Single-neuron bursts encode pathological oscillations in subcortical nuclei of patients with Parkinson’s disease and essential tremor

Significance

Leveraging intracranial recordings from patients with Parkinson’s disease and essential tremor, the applied analyses allowed for derivation of relationships between neural signals across spatiotemporal resolutions, techniques that may facilitate interpretation of aggregate-level oscillations in various neuroscientific contexts from the perspective of the single-neuron resolution. Of relevance in Parkinson’s disease, the applied methodologies allowed us to establish a link between single-neuron bursting and elevated local field potential (LFP) activities, reconciling parallel theories of neurocircuit dysfunction. Directional connectivity analyses between single-neuron and LFP signals furthermore allowed us to speculate on the origin of beta and tremor-related oscillations associated with Parkinson’s disease and essential tremor, respectively. Ultimately, our findings may aid in developing targeted neurotherapeutics to address aberrant pattens of neural activity.

Abstract

Deep brain stimulation procedures offer an invaluable opportunity to study disease through intracranial recordings from awake patients. Here, we address the relationship between single-neuron and aggregate-level (local field potential; LFP) activities in the subthalamic nucleus (STN) and thalamic ventral intermediate nucleus (Vim) of patients with Parkinson’s disease ( n = 19) and essential tremor ( n = 16), respectively. Both disorders have been characterized by pathologically elevated LFP oscillations, as well as an increased tendency for neuronal bursting. Our findings suggest that periodic single-neuron bursts encode both pathophysiological beta (13 to 33 Hz; STN) and tremor (4 to 10 Hz; Vim) LFP oscillations, evidenced by strong time-frequency and phase-coupling relationships between the bursting and LFP signals. Spiking activity occurring outside of bursts had no relationship to the LFP. In STN, bursting activity most commonly preceded the LFP oscillation, suggesting that neuronal bursting generated within STN may give rise to an aggregate-level LFP oscillation. In Vim, LFP oscillations most commonly preceded bursting activity, suggesting that neuronal firing may be entrained by periodic afferent inputs. In both STN and Vim, the phase-coupling relationship between LFP and high-frequency oscillation (HFO) signals closely resembled the relationships between the LFP and single-neuron bursting. This suggests that periodic single-neuron bursting is likely representative of a higher spatial and temporal resolution readout of periodic increases in the amplitude of HFOs, which themselves may be a higher resolution readout of aggregate-level LFP oscillations. Overall, our results may reconcile “rate” and “oscillation” models of Parkinson’s disease and shed light on the single-neuron basis and origin of pathophysiological oscillations in movement disorders.