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Thalamocortical dysconnectivity in schizophrenia.

ABSTRACT: The thalamus and cerebral cortex are connected via topographically organized, reciprocal connections. Previous studies have revealed thalamic abnormalities in schizophrenia; however, it is not known whether thalamocortical networks are differentially affected in the disorder. To explore this possibility, the authors examined functional connectivity in intrinsic low-frequency blood-oxygen-level-dependent (BOLD) signal fluctuations between major divisions of the cortex and thalamus using resting-state functional MRI (fMRI).Seventy-seven healthy subjects and 62 patients with schizophrenia underwent resting-state fMRI. To identify functional subdivisions of the thalamus, the authors parceled the cortex into six regions of interest: the prefrontal cortex, motor cortex/supplementary motor area, somatosensory cortex, temporal lobe, posterior parietal cortex, and occipital lobe. Mean BOLD time series were extracted for each region of interest and entered into a seed-based functional connectivity analysis.Consistent with previous reports, activity in distinct cortical areas correlated with specific, largely nonoverlapping regions of the thalamus in both healthy comparison subjects and schizophrenia patients. Direct comparison between groups revealed reduced prefrontal-thalamic connectivity and increased motor/somatosensory-thalamic connectivity in schizophrenia. The changes in connectivity were unrelated to local gray matter content within the thalamus and to antipsychotic medication dosage. No differences were observed in temporal, posterior parietal, or occipital cortex connectivity with the thalamus.These findings establish differential abnormalities of thalamocortical networks in schizophrenia. The etiology of schizophrenia may disrupt the development of prefrontal-thalamic connectivity and refinement of somatomotor connectivity with the thalamus that occurs during brain maturation.

SUBMITTER: Woodward ND

PROVIDER: S-EPMC3810300 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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Thalamocortical dysconnectivity in schizophrenia.

Woodward Neil D ND Karbasforoushan Haleh H Heckers Stephan S

The American journal of psychiatry 20121001 10

<h4>Objective</h4>The thalamus and cerebral cortex are connected via topographically organized, reciprocal connections. Previous studies have revealed thalamic abnormalities in schizophrenia; however, it is not known whether thalamocortical networks are differentially affected in the disorder. To explore this possibility, the authors examined functional connectivity in intrinsic low-frequency blood-oxygen-level-dependent (BOLD) signal fluctuations between major divisions of the cortex and thalam ...[more]

PMID: 23032387

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Project description:Schizophrenia is a psychotic disorder characterized by functional dysconnectivity or abnormal integration between distant brain regions. Recent functional imaging studies have implicated large-scale thalamo-cortical connectivity as being disrupted in patients. However, observed connectivity differences in schizophrenia have been inconsistent between studies, with reports of hyperconnectivity and hypoconnectivity between the same brain regions. Using resting state eyes-closed functional imaging and independent component analysis on a multi-site data that included 151 schizophrenia patients and 163 age- and gender matched healthy controls, we decomposed the functional brain data into 100 components and identified 47 as functionally relevant intrinsic connectivity networks. We subsequently evaluated group differences in functional network connectivity, both in a static sense, computed as the pairwise Pearson correlations between the full network time courses (5.4 minutes in length), and a dynamic sense, computed using sliding windows (44 s in length) and k-means clustering to characterize five discrete functional connectivity states. Static connectivity analysis revealed that compared to healthy controls, patients show significantly stronger connectivity, i.e., hyperconnectivity, between the thalamus and sensory networks (auditory, motor and visual), as well as reduced connectivity (hypoconnectivity) between sensory networks from all modalities. Dynamic analysis suggests that (1), on average, schizophrenia patients spend much less time than healthy controls in states typified by strong, large-scale connectivity, and (2), that abnormal connectivity patterns are more pronounced during these connectivity states. In particular, states exhibiting cortical-subcortical antagonism (anti-correlations) and strong positive connectivity between sensory networks are those that show the group differences of thalamic hyperconnectivity and sensory hypoconnectivity. Group differences are weak or absent during other connectivity states. Dynamic analysis also revealed hypoconnectivity between the putamen and sensory networks during the same states of thalamic hyperconnectivity; notably, this finding cannot be observed in the static connectivity analysis. Finally, in post-hoc analyses we observed that the relationships between sub-cortical low frequency power and connectivity with sensory networks is altered in patients, suggesting different functional interactions between sub-cortical nuclei and sensorimotor cortex during specific connectivity states. While important differences between patients with schizophrenia and healthy controls have been identified, one should interpret the results with caution given the history of medication in patients. Taken together, our results support and expand current knowledge regarding dysconnectivity in schizophrenia, and strongly advocate the use of dynamic analyses to better account for and understand functional connectivity differences.

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Thalamocortical dysconnectivity in schizophrenia.

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Thalamocortical dysconnectivity in schizophrenia.

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