Dryden Barrett, Matsubara Jesse, Wassermann Eric, Forssberg Hans, Damiano Diane L
Neurorehabilitation and Biomechanics Research Section, Rehabilitation Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD, United States of America.
National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, MD, United States of America.
PLoS One. 2025 Jan 9;20(1):e0314173. doi: 10.1371/journal.pone.0314173. eCollection 2025.
Children with cerebral palsy (CP) often participate in training to improve mobility, hand function and other motor abilities. However, responses to these interventions vary considerably across individuals even those with similar brain injuries, ages and functional levels. Dopamine is a neurotrasmitter known to affect motor skill acquistion in animals and humans and may be influenced by individual variations in genes related to brain transmission of dopamine. To evaluate potential genetic influences on learning in young people with and without CP, we calculated individual dopamine-related gene scores and compared these to the ability to learn two different tasks, an implicit sequence learning task and a probablistic classification task. Each task was also administered in an unrewarded condition and a rewarded one known to increase circulating levels of dopamine. The main finding was an interaction between gene score and condition for the sequence task such that those with low gene scores were poorer learners without rewards but responded positively to rewards whereas the converse was true for those with high gene scores. This is the first prospective study in CP suggesting that genetic variability may influence neurorehabilitation outcomes and could potentially be modulated using rewards or medications for those with poorer learning at baseline, thus promoting more personalized approaches to enhancing motor training in CP and other neurological conditions.
患有脑瘫(CP)的儿童经常参与训练以提高活动能力、手部功能及其他运动能力。然而,即使是那些脑损伤、年龄和功能水平相似的个体,对这些干预措施的反应也存在很大差异。多巴胺是一种神经递质,已知其会影响动物和人类的运动技能习得,并且可能受到与多巴胺脑传递相关基因的个体差异的影响。为了评估有无脑瘫的年轻人学习过程中潜在的基因影响,我们计算了个体多巴胺相关基因得分,并将其与学习两项不同任务(一项内隐序列学习任务和一项概率分类任务)的能力进行比较。每项任务也分别在无奖励条件和已知会增加多巴胺循环水平的奖励条件下进行。主要发现是序列任务中基因得分与条件之间存在相互作用,即基因得分低的人在无奖励时学习较差,但对奖励有积极反应,而基因得分高的人情况则相反。这是第一项针对脑瘫的前瞻性研究,表明基因变异性可能影响神经康复结果,对于基线学习较差的患者,可能通过奖励或药物进行调节,从而推动在脑瘫及其他神经系统疾病中采用更个性化的方法来加强运动训练。