Paydar Afshin, Khorasani Laila, Harris Neil G
UCLA Brain Injury Research Center, Department of Neurosurgery, Geffen Medical School, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
Intellectual Development and Disabilities Research Center, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
bioRxiv. 2024 Aug 6:2024.08.02.606449. doi: 10.1101/2024.08.02.606449.
Although the behavioral outcome of Constraint-Induced Movement Therapy (CIMT) is well known, and that a combination of CIMT and arm use training potentiates the effect, there has been limited study of the brain circuits involved that respond to therapy. An understanding of CIMT from a brain network level would be useful for guiding the duration of effective therapy, the type of training regime to potentiate the outcome, as well as brain regional targets that might be amenable for direct neuromodulation. Here we investigated the effect of CIMT therapy alone unconfounded by additional rehabilitation training in order to determine the impact of intervention at the circuit level. Adult rats were injured by controlled cortical impact injury and studied before and then after 2wks of CIMT or noCIMT at 1-3wks post-injury using a combination of forelimb behavioral tasks and task-based and resting state functional magnetic resonance imaging at 3 and 7wks post-injury and compared to sham rats. There was no difference in behavior or functional imaging between CIMT and noCIMT after injury before intervention so that data are unlikely to be confounded by differences in injury severity. CIMT produced only a transient reduction in limb deficits compared to noCIMT immediately after the intervention, but no difference thereafter. However, CIMT resulted in a persistent reduction in contralesional limb-evoked activation and a corresponding ipsilesional cortical plasticity compared to noCIMT that endured 4wks after intervention. This was associated with a significant amelioration of intra and inter-hemispheric connectivity present in the noCIMT group at 7wks post-injury.
尽管强制性使用运动疗法（CIMT）的行为效果已广为人知，且CIMT与手臂使用训练相结合可增强疗效，但对于响应该疗法的相关脑回路的研究却很有限。从脑网络层面理解CIMT，将有助于指导有效治疗的时长、增强疗效的训练方案类型，以及可能适合直接神经调节的脑区靶点。在此，我们研究了单纯CIMT疗法的效果，排除了额外康复训练的干扰，以确定在回路层面进行干预的影响。成年大鼠通过控制性皮质撞击损伤造模，在损伤后1 - 3周接受2周的CIMT或非CIMT治疗，治疗前后分别采用前肢行为任务以及基于任务和静息状态的功能磁共振成像进行研究，并在损伤后3周和7周与假手术大鼠进行比较。在干预前，CIMT组和非CIMT组在行为或功能成像方面没有差异，则数据不太可能因损伤严重程度的差异而混淆。与非CIMT组相比，干预后立即进行CIMT治疗仅使肢体缺陷有短暂减轻，但此后并无差异。然而，与非CIMT组相比，CIMT导致对侧肢体诱发激活持续减少，同侧皮质可塑性相应增加，且这种情况在干预后持续4周。这与损伤后7周非CIMT组存在的半球内和半球间连接性显著改善有关。
