Activity parameters of subthalamic nucleus neurons selectively predict motor symptom severity in Parkinson's disease.
Parkinson's disease (PD) is a heterogeneous disorder that leads to variable expression of several different motor symptoms. While changes in firing rate, pattern, and oscillation of basal ganglia neurons have been observed in PD patients and experimental animals, there is limited evidence linking them to specific motor symptoms. Here we examined this relationship using extracellular recordings of subthalamic nucleus neurons from 19 PD patients undergoing surgery for deep brain stimulation. For each patient, ≥ 10 single units and/or multi-units were recorded in the OFF medication state. We correlated the proportion of neurons displaying different activities with preoperative Unified Parkinson's Disease Rating Scale subscores (OFF medication). The mean spectral power at sub-beta frequencies and percentage of units oscillating at beta frequencies were positively correlated with the axial and limb rigidity scores, respectively. The percentage of units oscillating at gamma frequency was negatively correlated with the bradykinesia scores. The mean intraburst rate was positively correlated with both bradykinesia and axial scores, while the related ratio of interspike intervals below/above 10 ms was positively correlated with these symptoms and limb rigidity. None of the activity parameters correlated with tremor. The grand average of all the significantly correlated subthalamic nucleus activities accounted for >60% of the variance of the combined bradykinetic-rigid and axial scores. Our results demonstrate that the occurrence of alterations in the rate and pattern of basal ganglia neurons could partly underlie the variability in parkinsonian phenotype.
Department of Neurophysiology and Pathophysiology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany, Medical Research Council Anatomical Neuropharmacology Unit, Department of Pharmacology, University of Oxford, Oxford OX1 3TH, United Kingdom, Department of Neurology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany, Department of Pediatric and Adult Movement Disorders and Neuropsychiatry, Institute of Neurology, University Medical Center Schleswig-Holstein, Campus Lübeck, 23538 Lübeck, Germany, and Department of Neurosurgery, University Medical Centre Hamburg-Eppendorf, 20246 Hamburg, Germany.
Andrew
A
Sharott
Alessandro
A
Gulberti
Simone
S
Zittel
Adam A
AA
Tudor Jones
Ulrich
U
Fickel
Alexander
A
Münchau
Johannes A
JA
Köppen
Christian
C
Gerloff
Manfred
M
Westphal
Carsten
C
Buhmann
Wolfgang
W
Hamel
Andreas K
AK
Engel
Christian K E
CK
Moll
D000200:Action Potentials / Q000502:physiology*; D000368:Aged; D001611:Beta Rhythm / Q000502:physiology; D046690:Deep Brain Stimulation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009043:Motor Activity / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D010300:Parkinson Disease / Q000473:pathology* / Q000503:physiopathology*; D012044:Regression Analysis; D012720:Severity of Illness Index; D013238:Stereotaxic Techniques; D020531:Subthalamic Nucleus / Q000473:pathology* / Q000502:physiology
Parkinson's disease; deep brain stimulation; electrophysiology; neuronal oscillations; subthalamic nucleus