Thalamocortical dysconnectivity in schizophrenia

Abstract

Objective: 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).

Method: 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.

Results: 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.

Conclusions: 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.

Figure 1

Resting-state functional connectivity between cortex and thalamus is altered in schizophrenia. The cortex is partitioned into six, non-overlapping regions-of-interest which were used as seeds in a functional connectivity analysis (panel A). Activity in each cortical region-of-interest correlated with distinct areas of the thalamus in both healthy subjects (panel B) and patients with schizophrenia (panel C). Comparison between groups revealed decreased prefrontal connectivity with the thalamus, and increased motor and somatosensory thalamic connectivity in schizophrenia (panel D). Images thresholded at p=.05 (cluster-wise corrected) for voxel-wise p=.001. We used a similar presentation format as Zhang et al. (14,15) and Fair et al. (23) to facilitate comparison of the current results with prior findings in healthy subjects.