Abstract : Cerebral palsy is a heterogeneous group of neurodevelopmental disorders associated with lifelong motor impairment and disability. Current evidence based intervention programs are capitalizing on neuroplasticity of the undamaged brain to improve motor functions, by engaging individuals in active motor learning and training. An interesting observation in underlying clinical studies have been the large inter-individual variation in treatment response; an intervention that is effective for one child may not be effective for another.

Advances in neuroimaging technologies have provided opportunity to identify neural circuits in the human brain involved in motor skill learning, and new insights into how the brain is functionally re-organized during different phases of motor learning. These studies have revealed that the initial fast phase of motor skill learning is highly dynamic and associated with alteration of the activity in a bilateral network including frontal and parietal sensory and motor cortices, dorsomedial striatum, and posterior cerebellum.

Dopamine signalling is an essential component of many brain functions, including motor control and plasticity. Rodent studies have demonstrated that mesocortical dopaminergic pathways from the ventral tegmental area to the motor cortex are involved in skilled motor learning and associated synaptic plasticity, suggesting that the motor cortex requires an optimal level of dopamine for learning new motor skills The role of dopamine signalling is further corroborated by the association between acquisition of new motor skills and changes in the intracellular cAMP/PKA/DARPP-32 pathway; inhibition of this pathway impairs motor learning. A naturally occurring genetic variation in the rodent mesocortical dopamine system parallels differences in motor skill learning and plasticity.

Human studies indicate that functional polymorphisms in genes encoding for dopamine receptors, and dopamine transporter and degradation enzymes, contribute to inter-individual differences in learning and cognitive performance; polymorphisms that reduce dopamine transmission are associated with poorer function. Gene scores reflecting the collective effects of five dopamine polymorphisms associated with synaptic dopamine availability (COMT and DAT) and dopamine receptor binding (DRD1, DRD2, DRD3) affected motor learning in adults; individuals with higher dopamine scores, corresponding to higher dopaminergic neurotransmission, had better motor learning rates. In a recent proof-of-principle study, it was demonstrated for the first time, that the naturally occurring genetic variation in the dopamine system influenced treatment outcomes in children with cerebral palsy. A polygenic dopamine score might be valid for treatment outcome prediction and for designing individually tailored interventions for children with cerebral palsy, but also for other motor disorders using activity based interventions.