Auditory and Visual Thalamocortical Connectivity Alterations in Unmedicated People With Schizophrenia: An Individualized Sensory Thalamic Localization and Resting-State Functional Connectivity Study

John C Williams¹, Philip N Tubiolo², Roberto B Gil³, Zu Jie Zheng⁴, Eilon B Silver-Frankel⁵, Natalka K Haubold⁵, Sameera K Abeykoon⁵, Dathy T Pham⁶, Najate Ojeil⁷, Kelly Bobchin⁵, Mark Slifstein³, Jodi J Weinstein³, Greg Perlman⁵, Guillermo Horga⁷, Anissa Abi-Dargham⁸, Jared X Van Snellenberg⁹

Affiliations

¹ Department of Psychiatry and Behavioral Health, Renaissance School of Medicine at Stony Brook University, Stony Brook, New York; Department of Biomedical Engineering, Stony Brook University, Stony Brook, New York; Medical Scientist Training Program, Renaissance School of Medicine at Stony Brook University, Stony Brook, New York.
² Department of Psychiatry and Behavioral Health, Renaissance School of Medicine at Stony Brook University, Stony Brook, New York; Department of Biomedical Engineering, Stony Brook University, Stony Brook, New York; Scholars in BioMedical Sciences Training Program, Renaissance School of Medicine at Stony Brook University, Stony Brook, New York.
³ Department of Psychiatry and Behavioral Health, Renaissance School of Medicine at Stony Brook University, Stony Brook, New York; Department of Psychiatry, Vagelos College of Physicians and Surgeons, Columbia University, New York-Presbyterian / Columbia University Irving Medical Center, New York, New York; New York State Psychiatric Institute, New York, New York.
⁴ Department of Psychiatry and Behavioral Health, Renaissance School of Medicine at Stony Brook University, Stony Brook, New York; College of Medicine, State University of New York Downstate Health Sciences University, Brooklyn, New York.
⁵ Department of Psychiatry and Behavioral Health, Renaissance School of Medicine at Stony Brook University, Stony Brook, New York.
⁶ Department of Psychiatry and Behavioral Health, Renaissance School of Medicine at Stony Brook University, Stony Brook, New York; Department of Neurobiology and Behavior, Cornell University, Ithaca, New York.
⁷ Department of Psychiatry, Vagelos College of Physicians and Surgeons, Columbia University, New York-Presbyterian / Columbia University Irving Medical Center, New York, New York; New York State Psychiatric Institute, New York, New York.
⁸ Department of Psychiatry and Behavioral Health, Renaissance School of Medicine at Stony Brook University, Stony Brook, New York; Department of Biomedical Engineering, Stony Brook University, Stony Brook, New York; Department of Psychiatry, Vagelos College of Physicians and Surgeons, Columbia University, New York-Presbyterian / Columbia University Irving Medical Center, New York, New York; New York State Psychiatric Institute, New York, New York; Department of Radiology, Renaissance School of Medicine at Stony Brook University, Stony Brook, New York.
⁹ Department of Psychiatry and Behavioral Health, Renaissance School of Medicine at Stony Brook University, Stony Brook, New York; Department of Biomedical Engineering, Stony Brook University, Stony Brook, New York; Department of Psychiatry, Vagelos College of Physicians and Surgeons, Columbia University, New York-Presbyterian / Columbia University Irving Medical Center, New York, New York; New York State Psychiatric Institute, New York, New York; Department of Psychology, Stony Brook University, Stony Brook, New York. Electronic address: Jared.VanSnellenberg@stonybrookmedicine.edu.

PMID: 40484356
PMCID: PMC12377521 (available on 2026-06-06)
DOI: 10.1016/j.bpsc.2025.05.016

Auditory and Visual Thalamocortical Connectivity Alterations in Unmedicated People With Schizophrenia: An Individualized Sensory Thalamic Localization and Resting-State Functional Connectivity Study

John C Williams et al. Biol Psychiatry Cogn Neurosci Neuroimaging. 2025.

. 2025 Jun 6:S2451-9022(25)00175-2.

doi: 10.1016/j.bpsc.2025.05.016. Online ahead of print.

Authors

Affiliations

¹ Department of Psychiatry and Behavioral Health, Renaissance School of Medicine at Stony Brook University, Stony Brook, New York; Department of Biomedical Engineering, Stony Brook University, Stony Brook, New York; Medical Scientist Training Program, Renaissance School of Medicine at Stony Brook University, Stony Brook, New York.
² Department of Psychiatry and Behavioral Health, Renaissance School of Medicine at Stony Brook University, Stony Brook, New York; Department of Biomedical Engineering, Stony Brook University, Stony Brook, New York; Scholars in BioMedical Sciences Training Program, Renaissance School of Medicine at Stony Brook University, Stony Brook, New York.
³ Department of Psychiatry and Behavioral Health, Renaissance School of Medicine at Stony Brook University, Stony Brook, New York; Department of Psychiatry, Vagelos College of Physicians and Surgeons, Columbia University, New York-Presbyterian / Columbia University Irving Medical Center, New York, New York; New York State Psychiatric Institute, New York, New York.
⁴ Department of Psychiatry and Behavioral Health, Renaissance School of Medicine at Stony Brook University, Stony Brook, New York; College of Medicine, State University of New York Downstate Health Sciences University, Brooklyn, New York.
⁵ Department of Psychiatry and Behavioral Health, Renaissance School of Medicine at Stony Brook University, Stony Brook, New York.
⁶ Department of Psychiatry and Behavioral Health, Renaissance School of Medicine at Stony Brook University, Stony Brook, New York; Department of Neurobiology and Behavior, Cornell University, Ithaca, New York.
⁷ Department of Psychiatry, Vagelos College of Physicians and Surgeons, Columbia University, New York-Presbyterian / Columbia University Irving Medical Center, New York, New York; New York State Psychiatric Institute, New York, New York.
⁸ Department of Psychiatry and Behavioral Health, Renaissance School of Medicine at Stony Brook University, Stony Brook, New York; Department of Biomedical Engineering, Stony Brook University, Stony Brook, New York; Department of Psychiatry, Vagelos College of Physicians and Surgeons, Columbia University, New York-Presbyterian / Columbia University Irving Medical Center, New York, New York; New York State Psychiatric Institute, New York, New York; Department of Radiology, Renaissance School of Medicine at Stony Brook University, Stony Brook, New York.
⁹ Department of Psychiatry and Behavioral Health, Renaissance School of Medicine at Stony Brook University, Stony Brook, New York; Department of Biomedical Engineering, Stony Brook University, Stony Brook, New York; Department of Psychiatry, Vagelos College of Physicians and Surgeons, Columbia University, New York-Presbyterian / Columbia University Irving Medical Center, New York, New York; New York State Psychiatric Institute, New York, New York; Department of Psychology, Stony Brook University, Stony Brook, New York. Electronic address: Jared.VanSnellenberg@stonybrookmedicine.edu.

PMID: 40484356
PMCID: PMC12377521 (available on 2026-06-06)
DOI: 10.1016/j.bpsc.2025.05.016

Abstract

Background: Converging evidence from clinical neuroimaging and animal models has strongly implicated dysfunction of thalamocortical circuits in the pathophysiology of schizophrenia (SZ). Preclinical models of genetic risk for SZ have shown reduced synaptic transmission from the auditory thalamus to the primary auditory cortex, which may represent a correlate of auditory disturbances such as hallucinations. However, human neuroimaging studies have found a generalized increase in resting-state functional connectivity (RSFC) between whole thalamus and sensorimotor cortex in people with SZ (PSZ). We aimed to more directly translate preclinical findings by specifically localizing auditory and visual thalamic nuclei in unmedicated PSZ and measuring RSFC to primary sensory cortices.

Methods: In this case-control study, 82 unmedicated PSZ and 55 matched healthy control participants (HCs) completed RSFC functional magnetic resonance imaging (fMRI) (N = 137). Auditory and visual thalamic nuclei were localized for 55 unmedicated PSZ and 46 HCs who also completed a sensory thalamic nuclei localizer fMRI task (n = 101). Using localized nuclei as RSFC seeds, we assessed group differences in auditory and visual thalamocortical connectivity and associations with positive symptom severity.

Results: Auditory thalamocortical connectivity was not significantly different between PSZ and HCs, but hyperconnectivity was associated with greater positive symptom severity in the bilateral superior temporal gyrus. Visual thalamocortical connectivity was significantly greater in PSZ relative to HCs in the secondary and higher-order visual cortex but was not predictive of positive symptom severity.

Conclusions: These results indicate that visual thalamocortical hyperconnectivity is a generalized marker of SZ, while hyperconnectivity in auditory thalamocortical circuits relates more specifically to positive symptom severity.

Keywords: Functional localization; Positive symptoms; Resting-state functional connectivity; Schizophrenia; Sensory processing; Thalamus.

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Update of

Auditory and Visual Thalamocortical Connectivity Alterations in Unmedicated People with Schizophrenia: An Individualized Sensory Thalamic Localization and Resting-State Functional Connectivity Study.
Williams JC, Tubiolo PN, Gil RB, Zheng ZJ, Silver-Frankel EB, Haubold NK, Abeykoon SK, Pham DT, Ojeil N, Bobchin K, Slifstein M, Weinstein JJ, Perlman G, Horga G, Abi-Dargham A, Van Snellenberg JX. Williams JC, et al. medRxiv [Preprint]. 2024 Dec 22:2024.12.18.24319241. doi: 10.1101/2024.12.18.24319241. medRxiv. 2024. Update in: Biol Psychiatry Cogn Neurosci Neuroimaging. 2025 Jun 6:S2451-9022(25)00175-2. doi: 10.1016/j.bpsc.2025.05.016. PMID: 39763546 Free PMC article. Updated. Preprint.

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Auditory and Visual Thalamocortical Connectivity Alterations in Unmedicated People With Schizophrenia: An Individualized Sensory Thalamic Localization and Resting-State Functional Connectivity Study

Affiliations

Auditory and Visual Thalamocortical Connectivity Alterations in Unmedicated People With Schizophrenia: An Individualized Sensory Thalamic Localization and Resting-State Functional Connectivity Study

Authors

Affiliations

Abstract

Update of

References

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