Microstructural Changes in Higher-Order Nuclei of the Thalamus in Patients With First-Episode Psychosis

Background: Disruption in the thalamus, such as volume, shape, and cortical connectivity, is regarded as an important pathophysiological mechanism in schizophrenia. However, there is little evidence of nuclei-specific structural alterations in the thalamus during early-stage psychosis, mainly because of the methodological limitations of conventional structural imaging in identifying the thalamic nuclei. Methods: A total of 37 patients with first-episode psychosis and 36 matched healthy control subjects underwent diffusion tensor imaging, diffusion kurtosis imaging, and T1-weighted magnetic resonance imaging. Connectivity-based segmentation of the thalamus was performed using diffusion tensor imaging, and averages of the diffusion kurtosis values, which represent microstructural complexity, were estimated using diffusion kurtosis imaging and were compared in each thalamic nucleus between the groups. Results: The mean kurtosis values in the thalamic regions with strong connections to the orbitofrontal cortex (F_1,70 = 8.40, p < .01) and the lateral temporal cortex (F_1,70 = 8.46, p < .01) were significantly reduced in patients with first-episode psychosis compared with those of the healthy control subjects. The mean kurtosis values in the thalamic region with strong connection to the orbitofrontal cortex showed a significant correlation with spatial working memory accuracy in patients with first-episode psychosis (r = .36, p < .05), whereas no significant correlation between these variables was observed in the healthy control subjects. Conclusions: The observed pattern of reduced microstructural complexity in the nuclei not only highlights the involvement of the thalamus but also emphasizes the role of the higher-order nuclei in the pathophysiology beginning in the early stage of schizophrenia.