Elucidating neural mechanisms of hypo/mania using theta burst stimulation

使用θ爆发刺激阐明低/躁狂的神经机制

基本信息

批准号：
10513817
负责人：
Fabio Ferrarelli
金额：
$ 67.07万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-12-01 至 2025-10-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10513817
关键词：
Acute Adult Affect Age Amygdaloid structure Anterior Anxiety Anxiety Disorders Bipolar Disorder Brain Data Decision Making Development Disease Disease remission Dorsal Dose Esthesia Frustration Functional Magnetic Resonance Imaging Future Gender Impulsivity Individual Intervention Lead Left Link Manic Measures Mediating Mental disorders Mood Disorders Nature Neuroanatomy Outcome Participant Pharmaceutical Preparations Predisposition Prefrontal Cortex Randomized Recording of previous events Reporting Rest Rewards Risk Sampling Scanning Severities Somatosensory Cortex Stimulus Techniques Ventral Striatum brain circuitry cingulate cortex comparison group design gray matter hypomania negative affect neural neural circuit neural stimulation neuroimaging neuromechanism neuroregulation recruit repetitive transcranial magnetic stimulation response reward anticipation reward circuitry reward expectancy transcranial direct current stimulation white matter young adult

项目摘要

ABSTRACT. Bipolar Disorder (BD), defined by a history of hypo/mania, is common and debilitating. Yet, the neural mechanisms predisposing to hypo/mania, to guide new interventions for BD, are poorly understood. BD is characterized by abnormally elevated reward sensitivity, impulsivity and sensation seeking, response tendencies that predispose to hypo/mania in potentially rewarding contexts, e.g., uncertain reward expectancy (RE). In adults with BD, we reported abnormally elevated uncertain RE-related left ventrolateral prefrontal cortical (vlPFC) activity. Moreover, we showed a positive relationship between RE-related left vlPFC activity and an impulsivity component, negative urgency; and that negative urgency mediates a positive association between RE-related left vlPFC activity and the severity of lifetime predisposition to hypo/mania in young adults who have not yet developed BD. Abnormally elevated left vlPFC activity to RE is thus a potential neural mechanism underlying heightened negative urgency, which confers risk for development of/ worsening hypo/mania. Theta- burst stimulation (TBS) is a Repetitive Transcranial Magnetic Stimulation (rTMS) paradigm that can acutely, rapidly, and non-invasively modulate the left vlPFC. Examining if continuous (inhibitory) TBS (cTBS) over left vlPFC leads to acute changes in hypo/mania-related affect is thus a first step toward elucidating the neural mechanisms that predispose to hypo/mania. We will recruit 50 remitted/mild-moderate hypomanic adults with BD type I (in whom we reported the majority of RE-related neuroimaging data): 18-35 yrs (unmedicated/ on common BD medications), to avoid confounds of long psychiatric illness/ long medication history; and 50 age- and gender ratio-matched healthy/ non BD (history of anxiety/ non BD mood disorders) adults. We will examine activity in and functional connectivity (FC) among left vlPFC and reward regions: ventral striatum (VS), amygdala, orbitofrontal cortex (OFC) and dorsal/rostral anterior cingulate cortex (d/rACC). Each participant will have baseline assessments of negative urgency (and other BD-related response tendencies) and a baseline structural scan for neurotargeting and TBS dose thresholding. One week later, there will be 3 scan sessions over <2 weeks: each with 1 of 3 TBS conditions interleaved between pre and post cTBS scans, in randomized order: left vlPFC cTBS; left control region, somatosensory cortex, cTBS; and left vlPFC sham TBS. Positive and negative affect will be measured before each pre cTBS and after each post cTBS scan. We aim to: 1. Determine the impact of acute cTBS over left vlPFC (vs. other cTBS conditions) on RE-related activity in and FC among left vlPFC, VS, amygdala, d/rACC, OFC; 2. Determine if cTBS-induced neural changes lead to acute changes in hypo/mania- related affect, and if negative urgency moderates these relationships; 3. Compare effects of cTBS over left vlPFC (vs. other conditions) on neural-affect measures in BD vs. healthy/ non BD adults. We will explore whether other BD-related response tendencies moderate cTBS-induced neural-affect changes. We will examine the acute impact of cTBS on reward circuitry and affect, to elucidate neural mechanisms that predispose to hypo/mania.

抽象的。双相情感障碍 (BD) 的定义是有低度/躁狂史，是一种常见且令人衰弱的疾病。然而，对于指导双相情感障碍新干预措施的诱发低度/躁狂的神经机制知之甚少。 BD 其特点是异常升高的奖励敏感性、冲动性和感觉寻求、反应在潜在奖励的环境中容易产生低度/躁狂的倾向，例如不确定的奖励预期（关于）。在患有 BD 的成人中，我们报告了与 RE 相关的不确定性左腹外侧前额皮质异常升高 (vlPFC) 活动。此外，我们发现 RE 相关的左 vlPFC 活动与冲动成分，消极的紧迫感；负紧迫性介导了两者之间的正关联 RE 相关的左 vlPFC 活动以及患有轻症/躁狂症的年轻人终生易感性的严重程度尚未开发BD。因此，左 vlPFC 对 RE 的活性异常升高是一种潜在的神经机制潜在的负面紧迫感加剧，这会带来发展/恶化躁狂/躁狂的风险。西塔- 突发刺激 (TBS) 是一种重复经颅磁刺激 (rTMS) 范例，可以敏锐地、快速、无创地调节左侧 vlPFC。检查连续（抑制性）TBS (cTBS) 是否超出左侧 vlPFC 导致低度/躁狂相关情感的急剧变化，因此是阐明神经功能的第一步诱发低度/躁狂的机制。我们将招募 50 名患有缓解/轻中度轻躁狂成人 BD I 型（我们报告了大部分 RE 相关神经影像数据）：18-35 岁（未接受药物/正在服用药物）常见的 BD 药物），以避免长期精神疾病/长期用药史的混淆；和50岁- 以及性别比例匹配的健康/非 BD（焦虑/非 BD 情绪障碍史）成年人。我们将检查左侧 vlPFC 和奖励区域的活动和功能连接 (FC)：腹侧纹状体 (VS)、杏仁核、眶额皮质（OFC）和背侧/喙侧前扣带皮层（d/rACC）。每个参与者都会有负面紧迫性（以及其他 BD 相关响应倾向）的基线评估和基线结构扫描神经靶向和 TBS 剂量阈值。一周后，将在不到 2 周内进行 3 次扫描：每个都有 3 个 TBS 条件中的一个，在 cTBS 扫描之前和之后交错，按随机顺序：左 vlPFC TBBS；左控制区，体感皮层，cTBS；并离开 vlPFC 假 TBS。正面和负面影响将在每次 cTBS 扫描前和每次 cTBS 扫描后进行测量。我们的目标是： 1. 确定影响左侧 vlPFC 上的急性 cTBS（与其他 cTBS 情况相比）对左侧 vlPFC 中 RE 相关活动和 FC 的影响，VS、杏仁核、d/rACC、OFC； 2. 确定 cTBS 诱导的神经变化是否会导致低度/躁狂的急性变化相关影响，以及负面紧迫性是否缓和了这些关系； 3. 比较 cTBS 与左侧 vlPFC 的效果（与其他条件相比）BD 与健康/非 BD 成年人的神经影响测量。我们将探讨是否还有其他 BD 相关反应倾向缓和 cTBS 引起的神经影响变化。我们将检查急性 cTBS 对奖赏回路和情感的影响，以阐明易患低度/躁狂的神经机制。