Noninvasive neuromodulation of subregions of the human insula differentially affect pain processing and heart-rate variability: a within-subjects pseudo-randomized trial

dc.contributor.authorLegon, Wynnen
dc.contributor.authorStrohman, Andrewen
dc.contributor.authorIn, Alexanderen
dc.contributor.authorPayne, Brightonen
dc.date.accessioned2024-02-13T15:23:04Zen
dc.date.available2024-02-13T15:23:04Zen
dc.date.issued2024-02-01en
dc.descriptionPublished versionen
dc.description.abstractThe insula is an intriguing target for pain modulation. Unfortunately, it lies deep to the cortex making spatially specific noninvasive access difficult. Here, we leverage the high spatial resolution and deep penetration depth of low-intensity focused ultrasound (LIFU) to nonsurgically modulate the anterior insula (AI) or posterior insula (PI) in humans for effect on subjective pain ratings, electroencephalographic (EEG) contact heat–evoked potentials, as well as autonomic measures including heart-rate variability (HRV). In a within-subjects, repeated-measures, pseudo-randomized trial design, 23 healthy volunteers received brief noxious heat pain stimuli to the dorsum of their right hand during continuous heart-rate, electrodermal, electrocardiography and EEG recording. Low-intensity focused ultrasound was delivered to the AI (anterior short gyrus), PI (posterior longus gyrus), or under an inert Sham condition. The primary outcome measure was pain rating. Low-intensity focused ultrasound to both AI and PI similarly reduced pain ratings but had differential effects on EEG activity. Low-intensity focused ultrasound to PI affected earlier EEG amplitudes, whereas LIFU to AI affected later EEG amplitudes. Only LIFU to the AI affected HRV as indexed by an increase in SD of N-N intervals and mean HRV low-frequency power. Taken together, LIFU is an effective noninvasive method to individually target subregions of the insula in humans for site-specific effects on brain biomarkers of pain processing and autonomic reactivity that translates to reduced perceived pain to a transient heat stimulus.en
dc.description.sponsorshipThis work was funded in part by grants awarded to W.L. from the Seale Innovation Fund and the National Institute for Health (NIH) 1R21AT012247-01.en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1097/j.pain.0000000000003171en
dc.identifier.issue00en
dc.identifier.urihttps://hdl.handle.net/10919/117977en
dc.identifier.volume00en
dc.language.isoenen
dc.publisherWolters Kluwer Health, Inc.en
dc.subjectLow-intensity focused ultrasounden
dc.subjectTranscranialen
dc.subjectHumanen
dc.subjectNeuromodulationen
dc.subjectPainen
dc.subjectInsulaen
dc.subjectInteroceptionen
dc.subjectHeart-rate variabilityen
dc.titleNoninvasive neuromodulation of subregions of the human insula differentially affect pain processing and heart-rate variability: a within-subjects pseudo-randomized trialen
dc.title.serialPainen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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