Aberrant neurophysiological signaling underlies speech impairments in Parkinson’s disease

Abstract

Difficulty producing intelligible speech is a common and debilitating symptom of Parkinson's disease (PD). Yet, both the robust evaluation of speech impairments and the identification of the affected brain systems are challenging. We examine the spectral and spatial definitions of the functional neuropathology underlying reduced speech quality in patients with PD using a new approach to characterize speech impairments and a novel brain-imaging marker. We found that the interactive scoring of speech impairments in PD (N=59) is reliable across non-expert raters, and better related to the hallmark motor and cognitive impairments of PD than automatically-extracted acoustical features. By relating these speech impairment ratings to neurophysiological deviations from healthy adults (N=65), we show that articulation impairments in patients with PD are robustly predicted from aberrant activity in the left inferior frontal cortex, and that functional connectivity of this region with somatomotor cortices mediates the influence of cognitive decline on speech deficits.

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

“…After decades of literature suggesting a pathological shift in neurophysiological signal power from high to low frequencies in patients with neurodegenerative disorders 10-12,39-41,75-84 , recent advances in capturing these multi-spectral effects have documented their anatomical distribution and relevance to clinical features 19,42,52 . In the current work, we advance this line of research in patients with Parkinson’s disease using a marker of neurophysiological slowing that recently showed associations with cognitive impairments and amyloid proteinopathy in patients with Alzheimer’s disease 52 .…”

“…This has led to a hypothesized slowing of brain activity in patients with PD, but it remains unclear whether such a neurophysiological effect relates to clinical features of the disease, and whether any such relationships are of a deleterious or compensatory nature. These multi-spectral deviations from healthy levels also comprise rhythmic and/or arrhythmic components 43-46 , for which clinical interpretation and significance for frequency-specific neuromodulation therapies remain to be established in PD 19,42,47-51 .…”

“…Neurophysiological indicators of PD pathophysiology include frequency-specific components of the rich spectrum of brain electrophysiology. Notably, beta-band (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) activity is hypersynchronous across the cortico-basal ganglia circuit in patients with PD 17,[29][30][31][32][33] , relates to severity of motor dysfunction, and can be normalized by common therapeutics [34][35][36][37][38] . In the cortex of patients with PD, decades of electrophysiological studies have demonstrated a stereotyped pattern of frequency-defined neural changes relative to healthy adults, including both increased activity in low-frequency bands (e.g., delta [2][3][4] and theta [5][6][7]) and concurrent decreased power in high-frequency bands (e.g., alpha [8][9][10][11][12] and beta) 12,[39][40][41][42] .…”

“…Changes in cortical signaling are also well-documented in PD, yet the functional consequences of these cortical aberrations are not entirely clear. Some research has suggested that they convey compensatory effects (i.e., greater changes relative to healthy controls relating to better clinical outcomes) while others have instead indicated that they are deleterious [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] . These effects may not be mutually exclusive.…”

Spontaneous cortical dynamics from the first years to the golden years

“…The advent of resting-state neuroimaging has provided a window into dynamic functional architectures underlying a myriad of processes, including brain development, aging, disease states, and psychopathology ( 1 – 10 ). Resting-state brain activity has been extensively captured and described using a range of neuroimaging techniques including functional MRI based on the blood oxygenation-level dependent signal, as well as methods examining the oscillatory dynamics of resting-state activity (i.e., spontaneous cortical activity), such as electroencephalography (EEG) and magnetoencephalography (MEG), which provide exquisite temporal resolution.…”