Neuromodulation of Cognitive Control Neurocircuits for Stroke Rehabilitation

近70%的慢性中风患者至少在一个认知领域存在损害。其中许多赤字 是微妙的，没有由治疗师直接评估，但却是实现最佳康复的障碍。而当 认知缺陷可以被解析为独特的子域(例如，工作记忆、反应抑制、SET 不同的流程由一个共同的神经网络支持：多需求网络(MDN)。 MDN由“核心”节点组成：双侧背外侧(DlPFC)和腹外侧额前皮质， 顶内沟、前补充运动区、背侧前扣带回和双侧脑岛。这个 左侧dlPFC节点包括通常作为治疗性重复经颅磁刺激目标的部位 (RTMS)治疗抑郁症。因此，据报道，认知能力的改善是一种 治疗神经精神障碍和多种神经疾病的左侧dlpfc的rtms 包括轻到中度的认知障碍、痴呆症以及阿尔茨海默氏症和帕金森氏症。 使用rTMS靶向这一认知网络可能是一种卓有成效的、创新的认知辅助治疗方法。 慢性卒中的康复治疗。此外，也是该网络中的节点的preSMA很容易 TMS可访问。由于它完整地参与了电机控制，它可能是一个特别有希望的目标 纠正缺陷，因为它可能会影响认知和运动控制。在进行临床试验之前 MDN引导下的rTMS作为卒中患者的治疗工具，确定其功能完整性至关重要 慢性卒中患者的MDN。目的1是测试慢性卒中患者是否参与MDN 类似于内源性认知任务的控制参与者的方式，特别是工作记忆和 反应抑制。虽然这两个任务都激活了MDN，但反应抑制优先激活了 前SMA。此外，反应抑制代表了认知和运动控制的交集， 强调其在慢性卒中患者功能恢复中的相关性。评估这两项任务将提供 关于跨任务域的MDN功能完整性的信息，以及前SMA缺陷是否 特别突出。目标2是确定MDN的这两个节点中的哪一个(dlPFC与preSMA) 显示出较强的MDN激活。这将通过将一系列TMS脉冲施加到每个 当参与者在MRI扫描仪中时的位置，即并发TMS-FMRI，这是第一个 由南卡罗来纳州医科大学研发。这些内源性和内源性的结果 外源探针将用于确定哪个部位更有希望改善认知 通过rTMS。

Nearly 70% of chronic stroke patients have impairment in at least one cognitive domain. Many of these deficits are subtle, not directly assessed by therapists, and yet are barriers to achieving optimal recovery. While cognitive deficits can be parsed into unique subdomains (e.g., working memory, response inhibition, set shifting), diverse processes are supported by a common neural network: the Multiple Demand Network (MDN). The MDN consists of ‘core’ nodes: bilateral dorsolateral (dlPFC) and ventrolateral prefrontal cortex, intraparietal sulcus, pre-supplementary motor area (preSMA), dorsal anterior cingulate and bilateral insula. The left dlPFC node includes the site typically targeted with therapeutic repetitive transcranial magnetic stimulation (rTMS) for depression. Thus, it is not surprising that cognitive improvements have been a reported outcome of therapeutic rTMS to left dlPFC among neuropsychiatric disorders and a wide range of neurological conditions including mild to moderate cognitive impairment, dementia, and Alzheimer’s and Parkinson’s diseases. Targeting this cognitive network with rTMS may be a fruitful and innovative therapeutic adjuvant for cognitive rehabilitation in chronic stroke. Additionally, the preSMA, which also is a node in this network, is easily accessible to TMS. Since it is integrally involved in motor control, it could be an especially promising target for remediating deficits as it may affect both cognitive and motor control. Before proceeding to a clinical trial of MDN-guided rTMS as a therapeutic tool for stroke patients, it is critical to determine the functional integrity of the MDN in chronic stroke patients. Aim 1 is to test whether chronic stroke patients engage the MDN in a manner similar to control participants for endogenous cognitive tasks, specifically working memory and response inhibition. While these tasks both engage the MDN, response inhibition preferentially activates the preSMA. Furthermore, response inhibition represents the intersection of cognitive and motor control, underscoring its relevance in functional recovery in chronic stroke. Assessing both tasks will provide information on MDN functional integrity across task domains, as well as whether preSMA deficits are particularly prominent. Aim 2 is to determine which of these two nodes of the MDN (dlPFC versus preSMA) shows stronger activation of the MDN. This will be achieved by applying a series of TMS pulses to each location while the participant is in the MRI scanner, i.e., concurrent TMS-fMRI, a unique tool that was first developed here at the Medical University of South Carolina. The results from these endogenous and exogenous probes will be used to determine which site is a more promising target for cognitive improvement via rTMS.