A sagittal gradient of pathological and compensatory effects of neurophysiological slowing in Parkinson’s disease

Abstract

AbstractUsing magnetoencephalographic imaging and extensive clinical and neuropsychological assessments, we show that patients with Parkinson’s disease (PD; N = 79) exhibit a slowing of neurophysiological activity relative to healthy adults (N = 65), which relates to motor and cognitive abilities. Importantly, the association between neurophysiological slowing and PD clinical features varies systematically across the cortex along a sagittal gradient: cortical slowing is associated with worse impairment in dorsal-posterior cortices, and this association is reversed in ventral-anterior cortical regions. This pathological-to- compensatory anatomical gradient is sensitive to differences in patients’ individual clinical profiles, and co- localizes with normative atlases of neurotransmitter receptor/transporter density. Long-range functional connectivity between posterior regions and parietal and frontal cortices is also significantly shifted towards lower frequencies in PD, demonstrating a novel network-level slowing effect. Taken together, these findings demonstrate the multifaceted nature of neurophysiological slowing in patients with PD, with anatomically-dependent clinical relevance to motor and cognitive symptoms.