Τετάρτη 23 Αυγούστου 2017

Parkinsonism and Vigilance: Alteration in neural oscillatory activity and phase-amplitude coupling in the basal ganglia and motor cortex

Oscillatory neural activity in different frequency bands as well as phase-amplitude coupling (PAC) are hypothesized to be biomarkers of Parkinson's disease (PD) that could explain dysfunction in the motor circuit and be used for closed-loop deep brain stimulation (DBS). How these putative biomarkers change from the normal to the parkinsonian state, across nodes in the motor circuit, and within the same subject, however, remains unknown. In this study, we characterized how parkinsonism and vigilance altered oscillatory activity and PAC within the primary motor cortex (M1), subthalamic nucleus (STN), and globus pallidus (GP) in two nonhuman primates. Static and dynamic analyses of local field potential (LFP) recordings indicate that: 1) after induction of parkinsonism using the neurotoxin MPTP, low-frequency power (8-30 Hz) increased in the STN and GP in both subjects, but increased in M1 in only one subject; 2) high-frequency power (~330 Hz) was present in the STN in both normal subjects, but absent in the parkinsonian condition; 3) elevated PAC measurements emerged in the parkinsonian condition in both animals, but in different sites in each animal (M1 in one subject and GPe in the other) and 4) the state of vigilance significantly impacted how oscillatory activity and PAC was expressed in the motor circuit. These results support the hypothesis that changes in low and high frequency oscillatory activity and PAC are features of parkinsonian pathophysiology and provide evidence that closed-loop DBS systems based on these biomarkers may require subject-specific configurations as well as adaptation to changes in vigilance.



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