Nahian Shahmat Chowdhury

Affordable electroencephalography (EEG) headsets could widen access to EEG-based treatment and assessment, but require rigorous validation. We evaluated PainWaive, a custom-developed 2-channel central scalp EEG headset designed for remote EEG monitoring and neurofeedback research in chronic pain. Eighty participants completed two resting-state EEGs using PainWaive and a research-grade system (LiveAmp). Alpha, beta and theta power, and peak alpha frequency (PAF), were derived from homologous central channels. PainWaive demonstrated good-to-excellent test-retest reliability for alpha power and PAF (ICCs = 0.72-0.93), with beta and theta ranging from moderate-good (ICCs = 0.42-0.76). Across 160 home-based neurofeedback sessions in two chronic pain samples, reliability was good-to-excellent across metrics (ICCs = 0.72-0.88). Spectral-shape correlations between PainWaive and LiveAmp were excellent (r > 0.91). Cross-device agreement was moderate-to-good for alpha power and PAF (ICCs = 0.53-0.74), but weaker for beta and theta (ICCs = 0.16-0.51). Sensitivity analyses showed alpha power and PAF were robust across choices, whereas beta and theta agreement varied by pipeline. Overall, PainWaive demonstrated reliable measurement of central scalp EEG metrics, supporting repeated within-device monitoring. Cross-device findings showed correspondence with research-grade EEG for some measures but should not be interpreted as establishing direct numerical interchangeability between systems. These findings provide a technical foundation for future remote EEG and neurofeedback studies in chronic pain.

Recent research has linked individual peak alpha frequency (PAF) to pain sensitivity, but whether PAF alterations can influence pain remains unclear. Our study investigated the effects of nicotine on pain sensitivity and whether pain changes are mediated by PAF changes. In a randomised, double-blind, placebo-controlled experiment, 62 healthy adults (18–44 years) received either 4 mg nicotine (n=29) or placebo gum (n=33). Resting state EEG and pain ratings during prolonged heat and pressure models were collected before and after nicotine intake. The nicotine group showed a small decrease in heat-pain ratings compared to placebo group when controlling confounders, and a small increase in PAF across the scalp from pre- to post-gum, both with and without confounder adjustment. These effects were most pronounced in the central-parietal and right-frontal electrodes. However, mediation analysis did not support the notion that PAF changes mediate nicotine’s effects on pain sensitivity. While a growing body of literature supports a link between PAF and both acute and chronic pain, further work is needed to understand the mechanisms of this link.

Alpha-band oscillatory activity, assessed using electroencephalography (EEG), is among the most widely studied neurophysiological markers of pain. However, the literature has focused predominantly on resting-state measures, leaving unclear whether pain also alters evoked alpha-band dynamics, measured via cortical perturbation using transcranial magnetic stimulation (TMS). Here, we examined whether prolonged pain alters TMS-evoked alpha event-related spectral perturbation (ERSP) and intertrial coherence (ITC), reflecting cortical reactivity and phase consistency, and whether 10-Hz repetitive TMS (rTMS) modulates these responses. We performed a secondary analysis on 2 previous experiments, which used nerve growth factor (NGF) injection to induce prolonged elbow muscle pain. In experiment 1, participants underwent primary motor cortex (M1) TMS-EEG at baseline (day 0) pre-NGF injection and day 2 (peak pain) and day 7 (pain resolution) post-injection. In experiment 2, M1-TMS-EEG was assessed on day 0 before NGF injection and again on day 4 after injection, with active or sham 10-Hz rTMS delivered to M1 between these assessments. In experiment 1, M1 TMS-EEG showed reductions in alpha ERSP ( P = 0.014) and alpha ITC ( P = 0.041) from day 0 to day 2. In experiment 2, active rTMS produced a more positive pre-to-post change in alpha ERSP ( P = 0.006) relative to sham but did not alter alpha ITC ( P = 0.804). Our findings suggest that prolonged experimental pain is associated with diminished evoked alpha oscillatory activity, whereas high-frequency rTMS modulates this activity in the positive direction. These findings suggest that perturbation-evoked alpha metrics warrant further investigation as candidate biomarkers of pain state and response to neuromodulation.

Background: Spinal cord injury (SCI) is associated with widespread reorganisation of cortical sensorimotor circuits. Persistent complications such as spasticity and neuropathic pain suggest that homeostatic plasticity, which normally helps stabilise and constrain activity-dependent changes in sensorimotor circuits, may be disrupted after SCI. Homeostatic plasticity can be probed using repeated blocks of transcranial direct current stimulation (tDCS); in healthy individuals, two closely spaced excitatory blocks typically leads to an inhibitory response, reflected as a reduction in corticomotor excitability. Objective: To determine whether individuals with SCI show reduced homeostatic suppression of corticospinal excitability in response to repeated anodal tDCS, compared with healthy controls. Methods: Twenty adults with thoracic or below SCI and 20 healthy controls completed three counterbalanced sessions. Each session comprised two 10-minute blocks of 2 mA tDCS separated by 5 minutes, with the second block always being anodal tDCS over left primary motor cortex. The first block was either anodal, cathodal, or sham tDCS, yielding 3 condition types: anodal-anodal, cathodal-anodal, and sham-anodal. To assess corticomotor excitability, transcranial magnetic stimulation-evoked motor evoked potentials (MEPs) were elicited at baseline, after priming, and every 5 minutes for 60 minutes after the second block. The primary outcome was percent change in MEP amplitude from baseline. Results: In the anodal-anodal condition, the SCI group showed greater facilitation than controls over 0-30 minutes (estimate = 83.09, 95% CI 49.75 to 116.43, p < 0.001), suggestive of a weaker homeostatic response. The cathodal-anodal condition led to a significant overall facilitatory effect with no between-group difference, while the sham-anodal condition showed no change in MEP amplitude relative to baseline. Within the SCI group, exploratory subgroup analysis suggests that those with neuropathic pain and a traumatic injury showed greater facilitation in the anodal-anodal condition than those without these features, indicative of a weaker homeostatic response. Conclusions: SCI is associated with impairment in the homeostatic regulation of corticomotor excitability following repeated excitatory brain stimulation. Disrupted plasticity stabilisation may be relevant to persistent symptoms such as neuropathic pain.

Neuropathic pain (NP) affects approximately 60% of individuals with spinal cord injury (SCI). Existing pharmacological treatments provide only modest relief and are often limited by adverse effects, while non-pharmacological options show small effects at best. As such, there remains a need for accessible, mechanism-informed treatments for SCI-NP. This protocol describes a trial evaluating two promising home-based neuromodulatory interventions for SCI-NP - electroencephalography neurofeedback (EEG-NF) and transcranial direct current stimulation (tDCS) - tested both independently and when applied in combination. We will employ a partially double-blinded (i.e. 1 treatment blinded, the other not), 2×2 factorial randomised controlled trial. Adults with chronic SCI-NP (N=192) will be randomised to: (1) EEG-NF + active tDCS, (2) EEG-NF + sham tDCS, (3) active tDCS alone, or (4) sham tDCS alone, in addition to treatment as usual. Participants will complete 20 home-based sessions over 5 weeks. The primary outcome is change in overall pain severity with the primary endpoint being 6 weeks post-randomisation, with secondary endpoints at 16, 26 and 52 weeks post-randomisation. Secondary outcomes (worst pain intensity, pain interference, sleep, depressive symptoms, health-related quality of life) will be assessed at 6 weeks, 16 weeks, 26 weeks and 52 weeks post-randomisation. This will be the first large-scale trial of home-based EEG-NF and tDCS for SCI-NP. If found to be effective, these scalable interventions could be integrated into routine care and inform further optimisation of neuromodulation strategies for managing SCI-NP.

Affordable home-based electroencephalography (EEG) headsets could widen access to EEG assessment, but require rigorous validation before research or clinical use. Here, we evaluated a custom-developed 2-channel sensorimotor headset (PainWaive) intended for remote neuro-feedback and longitudinal monitoring in chronic pain. Eighty participants (47 female; mean age 24.0 years, SD 7.9) completed two resting-state sessions with PainWaive and a research-grade 64-channel EEG system (LiveAmp), under eyes-open (EO) and eyes-closed (EC) conditions. Alpha, beta and theta power and peak alpha frequency (PAF) were derived from homologous sensorimotor channels (C1/C2). Relative reliability was quantified with intraclass correlation coefficients (ICCs), absolute reliability with SEM%, and cross-device consistency with between-device ICCs and Pearson correlations of overall spectral shape. ICCs/correlations were interpreted using pre-specified thresholds: fair 0.20–0.39, moderate 0.40–0.59, good 0.60–0.79, excellent ≥0.80. PainWaive and LiveAmp showed comparable absolute reliability across metrics (similar SEM%). Under EC, PainWaive reliability was excellent for alpha (0.81), theta (0.85) and PAF (0.94), and good for beta (0.72). Under EO, reliability was excellent for alpha (0.82), good for beta and PAF (0.61–0.72), and moderate for theta (0.59). Spectral-shape correlations between devices were excellent (r>0.90). Cross-device ICCs were good under EC for alpha/theta/PAF (ICC=0.66–0.77) though fair for beta (0.35). Under EO, ICCs were good for alpha (0.62), moderate for PAF (0.53), and fair for beta/theta (0.26–0.32). To assess performance under real-world use, we additionally analysed 2 clinical samples of individuals (total n = 8) with chronic pain who each completed 20 home-based neurofeedback sessions using PainWaive (160 sessions total). Within-session stability was good-to-excellent across metrics (ICCs>0.72). Overall, our findings suggest PainWaive is a reliable tool for the assessment of EEG metrics, supporting its use in research and clinical applications.

Repetitive transcranial magnetic stimulation (rTMS) is a promising, safe, and non-invasive treatment for pain. However, there is no clear understanding of the cortical mechanisms underlying the analgesic effect of rTMS. One theory is that rTMS-induced analgesia is associated with alterations in corticomotor and cortical excitability, assessed using single-pulse TMS and TMS-electroencephalography (TMS-EEG), respectively. The aim of this systematic review and meta-analysis will be to synthesise the available literature to determine the following: (1) the effect of rTMS on corticospinal and cortical excitability across experimental pain and acute and chronic clinical pain conditions; (2) whether changes in cortical/corticospinal excitability correlate with changes in pain outcomes for these pain types following rTMS. Electronic databases (Scopus, PubMed, MEDLINE, PsycINFO, and Web of Science) will be searched using a predetermined strategy. All studies published before December 2024 that investigated the effects of rTMS on cortical/corticomotor excitability and pain (experimental, acute or chronic clinical pain) will be included if they meet eligibility criteria. Study identification, data extraction, and risk of bias assessment will be conducted by two independent reviewers, with a third reviewer consulted for any disagreements. We will extract the group level and individual level changes in corticomotor excitability and/or cortical excitability and pain outcomes before and after rTMS. Group level effect sizes of rTMS on corticomotor/cortical excitability and the individual level association between changes in pain and corticomotor/cortical excitability for different pain conditions (experimental, acute or chronic clinical pain) will be synthesized using a random effects meta-analysis. Subgroup analyses are planned, separating effect sizes for different pain conditions and different rTMS protocols. This review will provide the evidence for the cortical and corticomotor mechanisms associated with rTMS-induced analgesia, both at a group and individual level. International Prospective Register of Systematic Reviews CRD42024594054.

Recent studies using combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG) have shown that pain leads to an increase in the N45 peak of the TMS-evoked potential (TEP), potentially linked to changes in GABAergic activity. Conversely, 10 Hz repetitive TMS (10 Hz-rTMS), which provides pain relief, reduces the N45 peak. However, these studies used brief pain stimuli (lasting minutes), limiting their clinical relevance. The present study determined the effect of pain and 10 Hz-rTMS on the N45 peak in a prolonged pain model (lasting several days) induced by nerve growth factor (NGF) injection to the elbow muscle. In Experiment 1, TEPs were measured in 22 healthy participants on Day 0 (pre-NGF), Day 2 (peak pain), and Day 7 (pain recovery). In Experiment 2, we examined the effect of 5 days of active (n = 16) or sham (n = 16) rTMS to the left primary motor cortex (M1) on the N45 peak during prolonged NGF-induced pain, with TEPs measured on Day 0 and Day 4 (post-rTMS). Peak pain and muscle soreness was mild to moderate across experiments. In Experiment 1, there was no evidence for an increase in the N45 peak during prolonged pain. Exploratory analyses revealed evidence for a reduction in the N45 peak from Day 2 to 7, and a correlation between higher pain severity on Day 2 and a larger increase in the N45 peak. In Experiment 2, active rTMS reduced the N45 peak on Day 4 versus Day 0, with no effect in the sham group. Overall, our study showed that during prolonged pain, 5 days of 10 Hz rTMS induces a reduction in the TEP N45 peak. However, contrary to previous studies, prolonged pain itself did not increase the N45 peak. Taken together, this study provides weaker evidence for a link between the N45 peak and pain perception compared to previous research. Nonetheless, exploratory findings—such as a reduction in the N45 peak during the pain recovery phase and an individual-level relationship between increases in N45 and pain severity—suggest that further studies with larger sample sizes and more robust pain models are needed to clarify this connection.

Introduction: Repetitive transcranial magnetic stimulation (rTMS) is a promising, safe, and non-invasive treatment for pain. However, there is no clear understanding of the cortical mechanisms underlying the analgesic effect of rTMS. One theory is that rTMS-induced analgesia is associated with alterations in corticomotor and cortical excitability, assessed using single-pulse TMS and TMS-electroencephalography (TMS-EEG) respectively. The aim of this systematic review and meta-analysis will be to synthesise the available literature to determine: 1) the effect of rTMS on corticospinal and cortical excitability across experimental pain, and acute and chronic clinical pain conditions; 2) whether changes in cortical/corticospinal excitability correlate with reductions in pain severity for these pain types following rTMS. Methods/Analysis: Electronic databases (Scopus, PubMed, MEDLINE, PsycINFO and Web of Science) will be searched using a predetermined strategy. Studies published before December 2024 that investigated the effects of rTMS on cortical/ corticomotor excitability and pain (experimental, acute or chronic clinical pain) will be included if they meet eligibility criteria. Study identification, data extraction and risk of bias assessment will be conducted by two independent reviewers, with a third reviewer consulted for any disagreements. We will extract the group level and individual level changes in corticomotor excitability (i.e., motor evoked potential amplitude or motor map volume) and/or cortical excitability (TMS-evoked potential peak amplitude) and pain severity, before and after rTMS. Group level effect sizes of rTMS on corticomotor/cortical excitability and the individual level association between changes in pain and corticomotor/cortical excitability for different pain conditions (experimental, acute or chronic clinical pain) will be synthesized using a random effects meta-analysis. Subgroup analyses are planned, separating effect sizes for different pain conditions and different rTMS protocols. Discussion This review will provide the evidence for the cortical and corticomotor mechanisms associated with rTMS-induced analgesia, both at a group and individual level. Registration Number: The systematic review is registered with the International Prospective Register of Systematic Reviews (Insert number)

The glutathione shunt is one of the most important contributors to the cellular redox state, with implications across cancer, chronic diseases, diseases of ageing, and autoimmune diseases, including inflammatory bowel disease (IBD). Traditionally, the redox state is gauged by the ratio of the surrogate metabolites GSH and GSSG. However, this presents methodological challenges and offers a constrained illustration of metabolites without a systems-level understanding of redox dynamics, failing to elucidate variations across an entire biochemical network. Targeted proteomics can fill this void. Here, we describe an in-parallel metabolomic and proteomic targeted method to encompass measurements directly related to the shunt. Samples are simultaneously prepared to extract the substrate building blocks, cysteine, cystine, methionine, glutamic acid, and kynurenine; and the proteins, SLC7A11 (xCT), Glutamate Cysteine Ligase (GSH1), Glutathione Synthetase (GSH2), Glutathione Peroxidase (GPx), and Glutathione Reductase (GSHR) for targeted mass spectrometry. We demonstrate the method by targeted analysis of proteins in plasma, serum, nasal swab, and saliva and apply the multi-omic method to assess changes in the glutathione shunt in the serum of patients diagnosed with IBD. This allows for a broader narrative to establish context at which the glutathione shunt is operating.