Thalamic Dysconnectivity and Negative Symptoms in Schizophrenia Spectrum Disorder
- 1University of Texas Health Science Center at Houston
Abstract
Background and Hypothesis Negative symptoms in schizophrenia spectrum disorder (SSD) are associated with poor functional outcomes and reduced quality of life; however, effective treatments remain limited. A better understanding of the underlying brain mechanisms is needed to develop better treatments. Neuroimaging studies implicate multiple brain networks in negative symptoms, though findings remain heterogeneous, potentially reflecting the multidimensionality of both symptoms and brain networks. Larger, more systematic dissections are required to identify the key hub(s) underlying negative symptoms. Study Design Structural MRI data from 394 participants (210 SSD, 184 healthy controls [HC]) were analyzed to identify cortical thickness and subcortical volume demonstrating both SSD-HC differences and associations with negative symptoms measured by the Brief Negative Symptom Scale (BNSS). Regions meeting both criteria were selected as seeds for resting-state functional connectivity analyses in 143 SSD patients to examine association with negative symptoms and their subdomains. Study Results The thalamus was the only region demonstrating significant structural abnormalities both in SSD and an association with BNSS total score (p-FDR<0.05). Functional-network-defined thalamic subregions were subsequently examined. Several thalamic hypoconnectivities were significantly corresponded with negative symptoms, involving thalamic subregions associated with the cortical default mode, somatosensory, medial temporal, and dorsal attention networks (p=0.001, corrected<0.05). Blunted affect showed the most extensive thalamic connectivity alterations, involving the striatum, cerebellum, and temporoparietal junction/superior temporal sulcus (TPJ-STS). Thalamic hypoconnectivity with TPJ-STS was also associated with overall negative symptoms and anhedonia. Conclusions This study identifies the thalamus as a central hub of negative symptom-related dysfunction in SSD and highlights specific thalamic subnetworks as potential targets for circuit-based interventions.
Related
- Breaking the Cycle: Rewiring Negative Symptoms in Schizophrenia Through Physical Exercise
- Goals in Focus: A single-blind multi-method randomized‑controlled pilot feasibility trial of a targeted CBT approach for motivational negative symptoms of schizophrenia
- Beyond Negative Bias: Disrupted Positive Valence Processing and Asynchronous Hot–Cool Development in Youth Internalizing Symptoms
- The Association Between Prenatal Anxiety and Depression and Autism Spectrum Disorder With Gastrointestinal Symptoms in Children: Case-Control Study.
- Dynamic social envirotypes demonstrate adolescent brain dysconnectivity is contextual
BibTeX
@misc{kunitoki2026thalamic,
title = {{Thalamic Dysconnectivity and Negative Symptoms in Schizophrenia Spectrum Disorder}},
author = {K. Kunitoki and B. M. Adhikari and A. Ankeeta and S. Gao and Y. Ma and K. T. Straub and G. Dos Santos Alves Maria and A. F. Pagan and A. R. Warner and X. Du and P. Kochunov and L. E. Hong},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.04.756569},
url = {https://www.biorxiv.org/content/10.64898/2026.10.04.756569v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Thalamic Dysconnectivity and Negative Symptoms in Schizophrenia Spectrum Disorder
AU - K. Kunitoki
AU - B. M. Adhikari
AU - A. Ankeeta
AU - S. Gao
AU - Y. Ma
AU - K. T. Straub
AU - G. Dos Santos Alves Maria
AU - A. F. Pagan
AU - A. R. Warner
AU - X. Du
AU - P. Kochunov
AU - L. E. Hong
PY - 2026
DA - 2026/10/04
PB - bioRxiv
DO - 10.64898/2026.10.04.756569
UR - https://www.biorxiv.org/content/10.64898/2026.10.04.756569v1
AB - Background and Hypothesis Negative symptoms in schizophrenia spectrum disorder (SSD) are associated with poor functional outcomes and reduced quality of life; however, effective treatments remain limited. A better understanding of the underlying brain mechanisms is needed to develop better treatments. Neuroimaging studies implicate multiple brain networks in negative symptoms, though findings remain heterogeneous, potentially reflecting the multidimensionality of both symptoms and brain networks. Larger, more systematic dissections are required to identify the key hub(s) underlying negative symptoms. Study Design Structural MRI data from 394 participants (210 SSD, 184 healthy controls [HC]) were analyzed to identify cortical thickness and subcortical volume demonstrating both SSD-HC differences and associations with negative symptoms measured by the Brief Negative Symptom Scale (BNSS). Regions meeting both criteria were selected as seeds for resting-state functional connectivity analyses in 143 SSD patients to examine association with negative symptoms and their subdomains. Study Results The thalamus was the only region demonstrating significant structural abnormalities both in SSD and an association with BNSS total score (p-FDR<0.05). Functional-network-defined thalamic subregions were subsequently examined. Several thalamic hypoconnectivities were significantly corresponded with negative symptoms, involving thalamic subregions associated with the cortical default mode, somatosensory, medial temporal, and dorsal attention networks (p=0.001, corrected<0.05). Blunted affect showed the most extensive thalamic connectivity alterations, involving the striatum, cerebellum, and temporoparietal junction/superior temporal sulcus (TPJ-STS). Thalamic hypoconnectivity with TPJ-STS was also associated with overall negative symptoms and anhedonia. Conclusions This study identifies the thalamus as a central hub of negative symptom-related dysfunction in SSD and highlights specific thalamic subnetworks as potential targets for circuit-based interventions.
ER -