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

S.D. Hall, E.J. Prokic, C.J. McAllister, K.C. Rönnqvist, A.C. Williams, N. Yamawaki, C. Witton, G.L. Woodhall, I.M. Stanford

Research output: Contribution to journalArticle

Abstract

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.

LanguageEnglish
Pages68-76
Number of pages9
JournalNeuroscience
Volume281
Early online date28 Sep 2014
DOIs
Publication statusPublished - 5 Dec 2014

Fingerprint

gamma-Aminobutyric Acid
Parkinson Disease
GABA-A Receptors
Secondary Parkinson Disease
Magnetoencephalography
Motor Cortex
Parity
Hypnotics and Sedatives
Benzodiazepines
Fingers
Electrodes
Hand
Head
zolpidem
Pharmaceutical Preparations
Therapeutics

Bibliographical note

This is an Open Access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

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).

Keywords

  • magnetoencephalography
  • GABAA receptors
  • beta oscillations
  • primary motor cortex
  • Parkinson’s disease

Cite this

Hall, S.D. ; Prokic, E.J. ; McAllister, C.J. ; Rönnqvist, K.C. ; Williams, A.C. ; Yamawaki, N. ; Witton, C. ; Woodhall, G.L. ; Stanford, I.M. / GABA-mediated changes in inter-hemispheric beta frequency activity in early-stage Parkinson's disease. In: Neuroscience. 2014 ; Vol. 281. pp. 68-76.
@article{3edfad828dde4d5e99d2d5dac26eb012,
title = "GABA-mediated changes in inter-hemispheric beta frequency activity in early-stage Parkinson's disease",
abstract = "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.",
keywords = "magnetoencephalography, GABAA receptors, beta oscillations, primary motor cortex, Parkinson’s disease",
author = "S.D. Hall and E.J. Prokic and C.J. McAllister and K.C. R{\"o}nnqvist and A.C. Williams and N. Yamawaki and C. Witton and G.L. Woodhall and I.M. Stanford",
note = "This is an Open Access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/). 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).",
year = "2014",
month = "12",
day = "5",
doi = "10.1016/j.neuroscience.2014.09.037",
language = "English",
volume = "281",
pages = "68--76",
journal = "Neuroscience",
issn = "0306-4522",
publisher = "Elsevier",

}

GABA-mediated changes in inter-hemispheric beta frequency activity in early-stage Parkinson's disease. / Hall, S.D.; Prokic, E.J.; McAllister, C.J.; Rönnqvist, K.C.; Williams, A.C.; Yamawaki, N.; Witton, C.; Woodhall, G.L.; Stanford, I.M.

In: Neuroscience, Vol. 281, 05.12.2014, p. 68-76.

Research output: Contribution to journalArticle

TY - JOUR

T1 - GABA-mediated changes in inter-hemispheric beta frequency activity in early-stage Parkinson's disease

AU - Hall, S.D.

AU - Prokic, E.J.

AU - McAllister, C.J.

AU - Rönnqvist, K.C.

AU - Williams, A.C.

AU - Yamawaki, N.

AU - Witton, C.

AU - Woodhall, G.L.

AU - Stanford, I.M.

N1 - This is an Open Access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/). 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).

PY - 2014/12/5

Y1 - 2014/12/5

N2 - 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.

AB - 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.

KW - magnetoencephalography

KW - GABAA receptors

KW - beta oscillations

KW - primary motor cortex

KW - Parkinson’s disease

UR - http://www.scopus.com/inward/record.url?scp=84908074957&partnerID=8YFLogxK

U2 - 10.1016/j.neuroscience.2014.09.037

DO - 10.1016/j.neuroscience.2014.09.037

M3 - Article

VL - 281

SP - 68

EP - 76

JO - Neuroscience

T2 - Neuroscience

JF - Neuroscience

SN - 0306-4522

ER -