Local versus long-range connectivity patterns of auditory disturbance in schizophrenia

Auditory hallucinations are a debilitating symptom of schizophrenia. Effective treatment is limited because the underlying neural mechanisms remain unknown. Our study investigates how local and long-range functional connectivity is associated with auditory perceptual disturbances (APD) in schizophre...

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Bibliographic Details
Published in:	Schizophrenia research 2021-02, Vol.228, p.262-270
Main Authors:	Hare, Stephanie M., Adhikari, Bhim M., Du, Xiaoming, Garcia, Laura, Bruce, Heather, Kochunov, Peter, Simon, Jonathan Z., Hong, L. Elliot
Format:	Article
Language:	eng
Subjects:	Auditory Cortex - diagnostic imaging Hallucinations Hallucinations - diagnostic imaging Hallucinations - etiology Humans Magnetic Resonance Imaging Regional homogeneity (ReHo) Resting fMRI Schizophrenia Schizophrenia - complications Schizophrenia - diagnostic imaging Temporal Lobe
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Summary:	Auditory hallucinations are a debilitating symptom of schizophrenia. Effective treatment is limited because the underlying neural mechanisms remain unknown. Our study investigates how local and long-range functional connectivity is associated with auditory perceptual disturbances (APD) in schizophrenia. APD was assessed using the Auditory Perceptual Trait and State Scale. Resting state fMRI data were collected for N=99 patients with schizophrenia. Local functional connectivity was estimated using regional homogeneity (ReHo) analysis; long-range connectivity was estimated using resting state functional connectivity (rsFC) analysis. Mediation analyses tested whether local (ReHo) connectivity significantly mediated associations between long-distance rsFC and APD. Severity of APD was significantly associated with reduced ReHo in left and right putamen, left temporoparietal junction (TPJ), and right hippocampus-pallidum. Higher APD was also associated with reduced rsFC between the right putamen and the contralateral putamen and auditory cortex. Local and long-distance connectivity measures together explained 40.3% of variance in APD (P < 0.001), with the strongest predictor being the left TPJ ReHo (P < 0.001). Additionally, TPJ ReHo significantly mediated the relationship between right putamen – left putamen rsFC and APD (Sobel test, P = 0.001). Our findings suggest that both local and long-range functional connectivity deficits contribute to APD, emphasizing the role of striatum and auditory cortex. Considering the translational impact of these circuit-based findings within the context of prior clinical trials to treat auditory hallucinations, we propose a model in which correction of both local and long-distance functional connectivity deficits may be necessary to treat auditory hallucinations.
ISSN:	0920-9964 1573-2509