Repeated mild traumatic brain injuries impair visual discrimination learning in adolescent mice.

Cognitive deficits following a mild traumatic brain injury (mTBI) are common and are associated with learning deficits in school-age children. Some of these deficits include problems with long-term memory, working memory, processing speeds, attention, mental fatigue, and executive function. Processing speed deficits have been associated with alterations in white matter, but the underlying mechanisms of many of the other deficits are unclear. Without a clear understanding of the underlying mechanisms we cannot effectively treat these injuries. The goal of these studies is to validate a translatable touchscreen discrimination/reversal task to identify deficits in executive function following a single or repeated mTBIs. Using a mild closed skull injury model in adolescent mice we were able to identify clear deficits in discrimination learning following repeated injuries that were not present from a single mTBI. The repeated injuries were not associated with any deficits in motor-based behavior but did induce a robust increase in astrocyte activation. These studies provide an essential platform to interrogate the underlying neurological dysfunction associated with these injuries.

Using remotely delivered Spring Forest Qigong™ to reduce neuropathic pain in adults with spinal cord injury: A non-randomized controlled trial.

Importance: The manuscript proposes the feasibility and potential of a remote Qigong intervention to reduce neuropathic pain in adults with spinal cord injury (SCI)-related neuropathic pain. Objective: We determined the feasibility and estimates of efficacy of a remotely delivered Qigong intervention in adults with SCI-related neuropathic pain. Design: This is a non-randomized controlled trial with outcomes assessed at baseline-, 6- and 12-weeks of Qigong practice, and at 6-weeks and 1-year follow-up. Setting: Completely remote clinical trial. Participants: Adults with SCI-related neuropathic pain, with SCI ≥3 months, with complete or incomplete SCI, and highest neuropathic pain level of >3 on the Numeric Pain Rating Scale (NPRS). We used nationwide volunteer sampling.We recruited 23 adults with chronic SCI (7/2021-2/2022). Eighteen participants started the study and completed all study components, including the 6-week follow-up. Twelve participants completed the 1-year follow-up assessment. Intervention: Participants practiced the Spring Forest Qigong™ "Five Element Healing Movements" with an online video by combining movement with kinesthetic imagery, at least 3x/week for 12 weeks. Main Outcomes and Measures: To address the feasibility outcome and track adherence, the website automatically monitored the days and duration that the Qigong video was played. Self-report neuropathic pain intensity and SCI-related symptoms such as spasms, functional performance, mood, and body appreciation were also collected. Results: Eighteen participants, 60±12 years of age, 15±11 years post-SCI had a highest baseline neuropathic pain of 7.94±2.33 on the NPRS, which was reduced to 4.17±3.07 after 12 weeks of Qigong practice (Cohen's d =1.75). This pain relief remained at 6-week and 1-year follow-ups. Participants reported reduced spasm frequency (change score 1.17±1.20, d =0.98) and severity (0.72±1.02, d =0.71), and reduced interference of neuropathic pain on mood (3.44±2.53, d =1.36), sleep (3.39±2.40, d =1.41), and daily activities (3.17±2.77, d =1.14). They had a greater ability to perform functional activities (Patient Specific Functional Scale, 6.68±3.07, d =2.18) and had improved mood (Patient Health Questionnaire-9, 2.33±3.31, d =0.70). Conclusions and Relevance: Our preliminary data demonstrate the feasibility of Qigong practice in adults with SCI-related neuropathic pain and promising results of neuropathic pain relief and improvement in SCI-related symptoms after Qigong practice. Trial Registration this manuscript refers to the quasi-experimental substudy: CREATION: A Clinical Trial of Qigong for Neuropathic Pain Relief in Adults with Spinal Cord Injury, NCT04917107 , https://www.clinicaltrials.gov/ct2/show/NCT04917107 .

Feasibility of using remotely delivered Spring Forest Qigong to reduce neuropathic pain in adults with spinal cord injury: a pilot study.

Introduction: Approximately 69% of 299,000 Americans with spinal cord injury (SCI) suffer debilitating chronic neuropathic pain, which is intractable to treatment. The aim of this study is to determine feasibility, as the primary objective, and estimates of efficacy of a remotely delivered Qigong intervention in adults with SCI-related neuropathic pain, as the secondary objective. Methods: We recruited adults with SCI-related neuropathic pain, with SCI ≥3 months, with complete or incomplete SCI, and highest neuropathic pain level of >3 on the Numeric Pain Rating Scale (NPRS), using nationwide volunteer sampling. Using a non-randomized controlled trial design, participants practiced Spring Forest Qigong's "Five Element Qigong Healing Movements" (online video) by combining movement to the best of their ability with kinesthetic imagery, at least 3x/week for 12 weeks. Adherence was automatically tracked through the Spring Forest Qigong website. Outcomes of neuropathic pain intensity (NPRS) were assessed weekly, and SCI-related symptoms were assessed at baseline, 6, and 12 weeks of Qigong practice and at 6-week and 1-year follow-ups. Results: We recruited 23 adults with chronic SCI (7/2021-2/2023). In total, 18 participants started the study and completed all study components, including the 6-week follow-up. Twelve participants completed the 1-year follow-up assessment. Feasibility was demonstrated through participants' willingness to participate, adherence, and acceptability of the study. Mean age of the 18 participants was 60 ± 12 years, and they were 15 ± 11 years post-SCI with the highest baseline neuropathic pain of 7.94 ± 2.33, which was reduced to 4.17 ± 3.07 after 12 weeks of Qigong practice (Cohen's d = 1.75). This pain relief remained at 6-week and 1-year follow-ups. Participants reported reduced spasm frequency (change score 1.17 ± 1.20, d = 0.98) and severity (0.72 ± 1.02, d = 0.71), reduced interference of neuropathic pain on mood (3.44 ± 2.53, d = 1.36), sleep (3.39 ± 2.40, d = 1.41), daily activities (3.17 ± 2.77, d = 1.14), greater ability to perform functional activities (6.68 ± 3.07, d = 2.18), and improved mood (2.33 ± 3.31, d = 0.70) after Qigong. Discussion: Remote Spring Forest Qigong's "Five Element Qigong Healing Movements" practice is feasible in adults with SCI-related neuropathic pain, with promising prolonged results of neuropathic pain relief and improvement in SCI-related symptoms after Qigong practice. Clinical trial registration: https://www.clinicaltrials.gov/ct2/show/NCT04917107, identifier NCT04917107.

Identifying Body Awareness-Related Brain Network Changes after Cognitive Multisensory Rehabilitation for Neuropathic Pain Relief in Adults with Spinal Cord Injury: Delayed Treatment arm Phase I Randomized Controlled Trial.

Background: Neuropathic pain after spinal cord injury (SCI) is notoriously hard to treat. Mechanisms of neuropathic pain are unclear, which makes finding effective treatments challenging. Prior studies have shown that adults with SCI have body awareness deficits. Recent imaging studies, including ours, point to the parietal operculum and insula as key areas for both pain perception and body awareness. Cognitive multisensory rehabilitation (CMR) is a physical therapy approach that helps improve body awareness for pain reduction and sensorimotor recovery. Based on our prior brain imaging work in CMR in stroke, we hypothesized that improving body awareness through restoring parietal operculum network connectivity leads to neuropathic pain relief and improved sensorimotor and daily life function in adults with SCI. Thus, the objectives of this study were to (1) determine baseline differences in resting-state and task-based functional magnetic resonance imaging (fMRI) brain function in adults with SCI compared to healthy controls and (2) identify changes in brain function and behavioral pain and pain-associated outcomes in adults with SCI after CMR. Methods: Healthy adults underwent a one-time MRI scan and completed questionnaires. We recruited community-dwelling adults with SCI-related neuropathic pain, with complete or incomplete SCI >3 months, and highest neuropathic pain intensity level of >3 on the Numeric Pain Rating Scale (NPRS). Participants with SCI were randomized into two groups, according to a delayed treatment arm phase I randomized controlled trial (RCT): Group A immediately received CMR intervention, 3x/week, 45 min/session, followed by a 6-week and 1-year follow-up. Group B started with a 6-week observation period, then 6 weeks of CMR, and a 1-year follow-up. Highest, average, and lowest neuropathic pain intensity levels were assessed weekly with the NPRS as primary outcome. Other primary outcomes (fMRI resting-state and functional tasks; sensory and motor function with the INSCI AIS exam), as well as secondary outcomes (mood, function, spasms, and other SCI secondary conditions), were assessed at baseline, after the first and second 6-week period. The INSCI AIS exam and questionnaires were repeated at the 1-year follow-up. Findings: Thirty-six healthy adults and 28 adults with SCI were recruited between September 2020 and August 2021, and of those, 31 healthy adults and 26 adults with SCI were enrolled in the study. All 26 participants with SCI completed the intervention and pre-post assessments. There were no study-related adverse events. Participants were 52±15 years of age, and 1-56 years post-SCI. During the observation period, group B did not show any reductions in neuropathic pain and did not have any changes in sensation or motor function (INSCI ASIA exam). However, both groups experienced a significant reduction in neuropathic pain after the 6-week CMR intervention. Their highest level of neuropathic pain of 7.81±1.33 on the NPRS at baseline was reduced to 2.88±2.92 after 6 weeks of CMR. Their change scores were 4.92±2.92 (large effect size Cohen's d =1.68) for highest neuropathic pain, 4.12±2.23 ( d =1.85) for average neuropathic pain, and 2.31±2.07 ( d =1.00) for lowest neuropathic pain. Nine participants out of 26 were pain-free after the intervention (34.62%). The results of the INSCI AIS testing also showed significant improvements in sensation, muscle strength, and function after 6 weeks of CMR. Their INSCI AIS exam increased by 8.81±5.37 points ( d =1.64) for touch sensation, 7.50±4.89 points ( d =1.53) for pin prick sensation, and 3.87±2.81 ( d =1.38) for lower limb muscle strength. Functional improvements after the intervention included improvements in balance for 17 out of 18 participants with balance problems at baseline; improved transfers for all of them and a returned ability to stand upright with minimal assistance in 12 out of 20 participants who were unable to stand at baseline. Those improvements were maintained at the 1-year follow-up. With regard to brain imaging, we confirmed that the resting-state parietal operculum and insula networks had weaker connections in adults with SCI-related neuropathic pain (n=20) compared to healthy adults (n=28). After CMR, stronger resting-state parietal operculum network connectivity was found in adults with SCI. Also, at baseline, as expected, right toe sensory stimulation elicited less brain activation in adults with SCI (n=22) compared to healthy adults (n=26). However, after CMR, there was increased brain activation in relevant sensorimotor and parietal areas related to pain and mental body representations (i.e., body awareness and visuospatial body maps) during the toe stimulation fMRI task. These brain function improvements aligned with the AIS results of improved touch sensation, including in the feet. Interpretation: Adults with chronic SCI had significant neuropathic pain relief and functional improvements, attributed to the recovery of sensation and movement after CMR. The results indicate the preliminary efficacy of CMR for restoring function in adults with chronic SCI. CMR is easily implementable in current physical therapy practice. These encouraging impressive results pave the way for larger randomized clinical trials aimed at testing the efficacy of CMR to alleviate neuropathic pain in adults with SCI. Clinical Trial registration: ClinicalTrials.gov Identifier: NCT04706208. Funding: AIRP2-IND-30: Academic Investment Research Program (AIRP) University of Minnesota School of Medicine. National Center for Advancing Translational Sciences of the National Institutes of Health Award Number UL1TR002494; the Biotechnology Research Center: P41EB015894, the National Institute of Neurological Disorders & Stroke Institutional Center Core Grants to Support Neuroscience Research: P30 NS076408; and theHigh-Performancee Connectome Upgrade for Human 3T MR Scanner: 1S10OD017974.