Preclinical Data Suggest Beta Activity May Influence Daytime Wakefulness in Parkinson Disease

A recently published preclinical study reported that beta oscillatory activity in the cortico-basal ganglia network was associated with daytime vigilance in a pair of nonhuman primates, with low- and high-beta frequencies showing opposing relationships with wakefulness. Published in Communications Biology, these findings suggest that the modulation of specific beta frequency bands could pssobily influence the ability to sustain wakefulness in Parkinson disease (PD).¹

In both study animals, findings showed that the subthalamic nucleus (STN) low-beta power was inversely associated with wake quantity (P <.001), such that greater low-beta activity corresponded to reduced wakefulness. Notably, results revealed that low-beta power in the motor cortex was not associated with wake quantity. In contrast, high-beta power in both STN and MC positively demonstrated a positive association with wake quantity in both animals (P <.001).

“Our finding that low-beta STN power during wake negatively correlated with wake quantity provided support for our hypothesis that pathological beta oscillatory activity in parkinsonism could compromise the quality of wakefulness and lead to episodes of sleepiness during the day, senior author Luke A. Johnson, PhD, associate professor in the Department of Neurology at the University of Minnesota, and colleagues wrote.¹ “Although we demonstrated a correlative relationship between pathological subthalamic low-beta oscillatory activity and wake quantity, whether exaggerated low-beta oscillatory activity in parkinsonism is causal to disruption in wakefulness remains to be determined.”

In this study, researchers assessed the association between beta oscillatory power and daytime vigilance in 2 rhesus macaques by administering dopaminergic therapy levodopa to modulate cortico-basal ganglia activity. Beta power was recorded from the motor cortex and subthalamic nucleus, alongside measures of wakefulness, across OFF-medication, ON-medication, and medication washout conditions. The severity of parkinsonism was assessed using the modified version of the Unified Parkinson’s Disease Rating Scale and subthalamic neural activity was obtained via implanted deep brain stimulation leads.²

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“Our findings provide further evidence for the role of beta oscillatory activity in the disruption of daytime wake and nocturnal sleep in addition to its recognized role in the manifestation of cardinal motor signs of PD,” Johnson et al noted.¹ “We found that low-beta and high-beta power during wake epochs is differentially correlated with wake quantity; this correlative relationship could inform subject-specific neuromodulation treatments (e.g., adaptive DBS approaches) for maintaining the magnitude of low-beta and high-beta power within a range that is associated with sustained wakefulness.”

Wake power spectral densities, averaged across 8 sessions, showed that STN low-beta power was significantly reduced during the ON-medication state compared with OFF-medication in both animals (P < .001) and returned toward baseline as medication effects diminished. In contrast, authors noted that subthalamic high-beta power increased during ON-medication (animal 1, P < .001; animal 2, P = .0014) and subsequently declined during washout, with no observed difference relative to OFF-medication levels in either animal.

All told, changes in low-beta motor cortex power were not significant with the dopaminergic medication. In contrast, high-beta motor cortex power increased during the ON-medication condition compared with OFF-medication (study animal 1, P <.001; study animal 2, P = .0164) and returned to baseline levels during medication decay. Medication-associated alterations in cortico-basal ganglia beta oscillatory power were further assessed for their impact on daytime vigilance, with both animals exhibiting a significant increase in wake quantity during ON-medication relative to OFF-medication (P <.001).

“These understandings will be critical in the design of therapies for improving wakefulness during daytime in parkinsonism by differentially modulating low-beta and high-beta power in the cortico-basal ganglia network,” Johnson et al noted.¹ “Although we observed that subthalamic and cortical beta power was associated with wake quantity during daytime, we are still hesitant to claim beta power in the STN and cortex as the primary mechanism causal to excessive daytime sleepiness in parkinsonism.”

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REFERENCES
1. Verma AK, Acedillo K, Nandakumar B, et al. Excessive daytime sleepiness in parkinsonism is associated with cortical and basal ganglia beta oscillatory activity. Commun Biol. 2026;9(1):207. Published 2026 Jan 8. doi:10.1038/s42003-025-09483-w
2. Neudorfer C, Butenko K, Oxenford S, et al. Lead-DBS v3.0: Mapping deep brain stimulation effects to local anatomy and global networks. Neuroimage. 2023;268:119862. doi:10.1016/j.neuroimage.2023.119862