN and SN-CEN (cluster-level F=5.83, false discovery rate [FDR] corrected-p=0.001) connectivity than HCs. There was lower SN-DMN connectivity (cluster-level F=3.06, FDR corrected-p=0.053) at a trend level in CHR subjects compared to HCs. Between HCs and FEP patients, mediation analysis showed that SN-DMN connectivity was a mediator between group and SN-CEN connectivity. Additionally, SN-CEN connectivity functioned as a mediator between group and SN-DMN connectivity.
Conclusion:
Aberrant connectivity between the SN and DMN/CEN suggests disrupted network switching in FEP patients, although CHR subjects showed trend-level SN-DMN dysconnectivity. Our findings suggest that dysfunctional triple-network dynamics centered on the SN can appear in patients in the early stages of psychotic disorders.
