Background: Spinal cord injury (SCI) affects approximately 250,000 to 500,000 individuals annually. Current therapeutic interventions predominantly focus on mitigating the impact of physical and neurological impairments, with limited functional recovery observed in many patients. Electroencephalogram (EEG) oscillations have been investigated in this context of rehabilitation to identify effective markers for optimizing rehabilitation treatments. Methods: We performed an exploratory cross-sectional study assessing the baseline EEG resting state of 86 participants with SCI as part of the Deficit of Inhibitory as a Marker of Neuroplasticity in Rehabilitation Cohort Study (DEFINE). Results: Our multivariate models demonstrated a positive correlation between frontal delta asymmetry and depression symptoms, while the frontal alpha asymmetry band and anxiety symptoms were negatively correlated. Theta oscillations were negatively associated with motor-evoked potential (MEP), whereas alpha oscillations were positively associated with MEP in all regions of interest and with CPM response as a negative correlation. Based on the potential role of lower-frequency oscillations in exerting a salutogenic compensatory effect, detrimental clinical and neurophysiological markers, such as depression and lower ME, likely induce slow oscillatory rhythms. Alpha oscillations may indicate a more salutogenic state, often associated with various cognitive functions, such as attention and memory processing. Conclusions: These results show an attempt by the CNS to reorganize and restore function despite the disruption caused by SCI. Indeed, this finding also challenges the notion that low-frequency EEG rhythms are associated with cortical lesions. These results may contribute to the development of rehabilitation strategies and potentially improve the clinical outcomes of patients with SCI.

Objective: As outlined in our previous study, this study aims to investigate the role of body mass index (BMI) as an effect modifier in the relationship between conditioned pain modulation (CPM) and clinical outcomes, including depression, quality of life, and pain in individuals with knee osteoarthritis (KOA). Methods: This cross-sectional analysis is part of the DEFINE Study in Rehabilitation. A total of 113 participants with KOA, admitted to the Instituto de Medicina Física e Reabilitação (IMREA) rehabilitation program, were included. Clinical and neurophysiological assessments were conducted, focusing on CPM, the Hamilton Depression Rating Scale (HDRS), and the SF-36 health survey. BMI was stratified into two categories based on the mean BMI of 31.99 kg/m², and linear regression models were used to evaluate BMI as an effect modifier in the relationship between CPM and clinical outcomes. p-values below 0.10 for interaction terms (CPM × BMI) indicated effect modification. Results: In participants with BMI < 31.99 kg/m², increased CPM was significantly associated with improved depression scores (lower HDRS) and enhanced physical functioning, emotional well-being, and reduced limitations due to emotional problems (SF-36). In contrast, no significant associations between CPM and these outcomes were found in participants with BMI ≥ 31.99 kg/m². The results suggest that a higher BMI disrupts the salutogenic effects of endogenous pain control, diminishing the beneficial associations between CPM and both physical and psychological outcomes, as previously observed in fibromyalgia patients. Conclusions: BMI acts as an effect modifier in the relationship between CPM and clinical outcomes in individuals with KOA. Obesity appears to hinder the beneficial relationships between clinical symptoms and CPM, leading to a less favorable link between physical and emotional functioning and CPM. These findings highlight the importance of considering BMI in treatment strategies for KOA, particularly when addressing the impact of lifestyle and other modifiable factors that influence pain modulation.

Objective: This study aimed to explore longitudinal relationships between neurophysiological biomarkers and upper limb motor function recovery in stroke patients, focusing on electroencephalography (EEG) and transcranial magnetic stimulation (TMS) metrics. Methods: This longitudinal cohort study analyzed neurophysiological, clinical, and demographic data from 102 stroke patients enrolled in the DEFINE cohort. We investigated the associations between baseline and post-intervention changes in the EEG theta/alpha ratio (TAR) and TMS metrics with upper limb motor functionality, assessed using the outcomes of five tests: the Fugl-Meyer Assessment (FMA), Handgrip Strength Test (HST), Pinch Strength Test (PST), Finger Tapping Test (FTT), and Nine-Hole Peg Test (9HPT). Results: Our multivariate models identified that a higher baseline TAR in the lesioned hemisphere was consistently associated with poorer motor outcomes across all five assessments. Conversely, a higher improvement in the TAR was positively associated with improvements in FMA and 9HPT. Additionally, an increased TMS motor-evoked potential (MEP) amplitude in the non-lesioned hemisphere correlated with greater FMA-diff, while a lower TMS Short Intracortical Inhibition (SICI) in the non-lesioned hemisphere was linked to better PST improvements. These findings suggest the potential of the TAR and TMS metrics as biomarkers for predicting motor recovery in stroke patients. Conclusion: Our findings highlight the significance of the TAR in the lesioned hemisphere as a predictor of motor function recovery post-stroke and also a potential signature for compensatory oscillations. The observed relationships between the TAR and motor improvements, as well as the associations with TMS metrics, underscore the potential of these neurophysiological measures in guiding personalized rehabilitation strategies for stroke patients.

Background: Neuroplasticity, involving cortical and subcortical reorganization, plays a critical role in the adaptation and compensation process post-amputation. However, underlying neurophysiological changes remain unclear, particularly in brain oscillations. Methods: This is a cross-sectional analysis that includes baseline data from 48 individuals with lower limb amputation from our DEFINE Cohort Study project. EEG data were collected using a 64-channel system during a 5-min resting-state period. Preprocessed data were analyzed for delta and alpha oscillations across frontal, central, and parietal regions. Logistic regression models examined associations between EEG oscillations and clinical variables, including cognition (MoCA), functional independence (FIM), and phantom limb sensations (PLS). Results: The multivariate logistic regression analysis revealed distinct patterns of association between EEG oscillations and clinical variables. Delta oscillations were inversely associated with cognitive scores (OR: 0.69; p = 0.048), while higher delta power was related to the absence of PLS (OR: 58.55; p < 0.01). Frontal alpha power was positively linked to cognitive function (OR: 1.55; p = 0.02) but negatively associated with functional independence (OR: 0.75; p = 0.04). Conclusions: These findings suggest that lower frequencies, such as delta oscillations, play a role as potential compensatory brain rhythms. In contrast, alpha oscillations may reflect a more adapted pattern of brain reorganization after amputation.

Background: Amputation poses significant physical, psychological, and emotional challenges, with chronic pain being one of the most debilitating outcomes. Pain Pressure Threshold (PPT), a measure of nociceptive sensitivity, is a valuable tool for assessing changes in pain perception. Understanding PPT modulation in amputees is crucial for uncovering the mechanisms underlying pain and developing targeted interventions for pain management. Objective: This study aimed to evaluate PPT in amputees and identify factors associated with PPT variation in this population. Methods: This cross-sectional study analyzed neurophysiological, clinical, and demographic data from 86 amputee patients. PPT was assessed as the primary outcome, and its associations with demographic and clinical predictors were examined using both linear and quadratic regression models. Results: Multivariate analysis identified a significant association between PPT and biological sex, with females exhibiting lower PPT values than males. Quadratic regression analyses revealed inverted U-shaped associations between PPT and age, BMI, and duration since amputation. PPT increased with age, peaking at 45.8 years, followed by a decline. Similar patterns were observed for BMI, peaking at 27.0 kg/m², and for amputation duration, peaking at 26.6 months. Conclusions: Our findings indicate that sex, age, BMI, and time since amputation are significant factors influencing PPT in amputees, with nonlinear relationships observed for age, BMI, and amputation duration. These results suggest that physiological and disease-related factors (such as age, BMI, and duration of injury) have specific peaks for optimal PPT, highlighting their role in the brain’s compensatory system and potential implications for targeted pain management strategies.

Background: Spinal cord injury (SCI) frequently leads to pain, leading to significant disability. Pain sensitization, a key feature of SCI, is commonly assessed via quantitative sensory testing like the Pressure Pain Threshold (PPT), though the factors influencing PPT changes remain unclear. This study hypothesizes that specific clinical and neurophysiological factors modulate PPT in SCI patients. The primary objective is to identify predictors of PPT in SCI patients. Methods: We conducted a cross-sectional analysis of neurophysiological, clinical, and demographic data from 102 SCI patients in an ongoing prospective cohort study called “Deficit of Inhibition as a Marker of Neuroplasticity” (DEFINE study). Multivariable regression analyses were used to evaluate demographic, clinical, and functional variables associated with PPT, the primary outcome measure. Results: The sample comprised 87.9% males with an average age of 41. Trauma was the leading cause of SCI (77.45%), predominantly affecting the cervical and thoracic levels. Pain was reported by 44% of participants, and the mean PPT was 8.3 kPa, measured bilaterally. Multivariate analysis of PPT in the left, right, and bilateral thenar regions revealed consistent trends. Significant negative associations were found between bilateral PPT and low beta EEG frequency in the central area (β = −14.94, p = 0.017), traumatic lesion etiology (β = −1.99, p = 0.038), and incomplete lesions by the American Spinal Injury Association classification (β = −1.68, p = 0.012). In contrast, positive associations were observed with age (β = 0.08, p < 0.001). Conclusions: Our findings show that increased beta oscillations and traumatic brain injury having a lower PPT indicate that factors associated with maladaptive plasticity are associated with decreased and likely less functional PPT. On the other hand, increased motor function may help to regulate PPT in a more functional status.