Modulating arousal to overcome gait impairments in Parkinson ’s disease: how the noradrenergic system may act as a double-edged sword

AbstractIn stressful or anxiety-provoking situations, most people with Parkinson ’s disease (PD) experience a general worsening of motor symptoms, including their gait impairments. However, a proportion of patients actually report benefits from experiencing—or even purposely inducing—stressful or high-arousal situations. Using data from a large-scale international survey s tudy among 4324 people with PD and gait impairments within the online Fox Insight (USA) and ParkinsonNEXT (NL) cohorts, we demonstrate that individuals with PD deploy an array of mental state alteration strategies to cope with their gait impairment. Crucially, these strategies differ along an axis o f arousal—some act to heighten, whereas others diminish, overall sympathetic tone. Together, our observations suggest that arousal may act as a double-edged sword for gait control in PD. We propose a theoretical, neurobiological framework to explain why heightened arousal can have detrimental effe cts on the occurrence and severity of gait impairments in some individuals, while alleviating them in others. Specifically, we postulate that this seemingly contradictory phenomenon is explained by the inherent features of the ascending arousal system: namely, that arousal is related to task perform ance by an inverted u-shaped curve (the so-called Yerkes and Dodson relationship). We propose that the noradrenergic locus coeruleus plays an important role in modulating PD symptom severity and expression, by regul...
Source: Translational Neurodegeneration - Category: Neurology Source Type: research