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

摘要 近年来，非侵入性脑刺激的发展为探测神经功能提供了新的技术 并治疗各种神经精神疾病，但关于刺激如何相互作用， 大脑网络。我们将解决这个问题的经颅磁刺激（TMS），一个强大的， 一种灵活的非侵入性脑刺激，直接刺激神经元，并可诱导持续效应 和神经可塑性的变化，这些变化持续的时间超过了刺激的时间。我们将研究一种特殊类型的TMS， 被称为theta爆发刺激（TBS），它比其他形式的TMS产生更持久的效果， TBS是治疗应用的重要工具。虽然TBS提供相对集中的刺激，但对 大脑通过相互连接的网络以人们知之甚少的方式发生。此外，刺激是 高度依赖于状态，TMS在大多数治疗环境中的使用，如抑郁症的治疗， 精神状态不受控制通过将TMS与心理干预相结合来增强TMS是一种有吸引力的方法。 改进治疗性TMS的想法，但相关的知识基础是稀疏的。为了弥补这一关键差距， 这项探索性的R21建议将研究TBS对特定大脑网络的影响， TBS与心理状态的相互作用我们将测试广泛的假设，当TBS被应用时， 在受控的精神状态期间，与精神状态时的刺激相比， 国家不受控制。我们将重点关注背外侧前额叶皮层（dlPFC）和相关的额- 顶叶网络（FPN），有助于认知控制-灵活适应和调节行为的能力， 这种能力在神经精神疾病如抑郁症和痴呆症中受损。我们将使用 一个“n-back”任务，利用认知控制和FPN。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） 激活将测量FPN活动与n-back任务，休息状态BOLD功能磁共振成像将测量连接 静息状态动脉自旋标记（ASL）MRI将测量脑灌注。TBS将应用于40个 健康受试者在3种条件下，每一个随后的fMRI会话。分析将利用强大的受试者内 比较。在目标1中，我们将证明，与对照组相比，TBS诱导的dlPFC持续神经变化， TBS到顶点，将影响FPN。在目标2中，我们将证明dlPFC TBS的作用的调制 当受试者执行n-back任务时，与他们的精神状态相比， 无拘无束在目标3中，我们将测试n-back性能将在TBS到dlPFC之后提高的预测， 但不影响皮质顶点，并且在n-back性能期间将在TBS之后得到更大的改善。影响： 结果将提供对TMS对大脑影响的见解，识别由神经网络操纵的网络目标。 TBS和精神状态的相互作用。这种相互作用将为 未来的研究表明，在TMS期间控制精神状态如何提高治疗效果。

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.