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

Table 1 Demographic and clinical characteristics of patients with treatment-resistant schizophrenia and healthy controls

Characteristics	TRS (n = 50)	HCs (n = 61)	P value
Age (yr)	42.64 (9.79)	39.89 (9.52)	0.137
Sex
Male (%)	32 (64%)	29 (48%)	0.083
Female (%)	18 (36%)	32 (52%)
Education (years)	13.53 (2.27)	13.33 (1.92)	0.613
Duration of illness (mo)	215.22 (110.09)	-	-
PANSS
Positive symptoms	15.96 (4.99)	-	-
Negative symptoms	16.00 (7.30)	-	-
General psychopathology	28.40 (7.74)	-	-
Total	60.36 (17.52)	-	-
SOFAS	49.00 (8.81)	-	-
Medication
Chlorpromazine equivalent (mg/d)	915.33 (411.41)	-	-

Data given as mean (SD). HCs: Healthy controls; PANSS: Positive and Negative Syndrome Scale; SOFAS: Social and Occupational Functioning Assessment Scale; TRS: Treatment Resistant Schizophrenia.

Table 2 Comparison of between- and within-functional connectivity of thalamic subregions and cortical functional networks between patients with treatment-resistant schizophrenia (n = 50) and HCs (n = 61)

Seed region	t value	P FWE	P-unc	Brain region
TRS > HCs
Thalamic subregion 2	2.78	< 0.001	0.006	Medial occipital network
Cingulo-opercular network	3.29	0.008	0.001	Medial occipital network
	2.63	0.008	0.010	Superior fronto-parietal network
Medial temporal network	4.31	< 0.001	< 0.001	Superior fronto-parietal network
TRS < HCs
Thalamic subregion 1	-4.58	< 0.001	< 0.001	Thalamic subregion 2
	-2.95	0.019	0.004	Thalamic subregion 9
Thalamic subregion 2	-3.16	< 0.001	0.002	Thalamic subregion 3
	-3.38	< 0.001	0.001	Thalamic subregion 4
Fronto-parietal network	-2.69	< 0.001	0.008	Medial temporal network
	-2.73	0.008	0.007	Superior fronto-parietal network
Default mode network	-2.90	< 0.001	0.004	Cingulo-opercular network
	-3.37	< 0.001	0.001	Medial occipital network
	-5.40	< 0.001	< 0.001	Medial temporal network

Thresholded at P < 0.01, uncorrected; P < 0.05, Family Wise Error rate corrected. TRS: Treatment-resistant schizophrenia; HCs: Healthy controls.

Table 3 Comparison of functional connectivity of thalamic subregions with cortical voxels between patients with treatment-resistant schizophrenia (n = 50) and healthy controls (n = 61)

Seed Region	MNIcoordinate	Cluster Size	t value	P FWE	P-unc	Name (voxel size - region)
TRS > HCs
Thalamic subregion 1	-14 -44 -12	612	5.22	0.009	< 0.001	339 - Left lingual gyrus142 - Left cerebellum 4_5
Thalamic subregion 2	-28 -10 66	1309	5.30	< 0.001	< 0.001	604 - Left precentral gyrus483 - Left postcentral gyrus
Thalamic subregion 3	10 6 54	523	5.26	0.003	< 0.001	173 - Right supplementary motor cortex
Thalamic subregion 6	-8 38 -22	1229	7.05	< 0.001	< 0.001	186 - Frontal medial cortex
	-36 -34 62	358	5.26	0.030	< 0.001	342 - Left postcentral gyrus
	26 -28 60	467	4.79	0.006	< 0.001	305 - Right precentral gyrus132 - Right postcentral gyrus
Thalamic subregion 9	-44 -14 42	380	5.26	0.020	< 0.001	281 - Left precentral gyrus
TRS < HCs
Thalamic subregion 3	6 -90 -2	458	-4.18	0.008	< 0.001	163 - Left intracalcarine cortex

Thresholded at P < 0.01, uncorrected; P < 0.05, Family Wise Error rate corrected. TRS: Treatment-resistant schizophrenia; HCs: Healthy controls.

Table 4 Correlation between Z score of significantly altered between-and within-connectivity of thalamic subregions and cortical functional networks between groups and Positive and Negative Syndrome Scale¹

Connectivity	r value	P value
Positive symptoms
Thalamic subregion 1 - Thalamic subregion 9	-0.267	0.073
Fronto-parietal network - Medial temporal network	-0.411	0.005
Negative symptoms
Default mode network - Medial temporal network	-0.316	0.032
Fronto-parietal network - Medial temporal network	-0.414	0.004
General psychopathology
Default mode network - Medial occipital network	-0.257	0.085
Default mode network - Medial temporal network	-0.322	0.029
Fronto-parietal network - Medial temporal network	-0.427	0.003
Total
Default mode network - Medial temporal network	-0.298	0.044
Fronto-parietal network - Medial temporal network	-0.472	0.001

¹Partial correlation analysis with age, sex, and head motion (framewise displacement) as covariates; P < 0.01, uncorrected; P < 0.05, Family Wise Error rate corrected.

Table 5 Correlation between Z score of significantly altered connectivity between thalamic subregions and cortical voxels between groups and Positive and Negative Syndrome Scale¹

Connectivity	r value	P value
Positive symptoms
Thalamic subregion 3 - Right lingual gyrus	-0.342	0.020
Thalamic subregion 2 - Right precentral gyrus	0.270	0.069
Thalamic subregion 7 - Precuneus cortex	-0.285	0.055
Negative symptoms
Thalamic subregion 3 - Right lingual gyrus	-0.355	0.015
Thalamic subregion 6 - Right precentral gyrus	-0.247	0.098
General psychopathology
Thalamic subregion 2 - Left precentral gyrus	0.292	0.049
Thalamic subregion 3 - Right lingual gyrus	-0.350	0.017
Thalamic subregion 9 - Left precentral gyrus	0.262	0.079
Total
Thalamic subregion 3 - Right lingual gyrus	-0.396	0.007

¹Partial correlation analysis with age, sex, and head motion (framewise displacement) as covariates; P < 0.05, uncorrected; P < 0.05, Family Wise Error rate corrected.