Gamma Oscillations in the Hyperkinetic State Detected with Chronic Human Brain Recordings in Parkinson's Disease.
Hyperkinetic states are common in human movement disorders, but their neural basis remains uncertain. One such condition is dyskinesia, a serious adverse effect of medical and surgical treatment for Parkinson's disease (PD). To study this, we used a novel, totally implanted, bidirectional neural interface to obtain multisite long-term recordings. We focus our analysis on two patients with PD who experienced frequent dyskinesia and studied them both at rest and during voluntary movement. We show that dyskinesia is associated with a narrowband gamma oscillation in motor cortex between 60 and 90 Hz, a similar, though weaker, oscillation in subthalamic nucleus, and strong phase coherence between the two. Dyskinesia-related oscillations are minimally affected by voluntary movement. When dyskinesia persists during therapeutic deep brain stimulation (DBS), the peak frequency of this signal shifts to half the stimulation frequency. These findings suggest a circuit-level mechanism for the generation of dyskinesia as well as a promising control signal for closed-loop DBS.



Oscillations in brain networks link functionally related brain areas to accomplish thought and action, but this mechanism may be altered or exaggerated by disease states. Invasive recording using implanted electrodes provides a degree of spatial and temporal resolution that is ideal for analysis of network oscillations. Here we used a novel, totally implanted, bidirectional neural interface for chronic multisite brain recordings in humans with Parkinson's disease. We characterized an oscillation between cortex and subcortical modulators that is associated with a serious adverse effect of therapy for Parkinson's disease: dyskinesia. The work shows how a perturbation in oscillatory dynamics might lead to a state of excessive movement and also suggests a possible biomarker for feedback-controlled neurostimulation to treat hyperkinetic disorders.
Departments of Neurological Surgery and Nicole.Swann@ucsf.edu.
Nicole C
0000-0003-2463-5134
NC
Swann
Departments of Neurological Surgery and.
Coralie
C
de Hemptinne
Neurology.
Svjetlana
S
Miocinovic
Departments of Neurological Surgery and.
Salman
S
Qasim
Neurology.
Sarah S
0000-0002-3865-9594
SS
Wang
Neurology.
Nathan
N
Ziman
Neurology.
Jill L
JL
Ostrem
Neurology.
Marta
M
San Luciano
Neurology.
Nicholas B
NB
Galifianakis
Departments of Neurological Surgery and Kavli Institute for Fundamental Neuroscience, and Graduate Program in Neuroscience, University of California, San Francisco, California 94143.
Philip A
PA
Starr
D001289:Attention Deficit Disorder with Hyperactivity / Q000209:etiology* / Q000473:pathology*; D001921:Brain / Q000503:physiopathology*; D046690:Deep Brain Stimulation; D004569:Electroencephalography; D005260:Female; D065818:Gamma Rhythm / Q000502:physiology*; D006801:Humans; D008297:Male; D010300:Parkinson Disease / Q000150:complications* / Q000473:pathology; D012372:ROC Curve; D012720:Severity of Illness Index; D020531:Subthalamic Nucleus / Q000502:physiology
Parkinson's disease; deep brain stimulation; dyskinesia; electrocorticography; local field potentials; motor cortex