Neural signatures of hyperdirect pathway activity in Parkinson's disease

• Published in: Nature communications Vol. 12; no. 1; p. 5185
• Main Authors: Oswal, Ashwini, Cao, Chunyan, Yeh, Chien-Hung, Neumann, Wolf-Julian, Gratwicke, James, Akram, Harith, Horn, Andreas, Li, Dianyou, Zhan, Shikun, Zhang, Chao, Wang, Qiang, Zrinzo, Ludvic, Foltynie, Tom, Limousin, Patricia, Bogacz, Rafal, Sun, Bomin, Husain, Masud, Brown, Peter, Litvak, Vladimir
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 31.08.2021; Nature Publishing Group UK; Nature Portfolio
• Subjects: Basal ganglia; Circuits; Cohort Studies; Computational neuroscience; Electrical stimuli; Frequency ranges; Ganglia; Globus pallidus; Globus Pallidus - chemistry; Globus Pallidus - physiopathology; Humans; Magnetoencephalography; Motor Cortex - chemistry; Motor Cortex - physiopathology; Movement disorders; Neural Pathways; Neurodegenerative diseases; Oscillations; Parkinson Disease - physiopathology; Parkinson's disease; Solitary tract nucleus; Spectral signatures; Subthalamic nucleus; Subthalamic Nucleus - chemistry; Subthalamic Nucleus - physiopathology; Supplementary motor area; Synchronism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-25366-0

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.