Neuromodulation of Cognitive Control Neurocircuits for Stroke Rehabilitation

近70%的慢性脑卒中患者至少有一个认知领域受损。这些赤字中有许多 是微妙的，不直接评估的治疗师，但障碍，以实现最佳恢复。而 认知缺陷可以被解析成独特的子域（例如，工作记忆，反应抑制，集合 不同的过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）和腹外侧前额叶皮层， 顶叶内沟、前辅助运动区（pre-supplementary motor area，preSMA）、扣带回背侧前区和双侧背外侧区。的 左侧dlPFC淋巴结包括治疗性重复经颅磁刺激通常靶向的部位 （rTMS）抑郁症。因此，这并不奇怪，认知改善已被报道的结果， 在神经精神疾病和各种神经系统疾病中对左侧dlPFC进行治疗性rTMS 包括轻度至中度认知障碍、痴呆、阿尔茨海默氏症和帕金森氏症。 用rTMS靶向这一认知网络可能是认知障碍的一种富有成效的创新性治疗辅助手段。 慢性中风的康复治疗此外，也是该网络中的节点的preSMA很容易被 可进入TMS。由于它与运动控制密切相关，因此它可能是一个特别有前途的目标， 补救缺陷，因为它可能影响认知和运动控制。在进行临床试验之前， MDN引导的rTMS作为脑卒中患者的治疗工具，关键是确定 慢性脑卒中患者的MDN。目的1是测试慢性中风患者是否在一个 方式类似于控制参与者的内源性认知任务，特别是工作记忆， 反应抑制虽然这些任务都涉及MDN，但反应抑制优先激活MDN。 前SMA。此外，反应抑制代表了认知和运动控制的交叉点， 强调了其在慢性卒中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，以及是否 特别突出。目的2是确定MDN的这两个节点中的哪一个（dlPFC与preSMA） 显示出MDN的更强激活。这将通过将一系列TMS脉冲施加到每个 当受试者在MRI扫描仪中时，即，并行TMS功能磁共振成像，一个独特的工具， 是在南卡罗来纳州的医科大学发展起来的。这些内源性和 外源性探针将用于确定哪个位点是更有希望的认知改善靶点 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.