BACKGROUND Monitoring of adverse effects in neuromodulation relies largely on non-standardized or time-consuming instruments, limiting comparison of tolerability within and across transcranial magnetic stimulation (TMS), transcranial electrical stimulation (tES), and transcranial ultrasound stimulation (tUS). We developed the Non-Invasive Brain Stimulation Side Effect Scale (NIBS-SES), a brief questionnaire for repeated assessment of adverse effects. METHODS The NIBS-SES was designed iteratively, with an initial version evaluated in 44 patients receiving TMS for major depression to assess repeated-use feasibility and adverse-effect patterns. Items were expanded based on a literature review of adverse-effect prevalences across TMS, tES, and tUS (n=6,415 individuals) and refined by 12 NIBS experts. The final version was professionally translated into 15 languages (Arabic, Basque, Catalan, Dutch, French, Galician, German, Hindi, Italian, Japanese, Korean, Mandarin Chinese, Persian, Portuguese, Spanish). RESULTS Patient-reported adverse effects across 851 sessions declined despite titration of stimulation intensity. Prior-session occurrence was the strongest predictor of current-session reports (β=4.73, p<.001), detectable only through repeated session-level assessment. Adverse effects during and between sessions showed different patterns of persistence, supporting their separate assessment. The literature review revealed substantial overlap across neuromodulation modalities, supporting a unified instrument. CONCLUSIONS Our findings support the feasibility of repeated session-level assessment with the initial version, from which the final NIBS-SES was derived. This multilingual, open-access instrument comprises 10 within-session and 9 between-session items developed for monitoring across TMS, tES, and tUS (for questionnaire and digital implementation files, see OSF: https://doi.org/10.17605/OSF.IO/XZ3NB). Validation across brain stimulation modalities, protocols, and clinical populations will require prospective multi-site data.
Objective To develop and evaluate a thalamic γ-state-triggered closed-loop (CL) deep brain stimulation (DBS) strategy for modulation of neuropathic pain. Methods Neuropathic pain was induced with chronic constriction injury (CCI) in rats. Thalamic local field potentials (LFPs) were used to identify wavelet-packet (WP)-defined gamma (γ)-band states, γ0 and γ1, using coefficient magnitudes relative to an adaptive threshold and temporal confirmation. A CL DBS paradigm triggered stimulation contingent on either γ0 or γ1 states and was compared with conventional open-loop (OL) 40 Hz and 130 Hz stimulation using behavioral and neurophysiological outcomes. Results CCI increased thalamic γ power on days 3, 7 and 14 (raw p = 0.0004, 0.0078 and 0.0162; FDR-adjusted p = 0.0077, 0.0703 and 0.0731) and prolonged γ1-state duration (raw p = 0.0283; adjusted p = 0.1417). In the CCI model, γ power was negatively associated with mechanical withdrawal threshold (MWT; raw p = 0.0159; adjusted p = 0.0956). At 130 Hz, mean MWT changes were opposite under the two CL protocols: γ0 CL increased MWT by 47.07% and γ1 CL decreased it by 12.06% (raw p = 0.0234 and 0.0391; adjusted p = 0.0469 and 0.0586). The 40 Hz γ0 CL protocol produced the largest observed mean MWT increase of 81.91% (raw p = 0.0078; adjusted p = 0.0469), 46.02 percentage points above 40 Hz OL. Electrophysiological analyses also showed protocol-associated changes in γ-state dynamics and nominal spectral-power changes. Conclusion The tested WP-defined γ-state-triggered CL protocols were associated with differing changes in mechanical sensitivity in neuropathic rats. These findings support further evaluation of this approach as a candidate framework for adaptive neuromodulation of neuropathic pain.
