325: Cortical connectivity changes following infraslow gray noise stimulation in chronic low back pain

Topic: Clinical Science
Subtopic: Pain category (ICD-11), Chronic primary musculoskeletal pain, Non-pharmacological treatments, Neuromodulation (e.g. TMS, TDCS, FUS, SCS, MCS, DBS, vagus nerve stimulation)

Background and Aims: Aberrant functional connectivity among cortical networks involved in pain processing—including salience (SN), sensorimotor (SMN), and default mode networks (DMN)—is consistently observed in chronic low back pain (CLBP).(1-7) Increased infraslow phase synchronization between these networks may reflect maladaptive integration of sensory, affective, and self-referential processes.(8-12) High-definition transcranial infraslow grey noise stimulation (HD-tIGNS) is a novel neuromodulation approach designed to perturb pathological network coupling by inducing phase desynchronization and promoting network flexibility(13-15). This pilot study aimed to determine whether a single session of HD-tIGNS alters functional connectivity between key network nodes and to evaluate its safety in people with CLBP.

Methods: A pilot double-blind, randomised, placebo-controlled trial was conducted. People with CLBP recruited from an urban community were randomised to receive a single 30-minute session of either sham stimulation or HD-tIGNS targeting key nodes of triple brain networks: pregenual anterior cingulate (pgACC) of DMN; dorsal ACC (dACC) and bilateral insula of SN; and bilateral sensory and motor cortices (SSC and MC) of SMN. Primary outcomes were electroencephalographic lagged-phased functional connectivity (0.1Hz) evaluated immediately post-intervention. Safety and secondary outcomes of clinical pain measures were assessed the following day. Safety was described descriptively, and between-group differences were analysed using Mann–Whitney U tests.

Results: Forty participants (HD-tIGNS=20; sham=20) attended a single intervention session. EEG analyses revealed significant reductions in functional connectivity between the left SSC and left insula (U=127, p=0.048), and between the right MC and right insula (U=98, p=0.006) in the HD-tIGNS group, compared to sham group. An overall trend towards decreased functional connectivity between the key nodes of SMN and SN, and between the DMN and SN, was observed in the HD-tIGNS group when compared to sham group. No adverse events were reported following the intervention. No significant differences were found in clinical pain outcomes following a single stimulation session.

Conclusions: This pilot study suggests that a single session of HD-tIGNS may reduce functional connectivity between key nodes of the SMN, SN, and DMN in people with CLBP. HD-tIGNS was safe and well tolerated. Although no immediate clinical pain changes were observed, the modulation of large-scale brain networks implicated in pain processing highlights its potential as a mechanistically informed neuromodulatory approach. Larger, fully powered trials incorporating repeated stimulation sessions are warranted to determine clinical efficacy and optimize treatment parameters for CLBP management.

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Presenting Author: Divya Bharatkumar Adhia, Sobhan Mirzaee Porkoli
Submitting Author: Divya Adhia

Senior Author: Divya Bharatkumar Adhia

IASP 2026 Global Year theme of Neuropathic Pain: No

• Sobhan Mirzaee Porkoli,: NA - University of Otago
• Ramakrishnan Mani: PhD - University of Otago
• Dirk De Ridder: PhD - University of Otago