Adaptive yoga versus low-impact exercise for adults with chronic acquired brain injury: a pilot randomized control trial protocol

BackgroundEach year, millions of Americans sustain acquired brain injuries (ABI) which result in functional impairments, such as poor balance and autonomic nervous system (ANS) dysfunction. Although significant time and energy are dedicated to reducing functional impairment in acute phase of ABI, many individuals with chronic ABI have residual impairments that increase fall risk, decrease quality of life, and increase mortality. In previous work, we have found that yoga can improve balance in adults with chronic (i.e., ≥6 months post-injury) ABI. Moreover, yoga has been shown to improve ANS and brain function in healthy adults. Thus, adults with chronic ABI may show similar outcomes. This protocol details the methods used to examine the effects of a group yoga program, as compared to a group low-impact exercise, on primary and secondary outcomes in adults with chronic ABI.MethodsThis study is a single-blind randomized controlled trial comparing group yoga to group low-impact exercise. Participants must be ≥18 years old with chronic ABI and moderate balance impairments. Group yoga and group exercise sessions occur twice a week for 1 h for 8 weeks. Sessions are led by trained adaptive exercise specialists. Primary outcomes are balance and ANS function. Secondary outcomes are brain function and structure, cognition, quality of life, and qualitative experiences. Data analysis for primary and most secondary outcomes will be completed with mixed effect statistical methods to evaluate the within-subject factor of time (i.e., pre vs. post intervention), the between-subject factor of group (yoga vs. low-impact exercise), and interaction effects. Deductive and inductive techniques will be used to analyze qualitative data.DiscussionDue to its accessibility and holistic nature, yoga has significant potential for improving balance and ANS function, along with other capacities, in adults with chronic ABI. Because there are also known benefits of exercise and group interaction, this study compares yoga to a similar, group exercise intervention to explore if yoga has a unique benefit for adults with chronic ABI.Clinical trial registration:ClinicalTrials.gov, NCT05793827. Registered on March 31, 2023

Interdisciplinary views of fNIRS: Current advancements, equity challenges, and an agenda for future needs of a diverse fNIRS research community

Functional Near-Infrared Spectroscopy (fNIRS) is an innovative and promising neuroimaging modality for studying brain activity in real-world environments. While fNIRS has seen rapid advancements in hardware, software, and research applications since its emergence nearly 30 years ago, limitations still exist regarding all three areas, where existing practices contribute to greater bias within the neuroscience research community. We spotlight fNIRS through the lens of different end-application users, including the unique perspective of a fNIRS manufacturer, and report the challenges of using this technology across several research disciplines and populations. Through the review of different research domains where fNIRS is utilized, we identify and address the presence of bias, specifically due to the restraints of current fNIRS technology, limited diversity among sample populations, and the societal prejudice that infiltrates today's research. Finally, we provide resources for minimizing bias in neuroscience research and an application agenda for the future use of fNIRS that is equitable, diverse, and inclusive

The ENIGMA sports injury working group - an international collaboration to further our understanding of sport-related brain injury

Sport-related brain injury is very common, and the potential long-term effects include a wide range of neurological and psychiatric symptoms, and potentially neurodegeneration. Around the globe, researchers are conducting neuroimaging studies on primarily homogenous samples of athletes. However, neuroimaging studies are expensive and time consuming, and thus current findings from studies of sport-related brain injury are often limited by small sample sizes. Further, current studies apply a variety of neuroimaging techniques and analysis tools which limit comparability among studies. The ENIGMA Sports Injury working group aims to provide a platform for data sharing and collaborative data analysis thereby leveraging existing data and expertise. By harmonizing data from a large number of studies from around the globe, we will work towards reproducibility of previously published findings and towards addressing important research questions with regard to diagnosis, prognosis, and efficacy of treatment for sport-related brain injury. Moreover, the ENIGMA Sports Injury working group is committed to providing recommendations for future prospective data acquisition to enhance data quality and scientific rigor

Linking Symptom Inventories using Semantic Textual Similarity

An extensive library of symptom inventories has been developed over time to measure clinical symptoms, but this variety has led to several long standing issues. Most notably, results drawn from different settings and studies are not comparable, which limits reproducibility. Here, we present an artificial intelligence (AI) approach using semantic textual similarity (STS) to link symptoms and scores across previously incongruous symptom inventories. We tested the ability of four pre-trained STS models to screen thousands of symptom description pairs for related content - a challenging task typically requiring expert panels. Models were tasked to predict symptom severity across four different inventories for 6,607 participants drawn from 16 international data sources. The STS approach achieved 74.8% accuracy across five tasks, outperforming other models tested. This work suggests that incorporating contextual, semantic information can assist expert decision-making processes, yielding gains for both general and disease-specific clinical assessment

A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.

This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.3448Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.We thank all participants of all the studies included for enabling this research by their participation in these studies. Computer resources for this project have been provided by the high-performance computing centers of the University of Michigan and the University of Regensburg. Group-specific acknowledgments can be found in the Supplementary Note. The Center for Inherited Diseases Research (CIDR) Program contract number is HHSN268201200008I. This and the main consortium work were predominantly funded by 1X01HG006934-01 to G.R.A. and R01 EY022310 to J.L.H

Oral Abstracts 7: RA ClinicalO37. Long-Term Outcomes of Early RA Patients Initiated with Adalimumab Plus Methotrexate Compared with Methotrexate Alone Following a Targeted Treatment Approach

Background: This analysis assessed, on a group level, whether there is a long-term advantage for early RA patients treated with adalimumab (ADA) + MTX vs those initially treated with placebo (PBO) + MTX who either responded to therapy or added ADA following inadequate response (IR). Methods: OPTIMA was a 78- week, randomized, controlled trial of ADA + MTX vs PBO + MTX in MTX-naïve early (<1 year) RA patients. Therapy was adjusted at week 26: ADA + MTX-responders (R) who achieved DAS28 (CRP) <3.2 at weeks 22 and 26 (Period 1, P1) were re-randomized to withdraw or continue ADA and PBO + MTX-R continued randomized therapy for 52 weeks (P2); IR-patients received open-label (OL) ADA + MTX during P2. This post hoc analysis evaluated the proportion of patients at week 78 with DAS28 (CRP) <3.2, HAQ-DI <0.5, and/or ΔmTSS ≤0.5 by initial treatment. To account for patients who withdrew ADA during P2, an equivalent proportion of R was imputed from ADA + MTX-R patients. Results: At week 26, significantly more patients had low disease activity, normal function, and/or no radiographic progression with ADA + MTX vs PBO + MTX (Table 1). Differences in clinical and functional outcomes disappeared following additional treatment, when PBO + MTX-IR (n = 348/460) switched to OL ADA + MTX. Addition of OL ADA slowed radiographic progression, but more patients who received ADA + MTX from baseline had no radiographic progression at week 78 than patients who received initial PBO + MTX. Conclusions: Early RA patients treated with PBO + MTX achieved comparable long-term clinical and functional outcomes on a group level as those who began ADA + MTX, but only when therapy was optimized by the addition of ADA in PBO + MTX-IR. Still, ADA + MTX therapy conferred a radiographic benefit although the difference did not appear to translate to an additional functional benefit. Disclosures: P.E., AbbVie, Merck, Pfizer, UCB, Roche, BMS—Provided Expert Advice, Undertaken Trials, AbbVie—AbbVie sponsored the study, contributed to its design, and participated in the collection, analysis, and interpretation of the data, and in the writing, reviewing, and approval of the final version. R.F., AbbVie, Pfizer, Merck, Roche, UCB, Celgene, Amgen, AstraZeneca, BMS, Janssen, Lilly, Novartis—Research Grants, Consultation Fees. S.F., AbbVie—Employee, Stocks. A.K., AbbVie, Amgen, AstraZeneca, BMS, Celgene, Centocor-Janssen, Pfizer, Roche, UCB—Research Grants, Consultation Fees. H.K., AbbVie—Employee, Stocks. S.R., AbbVie—Employee, Stocks. J.S., AbbVie, Amgen, AstraZeneca, BMS, Celgene, Centocor-Janssen, GlaxoSmithKline, Lilly, Pfizer (Wyeth), MSD (Schering-Plough), Novo-Nordisk, Roche, Sandoz, UCB—Research Grants, Consultation Fees. R.V., AbbVie, BMS, GlaxoSmithKline, Human Genome Sciences, Merck, Pfizer, Roche, UCB Pharma—Consultation Fees, Research Support. Table 1.Week 78 clinical, functional, and radiographic outcomes in patients who received continued ADA + MTX vs those who continued PBO + MTX or added open-label ADA following an inadequate response ADA + MTX, n/N (%)a PBO + MTX, n/N (%)b Outcome Week 26 Week 52 Week 78 Week 26 Week 52 Week 78 DAS28 (CRP) <3.2 246/466 (53) 304/465 (65) 303/465 (65) 139/460 (30)*** 284/460 (62) 300/460 (65) HAQ-DI <0.5 211/466 (45) 220/466 (47) 224/466 (48) 150/460 (33)*** 203/460 (44) 208/460 (45) ΔmTSS ≤0.5 402/462 (87) 379/445 (86) 382/443 (86) 330/459 (72)*** 318/440 (72)*** 318/440 (72)*** DAS28 (CRP) <3.2 + ΔmTSS ≤0.5 216/462 (47) 260/443 (59) 266/443 (60) 112/459 (24)*** 196/440 (45) 211/440 (48)*** DAS28 (CRP) <3.2 + HAQ-DI <0.5 + ΔmTSS ≤0.5 146/462 (32) 168/443 (38) 174/443 (39) 82/459 (18)*** 120/440 (27)*** 135/440 (31)** aIncludes patients from the ADA Continuation (n = 105) and OL ADA Carry On (n = 259) arms, as well as the proportional equivalent number of responders from the ADA Withdrawal arm (n = 102). bIncludes patients from the MTX Continuation (n = 112) and Rescue ADA (n = 348) arms. Last observation carried forward: DAS28 (CRP) and HAQ-DI; Multiple imputations: ΔmTSS. ***P < 0.001 and **iP < 0.01, respectively, for differences between initial treatments from chi-squar

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Evaluating Dual Task Neurological Costs with Functional Near-Infrared Spectroscopy: A Preliminary Report in Healthy Athletes

Background: Dual task assessments, which simultaneously challenge and assess cognitive and motor performance, have been used to improve the assessment of athletes with sports-related concussions (SRC). Our lab created a Dual Task Screen (DTS) to evaluate athletes with SRCs, and we have established that it is a valid behavioral measure, as it consistently elicits poorer behavioral performance under dual, compared to single, task conditions. Here, we used a Neuroimaging-Compatible (NC) version of the DTS, named the NC-DTS, which uses portable functional near-infrared spectroscopy (fNIRS) to assess behavioral performance and neural recruitment during single and dual tasks. Our study objective was to evaluate healthy athletes and establish whether the NC-DTS is a valid dual task neurological assessment that can elicit different patterns of neural recruitment during dual versus single task conditions. Methods: Twenty-five healthy collegiate athletes completed the NC-DTS in a single laboratory visit. The NC-DTS includes a lower and upper extremity subtask; both include single motor, single cognitive, and dual task conditions. The NC-DTS was administered in a block design, where conditions (i.e., single motor, single cognitive, and dual task) were repeated five times to generate average behavioral performance and task-dependent neural recruitment in superficial cortical regions including: prefrontal cortex, bilateral primary motor and sensory cortices, and posterior parietal cortex. Neural recruitment was measured with fNIRS and quantified using oxygenated hemoglobin (HbO) and deoxygenated hemoglobin (HbR) metrics. A single-tailed, within subject t-test was used to compare average dual task behavioral performance to average single task behavioral performance. Pairwise comparisons, that were family-wise-error (FWE) corrected, were used to compare localized neural recruitment during dual versus single task conditions. Results: As observed in previous studies, the NC-DTS elicited significantly poorer behavioral performance under dual, compared to single, task conditions. Additionally, dual task conditions of the NC-DTS elicited significantly greater neural recruitment in regions of the brain associated with attention allocation and task-specific demands in three of four comparisons. Conclusions: These preliminary results suggest that the NC-DTS is a valid dual task neurological assessment which warrants future work using the NC-DTS to evaluate athletes with SRCs

Task demands, tDCS intensity, and the COMT val(158)met polymorphism impact tDCS-linked working memory training gains

Working memory (WM) training paired with transcranial direct current stimulation (tDCS) can improve executive function in older adults. The unclear mechanism of tDCS likely depends on tDCS intensity, and task relevant genetic factors (e.g., for WM: COMT val(158)met, DAT, BDNF val(66)met). Higher tDCS intensity does not always lead to greater cognitive gains, and genetic polymorphisms may modulate tDCS-linked WM improvements. To evaluate these factors, 137 healthy older adults provided DNA samples and received Visual and Spatial WM training paired with tDCS (sham, 1, 1.5, 2 mA). After one session of tDCS, significant group differences in WM performance were predicted by COMT val158met status. One month after training, there was a significant interaction of tDCS intensity, COMT genotype, and WM task. Specifically, val/val homozygotes benefited most from 1.5 mA tDCS on Visual WM and from 1 mA tDCS on Spatial WM. For met/met homozygotes, 2 mA resulted in significantly poorer performance compared to 1.5 mA on Spatial WM. While this pattern was observed with relatively small sample sizes, these data indicate that variations in COMT val158met may predict the nature of WM improvement after initial and longitudinal tDCS. This contributes to our understanding of the underlying mechanism by which tDCS affects behaviour