Objective: To characterize how parkinsonism alters directed connectivity across the motor cortex (M1), subthalamic nucleus (STN), and internal segment of the globus pallidus (GPi).

Background: Elevated beta-band (13-30 Hz) oscillatory activity within and coherence between nodal points of the basal ganglia thalamocortical circuit (BGTC) are hypothesized to contribute to the development of motor signs in Parkinson’s disease (PD) [1]. Circuit-level alterations in neural information flow underlying changes in coherence and power are, however, not well understood. In this study, we tested the hypothesis that parkinsonism is associated with amplification of neural oscillations in the beta-band that occur throughout the cortico-subthalamo-pallidal pathway and results in increased coherence and power.

Method: Three rhesus macaques were implanted with a deep brain stimulation (DBS) lead in both STN and GPi and a Utah array in M1. Local field potentials (LFPs) were recorded before and after the animals were rendered parkinsonian by systemic administration of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Directed connectivity was characterized based on LFPs collected in the alert-resting state and using multivariable-autoregressive models [2]. The degree of amplification in the circuit connections was quantified using frequency dependent gains. Analytic solutions of coherence and power were computed based on the circuit models and compared to measurements from the LFP data.

Results: In all of the animals, the connectivity gains from M1 to GPi, STN to GPi, and GPi to STN were increased in the parkinsonian condition, specifically in the beta-band. In two animals, the gain from M1 to STN in the beta-band was also increased in the parkinsonian condition. Elevated measurements of coherence between and power within the M1, STN, and GPi were observed and predicted by analytical solutions derived from the circuit models.

Conclusion: The results support the hypothesis that alterations in directed circuit connectivity are a signature of parkinsonism and contribute to the development of elevated beta-band coherence and power across nodes in the BGTC “motor” circuit. These results could also inform the development of DBS approaches directed at restoring motor function by reshaping connectivity gains in the BGTC circuit.

References: [1] Brown, P. (2003). Oscillatory nature of human basal ganglia activity: relationship to the pathophysiology of Parkinson’s disease. Mov. Disord. Off. J. Mov. Disord. Soc. 18, 357–363. [2] Ljung, L. (1999). System Identification: Theory for the User (Upper Saddle River, NJ: Prentice Hall).

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MDS Abstracts - https://www.mdsabstracts.org/abstract/parkinsonism-alters-directed-connectivity-in-the-cortico-subthalamo-pallidal-circuit/