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

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.
摘要。双相情感障碍(BD),定义为低/躁狂病史,是常见的和衰弱的。然而 神经机制诱发低/躁狂,以指导新的干预BD,是知之甚少。BD 其特征是异常升高的奖励敏感性,冲动性和感觉寻求,反应 在潜在的有益环境中倾向于轻度/躁狂的倾向,例如,不确定报酬期望 (RE)。在成人BD患者中,我们报告了不确定RE相关的左腹外侧前额叶皮质异常升高, (vlPFC)活性。此外,我们发现RE相关的左vlPFC活性与 冲动成分,消极紧迫感;消极紧迫感介导了 患有抑郁症的年轻人中RE相关的左侧vlPFC活动和终生低/躁狂倾向的严重程度 尚未开发BD。因此,RE引起的左侧vlPFC活性异常升高是一种潜在的神经机制 潜在的负面紧迫感增强,这会导致低血糖/躁狂发展/恶化的风险。西塔- 爆发刺激(TBS)是一种重复经颅磁刺激(rTMS)范例,可以剧烈地, 快速且非侵入性地调节左侧vlPFC。检查连续(抑制性)TBS(cTBS)是否超过左侧 因此,vlPFC导致轻躁狂相关情感的急性变化是阐明神经功能障碍的第一步。 易患轻躁狂症的机制。我们将招募50名缓解/轻中度轻躁狂成年人, BD I型(我们报告了其中大部分RE相关神经影像学数据):18-35岁(未用药/用药 常见的BD药物),以避免长期精神疾病/长期用药史的混淆; 50岁- 和性别比例匹配的健康/非BD(焦虑/非BD情绪障碍史)成年人。我们将研究 左vlPFC和奖赏区的活动和功能连接(FC):腹侧纹状体(VS),杏仁核, 眶额皮质(OFC)和背侧/喙侧前扣带回皮质(d/rACC)。每个参与者将有 消极紧迫性(和其他与BD相关的响应趋势)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<2周内进行3次扫描: 每种情况在cTBS扫描前和扫描后交错出现3种TBS状况之一,按随机顺序:左侧vlPFC cTBS;左侧对照区,体感皮层,cTBS;和左侧vlPFC假TBS。正性负性情绪 将在每次cTBS扫描前和每次cTBS扫描后测量。我们的目标是:1.确定影响 左vlPFC急性cTBS(与其他cTBS条件相比)对左vlPFC中RE相关活性和FC的影响,VS, 杏仁核、d/rACC、OFC; 2.确定cTBS诱导的神经变化是否导致轻度/躁狂的急性变化- 相关的影响,如果消极的紧迫性缓和这些关系; 3。比较cTBS对左侧vlPFC的影响 (vs.其他条件)对BD与健康/非BD成人神经影响测量的影响。我们将探讨其他 BD相关的反应倾向中度cTBS诱导的神经影响的变化。我们将检查急性 cTBS对奖赏回路和情感的影响,以阐明易患轻躁狂的神经机制。

项目成果

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Fabio Ferrarelli其他文献

Fabio Ferrarelli的其他文献

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{{ truncateString('Fabio Ferrarelli', 18)}}的其他基金

Establishing that sleep spindle and slow wave deficits are present, are associated with cognitive dysfunction, and can be acutely manipulated in early course schizophrenia
确定睡眠纺锤波和慢波缺陷的存在,与认知功能障碍相关,并且可以在早期精神分裂症中进行急性控制
  • 批准号:
    10733615
  • 财政年份:
    2023
  • 资助金额:
    $ 70.21万
  • 项目类别:
Enhancing prefrontal oscillatory activity and working memory performance with noninvasive brain stimulation in early-course schizophrenia
通过无创脑刺激治疗早期精神分裂症,增强前额叶振荡活动和工作记忆表现
  • 批准号:
    10364064
  • 财政年份:
    2021
  • 资助金额:
    $ 70.21万
  • 项目类别:
Enhancing prefrontal oscillatory activity and working memory performance with noninvasive brain stimulation in early-course schizophrenia
通过无创脑刺激治疗早期精神分裂症,增强前额叶振荡活动和工作记忆表现
  • 批准号:
    10483147
  • 财政年份:
    2021
  • 资助金额:
    $ 70.21万
  • 项目类别:
Enhancing prefrontal oscillatory activity and working memory performance with noninvasive brain stimulation in early-course schizophrenia
通过无创脑刺激治疗早期精神分裂症,增强前额叶振荡活动和工作记忆表现
  • 批准号:
    10668480
  • 财政年份:
    2021
  • 资助金额:
    $ 70.21万
  • 项目类别:
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
  • 批准号:
    10513817
  • 财政年份:
    2020
  • 资助金额:
    $ 70.21万
  • 项目类别:
Characterize differences in sleep spindles between Clinical High Risk and healthy controls longitudinally.
纵向描述临床高风险组和健康对照组之间睡眠纺锤波的差异。
  • 批准号:
    9376357
  • 财政年份:
    2017
  • 资助金额:
    $ 70.21万
  • 项目类别:
Characterize differences in sleep spindles between Clinical High Risk and healthy controls longitudinally.
纵向描述临床高风险组和健康对照组之间睡眠纺锤波的差异。
  • 批准号:
    9750107
  • 财政年份:
    2017
  • 资助金额:
    $ 70.21万
  • 项目类别:
Characterize differences in sleep spindles between Clinical High Risk and healthy controls longitudinally.
纵向描述临床高风险组和健康对照组之间睡眠纺锤波的差异。
  • 批准号:
    10160958
  • 财政年份:
    2017
  • 资助金额:
    $ 70.21万
  • 项目类别:

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