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Schizophrenia - Brain Regions and their Dysfunctions


"sMRI research indicates that schizophrenia is associated with volumetric reductions in a network of frontal, temporal, limbic, striatal, and thalamic regions." S

"TBSS (tract-based spatial statistics) revealed FA (white matter fractional anisotropy) reduction in left prefrontal and occipital regions in the patients. Mean FA values of both areas revealed significant correlation with gray matter reduction in multiple cortical and subcortical areas, with overlapping but different patterns." S

"Our findings suggest that thalamic volume and shape abnormalities are evident at the onset of FES (First-Episode Schizophrenia) prior to thalamic abnormal white matter integrity. Altered microstructural white matter integrity assessed using DTI may not be apparent in FES but may be observed as the disease progresses. Cognitive deficits related to spatial working memory and executive functioning in FES were observed in the context of loss of their normal relationship with the thalamic shapes (...)" S
Affected Region Dysfunctions
Orbitofrontal Cortex "Patients with chronic schizophrenia perform poorly on behavioral and neuropsychological tasks related to OFC functions. (...) This finding suggests that the OFC function, as measured by decision-making tasks, is preserved in the early phases of schizophrenia." S

Subregion-specific OFC grey matter volume deficit in patients with schizophrenia, independent of OFC sulcogyral pattern; associated with a longer duration of illness and greater formal thought disorder S
Medial PFC "Reality distortion is associated with hyperactivity of the MPFC in schizophrenic/schizoaffective patients whose symptoms persist in spite of antipsychotic treatment." S
Dorsolateral PFC "DLPFC dysfunction may be related to the genetic risk for schizophrenia as both patients and their unaffected relatives show reduced activity in this region." S

During a parametric verbal working memory task, activation in the (DLPFC) increased in controls as performance decreased, while patients showed the opposite. Overall, low performing patients were hypoactive and high performing patients hyperactive relative to controls. S
Ventrolateral PFC P-SCZ individuals (paranoid individuals with schizophrenia) showed significantly reduced neural activation in the left VLPFC as compared to controls and in the left VLPFC as compared to NP-SCZ individuals while rating faces for trustworthiness. S
Temporal lobe Abnormally decreased entorhinal volumes, particularly on the right side, in a large number of patients with schizophrenia S

"Higher NSS scores (in recent onset schizophrenia) were associated with morphological changes of cortical thickness in multiple areas comprising paracentral gyrus, postcentral lobule, precuneus, inferior parietal lobule and temporal lobe." S
Hippocampus "Hippocampal volume was bilaterally reduced in patients" S
Amygdala P-SCZ individuals (paranoid individuals with schizophrenia) showed significantly reduced neural activation in the right amygdala while rating faces for trustworthiness. S

"Abnormal amygdala activation in schizophrenia in response to presentation of fearful faces is paradoxically associated with failure to recognize the emotion and with more severe flat affect." S

"The schizophrenia patients without an AI (adhesio interthalamica) had a smaller bilateral amygdala than those with an AI, whereas the AI was not associated with the volume of the amygdala in the control subjects. These findings suggest that the absence of AI in schizophrenia could be a marker of developmental abnormalities in the neural network including the thalamus and connected amygdaloid regions, which may play an important role in the pathogenesis of schizophrenia." S
Anterior Cingulate Cortex ACC dysfunction in people with schizophrenia S

"Our results are in line with previous reports about dysfunctional ACC activation in schizophrenia and argue in favour of a selective deficit of cortical conflict resolution. It is further proposed that dysfunctional ACC activation during executive processing may be a neurophysiologic endophenotype candidate of schizophrenia." S

"Our findings demonstrate a blunted response to error commission that is associated with worse performance in two ACC circuits in schizophrenia. In the dACC circuit, the blunted response may reflect deficient modification of prepotent stimulus-response mappings in response to errors, and in the rACC network it may reflect diminished concern regarding behavioural outcomes. However, despite these deficits and in the absence of external feedback regarding errors, patients corrected their errors as frequently as controls suggesting intact error recognition and ability to institute corrective action. Impairments in evaluating and learning from errors in schizophrenia may contribute to behaviour that is rigid and perseverative rather than optimally guided by outcomes, and may compromise performance across a wide range of tasks." S
Posterior Cingulate Cortex Possible increased acetylcholine and down regulated GABA stimulation in the PCC of schizophrenia S

"The impaired RS-PCC functionality in a semantic task may relate to verbal memory deficits frequently observed in schizophrenia patients, because this region is pivotal for gating information into the medial temporal lobe memory system." S
Striatum Disturbance of frontostriatal circuits in schizophrenia; overall deficit of executive functioning in schizophrenia S
Caudate nucleus "Glutamatergic synaptic pathology in the caudate nucleus in schizophrenia (...) may reflect a loss of glutamatergic cortico-striatal pathways" S
Thalamus "The absence of AI in schizophrenia could be a marker of developmental abnormalities in the neural network including the thalamus and connected amygdaloid regions, which may play an important role in the pathogenesis of schizophrenia." S

Reduced thalamic volumes bilaterally S

"Thalamic shape abnormalities are present in relatively young individuals with schizophrenia and their siblings." S
Fornix "FA and cross-sectional area of the fornix were significantly reduced in (male schizophrenic) patients compared with control subjects." S

Reduced executive functioning and reduced memory scores correlated with lower fornix integrity S

"Results suggest that there are no marked changes in fornix volume in schizophrenia by MRI. The fornix, however, may be part of a network of structures affected in schizophrenia..." S

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