Never resting region — mPFC in schizophrenia

Bleich-Cohen, Maya; Kupchik, Marina; Gruberger, Michal; Kotler, Moshe; Hendler, Talma

doi:10.1016/j.schres.2012.06.030

Cited by 12 publications

(6 citation statements)

References 16 publications

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“…Previous studies have found impaired activity and structure of the mPFC in schizophrenia. 32 A study using an animal model reported that alteration of the functional connectivity between the hippocampus and the mPFC possibly contributed to schizophrenia-like symptoms. 33 Moreover, deficits in overnight memory consolidation in schizophrenia were found to be associated with hippocampus–mPFC connectivity.…”

Section: Discussionmentioning

confidence: 99%

Polygenic effects of schizophrenia on hippocampal grey matter volume and hippocampus–medial prefrontal cortex functional connectivity

Liu

et al. 2019

Br J Psychiatry

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BackgroundSchizophrenia is a complex mental disorder with high heritability and polygenic inheritance. Multimodal neuroimaging studies have also indicated that abnormalities of brain structure and function are a plausible neurobiological characterisation of schizophrenia. However, the polygenic effects of schizophrenia on these imaging endophenotypes have not yet been fully elucidated.AimsTo investigate the effects of polygenic risk for schizophrenia on the brain grey matter volume and functional connectivity, which are disrupted in schizophrenia.MethodGenomic and neuroimaging data from a large sample of Han Chinese patients with schizophrenia (N = 509) and healthy controls (N = 502) were included in this study. We examined grey matter volume and functional connectivity via structural and functional magnetic resonance imaging, respectively. Using the data from a recent meta-analysis of a genome-wide association study that comprised a large number of Chinese people, we calculated a polygenic risk score (PGRS) for each participant.ResultsThe imaging genetic analysis revealed that the individual PGRS showed a significantly negative correlation with the hippocampal grey matter volume and hippocampus–medial prefrontal cortex functional connectivity, both of which were lower in the people with schizophrenia than in the controls. We also found that the observed neuroimaging measures showed weak but similar changes in unaffected first-degree relatives of patients with schizophrenia.ConclusionsThese findings suggested that genetically influenced brain grey matter volume and functional connectivity may provide important clues for understanding the pathological mechanisms of schizophrenia and for the early diagnosis of schizophrenia.

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Section: Discussionmentioning

confidence: 99%

Polygenic effects of schizophrenia on hippocampal grey matter volume and hippocampus–medial prefrontal cortex functional connectivity

Liu

et al. 2019

Br J Psychiatry

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“…In addition, involvement of mental imagery in schizophrenia as a source of increased activation in the precuneus has been discussed in previous fMRI studies, which investigated cartoon jokes in individuals with enhanced risk of schizophrenia ( Marjoram et al, 2006 ), comprehension of the figurative meaning of language, such as metaphor ( Mashal et al, 2014 ) or verbal humor ( Adamczyk et al, 2017 ) in patients with schizophrenia. Moreover, hyper-activation in the DMN has been shown in patients with schizophrenia during task-related functioning suggesting inability to suppress non-relevant thinking ( Bleich-Cohen et al, 2012 ).…”

Section: Discussionmentioning

confidence: 99%

“…It is important to note, that language deficits in schizophrenia underlie the major symptoms of psychosis, specifically hallucinations (verbal, auditory) and disorganized language output (positive thought disorder) ( Brown and Kuperberg, 2015 ). Accordingly, a series of neurocognitive theories have proposed that clinical symptoms in schizophrenia reflect internal speech, or thinking in words, as one of the self-disturbances of the disease ( Bleich-Cohen et al, 2012 , Adams et al, 2013 , Sterzer et al, 2016 ). More recently, Tan et al (2016) , using synonym identification and sentence comprehension tasks, found that patients with schizophrenia made more errors relative to healthy controls in sentence comprehension but not with words, when the structure of the sentence was modified.…”

Section: Introductionmentioning

confidence: 99%

Abnormal neural hierarchy in processing of verbal information in patients with schizophrenia

Lerner

Bleich-Cohen

Solnik-Knirsh

et al. 2018

NeuroImage: Clinical

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Previous research indicates abnormal comprehension of verbal information in patients with schizophrenia. Yet the neural mechanism underlying the breakdown of verbal information processing in schizophrenia is poorly understood. Imaging studies in healthy populations have shown a network of brain areas involved in hierarchical processing of verbal information over time. Here, we identified critical aspects of this hierarchy, examining patients with schizophrenia. Using functional magnetic resonance imaging, we examined various levels of information comprehension elicited by naturally presented verbal stimuli; from a set of randomly shuffled words to an intact story. Specifically, patients with first episode schizophrenia (N = 15), their non-manifesting siblings (N = 14) and healthy controls (N = 15) listened to a narrated story and randomly scrambled versions of it. To quantify the degree of dissimilarity between the groups, we adopted an inter-subject correlation (inter-SC) approach, which estimates differences in synchronization of neural responses within and between groups. The temporal topography found in healthy and siblings groups were consistent with our previous findings – high synchronization in responses from early sensory toward high order perceptual and cognitive areas. In patients with schizophrenia, stimuli with short and intermediate temporal scales evoked a typical pattern of reliable responses, whereas story condition (long temporal scale) revealed robust and widespread disruption of the inter-SCs. In addition, the more similar the neural activity of patients with schizophrenia was to the average response in the healthy group, the less severe the positive symptoms of the patients. Our findings suggest that system-level neural indication of abnormal verbal information processing in schizophrenia reflects disease manifestations.

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“…Recent studies of primate dorsolateral PFC (dlPFC) have shown extensive DISC1 labeling in dendritic spines in layer III and in layer V, the microcircuits greatly afflicted in schizophrenia (7–9). These data revealed DISC1 co-localization with PDE4A and HCN channels near the synapse and in the spine neck, as well as near the spine apparatus that stores internal Ca 2+ (10, 11).…”

Section: Introductionmentioning

confidence: 99%

Disrupted in Schizophrenia 1 Modulates Medial Prefrontal Cortex Pyramidal Neuron Activity Through cAMP Regulation of Transient Receptor Potential C and Small-Conductance K+ Channels

El-Hassar¹,

Simen²,

Duque³

et al. 2014

Biological Psychiatry

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Background Disrupted in Schizophrenia 1 (DISC1) is a protein implicated in schizophrenia, bipolar disorder, major depressive disorder, and autism. To date, most of research examining DISC1 function has focused on its role in neurodevelopment, despite its presence throughout life. DISC1 also regulate cAMP signaling by increasing PDE4 catabolism of cAMP when cAMP concentrations are high. In this study, we tested the hypothesis that DISC1, through its regulation of cAMP, modulates I-SK and I-TRPC channel-mediated ionic currents that we have shown previously to regulate the activity of mature prefrontal cortical pyramidal neurons. Methods We used patch-clamp recordings in prefrontal cortical slices from adult rats in which DISC1 function was reduced in vivo by shRNA viral knockdown or in vitro by dialysis of DISC1 antibodies. Results We found that DISC1 disruption resulted in an increase of: mGluR-induced intracellular Ca2+ waves, SK-mediated hyperpolarization and a decrease of TRPC-mediated sustained depolarization. Consistent with a role for DISC1 in regulation of cAMP signaling, forskolin-induced cAMP production also increased intracellular Ca2+ waves, I-SK and decreased I-TRPC. Lastly, inhibiting cAMP generation with guanfacine, an α2A-noradrenergic agonist, normalized the function of SK and TRPC channels. Conclusions Based on our findings, we propose that diminished DISC1 function, such as occurs in some mental disorders, can lead to the disruption of normal patterns of PFC activity through the loss of cAMP regulation of mGluR-mediated intracellular Ca2+ waves, SK and TRPC channel activity.

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Never resting region — mPFC in schizophrenia

Cited by 12 publications

References 16 publications

Polygenic effects of schizophrenia on hippocampal grey matter volume and hippocampus–medial prefrontal cortex functional connectivity

Polygenic effects of schizophrenia on hippocampal grey matter volume and hippocampus–medial prefrontal cortex functional connectivity

Abnormal neural hierarchy in processing of verbal information in patients with schizophrenia

Disrupted in Schizophrenia 1 Modulates Medial Prefrontal Cortex Pyramidal Neuron Activity Through cAMP Regulation of Transient Receptor Potential C and Small-Conductance K+ Channels

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