Modulation of posterior insula selectively enhances nociceptive sensory gating in healthy humans

Abstract

Sensory gating - the brains ability to filter out repetitive sensory input - is essential for preventing sensory overload. Impaired gating is frequently observed in nociplastic and other chronic overlapping pain conditions, yet the specific brain regions supporting this inhibitory process in human remains unclear. Neuroimaging studies examining pain processing implicate the dorsal anterior insula (dAI), posterior insula (PI), and anterior mid-cingulate cortex (aMCC), but their deeper locations limit direct mechanistic testing using conventional non-invasive techniques. Here, we leveraged low-intensity focused ultrasound (LIFU), a novel non-invasive neuromodulation method with high depth-penetration and millimeter resolution, to examine the contributions of the dAI, PI, and aMCC to sensory gating of nociceptive stimuli. Twelve healthy adults completed four counterbalanced visits of a paired-pulse contact heat evoked potential (CHEP) paradigm while receiving LIFU targeted to each region or an active sham. Using surface electroencephalography (EEG), placed at site Cz, we quantified the peak-to-peak (P2P) amplitude of the cortical response to the first stimulus (S1), the second stimulus (S2), and used the ratio of the response to each stimulus (S2/S1 ratio) as an index of sensory gating. Subjective ratings of pain intensity to the second stimulus were also recorded. Results demonstrated that all subjects displayed sensory gating at baseline and that LIFU produced region-specific effects. Both PI and aMCC neuromodulation reduced subjective pain ratings and significantly decreased S2 amplitude relative to sham, whereas LIFU to AI had no effect. Critically, only PI neuromodulation enhanced sensory gating by reducing the S2/S1 ratio. These findings identify the PI as a key contributor to gating of repetitive nociceptive input and a promising neuromodulation target for remediating sensory gating deficits in nociplastic pain.

Abstract via pubmed.

Flags from extraction

• exposures[2].target.terms — Paper's own term is 'anterior midcingulate cortex (aMCC)', a Vogt-terminology region not separately enumerated in the target vocabulary; mapped to the closest listed term, dorsal_anterior_cingulate_cortex (dACC/BA24), which may not be an exact anatomical match.
• exposures[*].in_situ.pressure_kpa — Individual-participant acoustic simulation results (k-Wave) are shown only as figure colour maps in kPa (Fig. 2), with no numeric intracranial pressure stated in the main text.
• exposures[*].free_field.pressure_kpa — Empirical water-tank pressure measurements were used to calibrate stimulation but no numeric free-field pressure (kPa) value is given in the main text; a conservative 750 kPa 'outside the skull' value is used only for a separate thermal-safety simulation, not as the applied free-field pressure, so it was not used here.
• blinding — Abstract/Methods label the design 'single-blind', but Section 2.4.1 states both participants and the data-analysis team were blinded to condition; recorded as 'single' per the paper's own explicit label, but this may understate the blinding actually achieved.
• n_sessions_per_subject — 4 refers to the four LIFU intervention visits (AI, PI, aMCC, Sham); an additional non-stimulation MRI/CT visit (Visit 1) is not counted.