657: Age and Sex differences in pain-relevant cortical excitability, oscillatory dynamics, and complexity

Topic: Experimental (Non-clinical) Human Studies
Subtopic: Non -specific to any diagnosis, Gender/sex differences, Electrophysiology/Clinical neurophysiology (e.g. microneurography, EEG, MEG, OPMs, TMS)

Background and Aims: Transcranial Magnetic Stimulation coupled with electroencephalography (TMS-EEG) targeting the primary motor cortex (M1) enables the study of cortical excitability, oscillatory dynamics and cortical complexity during pain [1]. Experimental pain reduces cortical excitability [2] and alters oscillatory dynamics [3], while reduced cortical complexity has been reported in fibromyalgia [4]. Cortical excitability is known to be affected by age [5], but not by sex. Furthermore, it remains unclear whether cortical oscillatory dynamics and complexity show age and sex- related differences. Understanding the effect of age and sex is relevant when building normative data and designing pain studies where TMS-EEG is employed.

Methods: In 167 pain-free participants (20–77 years), participants above 40 years represented the oldest group (57.2±12.2; N = 43, 23 females). A comparison group was selected from the youngest participants and sex-matched to the older group (age: 22.7±1.3; N = 43). The left M1 was assessed using TMS-EEG (64 channels EEG, 200 trials TMS). Following automated a standardized preprocessing of EEG signals. Cortical excitability was analyzed using Local/Global Mean Field Power (LMFP/GMFP), cortical oscillatory dynamics were assessed by alpha-band Inter-Trial Coherence (ITC) in a cluster of electrodes at the stimulation site and cortical complexity by Perturbational Complexity Index (PCIST).

Results: The younger group had higher LMFP and GMFP compared to the older group (both p<0.05). By contrast, ITC and PCIst did not differ between groups (both p>0.05). When comparing sex, no differences were found in cortical excitability, oscillatory dynamics and complexity (all p>0.05) between male and females. There was no significant interaction between age and sex.

Conclusions: In this sample, higher age was associated with reduced cortical excitability. In contrast, no such differences were observed in cortical oscillatory dynamics or complexity between young and old participants, indicating that cortical synchronization and complexity are similar between older and younger subjects. No differences were found between sexes. Future studies should link the reduced age-related cortical excitability with changes in pain mechanisms. Further, these findings will inform efforts to establish normative data for TMS-EEG and control selection for pain studies using these techniques.

References: 1: De Martino, et al. (2025) – medRxiv, https://doi.org/10.1101/2025.10.11.25337793
2: De Martino et al., (2023) – Cerebral Cortex, https://www.doi.org/10.1093/cercor/bhad259
3: De Martino et al., (2024) - Human Brain Mapping, https://doi.org/10.1002/hbm.26679
4: Jakobsen et al., (2025) – Bioxiv, https://doi.org/10.1101/2025.09.29.678190
5: Ferreri et al., (2017) – Neuroscience, https://doi.org/10.1016/j.neuroscience.2017.06.014

Presenting Author: Anne Jakobsen
Submitting Author: Anne Jakobsen

Senior Author: Daniel Ciampi de Andrade

IASP 2026 Global Year theme of Neuropathic Pain: No

• Enrico De Martino: PhD - Center for Neuroplasticity and Pain (CNAP), Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark
• Bruno Nascimento Couto: Master's degree - Center for Neuroplasticity and Pain (CNAP), Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark
• Margit Midtgaard Bach: PhD - Center for Neuroplasticity and Pain (CNAP), Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark
• Stian Ingemann-Molden: Master's degree - Center for Neuroplasticity and Pain (CNAP), Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark
• Vithushan Amirthanathan: Bachelor degree - Center for Neuroplasticity and Pain (CNAP), Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark
• Thomas Graven-Nielsen: PhD - Center for Neuroplasticity and Pain (CNAP), Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark
• Daniel Ciampi de Andrade: PhD - Center for Neuroplasticity and Pain (CNAP), Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark