Supplementary file 1_Interoceptive dysfunction and its neural correlates in schizophrenia: protocol for a cross-sectional multimodal MRI study.docx

BackgroundInteroception—the perception and integration of internal bodily signals—is fundamental to emotion regulation, bodily self-awareness, and predictive coding. Emerging evidence suggests that interoceptive disturbances may contribute to core psychopathological features of schizophrenia. Our research group recently conducted a systematic review and meta-analysis demonstrating significant impairments in interoceptive accuracy and sensitivity among individuals with schizophrenia. However, the neural mechanisms underlying these deficits remain unclear.
MethodsThis cross-sectional protocol will recruit 30 individuals with schizophrenia and 30 age- and sex-matched healthy controls. Participants will complete (1) behavioral interoceptive assessment using the heartbeat counting task; (2) subjective interoceptive questionnaires, including the Multidimensional Assessment of Interoceptive Awareness (MAIA) and the Body Perception Questionnaire (BPQ); (3) clinical symptom ratings (PANSS, HAM-A, HAM-D); and (4) cognitive testing (TMT, animal fluency, DSST). All participants will undergo multimodal MRI scanning, including structural T1-weighted imaging, resting-state fMRI, and diffusion tensor imaging. Neuroimaging data will be preprocessed and analyzed using DPABISurf, SPM12, and GRETNA. Expected Results: We anticipate that individuals with schizophrenia will show reduced interoceptive accuracy, altered subjective interoceptive awareness, and abnormal intrinsic neural activity and connectivity within interoception-related circuits, including the anterior insula, anterior cingulate cortex, amygdala, and thalamus. Structural abnormalities within thalamo-cortical pathways are also expected. Interoceptive deficits are hypothesized to correlate with symptom severity and cognitive performance.
ConclusionsThis study will provide an integrated characterization of interoceptive dysfunction and its neural correlates in schizophrenia. Findings may advance understanding of bodily self-disturbance and emotional dysregulation and support the development of future interoception-focused therapeutic approaches.
Clinical trial registrationhttps://www.chictr.org.cn/, identifier ChiCTR2500110551.

背景：内感受（Interoception）指对体内生理信号的感知与整合过程，是情绪调节、躯体自我意识及预测编码的核心基础。近年来越来越多的研究证据表明，内感受异常可能与精神分裂症的核心精神病理特征密切相关。本研究团队近期完成了一项系统综述与元分析，结果显示精神分裂症患者的内感受准确性与敏感性均存在显著损伤，但此类缺损背后的神经机制仍有待进一步阐明。
方法：本横断面研究计划招募30名精神分裂症患者，以及30名年龄与性别相匹配的健康对照受试者。所有受试者将完成以下测评与扫描：(1) 采用心跳计数任务开展的行为层面内感受评估；(2) 主观内感受问卷测评，包括内感受意识多维评定量表（Multidimensional Assessment of Interoceptive Awareness, MAIA）与躯体感知问卷（Body Perception Questionnaire, BPQ）；(3) 临床症状评定，涵盖阳性与阴性症状量表（Positive and Negative Syndrome Scale, PANSS）、汉密尔顿焦虑量表（Hamilton Anxiety Rating Scale, HAM-A）及汉密尔顿抑郁量表（Hamilton Depression Rating Scale, HAM-D）；(4) 认知功能测评，包括数字连线测验（Trail Making Test, TMT）、动物流畅性测验与数字符号替换测验（Digit Symbol Substitution Test, DSST）。此外，所有受试者将接受多模态磁共振成像（MRI）扫描，具体包括结构T1加权成像、静息态功能磁共振成像（resting-state fMRI）及弥散张量成像（diffusion tensor imaging, DTI）。神经影像数据将采用DPABISurf、SPM12及GRETNA工具包进行预处理与分析。
预期结果：本研究预计，精神分裂症患者将表现出内感受准确性降低、主观内感受意识异常，以及内感受相关脑环路（包括前脑岛、前扣带回皮层、杏仁核与丘脑）内的固有神经活动与功能连接异常；同时预期丘脑-皮层通路存在结构异常。本研究假设，内感受缺损与精神分裂症患者的症状严重程度及认知表现存在相关性。
结论：本研究将全面刻画精神分裂症患者的内感受功能障碍及其神经关联特征。研究结果有助于深化对躯体自我紊乱与情绪调节异常的理解，并为未来开发聚焦内感受的治疗手段提供科学支撑。
临床试验注册：本研究已在中国临床试验注册中心完成注册，注册网址为https://www.chictr.org.cn/，注册号为ChiCTR2500110551。