Elsevier

Neuroscience

Volume 171, Issue 1, 24 November 2010, Pages 245-257
Neuroscience

Neurodegeneration, Neuroprotection, and Disease-Oriented Neuroscience
Research Paper
Parkinsonian impairment correlates with spatially extensive subthalamic oscillatory synchronization

https://doi.org/10.1016/j.neuroscience.2010.08.068Get rights and content

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question by the difficulty in showing a correlation between such activity at rest and the motor deficit in patients withdrawn from medication.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.

Section snippets

Patients and procedures

The patients (n=18, mean age 60.4±7.0 years, range 38–71, 9 males) participated with informed consent. All patients had advanced idiopathic PD with motor fluctuations and/or dyskinesia. The mean disease duration was 15.2±5.4 years (range 9–27 years). The mean pre-operative Unified Parkinson's Disease Rating Scale (UPDRS) motor score tested no more than 6 months prior to surgery was 42.9±15.7 when off drugs overnight and 11.1±7.4 after levodopa challenge (P<0.001, two tailed paired t-test). The

Amplitude spectra of subthalamic LFP activity

Fig 1 shows example raw and group mean LFP frequency spectra from the four monopolar contacts (Fig 1A) and the three corresponding bipolar contact pairs (Fig 1B) at the level at which bipolar contact pair 01 registers the highest step increase in beta power during the graded descent of the DBS electrode through the surgical target. This level, hereafter termed the PTL, is believed to correspond to the point at which the lowermost electrode contact, 0, enters into dorsal STN (Chen et al., 2006,

Discussion

The principal finding in the current study was the presence of correlations between the strength of spatially extended oscillatory synchronization in the STN and bordering zona incerta and motor impairment in PD patients; specifically, the greater the evidence for spatially extended oscillatory synchronization, the worse the bradykinesia and rigidity. Spatially extended oscillatory synchronization was indexed by phase coherence over distances of 2 or 4 mm. Correlations were evident in the beta

Conclusion

We have shown that the stronger spatially extended oscillatory synchronization is in the STN and bordering zona incerta, the worse the bradykinesia and rigidity in patients with Parkinson's disease. Clinical correlations with the phase coherence between sites were depth, frequency band and phenotype specific. These new data strengthen the link between pathological synchronization and the different motor features of Parkinsonism and suggest that the presence of synchronization over distance in

Acknowledgments

Alek Pogosyan was supported by the Medical Research Council, Patricia Limousin, Tom Foltynie, Ludvic Zrinzo and Marwan Hariz by the Parkinson's appeal, Irene Martinez-Torres by a grant from Fondo de Inversion Sanitaria (FIS), Instituto de Salud Carlos III, Spanish Department of Science and Innovation (FI08/00108), Fumiaki Yoshida by the Uehara Memorial Fundation, and Peter Brown by the Medical Research Council, Parkinson's Disease Society (UK) and the NIHR Biomedical Research Centre, Oxford.

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