Case Control Study
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World J Psychiatry. May 19, 2022; 12(5): 693-707
Published online May 19, 2022. doi: 10.5498/wjp.v12.i5.693
Altered thalamic subregion functional networks in patients with treatment-resistant schizophrenia
Woo-Sung Kim, Jie Shen, Uyanga Tsogt, Soyolsaikhan Odkhuu, Young-Chul Chung
Woo-Sung Kim, Jie Shen, Uyanga Tsogt, Soyolsaikhan Odkhuu, Young-Chul Chung, Department of Psychiatry, Jeonbuk National University, Jeon-ju 54907, South Korea
Author contributions: Chung YC conceptualized the study; Tsogt U, Shen J, Kim WS, Odkhuu S, and Chung YC performed the study and acquired data; Kim WS conducted experiment and statistical analysis; Kim WS drafted the manuscript; Tsogt U, Shen J, Kim WS, and Odkhuu critically reviewed the manuscript; Chung YC finalized the manuscript; all authors approved the final manuscript.
Supported by the Korean Mental Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea, No. HL19C0015; and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health & Welfare, Republic of Korea, No. HR18C0016.
Institutional review board statement: The study was approved by the Ethics Committee of Jeonbuk National University Hospital (approval number: CUH 2012-08-001).
Informed consent statement: All patients gave informed consent.
Conflict-of-interest statement: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Young-Chul Chung, MD, PhD, Professor, Department of Psychiatry, Jeonbuk National University, 20, Geonji-ro, Deokjin-gu, Jeonju-si, Jeollabuk-do, Republic of Korea, Jeon-ju 54907, South Korea. chungyc@jbnu.ac.kr
Received: September 28, 2021
Peer-review started: September 28, 2021
First decision: November 17, 2021
Revised: November 25, 2022
Accepted: April 2, 2022
Article in press: April 2, 2022
Published online: May 19, 2022
Processing time: 231 Days and 23.2 Hours
Abstract
BACKGROUND

The thalamus plays a key role in filtering information and has extensive interconnectivity with other brain regions. A large body of evidence points to impaired functional connectivity (FC) of the thalamocortical pathway in schizophrenia. However, the functional network of the thalamic subregions has not been investigated in patients with treatment-resistant schizophrenia (TRS).

AIM

To identify the neural mechanisms underlying TRS, we investigated FC of thalamic sub-regions with cortical networks and voxels, and the associations of this FC with clinical symptoms. We hypothesized that the FC of thalamic sub-regions with cortical networks and voxels would differ between TRS patients and HCs.

METHODS

In total, 50 patients with TRS and 61 healthy controls (HCs) matched for age, sex, and education underwent resting-state functional magnetic resonance imaging (rs-fMRI) and clinical evaluation. Based on the rs-fMRI data, we conducted a FC analysis between thalamic subregions and cortical functional networks and voxels, and within thalamic subregions and cortical functional networks, in the patients with TRS. A functional parcellation atlas was used to segment the thalamus into nine subregions. Correlations between altered FC and TRS symptoms were explored.

RESULTS

We found differences in FC within thalamic subregions and cortical functional networks between patients with TRS and HCs. In addition, increased FC was observed between thalamic subregions and the sensorimotor cortex, frontal medial cortex, and lingual gyrus. These abnormalities were associated with the pathophysiology of TRS.

CONCLUSION

Our findings suggest that disrupted FC within thalamic subregions and cortical functional networks, and within the thalamocortical pathway, has potential as a marker for TRS. Our findings also improve our understanding of the relationship between the thalamocortical pathway and TRS symptoms.

Keywords: Treatment-resistant schizophrenia; Thalamus; Rs-fMRI; Functional connectivity; Thalamocortical pathway

Core Tip: The thalamus represents the interface between the sensory and motor systems, and is a major hub for cognitive processes. A large body of evidence has demonstrated involvement of the thalamus in the pathophysiology of schizophrenia. Most previous studies employing resting state functional magnetic resonance imaging used the whole thalamus as a seed region to identify abnormalities in thalamic connectivity. To identify more specific disturbances, we conducted functional connectivity analysis of thalamic subregions with cortical networks and voxels in patients with treatment resistant schizophrenia. Important novel findings regarding the pathophysiology of treatment resistant schizophrenia were obtained.