Elucidating neural mechanisms of hypo/mania using theta burst stimulation

抽象的。双相情感障碍(BD)，由低/躁狂病史定义，是一种常见的、令人衰弱的疾病。然而， 导致低/躁狂的神经机制，用于指导BD的新干预措施，目前还知之甚少。屋宇署 其特征是奖赏敏感度、冲动和感觉寻求、反应 倾向于在潜在的奖励环境中倾向于低迷/狂躁，例如，不确定的奖励期望 (Re)。在成人BD患者中，我们报告了与RE相关的异常升高的左腹外侧前额叶皮质 (VLPFC)活动。此外，我们还发现与RE相关的左VLPFC活动与AN呈正相关。 冲动性成分，负紧迫度；和负紧迫度之间正相关 与左VLPFC活动和终生易患低/躁狂症严重程度相关的年轻人中，有 尚未开发的BD。因此，左VLPFC对RE的异常升高是一种潜在的神经机制 潜在的高度消极紧迫感，这增加了发展/恶化低迷/躁狂的风险。西塔-- 爆发式刺激(TBS)是一种重复的经颅磁刺激(RTMS)范例，它可以尖锐地、 快速、非侵入性地调制左侧VLPFC。检查左侧是否有持续性(抑制性)TBS(CTB) VLPFC导致低/躁狂相关情感的急性变化因此是阐明神经的第一步 易患低迷/躁狂的机制。我们将招募50名缓解/轻度-中度躁狂的成年人 I型BD(我们报告了大多数与RE相关的神经成像数据)：18-35岁(未服用药物/正在服用 常见的BD药物)，以避免长期精神疾病/长期服药史的混淆；以及50岁- 以及性别比例匹配的健康/非BD(焦虑史/非BD情绪障碍)成年人。我们将研究 左侧VLPFC和奖赏区域之间的活动和功能连接：腹侧纹状体(VS)，杏仁核， 眶前叶皮质(OFC)和背侧/吻侧前扣带回皮质(d/rACC)。每个参与者都将拥有 负面紧迫感的基线评估(和其他与业务发展相关的应对趋势)和基线结构 扫描神经靶向和TBS剂量阈值。一周后，将在&lt；2周内进行3次扫描： 每种情况在CTB扫描前后交错显示3种情况中的1种，按随机顺序排列：左侧VLPFC CTBS；左侧控制区，躯体感觉皮质，CTBS；左侧VLPFC假TBS。积极和消极的影响 将在每次CTB扫描前和每次CTB扫描后进行测量。我们的目标是：1.确定 急性CTBS超过左侧VLPFC(与其他CTBS条件相比)对左侧VLPFC、VS、 杏仁核，d/rACC，OFC；2.确定四氯化碳诱导的神经变化是否会导致低/躁狂的急性变化- 相关影响，如果负紧迫感缓和这些关系；3.比较CTBS对左侧VLPFC的影响 (与其他条件相比)BD与健康/非BD成人的神经影响测量。我们将探索是否还有其他 与BD相关的反应倾向缓和了CTBS诱导的神经影响变化。我们将检查急性呼吸道感染 CTBS对奖赏回路和情感的影响，以阐明易患低/躁狂的神经机制。

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.