Integrative Neuroscience Unit, Department of Neuroscience, Panum Institute, University of Copenhagen, Copenhagen, Denmark.
Neural Circuits of Disease Laboratory, School of Psychology and Neuroscience, University of St Andrews, St Andrews, United Kingdom.
Front Neural Circuits. 2023 Jul 4;17:1208876. doi: 10.3389/fncir.2023.1208876. eCollection 2023.
Action selection is a capital feature of cognition that guides behavior in processes that range from motor patterns to executive functions. Here, the ongoing actions need to be monitored and adjusted in response to sensory stimuli to increase the chances of reaching the goal. As higher hierarchical processes, these functions rely on complex neural circuits, and connective loops found within the brain and the spinal cord. Successful execution of motor behaviors depends, first, on proper selection of actions, and second, on implementation of motor commands. Thus, pathological conditions crucially affecting the integrity and preservation of these circuits and their connectivity will heavily impact goal-oriented motor behaviors. Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) are two neurodegenerative disorders known to share disease etiology and pathophysiology. New evidence in the field of ALS-FTD has shown degeneration of specific neural circuits and alterations in synaptic connectivity, contributing to neuronal degeneration, which leads to the impairment of motor commands and executive functions. This evidence is based on studies performed on animal models of disease, post-mortem tissue, and patient derived stem cells. In the present work, we review the existing evidence supporting pathological loss of connectivity and selective impairment of neural circuits in ALS and FTD, two diseases which share strong genetic causes and impairment in motor and executive functions.
动作选择是认知的一个重要特征，它指导着从运动模式到执行功能等各种过程中的行为。在这里，正在进行的动作需要根据感官刺激进行监控和调整，以增加达到目标的机会。作为更高层次的过程，这些功能依赖于复杂的神经回路，以及大脑和脊髓内的连接回路。运动行为的成功执行首先取决于动作的正确选择，其次取决于运动指令的执行。因此，严重影响这些回路及其连接完整性和保留的病理状况将严重影响面向目标的运动行为。肌萎缩侧索硬化症（ALS）和额颞叶痴呆症（FTD）是两种已知具有共同疾病病因和病理生理学的神经退行性疾病。ALS-FTD 领域的新证据表明，特定神经回路的退化和突触连接的改变导致神经元退化，从而导致运动指令和执行功能受损。这一证据基于疾病动物模型、尸检组织和患者来源的干细胞研究。在本工作中，我们回顾了现有的证据，支持 ALS 和 FTD 中连接的病理性丧失和神经回路的选择性损伤，这两种疾病具有强烈的遗传原因，并导致运动和执行功能受损。
