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Background The objective of this study was to examine the effects of aerobic exercise on evoked dopamine release and activity of the ventral striatum using positron emission tomography and functional magnetic resonance imaging in Parkinson's disease (PD). Methods Thirty‐five participants were randomly allocated to a 36‐session aerobic exercise or control intervention. Each participant underwent an functional magnetic resonance imaging scan while playing a reward task before and after the intervention to determine the effect of exercise on the activity of the ventral striatum in anticipation of reward. A subset of participants (n = 25) completed [11C] raclopride positron emission tomography scans to determine the effect of aerobic exercise on repetitive transcranial magnetic stimulation‐evoked release of endogenous dopamine in the dorsal striatum. All participants completed motor (MDS‐UPDRS part III, finger tapping, Timed‐up‐and‐go) and nonmotor assessments (Starkstein Apathy Scale, Beck Depression Inventory, reaction time, Positive and Negative Affect Schedule, Trail Making Test [A and B], and Montreal Cognitive Assessment) before and after the interventions. Results The aerobic group exhibited increased activity in the ventral striatum during functional magnetic resonance imaging in anticipation of 75% probability of reward (P = 0.01). The aerobic group also demonstrated increased repetitive transcranial magnetic stimulation‐evoked dopamine release in the caudate nucleus (P = 0.04) and increased baseline nondisplaceable binding potential in the posterior putamen of the less affected repetitive transcranial magnetic stimulation‐stimulated hemisphere measured by position emission tomography (P = 0.03). Conclusions Aerobic exercise alters the responsivity of the ventral striatum, likely related to changes to the mesolimbic dopaminergic pathway, and increases evoked dopamine release in the caudate nucleus. This suggests that the therapeutic benefits of exercise are in part related to corticostriatal plasticity and enhanced dopamine release. © 2019 International Parkinson and Movement Disorder Society

The ultimate goal of upper-limb rehabilitation after stroke is to promote real-world use, that is, use of the paretic upper-limb in everyday activities outside the clinic or laboratory. Although real-world use can be collected through self-report questionnaires, an objective indicator is preferred. Accelerometers are a promising tool. The current paper aims to explore the feasibility of accelerometers to measure upper-limb use after stroke and discuss the translation of this measurement tool into clinical practice. Accelerometers are non-invasive, wearable sensors that measure movement in arbitrary units called activity counts. Research to date indicates that activity counts are a reliable and valid index of upper-limb use. While most accelerometers are unable to distinguish between the type and quality of movements performed, recent advancements have used accelerometry data to produce clinically meaningful information for clinicians, patients, family and care givers. Despite this, widespread uptake in research and clinical environments remains limited. If uptake was enhanced, we could build a deeper understanding of how people with stroke use their arm in real-world environments. In order to facilitate greater uptake, however, there is a need for greater consistency in protocol development, accelerometer application and data interpretation.

Experience-dependent structural changes are widely evident in gray matter. Using diffusion weighted imaging (DWI), the neuroplastic effect of motor training on white matter in the brain has been demonstrated. However, in humans it is not known whether specific features of white matter relate to motor skill acquisition or if these structural changes are associated to functional network connectivity. Myelin can be objectively quantified in vivo and used to index specific experience-dependent change. In the current study, seventeen healthy young adults completed ten sessions of visuomotor skill training (10,000 total movements) using the right arm. Multicomponent relaxation imaging was performed before and after training. Significant increases in myelin water fraction, a quantitative measure of myelin, were observed in task dependent brain regions (left intraparietal sulcus [IPS] and left parieto-occipital sulcus). In addition, the rate of motor skill acquisition and overall change in myelin water fraction in the left IPS were negatively related, suggesting that a slower rate of learning resulted in greater neuroplastic change. This study provides the first evidence for experience-dependent changes in myelin that are associated with changes in skilled movements in healthy young adults.

In individuals with multiple sclerosis (MS), transcranial magnetic stimulation (TMS) may be employed to assess the integrity of corticospinal system and provides a potential surrogate biomarker of disability. The purpose of this study was to provide a comprehensive examination of the relationship between multiple measures corticospinal excitability and clinical disability in MS (expanded disability status scale (EDSS)). Bilateral corticospinal excitability was assessed using motor evoked potential (MEP) input–output (IO) curves, cortical silent period (CSP), short-interval intracortical inhibition (SICI), intracortical facilitation (ICF) and transcallosal inhibition (TCI) in 26 individuals with MS and 11 healthy controls. Measures of corticospinal excitability were compared between individuals with MS and controls. We evaluated the relationship(s) between age and clinical demographics such as age at MS onset (AO), disease duration (DD) and clinical disability (EDSS) with measures of corticospinal excitability. Corticospinal excitability thresholds were higher, MEP latency and CSP onset delayed and MEP durations prolonged in individuals with MS compared to controls. Age, DD and EDSS correlated with corticospinal excitability thresholds. Also, TCI duration and the linear slope of the MEP amplitude IO curve correlated with EDSS. Hierarchical regression modeling demonstrated that combining multiple TMS-based measures of corticospinal excitability accounted for unique variance in clinical disability (EDSS) beyond that of clinical demographics (AO, DD). Our results indicate that multiple TMS-based measures of corticospinal and interhemispheric excitability provide insights into the potential neural mechanisms associated with clinical disability in MS. These findings may aid in the clinical evaluation, disease monitoring and prediction of disability in MS.

This case report demonstrates potential short-term adaptations in compensatory stepping reactions following perturbation training in an individual with stroke. Future work should investigate the links between improved compensatory step characteristics and fall risk in this vulnerable population.

TMS-evoked cortical responses can be measured using simultaneous electroencephalography (TMS-EEG) to directly quantify cortical connectivity in the human brain. The purpose of this study was to evaluate interhemispheric cortical connectivity between the primary motor cortices (M1s) in participants with chronic stroke and controls using TMS-EEG. Ten participants with chronic stroke and four controls were tested. TMS-evoked responses were recorded at rest and during a typical TMS assessment of transcallosal inhibition (TCI). EEG recordings from peri-central gyral electrodes (C3 and C4) were evaluated using imaginary phase coherence (IPC) analyses to quantify levels of effective interhemispheric connectivity. Significantly increased TMS-evoked beta (15–30 Hz frequency range) IPC was observed in the stroke group during ipsilesional M1 stimulation compared to controls during TCI assessment but not at rest. TMS-evoked beta IPC values were associated with TMS measures of transcallosal inhibition across groups. These results suggest TMS-evoked EEG responses can index abnormal effective interhemispheric connectivity in chronic stroke.

Background Conventionally, change in motor performance is quantified with discrete measures of behaviour taken pre- and post-practice. As a high degree of movement variability exists in motor performance after stroke, pre- and post-testing of motor skill may lack sensitivity to predict potential for motor recovery. Objective Evaluate the use of predictive models of motor learning based on individual performance curves and clinical characteristics of motor function in individuals with stroke. Methods Ten healthy and fourteen individuals with chronic stroke performed a continuous joystick-based tracking task over 6 days, and at a 24 hour delayed retention test, to assess implicit motor sequence learning. Results Individuals with chronic stroke demonstrated significantly slower rates of improvements in implicit sequence-specific motor performance compared to a healthy control (HC) group when root mean squared error (RMSE) performance data were fit to an exponential function. The HC group showed a positive relationship between a faster rate of change in implicit sequence-specific motor performance during practice and superior performance at the delayed retention test. The same relationship was shown for individuals with stroke only after accounting for overall motor function by including Wolf Motor Function Test (WMFT) rate in our model. Conclusion Nonlinear information extracted from multiple time points across practice, specifically the rate of motor skill acquisition during practice, relates strongly with changes in motor behaviour at the retention test following practice and could be used to predict optimal doses of practice on an individual basis.