Interrogating basal ganglia circuit function in people with Parkinson's disease and dystonia.

Background: The dichotomy between the hypo- versus hyperkinetic nature of Parkinson's disease (PD) and dystonia, respectively, is thought to be reflected in the underlying basal ganglia pathophysiology. In this study, we investigated differences in globus pallidus internus (GPi) neuronal activity, and short- and long-term plasticity of direct pathway projections. Methods: Using microelectrode recording data collected from the GPi during deep brain stimulation surgery, we compared neuronal spiketrain features between people with PD and those with dystonia, as well as correlated neuronal features with respective clinical scores. Additionally, we characterized and compared readouts of short- and long-term synaptic plasticity using measures of inhibitory evoked field potentials. Results: GPi neurons were slower, bustier, and less regular in dystonia. In PD, symptom severity positively correlated with the power of low-beta frequency spiketrain oscillations. In dystonia, symptom severity negatively correlated with firing rate and positively correlated with neuronal variability and the power of theta frequency spiketrain oscillations. Dystonia was moreover associated with less long-term plasticity and slower synaptic depression. Conclusions: We substantiated claims of hyper- versus hypofunctional GPi output in PD versus dystonia, and provided cellular-level validation of the pathological nature of theta and low-beta oscillations in respective disorders. Such circuit changes may be underlain by disease-related differences in plasticity of striato-pallidal synapses. Funding: This project was made possible with the financial support of Health Canada through the Canada Brain Research Fund, an innovative partnership between the Government of Canada (through Health Canada) and Brain Canada, and of the Azrieli Foundation (LM), as well as a grant from the Banting Research Foundation in partnership with the Dystonia Medical Research Foundation (LM).

Improvement in executive function for older adults through smartphone apps: a randomized clinical trial comparing language learning and brain training.

Bilingualism has been linked to improved executive function and delayed onset of dementia, but it is unknown whether similar benefits can be obtained later in life through deliberate intervention. Given the logistical hurdles of second language acquisition in a randomized trial for older adults, few interventional studies have been done thus far. However, recently developed smartphone apps offer a convenient means to acquire skills in a second language and can be compared with brain training apps specifically designed to improve executive function. In a randomized clinical trial, 76 adults aged 65-75 were assigned to either 16 weeks of Spanish learning using the app Duolingo 30 minutes a day, an equivalent amount of brain training using the app BrainHQ, or a waitlist control condition. Executive function was assessed before and after the intervention with preregistered (NCT03638882) tests previously linked to better performance in bilinguals. For two of the primary measures: incongruent Stroop color naming and 2-back accuracy, Duolingo provided equivalent benefits as BrainHQ compared to a control group. On reaction time for N-back and Simon tests, the BrainHQ group alone experienced strong gains over the other two groups. Duolingo was rated as more enjoyable. These results suggest that app-based language learning may provide some similar benefits as brain training in improving executive function in seniors but has less impact on processing speed. However, future advancements in app design may optimize not only the acquisition of the target language but also the side benefits of the language learning experience.