Altered thalamic subregion functional networks in patients with treatment-resistant schizophrenia

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

Figure 1

Altered functional connectivity of thalamus subregions and cortical functional networks between treatment resistant schizophrenia and healthy control groups. Between- and within-connectivity were presented in grey color and in each network’s color respectively. CON: Cingulo-Opercular Network; DMN: Default Mode Network; FPN: Fronto-Parietal Network; LON: Lateral Occipital Network; MON: Medial Occipital Network; MTN: Medial Temporal Network; SFPN: Superior Fronto-Parietal Network; SMN: Somato-Motor Network; TN: Temporal Network.

Figure 2

Altered thalamus subregion-based functional connectivity between treatment resistant schizophrenia and healthy control groups. Significant differences were revealed between the (A) Thalamic subregion 1 and Left lingual gyrus; (B) Thalamic subregion 2 and Left precentral gyrus; (C) Thalamic subregion 3 and right supplementary motor area; (D) Thalamic subregion 6 and Frontal medial cortex; (E) Thalamic subregion 6 and Left postcentral gyrus; (F) Thalamic subregion 6 and Right precentral gyrus; (G) Thalamic subregion 9 and Left precentral gyrus; and (H) Thalamic subregion 3 and Left intracalcarine cortex. The functional connectivity Z values of regions showing significant differences are presented in bar graph.

Figure 3

Associations between the significantly altered region of interest to region of interest functional connectivity and Positive and Negative Syndrome Scale scores in the treatment resistant schizophrenia group.

Figure 4

Associations between the significantly altered seed to voxel functional connectivity and Positive and Negative Syndrome Scale scores in the treatment resistant schizophrenia group.