Cortical Control of Movement

描述（由申请人提供）：所有哺乳动物物种（包括人类）的运动皮质包含身体主要部分（如后肢、前肢和面部）的大体躯体位置表征。在每个身体部位内，存在个体运动模式的多个、不连续、部分重叠的表示。因此，运动皮层是由一个分布式网络组成的，在这个网络中，特定的运动从广泛的活动模式中产生。从这些动态网络中塑造自愿运动的神经机制尚不清楚。我们的目标是通过识别在随意运动过程中动态调节皮质运动网络组织的机制来缩小我们知识中的这一根本差距。在运动执行期间，本体感受和触觉传感器提供引导运动的连续输入。有令人信服的证据表明，这些躯体感觉输入作用于运动皮层网络，动态调节其输出。基于我们在大鼠中的初步发现，以及在人类中的研究，我们提出体感传入以中心-环绕方式调节运动皮层活动：来自激活的肌肉的体感刺激增强了对该肌肉的皮层输出（“中心-兴奋”），而对邻近肌肉的皮层输出被抑制（“环绕-抑制”）。我们在目标I中检验这个假设。躯体感觉输入通过两条主要通路到达运动皮层：来自丘脑腹外侧核（VL）的丘脑皮层传入和来自躯体感觉皮层（SCx）的皮质皮层传入。我们建议，丘脑输入提供了广泛的前馈抑制运动皮层的基板。相比之下，皮质输入的特异性表明，它们参与了中枢兴奋增强运动皮层输出到肌肉提供体感输入。我们将在Aim II中直接检验这一假设。躯体感觉传入如何不同地影响同型与异型皮质模块？我们建议，体感传入施加净抑制的运动皮层电路，这样，只有“强”传入输入发生在响应于从VL和SCx会聚输入克服这种抑制激活同型运动皮层神经元。因此，运动中的肢体产生的输入会汇聚并激发激活该肢体的皮层模块，而前馈抑制则主导了对相邻模块的输入。我们将在目标III中检验这一假设。公共卫生相关性：自主运动的执行依赖于皮质运动神经元之间的协调。因此，预期的研究结果解决了运动控制的基本原则。预期发现的一个直接实际应用是神经假体控制器领域，它将来自运动皮层的神经信号与机器人设备耦合。此外，一些神经紊乱与皮质运动模块之间的相互作用的缺陷有关。这些包括运动皮质梗死、肌张力障碍和基底神经节疾病。因此，了解协调运动皮层模块的机制对于理解和改善各种运动障碍的治疗至关重要。

DESCRIPTION (provided by applicant): The motor cortex of all mammalian species, including humans, contains a gross somatotopic representation of the major divisions of the body, such as hindlimb, forelimb, and face. Within each body part, there are multiple, non-contiguous, partially overlapping representations of individual movement patterns. Thus, the motor cortex is comprised of a distributed network in which specific movements emerge from broad patterns of activity. The neural mechanisms that sculpt voluntary movements from these dynamic networks are unknown. Our goal is to narrow this fundamental gap in our knowledge by identifying mechanisms that dynamically regulate the organization of cortical motor networks during voluntary movements. During movement execution, proprioceptive and tactile sensors provide continual inputs that guide the movements. There is compelling evidence that these somatosensory inputs act upon motor cortical networks to dynamically regulate their outputs. Based on our preliminary findings in rats, and on studies in humans, we propose that somatosensory afferents regulate motor cortical activity in a center-surround manner: Somatosensory stimuli from an activated muscle enhance cortical outputs to that muscle ("center-excitation"), whereas cortical outputs to adjacent muscles are suppressed ("surround- inhibition"). We test this hypothesis in Aim I. Somatosensory inputs reach the motor cortex through two major pathways: thalamocortical afferents from the ventral lateral thalami nucleus (VL), and corticocortical afferents from the somatosensory cortex (SCx). We propose that thalamic inputs provide the substrate for extensive feed-forward inhibition in motor cortex. By contrast, the specificity of corticocortical inputs suggests that they are involved in center- excitation - enhancing motor cortical outputs to the muscle providing somatosensory inputs. We will directly test this hypothesis in Aim II. How do somatosensory afferents differentially impact homotypical versus heterotypical cortical modules? We propose that somatosensory afferents exert a net inhibition of motor cortical circuits, such that only `strong' afferent inputs-occurring in response to converging inputs from VL and SCx-overcome this inhibition to activate homotypical motor cortical neurons. As a result, inputs arising from a limb in motion converge upon and excite cortical modules that activate that limb, while feed-forward inhibition dominates inputs to neighboring modules. We will test this hypothesis in Aim III. PUBLIC HEALTH RELEVANCE: The execution of voluntary movements relies on coordination among cortical motor neurons. Thus, the anticipated findings address principles fundamental to motor control. An immediate practical application of the anticipated findings is in the field of neuroprosthetic controllers, which couple neuronal signals from motor cortex with robotic devices. In addition, a number of neurological disturbances are associated with deficits in interactions among cortical motor modules. These include motor cortical infarcts, dystonia, and disorders of the basal ganglia. Knowledge of the mechanisms coordinating motor cortical modules is thus critical to the understanding and improved treatment of a wide range of motor disturbances.