• People with Parkinson’s disease (PwPD) display unique motor interneuron plasticity after paired-associative stimulation (PAS). • Prefrontal brain volume accounts for unique variance in PAS-induced motor interneuron plasticity in PwPD. • Motor cortex interneuron plasticity and prefrontal brain volume are potentially important pathophysiological features of PD. Parkinson’s disease (PD) is characterized by motor and cognitive deficits, including abnormal primary motor cortex (M1) excitability and diminished sensorimotor neuroplasticity. While paired associative stimulation (PAS) can induce M1 plasticity, people with PD (PwPD) demonstrate variability that cannot be accounted for by disease progression or medication status. Distinct M1 interneurSon populations and attention-related brain structures may influence the reduced PAS-induced neuroplasticity. We aimed to characterize M1 interneuron plasticity in PwPD using attention-modulated PAS and identify neurostructural correlates. PwPD underwent an MRI, followed by a PAS protocol with task-relevant attention. Transcranial magnetic stimulation (TMS) assessments of corticospinal excitability using posterior-to-anterior (PA) and anterior-to-posterior (AP) current directions were employed before and three post-PAS time-points. PAS induced distinct time-dependent M1 interneuron excitability changes. At 110% RMT, PA TMS showed increased corticospinal excitability at all post-PAS time points; AP TMS increased only at 30-min post. In contrast, 130% RMT revealed a substantial increase in corticospinal excitability for both current directions post-PAS, indicating a general enhancement in M1 plasticity. Rostral middle frontal gyrus volume uniquely explained variance in PA-sensitive M1 interneuron plasticity. In contrast, AP-sensitive plasticity was associated with baseline AP TMS excitability and age. These findings highlight that M1 interneuron circuits exhibit unique neuroplasticity patterns in PwPD and are associated with prefrontal brain volume. Significance : Our results suggest a complex interplay between motor and cognition-related deficits as interrelated pathophysiological features in PD.
O’Farrell et al. (Sun,) studied this question.