The Effect of Electrical Stimulation on Cognitive Control Networks in Treatment-Resistant Depression

电刺激对难治性抑郁症认知控制网络的影响

• 批准号: 10681201
• 负责人: Anusha Allawala
• 金额: $ 4.78万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10681201
• 关键词: Amygdaloid structure; Anterior; Behavior; Behavior Control; Behavioral; Biomedical Engineering; Brain; Cognition; Cognitive; Communication; Complement; Complex; Conflict (Psychology); Couples Therapy; Data; Data Analyses; Data Collection; Deep Brain Stimulation; Diagnosis; Disease; Dissection; Dorsal; Electric Stimulation; Electric Stimulation Therapy; Electroconvulsive Therapy; Electrodes; Electrophysiology (science); Ensure; Excision; Exertion; Experimental Designs; Frequencies; Functional disorder; Goals; Grain; Human; Impaired cognition; Impairment; Implanted Electrodes; Knowledge; Major Depressive Disorder; Measurement; Measures; Mental Depression; Mental Processes; Mental disorders; Mood Disorders; Morphologic artifacts; Neurosciences; Parents; Participant; Patient Self-Report; Patients; Pharmacologic Substance; Pharmacotherapy; Phase; Play; Population; Prefrontal Cortex; Psychotherapy; Research; Research Personnel; Research Project Grants; Research Proposals; Resistance; Rest; Rodent Model; Role; Schedule; Source; Stimulus; Structure; Symptoms; Techniques; Testing; Therapeutic; Thinking; Training; Ventral Striatum; Work; base; behavioral impairment; behavioral study; capsule; career; cell type; cingulate cortex; cognitive control; cognitive enhancement; computational neuroscience; disability; executive function; experimental study; flexibility; human subject; ideation; improved; interdisciplinary approach; multidisciplinary; multimodality; neural circuit; neuromechanism; neurophysiology; neuropsychiatric disorder; neuroregulation; novel; recruit; relating to nervous system; research clinical testing; rumination; task analysis; treatment optimization; treatment-resistant depression

Major Depressive Disorder (MDD) is a prevalent and debilitating disorder, where one-third of this population is treatment-resistant. Depression is characterized by cognitive dysfunction, including deficits in cognitive control, defined as flexible adaptation of cognitive and behavior commensurate with one’s current goals. Application of deep brain stimulation (DBS), a common therapy used for treatment-resistant depression (TRD), has previously shown enhancement in cognitive control during experimental tasks, but therapeutically shown mixed results, and our understanding of the effect of DBS on neural dynamics in brain networks associated with impaired cognitive dysfunction and control in neuropsychiatric disorders is not well-known. In addition, our understanding of how the frequency of neurostimulation plays a role in modulating neural activity and communication in cognitive control networks in depression is limited. To tackle these unknowns, in the F99 phase, Anusha will collect intracranial local field potential recordings (LFP) through depth electrodes implanted across the prefrontal cortex, orbitofrontal cortex, amygdala and anterior cingulate cortex in patients with TRD, recruited through a parent UH3 study (UH3-NS103549). Participants perform a cognitive control behavioral task before, and during high-frequency electrical stimulation delivered through DBS electrodes implanted in the ventral capsule/ventral striatum and subcallosal cingulate. Additionally, Anusha will collect LFP recordings during stimulation experiments where a range of electrical stimulation frequencies (6,50,130 Hz) are applied systematically during resting state through DBS electrodes. Using the collected data, Anusha will characterize behaviorally defined cognitive control subnetworks in participants with TRD, and explore the effect of low-frequency oscillations that are known to be associated with conflict processing and cognitive control in healthy subjects. She will expand this work to perform functional connectivity analysis during the behavioral task. Anusha will also apply these techniques for analysis of data collected in stimulation experiments during resting state. Understanding cognitive control is imperative to not only improving our understanding of cognitive dysfunction in depression, but is a step towards individualizing and optimizing therapy around electrophysiological markers associated with behavioral impairment in neuropsychiatric disorders, in lieu of or in addition to clinical evaluation of symptoms. In the K00 phase, Anusha will extend her research to more granular circuit dissection using rodent models of psychiatric disease, and leverage her doctoral training in statistical and computational neuroscience to analyze data from such studies, while continuing to perform research in human subjects to study cognitive control. The proposed training during the F99 and K00 phases will ensure multidisciplinary training to reach her career goal as an independent research investigator focused on using a multidisciplinary approach to help achieve a comprehensive understanding of cognitive dysfunction in neuropsychiatric disorders.

重度抑郁症 (MDD) 是一种普遍且令人衰弱的疾病，其中三分之一 人群对治疗有抵抗力。抑郁症的特点是认知功能障碍，包括认知功能障碍 认知控制，定义为与当前状态相称的认知和行为的灵活适应 目标。深部脑刺激 (DBS) 的应用是治疗难治性抑郁症的常用疗法 （TRD），之前已显示实验任务期间认知控制的增强，但在治疗上 显示出不同的结果，以及我们对 DBS 对大脑网络神经动力学影响的理解 与神经精神疾病中认知功能障碍和控制受损的相关性尚不清楚。在 此外，我们对神经刺激频率如何在调节神经活动中发挥作用的理解 抑郁症患者的认知控制网络中的交流是有限的。 为了解决这些未知问题，在 F99 阶段，Anusha 将收集颅内局部场电位 通过植入前额皮质、眶额皮质的深度电极进行记录（LFP） TRD 患者的杏仁核和前扣带皮层，通过 UH3 亲本研究招募 （UH3-NS103549）。参与者在高频之前和期间执行认知控制行为任务 通过植入腹侧囊/腹侧纹状体的 DBS 电极传递电刺激， 胼胝体下扣带回。此外，Anusha 将在刺激实验期间收集 LFP 录音，其中 在静息状态下系统地应用一系列电刺激频率（6,50,130 Hz） DBS 电极。使用收集到的数据，Anusha 将描述行为定义的认知控制 TRD 参与者的子网络，并探索已知的低频振荡的影响 与健康受试者的冲突处理和认知控制有关。她将把这项工作扩展到 在行为任务期间进行功能连接分析。阿努沙还将应用这些技术 分析静息状态下刺激实验中收集的数据。了解认知控制是 不仅必须提高我们对抑郁症认知功能障碍的理解，而且是朝着这一目标迈出的一步 围绕与行为相关的电生理标志物进行个体化和优化治疗 神经精神疾病的损害，代替症状的临床评估或作为症状的临床评估的补充。 在 K00 阶段，Anusha 将把她的研究扩展到使用啮齿动物进行更精细的电路解剖 精神疾病模型，并利用她在统计和计算神经科学方面的博士训练 分析此类研究的数据，同时继续对人类受试者进行认知研究 控制。 F99 和 K00 阶段拟议的培训将确保她接受多学科培训 作为一名独立研究人员的职业目标，专注于使用多学科方法来帮助 全面了解神经精神疾病中的认知功能障碍。