Journal article
High-Frequency Spinal Cord Stimulation Modifies Tibial Nerve-Stimulation-Evoked Cortical Theta-Gamma Coupling in Sheep Cortex
The European journal of neuroscience, Vol.64(2), e70628
07/2026
DOI: 10.1111/ejn.70628
PMID: 42459130
Abstract
Pain management strategies have progressed beyond traditional pharmacologic and physical interventions, integrating advanced neuromodulation techniques such as deep brain stimulation, peripheral nerve stimulation, and high-frequency spinal cord stimulation (hSCS). Despite its clinical efficacy, the supraspinal mechanisms underlying hSCS remain poorly understood. Prior work in sheep demonstrated that hSCS modulates gamma (γ) band (70-150 Hz) activity in the primary somatosensory and association cortices, implicating cortical involvement in pain modulation. Given the interaction between low- and high-oscillations, we hypothesized that hSCS modulates γ activity in a region- and time-dependent manner through specific coupling with theta rhythms (θ, 4-8 Hz). To test this, we quantified θ-γ phase-amplitude coupling (PAC) during tibial nerve stimulation (TNS) before (TNS
) and after (TNS
) hSCS to assess cortical processing of TNS-evoked activity, while recording cortical (association and somatosensory cortices) neural activity using 96-channel subdural electrocorticography (ECoG). We then computed the corresponding modulation index (MI) to quantify PAC strength. While the preferred θ phase of γ activity remained consistent across conditions in both cortical areas, θ-γ coupling was more robust and stable in the association than the somatosensory cortex. However, MI increased significantly post-hSCS in both cortices, indicating enhanced θ-γ coupling during TNS
. Temporally, both cortices showed distinct response patterns: the somatosensory cortex exhibited strongest coupling increase early post-hSCS, followed by a progressive decline, whereas the association cortex showed a more delayed and temporally distributed enhancement. These findings indicate that hSCS modulates cortical cross-frequency interactions during TNS-evoked sensory processing, wherein somatosensory and association cortices show distinct temporal coupling dynamics that may contribute to supraspinal mechanisms of pain modulation.
Details
- Title: Subtitle
- High-Frequency Spinal Cord Stimulation Modifies Tibial Nerve-Stimulation-Evoked Cortical Theta-Gamma Coupling in Sheep Cortex
- Creators
- Vishal Bharmauria - University of South FloridaHiroyuki Oya - University of IowaYarema Bezchlibnyk - University of South FloridaNour Shaheen - Alexandria UniversityAmirhossein Ghaderi - University of Southern CaliforniaYahia Yassine Belkacemi - Université de MontréalKarim Johari - Louisiana State University SystemArun Singh - University of South DakotaAlexander L Green - University of OxfordHiroto Kawasaki - University of IowaCan Sarica - University Health NetworkBrian Dalm - The Ohio State UniversityAndres M Lozano - University Health NetworkMatthew A Howard III - Department of Neurosurgery, University of Iowa Hospital and Clinics, University of Iowa, Iowa City, Iowa, USAOliver Flouty - University of South Florida
- Resource Type
- Journal article
- Publication Details
- The European journal of neuroscience, Vol.64(2), e70628
- DOI
- 10.1111/ejn.70628
- PMID
- 42459130
- NLM abbreviation
- Eur J Neurosci
- ISSN
- 1460-9568
- eISSN
- 1460-9568
- Publisher
- WILEY
- Grant note
- University of South Florida University of Iowa
- Language
- English
- Date published
- 07/2026
- Academic Unit
- Neurology; Iowa Neuroscience Institute; Neurosurgery; Otolaryngology
- Record Identifier
- 9985183419502771
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