title: Parkinsonian impairment correlates with spatially extensive subthalamic oscillatory synchronization.
abstract: The local strength of pathological synchronization in the region of the subthalamic nucleus (STN) is emerging as a possible factor in the motor impairment of Parkinson's Disease (PD). In particular, correlations have been repeatedly demonstrated between treatment-induced suppressions of local oscillatory activity in the beta frequency band and improvements in motor performance. However, a mechanistic role for beta activity is brought into question by the difficulty in showing a correlation between such activity at rest and the motor deficit in patients withdrawn from medication. Here we recorded local field potential (LFP) activity from 36 subthalamic regions in 18 patients undergoing functional neurosurgery for the treatment of PD. We recorded directly from the contacts of the deep brain stimulation (DBS) electrodes as they were introduced in successive 2 mm steps, and assessed phase coherence as a measure of spatially extended, rather than local, oscillatory synchronization. We found that phase coherence in the beta frequency band correlated with the severity of Parkinsonian bradykinesia and rigidity, both in the limbs and axial body. Such correlations were frequency and site specific in so far as they were reduced when the lowermost contact of the DBS electrode was above the dorsal STN. Correlations with limb tremor occurred at sub-beta band frequencies and were more lateralized than those between beta activity and limb bradykinesia and rigidity. Phase coherence could account for up to ∼25% of the variance in motor scores between sides and patients. These new data suggest that the strength of spatially extended oscillatory synchronization, as well as the strength of local synchronization, may be worthwhile incorporating into modelling studies designed to inform surgical targeting, post-operative stimulation parameter selection and closed-loop stimulation regimes in PD. In addition, they strengthen the link between pathological synchronization and the different motor features of Parkinsonism.
authors.affiliation: Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, London, WC1N 3BG UK.
authors.forename: A
authors.initials: A
authors.lastname: Pogosyan
authors.forename: F
authors.initials: F
authors.lastname: Yoshida
authors.forename: C C
authors.initials: CC
authors.lastname: Chen
authors.forename: I
authors.initials: I
authors.lastname: Martinez-Torres
authors.forename: T
authors.initials: T
authors.lastname: Foltynie
authors.forename: P
authors.initials: P
authors.lastname: Limousin
authors.forename: L
authors.initials: L
authors.lastname: Zrinzo
authors.forename: M I
authors.initials: MI
authors.lastname: Hariz
authors.forename: P
authors.initials: P
authors.lastname: Brown
mesh_terms: D000328:Adult; D000368:Aged; D001683:Biological Clocks / Q000502:physiology*; D046690:Deep Brain Stimulation / Q000379:methods; D004567:Electrodes, Implanted; D019054:Evoked Potentials, Motor / Q000502:physiology*; D005260:Female; D007839:Functional Laterality; D006801:Humans; D018476:Hypokinesia / Q000209:etiology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009127:Muscle Rigidity / Q000209:etiology / Q000628:therapy; D010300:Parkinson Disease / Q000150:complications* / Q000473:pathology* / Q000628:therapy; D012720:Severity of Illness Index; D013057:Spectrum Analysis; D013223:Statistics as Topic; D020531:Subthalamic Nucleus / Q000503:physiopathology*