Theta burst transcranial magnetic stimulation of fronto-parietal networks: Modulation by mental state

摘要 最近无创脑刺激的发展为探索神经功能提供了新的技术。 并治疗不同的神经精神疾病，但关于刺激如何相互作用仍有许多需要了解 通过大脑网络。我们将为经颅磁刺激(TMS)解决这个问题，TMS是一种强大的 灵活的非侵入性脑刺激，可直接刺激神经元，并可产生持久效应 以及持续时间长于刺激期的神经可塑性变化。我们将研究一种特定类型的TMS， 被称为爆发性刺激(TBS)，它比其他形式的TMS产生更持久的影响，使 TBS是治疗应用的重要工具。虽然TBS提供了相对局部的刺激，但对 大脑通过相互连接的网络以一种鲜为人知的方式发生。此外，刺激是 高度依赖状态，在大多数治疗环境中使用TMS，例如治疗抑郁症， 让精神状态不受控制。通过将心理干预与TMS相结合来增强TMS是一种有吸引力的 改善治疗性TMS的想法，但相关的知识库稀少。为了解决这一关键差距， 这一探索性的R21方案将研究TBS对特定大脑网络和 TBS与心理状态的相互作用。我们将检验广泛的假设，即当应用TBS时 在受控的精神状态下，与精神状态下的刺激相比，网络的变化会更容易 状态不受控制。我们将集中在背外侧前额叶皮质(DlPFC)和相关的额叶- 顶层网络(FPN)，它从属于认知控制--灵活适应和调节行为的能力， 一种已知在抑郁症和痴呆症等神经精神疾病中受损的能力。我们将使用 利用认知控制和FPN的n-back任务。我们将全面评估大脑活动， 三种功能磁共振成像(FMRI)模式：血氧水平依赖(BOLD) 激活将使用n-back任务测量FPN活动，休息状态粗体fMRI将测量连接性 而静息状态的动脉自旋标记(ASL)MRI将测量脑血流。TBS将适用于40 健康受试者分为3组，每组均接受功能磁共振成像检查。分析将利用强大的主体内部 比较。在目标1中，我们将展示持续的由TBS引起的神经变化到dlPFC，与 TBS到顶点，会影响FPN。在目标2中，我们将演示对dlPFC TBS效应的调制 当受试者正在执行n-back任务时，与他们的精神状态相比， 不受约束。在目标3中，我们将测试n-back性能将在TBS到dlPFC之后提高的预测， 但不是大脑皮层顶点，在n-back表现期间，TBS之后会有更大的改善。影响： 结果将提供对TMS对大脑影响的洞察，识别由 TBS，与精神状态互动。展示了这种互动将为以下方面奠定关键基础 未来的研究表明，在TMS期间控制精神状态如何能够改善治疗效果。

Abstract The recent growth of non-invasive brain stimulation has provided new technologies to probe neural function and treat diverse neuropsychiatric conditions, but much remains to be learned about how stimulation interacts with brain networks. We will address this question for transcranial magnetic stimulation (TMS), a powerful and flexible type of non-invasive brain stimulation that directly stimulates neurons and can induce persisting effects and neuroplastic changes which outlast the period of stimulation. We will examine a particular type of TMS, known as theta burst stimulation (TBS), which induces longer lasting effects than other forms of TMS, making TBS an important tool for therapeutic applications. While TBS provides relatively focal stimulation, effects on the brain occur through interconnected networks in ways that are poorly understood. Moreover, stimulation is highly state-dependent, and the use of TMS in most therapeutic settings, such as the treatment of depression, leaves mental state uncontrolled. Augmenting TMS by pairing it with psychological interventions is an attractive idea for improving therapeutic TMS, but the relevant knowledge base is sparse. To address this critical gap, this exploratory R21 proposal will examine the effects of TBS on specific brain networks and the interaction between TBS and mental state. We will test the broad hypothesis that when TBS is applied during a controlled mental state, network changes will be facilitated, compared to stimulation when mental state is uncontrolled. We will focus on the dorsolateral prefrontal cortex (dlPFC) and the associated fronto- parietal network (FPN), which subserves cognitive control -- the ability to flexibly adapt and regulate behavior, an ability known to be impaired in neuropsychiatric conditions such as depression and dementia. We will use an ‘n-back’ task tapping cognitive control and the FPN. We will comprehensively assess brain activity with three functional magnetic resonance imaging (fMRI) modalities: blood oxygenation level-dependent (BOLD) activation will measure FPN activity with the n-back task, resting state BOLD fMRI will measure connectivity and resting state arterial spin labeling (ASL) MRI will measure cerebral perfusion. TBS will be applied to 40 healthy subjects in 3 conditions, each followed by an fMRI session. Analysis will utilize powerful within-subject comparisons. In Aim 1, we will show that persisting neural changes induced by TBS to the dlPFC, compared to TBS to the vertex, will affect the FPN. In Aim 2, we will demonstrate modulation of the effect of dlPFC TBS administered when subjects are performing the n-back task, compared to when their mental state is unconstrained. In Aim 3, we will test predictions that n-back performance will improve following TBS to dlPFC, but not to the cortical vertex, and will improve even more following TBS during n-back performance. Impact: Results will provide insights into the effect of TMS on the brain, identifying a network target manipulated by TBS and interacting with mental state. Demonstrated this interaction will lay critical groundwork for future studies to show how controlling mental state during TMS can improve therapeutic effects.