GABA-mediated changes in inter-hemispheric beta frequency activity in early-stage Parkinson's disease


In Parkinson's disease (PD), elevated beta (15-35Hz) power in subcortical motor networks is widely believed to promote aspects of PD symptomatology, moreover, a reduction in beta power and coherence accompanies symptomatic improvement following effective treatment with l-DOPA. Previous studies have reported symptomatic improvements that correlate with changes in cortical network activity following GABAA receptor modulation. In this study we have used whole-head magnetoencephalography to characterize neuronal network activity, at rest and during visually cued finger abductions, in unilaterally symptomatic PD and age-matched control participants. Recordings were then repeated following administration of sub-sedative doses of the hypnotic drug zolpidem (0.05mg/kg), which binds to the benzodiazepine site of the GABAA receptor. A beamforming based 'virtual electrode' approach was used to reconstruct oscillatory power in the primary motor cortex (M1), contralateral and ipsilateral to symptom presentation in PD patients or dominant hand in control participants. In PD patients, contralateral M1 showed significantly greater beta power than ipsilateral M1. Following zolpidem administration contralateral beta power was significantly reduced while ipsilateral beta power was significantly increased resulting in a hemispheric power ratio that approached parity. Furthermore, there was highly significant correlation between hemispheric beta power ratio and Unified Parkinson's Disease Rating Scale (UPDRS). The changes in contralateral and ipsilateral beta power were reflected in pre-movement beta desynchronization and the late post-movement beta rebound. However, the absolute level of movement-related beta desynchronization was not altered. These results show that low-dose zolpidem not only reduces contralateral beta but also increases ipsilateral beta, while rebalancing the dynamic range of M1 network oscillations between the two hemispheres. These changes appear to underlie the symptomatic improvements afforded by low-dose zolpidem.

Publication DOI:
Divisions: Life & Health Sciences > Pharmacy
Life & Health Sciences > Psychology
Life & Health Sciences > Clinical and Systems Neuroscience
Life & Health Sciences > Aston Brain Centre
Life & Health Sciences
Life & Health Sciences > Biosciences
Life & Health Sciences > Vision, Hearing and Language
Additional Information: This is an Open Access article under the CC BY-NC-ND license ( Funding: Parkinson’s UK (G-1008); BBSRC (BB/H003894/1); Dr Hadwen Trust and Lord Dowding Fund; and Wellcome Trust (grant 088314/Z/09/Z).
Uncontrolled Keywords: magnetoencephalography,GABAA receptors,beta oscillations,primary motor cortex,Parkinson’s disease,Neuroscience(all)
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Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2014-12-05
Published Online Date: 2014-09-28
Authors: Hall, S.D.
Prokic, E.J.
McAllister, C.J.
Rönnqvist, K.C.
Williams, A.C.
Yamawaki, N.
Witton, C. ( 0000-0002-5610-4234)
Woodhall, G.L. ( 0000-0003-1281-9008)
Stanford, I.M. ( 0000-0002-5677-8538)


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