Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA; Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD, USA.
Department of Electrical and Computer Engineering, College Park, MD, USA.
Schizophr Res. 2021 Feb;228:262-270. doi: 10.1016/j.schres.2020.11.052. Epub 2021 Jan 22.
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.
听觉幻觉是精神分裂症的一种使人虚弱的症状。由于潜在的神经机制尚不清楚，有效的治疗方法有限。我们的研究调查了局部和远距离功能连接与精神分裂症患者听觉感知障碍（APD）之间的关系。APD 采用听觉感知特质和状态量表进行评估。为 99 名精神分裂症患者采集静息状态 fMRI 数据。局部功能连接使用局部一致性（ReHo）分析进行估计；远距离连接使用静息状态功能连接（rsFC）分析进行估计。中介分析测试了局部（ReHo）连接是否显著介导远距离 rsFC 与 APD 之间的关联。APD 的严重程度与左、右侧壳核、左颞顶联合区（TPJ）和右海马-苍白球的 ReHo 降低显著相关。APD 程度较高还与右侧壳核与对侧壳核和听觉皮层之间的 rsFC 降低相关。局部和远距离连接测量共同解释了 APD 变异的 40.3%（P < 0.001），最强的预测因子是左 TPJ ReHo（P < 0.001）。此外，TPJ ReHo 显著介导了右侧壳核-左侧壳核 rsFC 与 APD 之间的关系（Sobel 检验，P = 0.001）。我们的研究结果表明，局部和远距离功能连接缺陷均与 APD 有关，强调了纹状体和听觉皮层的作用。考虑到这些基于回路的发现在治疗听觉幻觉的先前临床试验背景下的转化意义，我们提出了一种模型，即纠正局部和远距离功能连接缺陷可能是治疗听觉幻觉所必需的。
