Hanganu, A. | Search bioRxiv

bioRxiv2025

Distinct Motor Cortex Interneuron Plasticity and Its Association with Prefrontal Brain Volume in Parkinson's Disease

Parkinsons 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 interneuron 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 MRI, then 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. PA TMS showed increased corticospinal excitability at all post-PAS time-points; AP TMS increased only at 30 minutes. 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 show unique neuroplasticity patterns in PwPD and relate to prefrontal brain volume. Our results suggest a complex interplay between motor and cognition-related deficits as interrelated pathophysiological features in PD.

neuroscience↗

bioRxiv2023

Longitudinal brain structure changes in Parkinson's disease: a replication study

ContextAn existing major challenge in Parkinsons disease (PD) research is the identification of biomarkers of disease progression. While Magnetic Resonance Imaging (MRI) is a potential source of PD biomarkers, none of the MRI measures of PD are robust enough to warrant their adoption in clinical research. This study is part of a project that aims to replicate 11 PD studies reviewed in a recent survey (JAMA neurology, 78(10) 2021) to investigate the robustness of PD neuroimaging findings to data and analytical variations. ObjectiveThis study attempts to replicate the results in Hanganu et al. (Brain, 137(4) 2014) using data from the Parkinsons Progression Markers Initiative (PPMI). MethodsUsing 25 PD subjects and 18 healthy controls, we analyzed the rate of change of cortical thickness and of the volume of subcortical structures, and we measured the relationship between MRI structural changes and cognitive decline. We compared our findings to the results in the original study. ResultsSimilarly to the original study, PD patients with mild cognitive impairment (MCI) exhibited increased cortical thinning over time compared to patients without MCI in the right middle temporal gyrus, insula, and precuneus. (2) The rate of cortical thinning in the left inferior temporal and precentral gyri in PD patients correlated with the change in cognitive performance. (3) There were no group differences in the change of subcortical volumes. (4) We did not find a relationship between the change in subcortical volumes and the change in cognitive performance. ConclusionDespite important differences in the dataset used in this replication study, and despite differences in sample size, we were able to partially replicate the original results. We produced a publicly available reproducible notebook allowing researchers to further investigate the reproducibility of the results in Hanganu et al. (2014) when more data becomes available in PPMI.

neuroscience↗