Exercise-enhanced neuroplasticity targeting motor and cognitive circuitry in Parkinson's disease

Abstract

Exercise interventions in individuals with Parkinson's disease incorporate goal-based motor skill training to engage cognitive circuitry important in motor learning. With this exercise approach, physical therapy helps with learning through instruction and feedback (reinforcement) and encouragement to perform beyond self-perceived capability. Individuals with Parkinson's disease become more cognitively engaged with the practice and learning of movements and skills that were previously automatic and unconscious. Aerobic exercise, regarded as important for improvement of blood flow and facilitation of neuroplasticity in elderly people, might also have a role in improvement of behavioural function in individuals with Parkinson's disease. Exercises that incorporate goal-based training and aerobic activity have the potential to improve both cognitive and automatic components of motor control in individuals with mild to moderate disease through experience-dependent neuroplasticity. Basic research in animal models of Parkinson's disease is beginning to show exercise-induced neuroplastic effects at the level of synaptic connections and circuits.

Figure 1. Cognitive and Automatic Motor Control

Motor control incorporates multiple cortical and subcortical structures. Most important are the connections between the basal ganglia and cortex that are involved in cognitive and automatic aspects of motor control. In PD, loss of DA in the caudal basal ganglia leads to impaired automatic movements involving circuits important in stimulus based habitual learning (red arrows) and over-reliance on cognitive components of motor control and circuits involved in reward based learning (blue arrows).

Figure 2. Exercise and Neuroprotection and Neurorestoration in Rodent Models of PD

The figure highlights some reported benefits of the effects of exercise in rodent PD neurotoxin models. The left panel indicates exercise effects when exercise is delivered either before or during the period of toxin-induced (6-OHDA, or MPTP) dopaminergic cell death. Intensive exercise promotes elevation of neurotrophic factors, such as BDNF, and protects from toxin-induced striatal DA depletion and cell loss of SNpc neurons. These findings are consistent with epidemiological data reporting the effect of intensive exercise in lowering the risk for PD. The right panel indicates exercise effects when exercise is administered days to weeks after toxin-induced dopaminergic cell death. Studies suggest that intensive exercise may strengthen motor (dorsal basal ganglia) circuits and behavioral performance through mechanisms that include improved DA and glutamate neurotransmission and global brain health. These data are consistent with the potential role of exercise in modifying the course of PD.

Figure 3. Exercise and Neuroplasticity in PD

Clinical and basic research studies support the effects of exercise on neuroplasticity in PD. Neuroplasticity is a process by which the brain encodes experiences and learns new behaviors and is defined as the modification of existing neural networks by adding or modifying synapses. Evidence is accumulating that both goal directed and aerobic exercise may strengthen and improve motor circuitry through mechanisms that include but are not limited to alterations in DA and glutamate neurotransmission, as well as structural modifications of synapses. In addition, exercise may promote neuroprotection of substantia nigra neurons and their existing connections. Finally, exercise-induced alterations in blood flow and general brain health may promote conditions for neuroplasticity important for facilitating motor skill learning, including cognitive and automatic motor control and overall behavioral performance. While more studies are clearly needed, taken together these findings are supportive of a disease modifying effect of exercise in PD.