673: Cortical homeostatic-like plasticity of heat-pain and motor evoked potentials

Topic: Experimental (Non-clinical) Human Studies
Subtopic: Non -specific to any diagnosis, Electrophysiology/Clinical neurophysiology (e.g. microneurography, EEG, MEG, OPMs, TMS), Pain mechanisms (e.g. descending inhibitory control, placebo, inflammation), Neuromodulation (e.g. rTMS, tDCS, FUS, DBS, biofeedback)

Background and Aims: Homeostatic plasticity maintains neuronal activity within a physiological balance, preventing excessive excitability[1]. In humans, cortical homeostatic-like plasticity (HP-like) can be investigated with two blocks of anodal transcranial direct current stimulation (tDCS). A normal HP-like response is characterized by e.g. decreased motor-evoked potential (MEPs) after two blocks of anodal tDCS (i.e., reversal of excitability) over the primary motor cortex (M1)[2]. The latter HP-like response is impaired during chronic and experimental pain, suggesting a role in pain pathophysiology [3]. Yet, motor and nociceptive HP-like responses have not been examined in parallel. This study aimed to investigate the HP-like response of the motor and nociceptive system using different neurophysiological methods during the same session.

Methods: Twenty-four healthy individuals participated in two randomized-sham-controlled HP-like induction sessions (31±8 years, 13 females). ActiveHP consisted of two blocks (7min+5min) of sensorimotor-anodal tDCS (C3, 1 mA, return electrode FP2 −1 mA). During ShamHP, the tDCS device ramped up-and-down over 30 s but otherwise delivered no stimulation. The HP-like response was assessed pre and 20 min post-HP-induction using MEPs (120% resting motor threshold, first dorsal interosseous muscle) and contact heat-evoked potentials (CHEPs; volar forearm, baseline 35°C, peak 60°C) recorded by 64-channels electroencephalography. Following preprocessing, the N1 amplitude and latency were extracted at TP7, T7 and C5 (referenced to Fz; 170–330 ms), and N2P2 amplitude and latency at Cz, CPz, C1 and C2. Twenty trials were averaged for MEPs and 15 for CHEPs. Session-level effects were assessed using linear mixed models and estimated marginal means for significant effects. Cross-modal associations between MEPs and CHEPs were examined using Pearson correlations.

Results: ActiveHP showed a significant interaction for the CHEPs N1 latency (p=0.02), preventing the latency slowing observed over time in ShamHP (ActiveHP: −11 ms, p= 0.3; ShamHP: +21 ms, p=0.03). The effect of this HP-like response is supported by a trending interaction for a decrease in N1 amplitude after HP-like induction for ActiveHP (p = 0.07). No significant effects emerged for N2, P2, or N2P2 components, and MEP amplitudes remained unchanged across conditions (all p > 0.1). In the ActiveHP session, explorative cross-modal analysis revealed that MEP decreases after HP-like induction were associated with P2 amplitude increase (CPz: r = −0.54, p = 0.015) and faster P2 latency (C2: r = +0.45, p = 0.04). No cross-modal associations were observed in ShamHP (all p > 0.1).

Conclusions: This is the first study to simultaneously assess HP-like responses in the motor and nociceptive systems within the same session, enabling direct evaluation of cross-modal plasticity. The selective modulation of the N1 component, the earliest cortical index of event-related input such as nociception, suggests that HP-like mechanisms preferentially target early nociceptive processing rather than later aspects of the pain response (e.g., attention, awareness). Exploratory cross-modal associations between MEP decreases and CHEP changes could suggest a cross-modal HP-like coupling between motor and nociceptive systems. These findings need further analysis. The absence of group-level MEP effects likely reflects high inter-individual variability in HP-like responses, which attenuates mean effects while preserving individual-level associations, with potential relevance for understanding maladaptive plasticity in chronic pain.

References: [1] Karabanov A, Ziemann U, Hamada M, George MS, Quartarone A, Classen J, Massimini M, Rothwell J, Siebner HR. Consensus Paper: Probing Homeostatic Plasticity of Human Cortex With Non-invasive Transcranial Brain Stimulation. Brain Stimul 2015;8:442–454.
[2] Thapa T, Schabrun SM. Test-Retest Reliability of Homeostatic Plasticity in the Human Primary Motor Cortex. Neural Plast 2018;2018:1–9.
[3] Zolezzi DM, Larsen DB, McPhee M, Graven-Nielsen T. Effects of pain on cortical homeostatic plasticity in humans: a systematic review. Pain Rep 2024;9:e1141.

Presenting Author: Daniela M. Zolezzi
Submitting Author: Daniela M. Zolezzi

Senior Author: Thomas Graven-Nielsen

IASP 2026 Global Year theme of Neuropathic Pain: No

• Carolina Queiroz: MSc - Center for Neuroplasticity and Pain, Aalborg University
• Bárbara Silva-Passadouro: MSc. - University of Leeds
• Dennis Boye Larsen: PhD - Center for Neuroplasticity and Pain, Aalborg University
• Thomas Graven-Nielsen: DMSc. PhD. - Center for Neuroplasticity and Pain, Aalborg University