Facilitation of working memory capacity by transcranial direct current stimulation: a secondary analysis from the augmenting cognitive training in older adults (ACT) study.

Aging is a public health concern with an ever-increasing magnitude worldwide. An array of neuroscience-based approaches like transcranial direct current stimulation (tDCS) and cognitive training have garnered attention in the last decades to ameliorate the effects of cognitive aging in older adults. This study evaluated the effects of 3 months of bilateral tDCS over the frontal cortices with multimodal cognitive training on working memory capacity. Two hundred ninety-two older adults without dementia were allocated to active or sham tDCS paired with cognitive training. These participants received repeated sessions of bilateral tDCS over the bilateral frontal cortices, combined with multimodal cognitive training. Working memory capacity was assessed with the digit span forward, backward, and sequencing tests. No baseline differences between active and sham groups were observed. Multiple linear regressions indicated more improvement of the longest digit span backward from baseline to post-intervention (p = 0.021) and a trend towards greater improvement (p = 0.056) of the longest digit span backward from baseline to 1 year in the active tDCS group. No significant between-group changes were observed for digit span forward or digit span sequencing. The present results provide evidence for the potential for tDCS paired with cognitive training to remediate age-related declines in working memory capacity. These findings are sourced from secondary outcomes in a large randomized clinical trial and thus deserve future targeted investigation in older adult populations.

Learning ratio performance on a brief visual learning and memory test moderates cognitive training gains in Double Decision task in healthy older adults.

Cognitive training using a visual speed-of-processing task, called the Useful Field of View (UFOV) task, reduced dementia risk and reduced decline in activities of daily living at a 10-year follow-up in older adults. However, there was variability in the achievement of cognitive gains after cognitive training across studies, suggesting moderating factors. Learning trials of visual and verbal learning tasks recruit similar cognitive abilities and have overlapping neural correlates with speed-of-processing/working memory tasks and therefore could serve as potential moderators of cognitive training gains. This study explored the association between the Hopkins Verbal Learning Test-Revised (HVLT-R) and Brief Visuospatial Memory Test-Revised (BVMT-R) learning with a commercial UFOV task called Double Decision. Through a secondary analysis of a clinical trial, we assessed the moderation of HVLT-R and BVMT-R learning on Double Decision improvement after a 3-month speed-of-processing/attention and working memory cognitive training intervention in a sample of 75 cognitively healthy older adults. Multiple linear regressions showed that better baseline Double Decision performance was significantly associated with better BVMT-R learning (ß = - .303). This association was not significant for HVLT-R learning (ß = - .142). Moderation analysis showed that those with poorer BVMT-R learning improved the most on the Double Decision task after cognitive training. This suggests that healthy older adults who perform below expectations on cognitive tasks related to the training task may show the greatest training gains. Future cognitive training research studying visual speed-of-processing interventions should account for differing levels of visuospatial learning at baseline, as this could impact the magnitude of training outcomes and efficacy of the intervention.

The Lipid Intensive Drug Therapy for Sepsis Phase II Pilot Clinical Trial.

OBJECTIVES: Low cholesterol levels in early sepsis patients are associated with mortality. We sought to test if IV lipid emulsion administration to sepsis patients with low cholesterol levels would prevent a decline or increase total cholesterol levels at 48 hours. DESIGN: Phase II, adaptive, randomized pilot clinical trial powered for 48 patients. SETTING: Emergency department or ICU of an academic medical center. PATIENTS: Sepsis patients (first 24 hr) with Sequential Organ Failure Assessment greater than or equal to 4 or shock. INTERVENTIONS: Patients meeting study criteria, including screening total cholesterol levels less than or equal to 100 mg/dL or high-density lipoprotein cholesterol (HDL-C) + low-density lipoprotein cholesterol (LDL-C) less than or equal to 70 mg/dL, were randomized to receive one of three doses of lipid emulsion administered twice in 48 hours or no drug (controls). The primary endpoint was a change in serum total cholesterol (48 hr - enrollment) between groups. MEASUREMENTS AND MAIN RESULTS: Forty-nine patients were enrolled and randomized. Two patients randomized to lipid emulsion were withdrawn before drug administration. Data for 24 control patients and 23 lipid emulsion patients were analyzed. The mean change in total cholesterol from enrollment to 48 hours was not different between groups and was 5 mg/dL (sd 20) for lipid emulsion patients, and 2 mg/dL (sd 18) for control patients (p = 0.62). The mean changes in HDL-C and LDL-C were similar between groups. Mean change in triglycerides was elevated in lipid emulsion patients (61 mg/dL, sd 87) compared with controls (20 mg/dL, sd 70, p = 0.086). The 48-hour change in SOFA score was -2 (interquartile range [IQR] -4, -1) for control patients and -2 (IQR -3, 0) for lipid emulsion patients (p = 0.46). CONCLUSIONS: Administration of IV lipid emulsion to early sepsis patients with low cholesterol levels did not influence change in cholesterol levels from enrollment to 48 hours.

Comparison of Pocock and Simon's covariate-adaptive randomization procedures in clinical trials.

When multiple influential covariates need to be balanced during a clinical trial, stratified blocked randomization and covariate-adaptive randomization procedures are frequently used in trials to prevent bias and enhance the validity of data analysis results. The latter approach is increasingly used in practice for a study with multiple covariates and limited sample sizes. Among a group of these approaches, the covariate-adaptive procedures proposed by Pocock and Simon are straightforward to be utilized in practice. We aim to investigate the optimal design parameters for the patient treatment assignment probability of their developed three methods. In addition, we seek to answer the question related to the randomization performance when additional covariates are added to the existing randomization procedure. We conducted extensive simulation studies to address these practically important questions.

Learning from vertically distributed data across multiple sites: An efficient privacy-preserving algorithm for Cox proportional hazards model with variable selection.

OBJECTIVE: To develop a lossless distributed algorithm for regularized Cox proportional hazards model with variable selection to support federated learning for vertically distributed data. METHODS: We propose a novel distributed algorithm for fitting regularized Cox proportional hazards model when data sharing among different data providers is restricted. Based on cyclical coordinate descent, the proposed algorithm computes intermediary statistics by each site and then exchanges them to update the model parameters in other sites without accessing individual patient-level data. We evaluate the performance of the proposed algorithm with (1) a simulation study and (2) a real-world data analysis predicting the risk of Alzheimer's dementia from the Religious Orders Study and Rush Memory and Aging Project (ROSMAP). Moreover, we compared the performance of our method with existing privacy-preserving models. RESULTS: Our algorithm achieves privacy-preserving variable selection for time-to-event data in the vertically distributed setting, without degradation of accuracy compared with a centralized approach. Simulation demonstrates that our algorithm is highly efficient in analyzing high-dimensional datasets. Real-world data analysis reveals that our distributed Cox model yields higher accuracy in predicting the risk of Alzheimer's dementia than the conventional Cox model built by each data provider without data sharing. Moreover, our algorithm is computationally more efficient compared with existing privacy-preserving Cox models with or without regularization term. CONCLUSION: The proposed algorithm is lossless, privacy-preserving and highly efficient to fit regularized Cox model for vertically distributed data. It provides a suitable and convenient approach for modeling time-to-event data in a distributed manner.

A Research Protocol to Study the Priming Effects of Breathing Low Oxygen on Enhancing Training-Related Gains in Walking Function for Persons With Spinal Cord Injury: The BO2ST Trial.

Brief episodes of low oxygen breathing (therapeutic acute intermittent hypoxia; tAIH) may serve as an effective plasticity-promoting primer to enhance the effects of transcutaneous spinal stimulation-enhanced walking therapy (WALKtSTIM) in persons with chronic (>1 year) spinal cord injury (SCI). Pre-clinical studies in rodents with SCI show that tAIH and WALKtSTIM therapies harness complementary mechanisms of plasticity to maximize walking recovery. Here, we present a multi-site clinical trial protocol designed to examine the influence of tAIH + WALKtSTIM on walking recovery in persons with chronic SCI. We hypothesize that daily (eight sessions, 2 weeks) tAIH + WALKtSTIM will elicit faster, more persistent improvements in walking recovery than either treatment alone. To test our hypothesis, we are conducting a placebo-controlled clinical trial on 60 SCI participants who randomly receive one of three interventions: tAIH + WALKtSTIM; Placebo + WALKtSTIM; and tAIH + WALKtSHAM. Participants receive daily tAIH (fifteen 90-sec episodes at 10% O2 with 60-sec intervals at 21% O2) or daily placebo (fifteen 90-sec episodes at 21% O2 with 60-sec intervals at 21% O2) before a 45-min session of WALKtSTIM or WALKtSHAM. Our primary outcome measures assess walking speed (10-Meter Walk Test), endurance (6-Minute Walk Test), and balance (Timed Up and Go Test). For safety, we also measure pain levels, spasticity, sleep behavior, cognition, and rates of systemic hypertension and autonomic dysreflexia. Assessments occur before, during, and after sessions, as well as at 1, 4, and 8 weeks post-intervention. Results from this study extend our understanding of the functional benefits of tAIH priming by investigating its capacity to boost the neuromodulatory effects of transcutaneous spinal stimulation on restoring walking after SCI. Given that there is no known cure for SCI and no single treatment is sufficient to overcome walking deficits, there is a critical need for combinatorial treatments that accelerate and anchor walking gains in persons with lifelong SCI. Trial Registration: ClinicalTrials.gov, NCT05563103.

Continuity corrected Wilson interval for the difference of two independent proportions.

Confidence interval for the difference of two proportions has been studied for decades. Many methods were developed to improve the approximation of the limiting distribution of test statistics, such as the profile likelihood method, the score method, and the Wilson method. For the Wilson interval developed by Beal (1987), the approximation of the Z test statistic to the standard normal distribution may be further improved by utilizing the continuity correction, in the observation of anti-conservative intervals from the Wilson interval. We theoretically prove that the Wilson interval is nested in the continuity corrected Wilson interval under mild conditions. We compare the continuity corrected Wilson interval with the commonly used methods with regards to coverage probability, interval width, and mean squared error of coverage probability. The proposed interval has good performance in many configurations. An example from a Phase II cancer trial is used to illustrate the application of these methods.

Connecting memory and functional brain networks in older adults: a resting-state fMRI study.

Limited research exists on the association between resting-state functional network connectivity in the brain and learning and memory processes in advanced age. This study examined within-network connectivity of cingulo-opercular (CON), frontoparietal control (FPCN), and default mode (DMN) networks, and verbal and visuospatial learning and memory in older adults. Across domains, we hypothesized that greater CON and FPCN connectivity would associate with better learning, and greater DMN connectivity would associate with better memory. A total of 330 healthy older adults (age range = 65-89) underwent resting-state fMRI and completed the Hopkins Verbal Learning Test-Revised (HVLT-R) and Brief Visuospatial Memory Test-Revised (BVMT-R) in a randomized clinical trial. Total and delayed recall scores were assessed from baseline data, and a learning ratio calculation was applied to participants' scores. Average CON, FPCN, and DMN connectivity values were obtained with CONN Toolbox. Hierarchical regressions controlled for sex, race, ethnicity, years of education, and scanner site, as this was a multi-site study. Greater within-network CON connectivity was associated with better verbal learning (HVLT-R Total Recall, Learning Ratio), visuospatial learning (BVMT-R Total Recall), and visuospatial memory (BVMT-R Delayed Recall). Greater FPCN connectivity was associated with better visuospatial learning (BVMT-R Learning Ratio) but did not survive multiple comparison correction. DMN connectivity was not associated with these measures of learning and memory. CON may make small but unique contributions to learning and memory across domains, making it a valuable target in future longitudinal studies and interventions to attenuate memory decline. Further research is necessary to understand the role of FPCN in learning and memory.

Circulating Inflammatory Biomarkers Predict Pain Change Following Exercise-Induced Shoulder Injury: Findings From the Biopsychosocial Influence on Shoulder Pain Preclinical Trial.

Shoulder pain is a highly prevalent musculoskeletal condition that frequently leads to suboptimal clinical outcomes. This study tested the extent to which circulating inflammatory biomarkers are associated with reports of shoulder pain and upper-extremity disability for a high-risk genetic by psychological subgroup (catechol-O-methyltransferase [COMT] variation by pain catastrophizing [PCS]). Pain-free adults meeting high-risk COMT × PCS subgroup criteria completed an exercise-induced muscle injury protocol. Thirteen biomarkers were collected and analyzed from plasma 48 hours after muscle injury. Shoulder pain intensity and disability (Quick-DASH) were reported at 48 and 96 hours to calculate change scores. Using an extreme sampling technique, 88 participants were included in this analysis. After controlling for age, sex, and BMI, there were moderate positive associations between higher c-reactive protein (CRP; ߈ = .62; 95% confidence interval [CI] = -.03, 1.26), interleukin-6 (IL-6; ߈ = 3.13; CI = -.11, 6.38), and interleukin-10 (IL-10; ߈ = 2.51; CI = -.30, 5.32); and greater pain reduction from 48 to 96 hours post exercise muscle injury. Using an exploratory multivariable model to predict pain changes from 48 to 96 hours, we found participants with higher IL-10 were less likely to experience a high increase in pain (߈ = -10.77; CI = -21.25, -2.69). Study findings suggest CRP, IL-6, and IL-10 are related to shoulder pain change for a preclinical high-risk COMT × PCS subgroup. Future studies will translate to clinical shoulder pain and decipher the complex and seemingly pleiotropic interplay between inflammatory biomarkers and shoulder pain change. PERSPECTIVE: In a preclinical high-risk COMT × PCS subgroup, 3 circulating inflammatory biomarkers (CRP, IL-6, and IL-10) were moderately associated with pain improvement following exercise-induced muscle injury.

Study protocol of a telephone problem-solving intervention for Spanish-speaking caregivers of veterans post-stroke: an 8-session investigator-blinded, two-arm parallel (intervention vs usual care), randomized clinical trial.

BACKGROUND: Stroke is one of the leading causes of death and the main cause of long-term disability in the United States. The significant risk factors of stroke among Hispanics are well-documented. The majority of stroke survivors return home following a stroke and are cared for by family caregivers. Due to the abrupt nature of strokes, caregivers experience unexpected changes and demands that oftentimes lead to caregiver burden and depression. Given the significant risk factors for stroke in Hispanics and the influence of culture in family norms and family management, we developed a telephone and online problem-solving intervention for Spanish-speaking stroke caregivers. This study tests the impact of a telephone and online problem-solving intervention for Spanish-speaking stroke caregivers on caregiver outcomes. METHODS: The design is a two-arm parallel randomized clinical trial with repeated measures. We will enroll 290 caregivers from 3 Veterans Affairs (VA) medical centers. Participants randomized into the intervention arm receive a problem-solving intervention that uses telephone and online education and care management tools on the previously developed and nationally available RESCUE en Español Caregiver website. In the usual care group, participants receive the information and/or support caregivers of veterans with stroke normally receive through existing VA resources (e.g., stroke-related information and support). The primary outcome is change in caregiver's depressive symptoms at 1- and 12-weeks post-intervention. Secondary outcomes include changes in stroke caregivers' burden, self-efficacy, problem-solving, and health-related quality of life (HRQOL) and veterans' functional abilities. We will also determine the budgetary impact, the acceptability of the intervention and participation barriers and facilitators for Spanish-speaking stroke caregivers. DISCUSSION: This is an ongoing study. It is the first known randomized controlled trial testing the effect of a telephone and online problem-solving intervention in Spanish for caregivers of veterans post-stroke. If successful, findings will support an evidence-based model that can be transported into clinical practice to improve the quality of caregiving post-stroke. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03142841- Spanish Intervention for Caregivers of Veterans with Stroke (RESCUE Español). Registered on February 23, 2018. Protocol version 8. 08.11.2022.

Effects of Prefrontal Transcranial Direct Current Stimulation on Retention of Performance Gains on an Obstacle Negotiation Task in Older Adults.

OBJECTIVES: Complex walking in older adults can be improved with task practice and might be further enhanced by pairing transcranial direct current stimulation (tDCS) to the dorsolateral prefrontal cortex. We tested the hypothesis that a single session of practice of a complex obstacle negotiation task paired with active tDCS in older adults would produce greater within-session improvements in walking performance and retention of gains, compared to sham tDCS and no tDCS conditions. MATERIALS AND METHODS: A total of 50 older adults (mean age = 74.46 years ± 6.49) with self-reported walking difficulty were randomized to receive either active tDCS (active-tDCS group) or sham tDCS (sham-tDCS group) bilaterally to the dorsolateral prefrontal cortex or no tDCS (no-tDCS group). Each group performed ten practice trials of an obstacle negotiation task at their fastest safe speed. Retention of gains in walking performance was assessed with three trials conducted one week later. Within-session effects of practice and between-session retention effects on obstacle negotiation speed were examined. RESULTS: At the practice session, all three groups exhibited significant within-session gains in walking speed (p ≤ 0.005). However, the gains were significantly greater in the sham-tDCS group than in the active-tDCS and no-tDCS groups (p ≤ 0.03) and were comparable between the active-tDCS and no-tDCS groups (p = 0.89). At one-week follow-up, the active-tDCS group exhibited significant between-session retention of gains and continued "offline" improvement in walking speed (p = 0.005). The active-tDCS group showed significantly greater retention of gains than the no-tDCS (p = 0.02) but not the sham-tDCS group (p = 0.24). CONCLUSIONS: Pairing prefrontal active tDCS with a single session of obstacle negotiation practice may enhance one-week retention of gains in walking performance compared to no tDCS. However, the evidence is insufficient to suggest a benefit of active tDCS over sham tDCS for enhancing the gains in walking performance. Additional studies with a multisession intervention design and larger sample size are needed to further investigate these findings. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT03122236.

Biopsychosocial influence on shoulder pain: results from a randomized preclinical trial of exercise-induced muscle injury.

ABSTRACT: Prior cohort studies validated that a subgroup defined by a specific COMT genotype and pain catastrophizing is at increased risk for heightened responses to exercise-induced or surgically induced shoulder pain. In this clinical trial, we used our preclinical model of exercise-induced muscle injury and pain to test the efficacy of interventions matched to characteristics of this high-risk subgroup (ie, personalized medicine approach). Potential participants provided informed consent to be screened for eligibility based on subgroup membership and then, as appropriate, were enrolled into the trial. Participants (n = 261) were randomized to 1 of 4 intervention groups comprised of pharmaceutical (propranolol or placebo) and informational (general education or psychologic intervention) combinations. After muscle injury was induced, participants received randomly assigned treatment and were followed for the primary outcome of shoulder pain intensity recovery over 4 consecutive days. Recovery rates were 56.4% (placebo and psychologic intervention), 55.4% (placebo and general education), 62.9% (propranolol and psychologic intervention), and 56.1% (propranolol and general education). No statistical differences were found between intervention groups in the primary analyses. Additional analyses found no differences between these intervention groups when shoulder pain duration was an outcome, and no differential treatment responses were detected based on sex, race, or level of pain catastrophizing. This trial indicates that these treatments were not efficacious for this high-risk subgroup when shoulder pain was induced by exercise-induced muscle injury. Accordingly, this phenotype should only be used for prognostic purposes until additional trials are completed in clinical populations.

The longitudinal impact of the COVID-19 pandemic on health behaviors, psychosocial factors, and cognitive functioning in older adults.

Background: Older adults are at a greater risk for contracting and experiencing severe illness from COVID-19 and may be further affected by pandemic-related precautions (e.g., social distancing and isolation in quarantine). However, the longitudinal impact of the COVID-19 pandemic on older adults is unclear. The current study examines changes in health behaviors, psychosocial factors, and cognitive functioning in a large sample of older adults using a pre-pandemic baseline and longitudinal follow-up throughout 9 months of the COVID-19 pandemic. Methods: One hundred and eighty-nine older adults (ages 65-89) were recruited from a multisite clinical trial to complete additional virtual assessments during the COVID-19 pandemic. Mixed effects models evaluated changes in health behaviors, psychosocial factors, and cognitive functioning during the pandemic compared to a pre-pandemic baseline and over the course of the pandemic (i.e., comparing the first and last COVID-19 timepoints). Results: Compared to their pre-pandemic baseline, during the pandemic, older adults reported worsened sleep quality, perceived physical health and functioning, mental health, slight increases in depression and apathy symptoms, reduced social engagement/perceived social support, but demonstrated better performance on objective cognitive tasks of attention and working memory. Throughout the course of the pandemic, these older adults reported continued worsening of perceived physical health and function, fewer depression symptoms, and they demonstrated improved cognitive performance. It is important to note that changes on self-report mood measures and cognitive performance were relatively small regarding clinical significance. Education largely served as a protective factor, such that greater years of education was generally associated with better outcomes across domains. Conclusions: The present study provides insights into the longitudinal impact of the COVID-19 pandemic on health behaviors, psychosocial factors, and cognitive functioning in a population disproportionately affected by the virus. Replicating this study design in a demographically representative older adult sample is warranted to further inform intervention strategies targeting older adults negatively impacted by the COVID-19 pandemic.

Somatosensory impairment of the feet is associated with higher activation of prefrontal cortex during walking in older adults.

BACKGROUND: Over-activation of prefrontal cortex during walking has been reported in older adults versus young adults. Heighted activity in prefrontal cortex suggests a shift toward an executive control strategy to control walking. A potential contributing factor is degraded functioning of pattern-generating locomotor circuits in the central nervous system that are important to walking coordination. Somatosensory information is a crucial input to these circuits, so age-related impairment of somatosensation would be expected to compromise the neural control of walking. The present study tested the hypothesis that poorer somatosensation in the feet of older adults will be associated with greater recruitment of the prefrontal cortex during walking. This study also examines the extent to which somatosensory function and prefrontal activity are associated with performance on walking and balance assessments. METHODS: Forty seven older adults (age 74.6 ± 6.8 years; 32 female) participated in walking assessments (typical walking and obstacle negotiation) and Berg Balance Test. During walking, prefrontal activity was measured with functional near infrared spectroscopy (fNIRS). Participants also underwent somatosensory testing with Semmes-Weinstein monofilaments. RESULTS: The primary findings is that worse somatosensory monofilament level was associated with greater prefrontal cortical activity during typical walking (r = 0.38, p = 0.008) and obstacle negotiation (r = 0.40, p = 0.006). For the obstacle negotiation task, greater prefrontal activity was associated with faster walking speed (p = 0.004). Poorer somatosensation was associated with slower typical walking speed (p = 0.07) and obstacles walking speed (p < 0.001), as well as poorer balance scores (p = 0.03). CONCLUSIONS: The study findings are consistent with a compensation strategy of recruiting prefrontal/executive control resources to overcome loss of somatosensory input to the central nervous system. Future research should further establish the mechanisms by which somatosensory impairments are linked to the neural control and performance of walking tasks, as well as develop intervention approaches.

Higher white matter hyperintensity load adversely affects pre-post proximal cognitive training performance in healthy older adults.

Cognitive training has shown promise for improving cognition in older adults. Age-related neuroanatomical changes may affect cognitive training outcomes. White matter hyperintensities are one common brain change in aging reflecting decreased white matter integrity. The current study assessed (1) proximal cognitive training performance following a 3-month randomized control trial and (2) the contribution of baseline whole-brain white matter hyperintensity load, or total lesion volume (TLV), on pre-post proximal training change. Sixty-two healthy older adults were randomized to either adaptive cognitive training or educational training control interventions. Repeated-measures analysis of covariance revealed two-way group × time interactions such that those assigned cognitive training demonstrated greater improvement on proximal composite (total training composite) and sub-composite (processing speed training composite, working memory training composite) measures compared to education training counterparts. Multiple linear regression showed higher baseline TLV associated with lower pre-post change on processing speed training sub-composite (ß = -0.19, p = 0.04), but not other composite measures. These findings demonstrate the utility of cognitive training for improving post-intervention proximal performance in older adults. Additionally, pre-post proximal processing speed training change appears to be particularly sensitive to white matter hyperintensity load versus working memory training change. These data suggest that TLV may serve as an important factor for consideration when planning processing speed-based cognitive training interventions for remediation of cognitive decline in older adults.

Proximal improvement and higher-order resting state network change after multidomain cognitive training intervention in healthy older adults.

Prior randomized control trials have shown that cognitive training interventions resulted in improved proximal task performance, improved functioning of activities of daily living, and reduced dementia risk in healthy older adults. Neural correlates implicated in cognitive training include hub brain regions of higher-order resting state networks including the default mode network, dorsal attention network, frontoparietal control network, and cingulo-opercular network. However, little is known about resting state network change after cognitive training, or the relation between functional brain changes and improvement in proximal task performance. We assessed the 1) change in proximal task performance, 2) change in higher-order resting state network connectivity via functional magnetic resonance imaging, and 3) association between these variables after a multidomain attention/speed-of-processing and working memory randomized control trial in a sample of 58 healthy older adults. Participants in the cognitive training group improved significantly on seven out of eight training tasks immediately after the training intervention with the largest magnitude of improvement in a divided attention/speed-of-processing task, the Double Decision task. Only the frontoparietal control network had significantly strengthened connectivity in the cognitive training group at the post-intervention timepoint. Lastly, higher frontoparietal control network connectivity was associated with improved Double Decision task performance after training in the cognitive training group. These findings show that the frontoparietal control network may strengthen after multidomain cognitive training interventions, and this network may underlie improvements in divided attention/speed-of-processing proximal improvement.

Associations between exercise classes and self-reported exercise by people with Parkinson's disease at Parkinson's foundation centers of excellence.

INTRODUCTION: Despite evidence of the benefits of exercise, people with Parkinson's disease (PD) often exercise less than recommended. We sought to identify exercise class-related factors associated with the amount of exercise in PD communities. METHODS: We used Parkinson's Outcome Project (POP) data from 3146 people with PD at 19 participating Centers of Excellence (COEs). POP data included self-reported moderate-vigorous exercise (MVE) hours, light physical activity (PA) hours, demographic and disease severity variables. We also collected information about weekly exercise class availability, intensity, cost, and distance from class location to the COE. We examined differences between COE-based and community-based exercise classes using the Akritas test for paired and unpaired samples. We tested associations between class characteristics and exercise hours based on a two-part model: logistic regression on whether a participant does MVE or light PA and linear regression for log-transformed time of exercise. RESULTS: Community-based exercise classes had a significantly higher weekly availability than COE-based classes (class hours per week: 47.5 ± 25.6 vs 6.5 ± 8.6, p < 0.001), a higher percentage of vigorous-intensity classes (24.2 ± 17.8 vs 11 ± 14.7, p < 0.001), and a broader geographic distribution (miles to COE: 12.8 ± 4.6 vs 6.2 ± 5.7, p < 0.001). Greater weekly hours of availability, intensity, and distance to COE were associated with increased MVE and light PA hours among participants who exercised (p < 0.01). Of these, higher weekly class availability explained the most variability in reported exercise hours. CONCLUSION: Parkinson's COEs may be able to increase exercise by facilitating a high weekly availability of exercise classes with higher intensity levels and broader geographical distribution.

American Physical Therapy Association Clinical Practice Guideline Implementation for Neck and Low Back Pain in Outpatient Physical Therapy: A Nonrandomized, Cross-sectional Stepped-Wedge Pilot Study.

OBJECTIVE: To determine whether a multifaceted implementation strategy for American Physical Therapy Association neck and low back pain clinical practice guidelines (CPGs) was associated with changes in clinician and patient outcomes. DESIGN: Cross-sectional stepped-wedge pilot study. METHODS: Physical therapy clinics (n = 9) were allocated to 1 of 4 clusters that varied by CPG implementation timing. Clinics crossed over from usual care (control) to CPG implementation (intervention) every 8 weeks and ended with a 24-week follow-up period. Implementation outcomes were measured at the clinician (perspectives and behaviors) and patient (pain and disability outcomes) levels. Descriptive statistics were used to summarize clinician perspectives and behaviors. Generalized linear mixed models were used to analyze patient-level outcomes data (pain and disability) and total number of physical therapy visits. RESULTS: Improvements in several clinician perspectives about CPGs were observed 8 weeks after training and sustained at 16 weeks (P<.05), although it is unclear whether these changes were meaningful. Training on CPGs was relevant to physical therapists and more acceptable at 16 weeks (P<.05). In a random sample (n = 764/1994, 38.3%), the overall rate of CPG classification was 65.0% (n = 497/764), and CPG intervention concordance was 71.2% (n = 354/497). Implementation of a CPG was not associated with final pain and disability scores (P>.05) but was associated with an approximate increase of 8% in total visits. CONCLUSION: Our multifaceted implementation strategy was associated with statistical changes in clinician perspectives and behaviors, but not in patient outcomes. J Orthop Sports Phys Ther 2022;52(2):113-123. doi:10.2519/jospt.2022.10545.

Distinct Roles of the Human Subthalamic Nucleus and Dorsal Pallidum in Parkinson's Disease Impulsivity.

BACKGROUND: Impulsivity and impulse control disorders are common in Parkinson's disease and lead to increased morbidity and reduced quality of life. Impulsivity is thought to arise from aberrant reward processing and inhibitory control, but it is unclear why deep brain stimulation of either the subthalamic nucleus (STN) or globus pallidus internus (GPi) affects levels of impulsivity. Our aim was to assess the role of the STN and GPi in impulsivity using invasive local field potential (LFP) recordings from deep brain stimulation electrodes. METHODS: We measured LFPs during a simple rewarding Go/NoGo paradigm in 39 female and male human patients with Parkinson's disease manifesting variable amounts of impulsivity who were undergoing unilateral deep brain stimulation of either the STN (18 nuclei) or GPi (28 nuclei). We identified reward-specific LFP event-related potentials and correlated them to impulsivity severity. RESULTS: LFPs in both structures modulated during reward-specific Go and NoGo stimulus evaluation, reward feedback, and loss feedback. Motor and limbic functions were anatomically separable in the GPi but not in the STN. Across participants, LFP reward processing responses in the STN and GPi uniquely depended on the severity of impulsivity. CONCLUSIONS: This study establishes LFP correlates of impulsivity within the STN and GPi regions. We propose a model for basal ganglia reward processing that includes the bottom-up role of the GPi in reward salience and the top-down role of the STN in cognitive control.