Abstract
Parkinson’s disease (PD) is characterised by the emergence of beta frequency oscillatory synchronisation across the cortico-basal-ganglia circuit. The relationship between the anatomy of this circuit and oscillatory synchronisation within it remains unclear. We address this by combining recordings from human subthalamic nucleus (STN) and internal globus pallidus (GPi) with magnetoencephalography, tractography and computational modelling. Coherence between supplementary motor area and STN within the high (21–30 Hz) but not low (13-21 Hz) beta frequency range correlated with ‘hyperdirect pathway’ fibre densities between these structures. Furthermore, supplementary motor area activity drove STN activity selectively at high beta frequencies suggesting that high beta frequencies propagate from the cortex to the basal ganglia via the hyperdirect pathway. Computational modelling revealed that exaggerated high beta hyperdirect pathway activity can provoke the generation of widespread pathological synchrony at lower beta frequencies. These findings suggest a spectral signature and a pathophysiological role for the hyperdirect pathway in PD.
Highlights
Parkinson’s disease (PD) is characterised by the emergence of beta frequency oscillatory synchronisation across the cortico-basal-ganglia circuit
Subjects displayed oscillatory peaks within the low (13-21 Hz) and high beta (21–30 Hz) frequency ranges. For both the Shanghai and UCL cohorts, we observed that power within the high beta frequency range was significantly greater within the subthalamic nucleus (STN) than within the globus pallidus (GPi)
For further visualization of the overlap between MEG derived functional connectivity and tractography derived structural connectivity, we studied fiber tracts passing through the predefined spherical ROI for each contact which originated within cortical volumes for which: (1) there was either a main effect of the band or a simple main effect of the band for the STN—which we name the ‘high beta network’ and (2)
Summary
Parkinson’s disease (PD) is characterised by the emergence of beta frequency oscillatory synchronisation across the cortico-basal-ganglia circuit. By simultaneously recording cortical activity with EEG or magnetoencephalography (MEG) and intracranial local field potentials (LFP) in patients undergoing surgery for the insertion of Deep Brain Stimulation (DBS) electrodes it is possible to explore patterns of long-range synchronization that emerge within corticobasal-ganglia circuits[1,2,3] Using this approach, it has been previously shown that the STN couples with motor/premotor activity at beta frequencies, with the cortex, predominantly driving STN activity[2,4]. An improved understanding of the relationship between cortico-basal-ganglia anatomical projections and the generation of beta-band oscillatory synchrony is essential to fulfilling a critical gap in our understanding of network dysfunction in PD and could inform the development of more spatially and temporally patterned DBS therapies[17] In this regard, previous studies have speculated on the potential importance of an exaggerated hyperdirect pathway[4,18,19,20,21], but details regarding pathophysiological mechanisms are lacking. Previous work demonstrates that synchronous activity between the cortex and the STN predominates
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