Side of motor symptom onset predicts sustained attention deficits and motor improvements after attention training in Parkinson's disease.

OBJECTIVE: Parkinson's disease (PD) side of motor symptom onset has been associated with distinct cognitive deficits; individuals with left-side onset (LPD) show more visuospatial impairments, whereas those with right-side onset (RPD) show more verbal impairments. Non-spatial attention is a critical cognitive ability associated with motor functioning that is right hemisphere lateralized but has not been characterized with regard to PD side of onset. We compared individuals with LPD and RPD on non-spatial attention tasks and examined differential responses to a 4-week sustained attention training program. METHOD: Participants included 9 with LPD and 12 with RPD, who performed both brief and extended go/no-go continuous performance tasks and an attentional blink task. Participants also engaged in an at-home sustained attention training program, Tonic and Phasic Alertness Training (TAPAT), 5 days/week for 4 weeks. We assessed cognitive and motor symptoms before and after training, and after a 4-week no-contact period. RESULTS: At baseline, participants with LPD exhibited worse performance than those with RPD on the extended continuous performance task, indicating specific deficits in sustaining attention. Poorer attention was associated with worse clinical motor scores. Notably, side of onset had a significant effect on clinical motor changes after sustained attention training, with only LPD participants improving after training, and 4/9 showing clinically meaningful improvements. CONCLUSIONS: Compared to RPD, participants with LPD had poorer sustained attention pre-training and were more likely to improve on clinical motor functioning after sustained attention training. These findings support mechanistic differences between LPD and RPD and suggest potential differential treatment approaches.

Effects of levetiracetam on axon excitability and synaptic transmission at the crayfish neuromuscular junction.

Levetiracetam (LEV) is a widely prescribed antiepileptic drug, but its actions on neuronal function are not fully characterized. Since this drug is believed to enter neurons by binding to a vesicular protein during endocytosis, we used motor axons of the crayfish opener neuromuscular junction to examine potential impacts of LEV on axon excitability. Two electrode current clamp from the inhibitory axon of the opener showed that LEV reduced action potential (AP) amplitude (APamp ) and suppressed synaptic transmission, although the latter occurred with a longer delay than the reduction in APamp . Comparison of antidromic and orthodromic conducting APs in LEV suggested that this drug preferentially reduced excitability of the proximal axon, despite the expectation that it entered the axon at the terminals and should affect the distal branches first. Results presented here suggest that LEV modulates axonal excitability, which may in turn contribute to its antiepileptic effects.