Targeting the Auditory Control Network with Auditory Control Enhancement (ACE) in Schizophrenia

通过听觉控制增强 (ACE) 治疗精神分裂症的听觉控制网络

• 批准号: 10593386
• 负责人: Brian A Coffman
• 金额: $ 19.77万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10593386
• 关键词: Acoustic Stimulation; Acute; Address; Anodes; Antipsychotic Agents; Area; Attention; Auditory; Auditory Hallucination; Auditory area; Auditory system; Behavior Control; Behavioral; Behavioral Assay; Biological; Biophysics; Cathodes; Cerebrovascular Circulation; Clinical; Cognitive; Computer Models; Data; Development; Disease; Dose; Echo-Planar Imaging; Effectiveness; Electrodes; Electroencephalography; Electromagnetic Fields; Elements; Etiology; Functional disorder; Hypersensitivity; Impaired cognition; Impairment; Individual; Institutionalization; Intervention; Language; Lead; Learning; Left; Magnetic Resonance Imaging; Measures; Metabolic; Methods; Modeling; Neurobehavioral Manifestations; Orthostatic Hypotension; Persons; Pharmaceutical Preparations; Pharmacotherapy; Prefrontal Cortex; Psychiatric Hospitals; Refractory; Reporting; Resistance; Rest; Schizophrenia; Sedation procedure; Severities; Sexual Dysfunction; Surveys; Symptoms; System; Testing; Time; Training; Training Programs; Treatment Efficacy; Update; acceptability and feasibility; behavior measurement; blood oxygen level dependent; blood oxygenation level dependent response; brain circuitry; brain tissue; cognitive control; cognitive enhancement; cognitive performance; common symptom; design; disability; distraction; efficacy trial; electric field; experimental study; follow-up; hemodynamics; improved; improved outcome; magnetic field; medication compliance; network dysfunction; neural; neurophysiology; noninvasive brain stimulation; novel; oscillatory blood flow; participant enrollment; psychotic symptoms; response; side effect; transcranial direct current stimulation; verbal; visual search

Project Summary/Abstract Auditory hallucinations associated with schizophrenia (Sz) are pervasive, debilitating, and disturbing. Unfortunately, they are also difficult to treat – auditory hallucinations persist in about 25% of cases despite pharmacotherapy1 and treatment of cognitive symptoms (the symptoms most strongly related to global functioning) is modest at best. We propose a novel, inexpensive, and noninvasive intervention to address treatment-refractory symptoms, a critical need in Sz. Auditory hallucinations and impaired cognition in schizophrenia are not independent. Both are associated with system-level dysfunction of the fronto-temporal auditory control network, comprising auditory/verbal perceptual areas in temporoparietal junction (TPJ) and cognitive/behavioral control systems in ventrolateral prefrontal cortex (VLPFC). VLPFC traditionally inhibits and reattributes perceptual misrepresentations in most people2. For those with schizophrenia, impairment of auditory cognitive control makes this impossible. Data from our lab suggest that auditory control network dysfunction may be central to the early etiology of the disorder3. Auditory control enhancement (ACE) is designed to improve auditory control network function, thereby increasing inhibition of spurious auditory system activity in temporoparietal cortex and reducing auditory hallucinations. ACE combines a time-tested psychotherapeutic behavioral training program with targeted non-invasive brain stimulation using transcranial Direct Current Stimulation (tDCS). Our pilot data demonstrate the effectiveness of the behavioral training program and synergistic effects with tDCS of the auditory control network for treating treatment-refractory auditory hallucinations in schizophrenia. To further develop ACE for efficacy trials, we plan to investigate neural markers of target engagement in two sham-controlled experiments. Aim 1 will determine whether tDCS of right vlPFC (anode) and left TPJ (cathode) during MRI alters electric field measures and blood oxygenation level dependent (BOLD) response during stimulation to demonstrate that markers of tDCS current flow and BOLD fluctuate with induced current, and these fluctuations align spatially with computer models. Aim 2 will examine feasibility of subject retention and blinding for ACE. Aim 3 will examine the degree to which ACE modifies behavioral, neurophysiological, and hemodynamic markers of target engagement using neural oscillatory and cerebral blood flow (CBF) measures. Pilot data show feasibility of our aims and provide preliminary evidence that ACE has strong and lasting effects on auditory hallucinations assessed with the psychotic symptoms rating scale (PSYRATS), and that changes in cognitive factors associated with auditory hallucinations strongly correlate with changes in neural oscillatory measures of cognitive control. ACE represents a novel, transformative intervention with long-lasting effects that has the potential to change the treatment of schizophrenia and vastly improve the outcome for afflicted individuals.

项目概要/摘要 与精神分裂症 (Sz) 相关的幻听是普遍存在的、令人衰弱且令人不安的。 不幸的是，它们也很难治疗——尽管有幻听，但仍有约 25% 的病例持续出现幻听。 药物治疗1和认知症状的治疗（与全球性最密切相关的症状） 我们提出了一种新颖的、廉价的、非侵入性的干预措施来解决这个问题。 治疗难治性症状，幻听和认知受损的迫切需要。 精神分裂症并不是独立的，两者都与额颞叶的系统级功能障碍有关。 听觉控制网络，包括颞顶交界处（TPJ）的听觉/言语感知区域和 腹外侧前额叶皮层 (VLPFC) 的认知/行为控制系统传统上抑制和控制。 重新归因大多数人的知觉错误表述2。 我们实验室的数据表明，认知控制使这成为不可能。 听觉控制增强（ACE）是该疾病早期病因的核心3。 听觉控制网络功能，从而增加对虚假听觉系统活动的抑制 颞顶皮层和减少幻听相结合是经过时间考验的心理治疗方法。 使用经颅直流电进行有针对性的非侵入性脑刺激的行为训练计划 刺激 (tDCS)。我们的试点数据证明了行为训练计划的有效性和 听觉控制网络与 tDCS 治疗难治性听觉的协同效应 为了进一步开发 ACE 进行疗效试验，我们计划研究神经标记物。 目标 1 将确定右侧 vlPFC 的 tDCS 是否有效。 MRI 期间（阳极）和左侧 TPJ（阴极）会改变电场测量和血氧水平依赖性 (BOLD) 刺激期间的响应，以证明 tDCS 电流和 BOLD 的标记随 感应电流，并且这些波动在空间上与计算机模型一致，目标 2 将检验其可行性。 ACE 的受试者保留和盲法目标 3 将检查 ACE 改变行为的程度， 使用神经振荡和脑血进行目标参与的神经生理学和血流动力学标记 试点数据显示了我们目标的可行性，并提供了 ACE 已实现的初步证据。 用精神病症状评定量表评估对幻听的强烈而持久的影响 （PSYRATS），与幻听相关的认知因素的变化与 认知控制的神经振荡测量的变化代表了一种新颖的、变革性的干预措施。 具有持久的效果，有可能改变精神分裂症的治疗并极大地改善 受影响个人的结果。