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Key functional circuitry altered in schizophrenia involves parietal regions associated with sense of self.

ABSTRACT: There is still no clear consensus as to which of the many functional and structural changes in the brain in schizophrenia are of most importance, although the main focus to date has been on those in the frontal and cingulate cortices. In the present study, we have used a novel holistic approach to identify brain-wide functional connectivity changes in medicated schizophrenia patients, and functional connectivity changes were analyzed using resting-state fMRI data from 69 medicated schizophrenia patients and 62 healthy controls. As far as we are aware, this is the largest population reported in the literature for a resting-state study. Voxel-based morphometry was also used to investigate gray and white matter volume changes. Changes were correlated with illness duration/symptom severity and a support vector machine analysis assessed predictive validity. A network involving the inferior parietal lobule, superior parietal gyrus, precuneus, superior marginal, and angular gyri was by far the most affected (68% predictive validity compared with 82% using all connections) and different components correlated with illness duration and positive and negative symptom severity. Smaller changes occurred in emotional memory and sensory and motor processing networks along with weakened interhemispheric connections. Our findings identify the key functional circuitry altered in schizophrenia involving the default network midline cortical system and the cortical mirror neuron system, both playing important roles in sensory and cognitive processing and particularly self-processing, all of which are affected in this disorder. Interestingly, the functional connectivity changes with the strongest links to schizophrenia involved parietal rather than frontal regions.

SUBMITTER: Guo S

PROVIDER: S-EPMC6869177 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Key functional circuitry altered in schizophrenia involves parietal regions associated with sense of self.

Guo Shuixia S Kendrick Keith M KM Yu Rongjun R Wang Hsiao-Lan Sharon HL Feng Jianfeng J

Human brain mapping 20120924 1

There is still no clear consensus as to which of the many functional and structural changes in the brain in schizophrenia are of most importance, although the main focus to date has been on those in the frontal and cingulate cortices. In the present study, we have used a novel holistic approach to identify brain-wide functional connectivity changes in medicated schizophrenia patients, and functional connectivity changes were analyzed using resting-state fMRI data from 69 medicated schizophrenia ...[more]

PMID: 23008170

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Project description:Background:The innate alarm system consists of a subcortical network of interconnected midbrain, lower brainstem, and thalamic nuclei, which together mediate the detection of evolutionarily-relevant stimuli. The periaqueductal gray is a midbrain structure innervated by the innate alarm system that coordinates the expression of defensive states following threat detection. In participants with post-traumatic stress disorder, the periaqueductal gray displays overactivation during the subliminal presentation of trauma-related stimuli as well as altered resting-state functional connectivity. Aberrant functional connectivity is also reported in post-traumatic stress disorder for the default-mode network, a large-scale brain network recruited during self-referential processing and autobiographical memory. Here, research lacks investigation on the extent to which functional interactions are displayed between the midbrain and the large-scale cortical networks in post-traumatic stress disorder. Methods:Using a subliminal threat presentation paradigm, we investigated psycho-physiological interactions during functional neuroimaging in participants with post-traumatic stress disorder (n = 26) and healthy control subjects (n = 20). Functional connectivity of the periaqueductal gray was investigated across the whole-brain of each participant during subliminal exposure to trauma-related and neutral word stimuli. Results:As compared to controls during subliminal threat presentation, the post-traumatic stress disorder group showed significantly greater periaqueductal gray functional connectivity with regions of the default-mode network (i.e., angular gyrus, precuneus, superior frontal gyrus). Moreover, multiple regression analyses revealed that the functional connectivity between the periaqueductal gray and the regions of the default-mode network correlated positively to symptoms of avoidance and state dissociation in post-traumatic stress disorder. Conclusion:Given that the periaqueductal gray engages the expression of defensive states, stronger midbrain functional coupling with the default-mode network may have clinical implications to self-referential and trauma-related processing in participants with post-traumatic stress disorder.

Dataset Information

Key functional circuitry altered in schizophrenia involves parietal regions associated with sense of self.

Publications

Key functional circuitry altered in schizophrenia involves parietal regions associated with sense of self.

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