Subthalamic beta oscillations correlate with dopaminergic degeneration in experimental parkinsonism

Abstract

Excessive beta activity has been shown in local field potential recordings from the cortico-basal ganglia loop of Parkinson's disease patients and in its various animal models. Recent evidence suggests that enhanced beta oscillations may play a central role in the pathophysiology of the disorder and that beta activity may be directly linked to the motor impairment. However, the temporal evolution of exaggerated beta oscillations during the ongoing dopaminergic neurodegeneration and its relation to the motor impairment and histological changes are still unknown. We investigated motor behavioral, in-vivo electrophysiological (subthalamic nucleus, motor cortex) and histological changes (striatum, substantia nigra compacta) 2, 5, 10 and 20-30 days after a 6-hydroxydopamine injection into the medial forebrain bundle in Wistar rats. We found strong correlations between subthalamic beta power and motor impairment. No correlation was found for beta power in the primary motor cortex. Only subthalamic but not cortical beta power was strongly correlated with the histological markers of the dopaminergic neurodegeneration. Significantly increased subthalamic beta oscillations could be detected before this increase was found in primary motor cortex. At the latest observation time point, a significantly higher percentage of long beta bursts was found. Our study is the first to show a strong relation between subthalamic beta power and the dopaminergic neurodegeneration. Thus, we provide additional evidence for an important pathophysiological role of subthalamic beta oscillations and prolonged beta bursts in Parkinson's disease.

Lack of progression of beta dynamics after long‐term subthalamic neurostimulation

“…In animal models of Parkinsonism, it has been demonstrated that increasing beta band power and longer beta bursts are markers of progressive Parkinsonian pathophysiology. [15][16][17][18][19] There have been repeated demonstrations of the short-term effect of therapy (both DBS and medication) on the beta oscillopathy. 7,11,44 The only longitudinal studies to date tracking beta power have been limited to the first year post-DBS and have each shown either a reduction or stability of beta over that time.…”

“…[7][8][9][10][11][12][13][14] Increasing beta power over time is linked to progressive Parkinsonian pathophysiology in neural recordings from both non-human primate and rodent models of progressive Parkinsonism. [15][16][17][18][19] Although a causal link between beta power and PD impairment in humans is still lacking, resting state beta power is greater in the more affected compared to the lesser affected STN, 6 and beta power has been found to increase over time in the untreated STN in two individuals with Parkinson's disease, further suggesting a relationship to disease progression. 20 Beta power was attenuated and burst durations were shortened during short periods of high frequency STN DBS in a dose-dependent manner while improving motor disability 14,21,22 and for a period after STN DBS was turned off, [23][24][25] particularly when neurostimulation targeted the sensorimotor portion of the STN.…”

“… 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 Increasing beta power over time is linked to progressive Parkinsonian pathophysiology in neural recordings from both non‐human primate and rodent models of progressive Parkinsonism. 15 , 16 , 17 , 18 , 19 Although a causal link between beta power and PD impairment in humans is still lacking, resting state beta power is greater in the more affected compared to the lesser affected STN, 6 and beta power has been found to increase over time in the untreated STN in two individuals with Parkinson's disease, further suggesting a relationship to disease progression. 20 …”

State anxiety alters the neural oscillatory correlates of predictions and prediction errors during reward learning

“…A further consideration for future work is the role of dopamine in mediating anxiety-related changes in alpha-beta activity during Bayesian PC. Dopamine is considered a relevant signal encoding the precision of beliefs during reward learning (FitzGerald et al, 2015) and is associated with sensorimotor beta oscillations in research on Parkinson’s (Haumesser et al, 2021; Jenkinson and Brown 2011). Dopamine also plays an important modulatory role in fear and anxiety disorders (de la Mora et al, 2010).…”

Dopamine depletion can be predicted by the aperiodic component of subthalamic local field potentials

“…Since the finding that the subthalamic nucleus (STN) shows exaggerated and synchronized oscillatory activity in the beta frequency range in PD patients 5,6 , the majority of neurophysiological research in this field has postulated beta activity as a stereotypical biomarker across species from animals [7][8][9][10] to PD patients. [11][12][13][14] Abnormal beta power was shown to correlate with the clinical severity of parkinsonian motor symptoms.…”