Abstracts

Rationale: Although vagus nerve stimulation (VNS) is a common treatment for intractable epilepsy, its mechanisms of action remain unknown. Increasing evidence has implicated the modulation of thalamocortical circuitry in the antiepileptic effects of VNS. Cross-frequency phase-amplitude coupling (PAC) is a mechanism by which coordinated interactions are modulated within neural networks across different spatiotemporal scales. Here, we sought to study changes in PAC in thalamic local field potentials (LFPs) from the centromedian (CM) and anterior nuclei (AN) during active VNS.

Methods: Five patients with intractable epilepsy and VNS underwent implantation of deep brain stimulation (DBS) using the Medtronic Percept device in the CM (3 subjects) or AN (2 subjects). LFP data were recorded in both the VNS “on” and “off” states in the postoperative period. In the off state, five minutes of broadband LFPs were recorded with the VNS device off, and five minutes of broadband LFPs were recorded in the on state with continuous stimulation at 2.25mA and 250 ms. Bipolar LFP recordings were analyzed from contact pairs spanning the target nucleus. PAC was calculated using the modulation index, and interhemispheric functional connectivity was assessed using weighted-phase lag index (PLI). Within-subject statistical analysis was performed using nonparametric permutation testing, correcting for multiple comparisons using Gaussian field theory.

Results: Within the CM, the VNS on-condition was associated with a significant increase in PAC, most notably involving cross-frequency relations between theta phase and gamma amplitude (p < 0.05, voxelwise corrected paired-samples t-test, Figure 1). Within the AN, changes in PAC induced by VNS were less robust and asymmetric (p < 0.05). In both CM and AN, active VNS increased interhemispheric gamma-band functional connectivity between LFPs from the bilaterally implanted electrodes (Figure 2). Within the CM, a concurrent decrease in delta band connectivity was also observed.