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.
Highlights
Physiological neuronal network oscillations at beta frequency (15–35 Hz) occur spontaneously in the primary motor cortex (M1) of humans (Jensen et al, 2005; Hall et al, 2010a) and in animal models (Murthy and Fetz, 1996; Baker et al, 1997)
In Parkinson’s disease (PD) exaggerated beta oscillations are observed in recordings from subcortical structures such as the subthalamic nucleus (STN) and cortex of both animal models (Sharott et al, 2005; Chen et al, 2007; Mallet et al, 2008) and PD patients (Cassidy et al, 2002; Pollok et al, 2012)
Data collected from the remaining PD patient included non-experimental noise, that prevented reliable localization of M1 and these data were excluded from further analysis
Summary
Physiological neuronal network oscillations at beta frequency (15–35 Hz) occur spontaneously in the primary motor cortex (M1) of humans (Jensen et al, 2005; Hall et al, 2010a) and in animal models (Murthy and Fetz, 1996; Baker et al, 1997). Zolpidem greatly reduced the synchronous power of pathological oscillations in these loci, which correlated well with zolpidem uptake and restoration of function These results suggest that specific motor and cognitive impairments are related to increased low-frequency oscillatory neuronal network activity, and that zolpidem is able to desynchronize such pathological lowfrequency activity, restoring cognitive and motor function (for further details see Hall et al, 2010b). When we analyzed changes in beta activity that accompany movement we found that following zolpidem, MRBD and PMBR were similar on contralateral and ipsilateral sides. This rebalancing of interhemispheric oscillatory dynamics appears to correlate with the symptomatic improvements afforded by low-dose zolpidem
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