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Pharmacological interventions for depression and anxiety in older adults often have significant side effects, presenting the need for more tolerable alternatives. Transcranial direct current stimulation (tDCS) is a promising non-pharmacological intervention for depression in clinical populations. However, its effects on depression and anxiety symptoms, particularly in older adults from the general public, are understudied. We conducted a secondary analysis of the Augmenting Cognitive Training in Older Adults (ACT) trial to assess tDCS efficacy in reducing psychological symptoms in older adults. We hypothesized that active stimulation would yield greater reductions in depression and state anxiety compared to sham post-intervention and at the one-year follow-up. We also explored tDCS effects in subgroups characterized by baseline symptom severity. A sample of 378 older adults recruited from the community completed a 12-week tDCS intervention with cognitive or education training. Electrodes were placed at F3/F4, and participants received active or sham tDCS during training sessions. We assessed the association between tDCS group and changes in depression, state anxiety, and trait anxiety from baseline to post-intervention and one-year controlling for covariates. The active tDCS group demonstrated greater reductions in depression and state anxiety compared to sham post-intervention, particularly in individuals with mild depression and moderate/severe state anxiety at baseline. Furthermore, the active tDCS group with moderate/severe state anxiety maintained greater symptom reductions at one-year. tDCS effectively reduced depression and state anxiety symptoms in a large sample of older adults. These findings highlight the importance of considering symptom severity when identifying those who may benefit most from this intervention. • Active tDCS yielded greater reductions in depression and state anxiety than sham. • These reductions were largest for those with mild depression and moderate/severe state anxiety. • tDCS effects on state anxiety remained at one-year for those with moderate/severe state anxiety. • There were no significant tDCS effects on trait anxiety. • tDCS effectively reduces psychological symptoms in a community sample of older adults. [ABSTRACT FROM AUTHOR]

Bariatric surgery is an increasingly popular treatment for patients with severe obesity and related health issues (e.g., diabetes, cardiovascular disease). Studies have identified alterations in functional connectivity both in obesity and following surgical treatment for severe obesity. This study aimed to assess brain function via resting-state within-network connectivity in bariatric surgery patients with severe obesity. University hospital. Thirty-four bariatric surgery patients completed functional neuroimaging at baseline and postoperatively (goal, 12 weeks; actual, 16 weeks, on average). They also self-reported health information. Baseline resting-state functional connectivity (RSFC) was predicted by baseline age, body mass index (BMI), continuous positive airway pressure use, and reported history of rheumatoid arthritis and type 2 diabetes. Change in RSFC was assessed using the same predictors. This model was run with and without controlling for baseline RSFC. Higher baseline BMI predicted lower baseline RSFC in 3 networks. Lower baseline RSFC also was related to rheumatoid arthritis and type 2 diabetes. Difference between baseline and follow-up RSFC was strongly negatively associated with baseline RSFC. Controlling for baseline RSFC, type 2 diabetes negatively predicted RSFC difference. RSFC may reflect brain dysfunction in patients with obesity and related diseases. That less connectivity at baseline predicted greater positive change suggests that RSFC may be a biomarker of neurocognitive improvement following bariatric surgery. Diseases more prevalent in patients with obesity (e.g., rheumatoid arthritis and type 2 diabetes) along with elevated BMI negatively affect RSFC likely through inflammatory pathways. [ABSTRACT FROM AUTHOR]

There is a need for effective interventions to stave off cognitive decline in older adults. Cognitive training has variably produced gains in untrained tasks and daily functioning. Combining cognitive training with transcranial direct current stimulation (tDCS) may augment cognitive training effects; however, this approach has yet to be tested on a large-scale. This paper will present the primary findings of the Augmenting Cognitive Training in Older Adults (ACT) clinical trial. We hypothesize that receiving active stimulation with cognitive training will result in greater improvements on an untrained fluid cognition composite compared to sham following intervention. 379 older adults were randomized, and 334 were included in intent-to-treat analyses for a 12-week multidomain cognitive training and tDCS intervention. Active or sham tDCS was administered at F3/F4 during cognitive training daily for two weeks then weekly for 10 weeks. To assess the tDCS effect, we fitted regression models for changes in NIH Toolbox Fluid Cognition Composite scores immediately following intervention and one year from baseline controlling for covariates and baseline scores. Across the entire sample, there were improvements in NIH Toolbox Fluid Cognition Composite scores immediately post-intervention and one year following baseline; however, there were no significant tDCS group effects at either timepoint. The ACT study models rigorous, safe administration of a combined tDCS and cognitive training intervention in a large sample of older adults. Despite potential evidence of near-transfer effects, we failed to demonstrate an additive benefit of active stimulation. Future analyses will continue to assess the intervention's efficacy by examining additional measures of cognition, functioning, mood, and neural markers. • Post-tDCS and cognitive training, the sample improved on an untrained fluid cognition composite. • Improvements on the untrained fluid cognition composite maintained one year following baseline. • In the overall sample, there were no significant tDCS effects on changes in cognitive performance. • It is feasible to administer tDCS and cognitive training safely in older adults on a large scale. • Using individualized tDCS dosing parameters may better facilitate a treatment response. [ABSTRACT FROM AUTHOR]

Transcranial direct current stimulation (tDCS) paired with cognitive training (CT) is widely investigated as a therapeutic tool to enhance cognitive function in older adults with and without neurodegenerative disease. Prior research demonstrates that the level of benefit from tDCS paired with CT varies from person to person, likely due to individual differences in neuroanatomical structure. The current study aims to develop a method to objectively optimize and personalize current dosage to maximize the functional gains of non-invasive brain stimulation. A support vector machine (SVM) model was trained to predict treatment response based on computational models of current density in a sample dataset (n = 14). Feature weights of the deployed SVM were used in a weighted Gaussian Mixture Model (GMM) to maximize the likelihood of converting tDCS non-responders to responders by finding the most optimum electrode montage and applied current intensity (optimized models). Current distributions optimized by the proposed SVM-GMM model demonstrated 93% voxel-wise coherence within target brain regions between the originally non-responders and responders. The optimized current distribution in original non-responders was 3.38 standard deviations closer to the current dose of responders compared to the pre-optimized models. Optimized models also achieved an average treatment response likelihood and normalized mutual information of 99.993% and 91.21%, respectively. Following tDCS dose optimization, the SVM model successfully predicted all tDCS non-responders with optimized doses as responders. The results of this study serve as a foundation for a custom dose optimization strategy towards precision medicine in tDCS to improve outcomes in cognitive decline remediation for older adults. • Optimized dosing produced an average treatment response likelihood of 99.993%. • Voxelwise similarity of optimized doses was 40.8% better than conventional tDCS. • Optimized dosing matches 93% of the variance in the responder current profile. • All optimized doses of previous non-responders were predicted as responders. [ABSTRACT FROM AUTHOR]

• Existing tDCS models largely include artificially created electrodes adapted from planned montages. • Final location of real electrodes during live tDCS sessions may deviate from the planned montages. • Discrepancies between artificial and real electrode placements significantly affect delivered current dose in the brain. • Rigorous documentation is crucial for accurately representing electrodes in tDCS models. [ABSTRACT FROM AUTHOR]

Working memory decline has been associated with normal aging. The frontal brain structure responsible for this decline is primarily located in the prefrontal cortex (PFC). Our previous neuroimaging study demonstrated a significant change in functional connectivity between the left dorsolateral PFC (DLPFC) and left ventrolateral PFC (VLPFC) when applying 2 mA tDCS in MRI scanner during an N-Back task. These regions were part of the working memory network. The present study is the first study that utilizes individualized finite element models derived from older adults' MRI to predict significant changes of functional connectivity observed from an acute tDCS application. Individualized head models from 15 healthy older adults (mean age = 71.3 years) were constructed to create current density maps. Each head model was segmented into 11 tissue types: white matter, gray matter, CSF, muscle, blood vessels, fat, eyes, air, skin, cancellous, and cortical bone. Electrodes were segmented from T1-weighted images and added to the models. Computed median and maximum current density values in the left DLPFC and left VLPFC regions of interest (ROIs) were correlated with beta values as functional connectivity metrics measured in different timepoint (baseline, during stimulation) and stimulation condition (active and sham). Positive significant correlations (R2 = 0.523 for max J, R2 = 0.367 for median J, p < 0.05) were found between the beta values and computed current densities in the left DLPFC ROIs for active stimulation, but no significant correlation was found during sham stimulation. We found no significant correlation between connectivity and current densities computed in the left VLPFC for both active and sham stimulation. The amount of current within the left DLPFC ROIs was found positively correlated with changes in functional connectivity between left DLPFC and left VLPFC during active 2 mA stimulation. Future work may include expansion of number of participants to further test the accuracy of tDCS models used to predict tDCS-induced functional connectivity changes within the working memory network. • Head models comprising eleven tissue types were used to compute current density. • Electrode pads and paste were directly segmented from T1-weighted images. • Current density in lh-DLPFC correlated with connectivity changes in active stimulation. • Individual anatomy remains crucial in predicting brain-based changes induced by tDCS. • Our results may inform future tDCS current dosing strategy in older adults. [ABSTRACT FROM AUTHOR]

White matter hyperintensities (WMH) are estimated to occur in greater than 63% of older adults over the age of 60 years. WMH identified in the T2-weighted FLAIR images can be combined with T1-weighted images to enhance individualized current flow models of older adults by accounting for the presence of WMH and its effects on delivered tES current in the aging brain. Individualized head models were derived from T1-weighted images of 130 healthy older adults (mean = 71 years). Lesions segmented from FLAIR acquisition were added to individualized models. Current densities were computed in the brain and compared between models with and without lesions. Integrating WMH into the models resulted in an overall decrease (up to 7%) in median current densities in the brain outside lesion regions. Changes in current density and total lesion volume was positively correlated (R2 = 0.31, p < 0.0001). Incorporating WMH into individualized models may increase the accuracy of predicted tES current flow in the aging brain. [ABSTRACT FROM AUTHOR]

Studies applying transcranial direct-current stimulation (tDCS) to motor regions to enhance surgical skills have observed modest benefits in performance. Early surgical skills acquisition is known to be dependent on the prefrontal cortex (PFC) which could be a suitable target for performance enhancement in fields with high cognitive demand. To assess whether prefrontal tDCS could improve early phases of surgical skill development. In a randomized sham-controlled double-blind parallel design, 40 surgical novices performed an open knot-tying task repeated in three blocks; pre-, online- and post-tDCS. During online stimulation, participants were randomized to either active tDCS (2 mA for 15 min) to the prefrontal cortex (anode over F3, cathode over F4) or sham tDCS. Performance score (PS) was computed using a validated algorithm and introspective workload domains were assessed using a SURG-TLX questionnaire. There was no difference in demographics or PS between groups prior to receiving tDCS. PS significantly improved from pre-to online- (p < 0.001) and from pre-to post-tDCS (p < 0.001) in the active group only. Following active tDCS, PS was closer to the defined proficiency benchmark and significantly greater compared to sham (p = 0.002). Only the active group reported significantly improved temporal demand scores from pre-to online- (p = 0.004) to post-tDCS (p = 0.002). This study demonstrates significantly improved early phase surgical-skill acquisition following prefrontal tDCS. Further work is required to determine the underlying neurophysiological mechanisms and whether the benefits observed are retained long-term. • Randomized double-blind trial assessing tDCS in early surgical skill learning. • TDCS significantly improved knot-tying scores compared to baseline and versus sham. • Significantly closer scores to proficiency levels following tDCS compared to sham. • Surgical novices perceived reduced temporal demand following stimulation. [ABSTRACT FROM AUTHOR]

Transcranial direct current stimulation (tDCS) is widely investigated as a therapeutic tool to enhance cognitive function in older adults with and without neurodegenerative disease. Prior research demonstrates that electric current delivery to the brain can vary significantly across individuals. Quantification of this variability could enable person-specific optimization of tDCS outcomes. This pilot study used machine learning and MRI-derived electric field models to predict working memory improvements as a proof of concept for precision cognitive intervention. Fourteen healthy older adults received 20 minutes of 2 mA tDCS stimulation (F3/F4) during a two-week cognitive training intervention. Participants performed an N-back working memory task pre-/post-intervention. MRI-derived current models were passed through a linear Support Vector Machine (SVM) learning algorithm to characterize crucial tDCS current components (intensity and direction) that induced working memory improvements in tDCS responders versus non-responders. SVM models of tDCS current components had 86% overall accuracy in classifying treatment responders vs. non-responders, with current intensity producing the best overall model differentiating changes in working memory performance. Median current intensity and direction in brain regions near the electrodes were positively related to intervention responses (r = 0.811 , p < 0.001 and r = 0.774 , p = 0.001). This study provides the first evidence that pattern recognition analyses of MRI-derived tDCS current models can provide individual prognostic classification of tDCS treatment response with 86% accuracy. Individual differences in current intensity and direction play important roles in determining treatment response to tDCS. These findings provide important insights into mechanisms of tDCS response as well as proof of concept for future precision dosing models of tDCS intervention. Image 1 • MRI-derived electric field characteristics predict tDCS treatment responses. • Current intensity and direction play significant roles in tDCS treatment response. • Support vector machine learning algorithm predicts patients' allocation to responders vs. non-responders at 86% accuracy. • Current intensity yields best overall machine learning classifier of tDCS response. • Precision dosing accounting for individual anatomy is promising for optimizing tDCS. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has broadly disrupted biomedical treatment and research including non-invasive brain stimulation (NIBS). Moreover, the rapid onset of societal disruption and evolving regulatory restrictions may not have allowed for systematic planning of how clinical and research work may continue throughout the pandemic or be restarted as restrictions are abated. The urgency to provide and develop NIBS as an intervention for diverse neurological and mental health indications, and as a catalyst of fundamental brain research, is not dampened by the parallel efforts to address the most life-threatening aspects of COVID-19; rather in many cases the need for NIBS is heightened including the potential to mitigate mental health consequences related to COVID-19. To facilitate the re-establishment of access to NIBS clinical services and research operations during the current COVID-19 pandemic and possible future outbreaks, we develop and discuss a framework for balancing the importance of NIBS operations with safety considerations, while addressing the needs of all stakeholders. We focus on Transcranial Magnetic Stimulation (TMS) and low intensity transcranial Electrical Stimulation (tES) - including transcranial Direct Current Stimulation (tDCS) and transcranial Alternating Current Stimulation (tACS). The present consensus paper provides guidelines and good practices for managing and reopening NIBS clinics and laboratories through the immediate and ongoing stages of COVID-19. The document reflects the analysis of experts with domain-relevant expertise spanning NIBS technology, clinical services, and basic and clinical research – with an international perspective. We outline regulatory aspects, human resources, NIBS optimization, as well as accommodations for specific demographics. A model based on three phases (early COVID-19 impact, current practices, and future preparation) with an 11-step checklist (spanning removing or streamlining in-person protocols, incorporating telemedicine, and addressing COVID-19-associated adverse events) is proposed. Recommendations on implementing social distancing and sterilization of NIBS related equipment, specific considerations of COVID-19 positive populations including mental health comorbidities, as well as considerations regarding regulatory and human resource in the era of COVID-19 are outlined. We discuss COVID-19 considerations specifically for clinical (sub-)populations including pediatric, stroke, addiction, and the elderly. Numerous case-examples across the world are described. There is an evident, and in cases urgent, need to maintain NIBS operations through the COVID-19 pandemic, including anticipating future pandemic waves and addressing effects of COVID-19 on brain and mind. The proposed robust and structured strategy aims to address the current and anticipated future challenges while maintaining scientific rigor and managing risk. • Clinical and research NIBS operations are important and in some cases critical to continue through the COVID-19 pandemic. • We provide a framework for maintaining NIBS operations and their safety during COVID-19 and future outbreaks. • Guidelines and good practices for managing and reopening NIBS clinics and laboratories during COVID-19 are presented. • Remotely supervised tDCS provides the opportunity to continue clinical and research treatments for patients at home and while staff are offsite. • Onsite brain stimulation, such as TMS, can proceed when implementing workflows ensuring safety related to COVID-19. [ABSTRACT FROM AUTHOR]

Transcranial direct current stimulation (tDCS) is a method of noninvasive neuromodulation and potential therapeutic tool to improve functioning and relieve symptoms across a range of central and peripheral nervous system conditions. Evidence suggests that the effects of tDCS are cumulative with consecutive daily applications needed to achieve clinically meaningful effects. Therefore, there is growing interest in delivering tDCS away from the clinic or research facility, usually at home. To provide a comprehensive guide to operationalize safe and responsible use of tDCS in home settings for both investigative and clinical use. Providing treatment at home can improve access and compliance by decreasing the burden of time and travel for patients and their caregivers, as well as to reach those in remote locations and/or living with more advanced disabilities. To date, methodological approaches for at-home tDCS delivery have varied. After implementing the first basic guidelines for at-home tDCS in clinical trials, this work describes a comprehensive guide for facilitating safe and responsible use of tDCS in home settings enabling access for repeated administration over time. These guidelines provide a reference and standard for practice when employing the use of tDCS outside of the clinic setting. • Guidelines for research and clinical use of tDCS at-home are described by experts. • Minimum device specifications for at-home use are outlined. • Specific considerations for best practices of tDCS are presented in detail. [ABSTRACT FROM AUTHOR]

Varying treatment outcomes in transcranial electrical stimulation (tES) recipients may depend on the amount of current reaching the brain. Brain atrophy associated with normal aging may affect tES current delivery to the brain. Computational models have been employed to compute predicted tES current inside the brain. This study is the largest study that uses computational models to investigate tES field distribution in healthy older adults. Individualized head models from 587 healthy older adults (mean = 73.9years, 51–95 years) were constructed to create field maps. Two electrode montages (F3-F4, M1-SO) with 2 mA input current were modeled using ROAST with modified codes. A customized template of healthy older adults, the UFAB-587, was created from the same dataset and used to warp individual brains into the same space. Warped models were analyzed to determine the relationship between computed field measures, brain atrophy and age. Computed field measures were inversely correlated with brain atrophy (R2 = 0.0829, p = 1.14e-12). Field pattern showed negative correlation with age in brain sub-regions including part of DLPFC and precentral gyrus. Mediation analysis revealed that the negative correlation between age and current density is partially mediated by brain-to-CSF ratio. Computed field measures showed decreasing amount of tES current reaching the brain with increasing atrophy. Therefore, adjusting current dose by modifying tES stimulation parameters in older adults based on degree of atrophy may be necessary to achieve desired stimulation benefits. Results from this study may inform future tES application in healthy older adults. • The majority of older adults have less current in their brains than young adults. • Brain tissue loss in healthy older adults can affect tES current dose. • Individuals with a larger degree of brain atrophy have less current in their brains. • Our results may inform future tES current dose determination in older adults. [ABSTRACT FROM AUTHOR]

Transcranial electrical stimulation (tES) aims to alter brain function non-invasively by applying current to electrodes on the scalp. Decades of research and technological advancement are associated with a growing diversity of tES methods and the associated nomenclature for describing these methods. Whether intended to produce a specific response so the brain can be studied or lead to a more enduring change in behavior (e.g. for treatment), the motivations for using tES have themselves influenced the evolution of nomenclature, leading to some scientific, clinical, and public confusion. This ambiguity arises from (i) the infinite parameter space available in designing tES methods of application and (ii) varied naming conventions based upon the intended effects and/or methods of application. Here, we compile a cohesive nomenclature for contemporary tES technologies that respects existing and historical norms, while incorporating insight and classifications based on state-of-the-art findings. We consolidate and clarify existing terminology conventions, but do not aim to create new nomenclature. The presented nomenclature aims to balance adopting broad definitions that encourage flexibility and innovation in research approaches, against classification specificity that minimizes ambiguity about protocols but can hinder progress. Constructive research around tES classification, such as transcranial direct current stimulation (tDCS), should allow some variations in protocol but also distinguish from approaches that bear so little resemblance that their safety and efficacy should not be compared directly. The proposed framework includes terms in contemporary use across peer-reviewed publications, including relatively new nomenclature introduced in the past decade, such as transcranial alternating current stimulation (tACS) and transcranial pulsed current stimulation (tPCS), as well as terms with long historical use such as electroconvulsive therapy (ECT). We also define commonly used terms-of-the-trade including electrode, lead, anode, and cathode, whose prior use, in varied contexts, can also be a source of confusion. This comprehensive clarification of nomenclature and associated preliminary proposals for standardized terminology can support the development of consensus on efficacy, safety, and regulatory standards. • Modern tES suffers from a diversity of ill-defined nomenclature. • A consistent and clear taxonomy for tES will support clear and reproducible research. • This review presents the first comprehensive nomenclature scheme for tES. [ABSTRACT FROM AUTHOR]

Although single or multiple sessions of transcranial direct current stimulation (tDCS) on the prefrontal cortex over a few weeks improved cognition in patients with Alzheimer's disease (AD), effects of repeated tDCS over longer period and underlying neural correlates remain to be elucidated. This study investigated changes in cognitive performances and regional cerebral metabolic rate for glucose (rCMRglc) after administration of prefrontal tDCS over 6 months in early AD patients. Patients with early AD were randomized to receive either active (n = 11) or sham tDCS (n = 7) over the dorsolateral prefrontal cortex (DLPFC) at home every day for 6 months (anode F3/cathode F4, 2 mA for 30 min). All patients underwent neuropsychological tests and brain 18F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) scans at baseline and 6-month follow-up. Changes in cognitive performances and rCMRglc were compared between the two groups. Compared to sham tDCS, active tDCS improved global cognition measured with Mini-Mental State Examination (p for interaction = 0.02) and language function assessed by Boston Naming Test (p for interaction = 0.04), but not delayed recall performance. In addition, active tDCS prevented decreases in executive function at a marginal level (p for interaction < 0.10). rCMRglc in the left middle/inferior temporal gyrus was preserved in the active group, but decreased in the sham group (p for interaction < 0.001). Daily tDCS over the DLPFC for 6 months may improve or stabilize cognition and rCMRglc in AD patients, suggesting the therapeutic potential of repeated at-home tDCS. • We examined effects of 6-month at-home tDCS over the DLPFC in AD patients. • tDCS improved global cognition and language function. • tDCS prevented decreases in glucose metabolism in the middle/inferior temporal gyrus. • Repeated at-home tDCS may be a promising treatment option for AD. [ABSTRACT FROM AUTHOR]

Abstract Background Inaccurate electrode placement and electrode drift during a transcranial electrical stimulation (tES) session have been shown to alter predicted field distributions in the brain and thus may contribute to a large variation in tES study outcomes. Currently, there is no objective and independent measure to quantify electrode placement accuracy/drift in tES clinical studies. Objective/hypothesis We proposed and tested novel methods to quantify accurate and consistent electrode placements in tES using models generated from a 3D scanner. Methods Accurate electrode placements were quantified as Discrepancy in eight tES participants by comparing landmark distances of physical electrode locations F3/F4 to their model counterparts. Distances in models were computed using curve and linear based methods. Variability of landmark locations in a single subject was computed for multiple stimulation sessions to determine consistent electrode placements across four experimenters. Main results We obtained an average of 0.4 cm in Discrepancy, which was within the placement accuracy/drift threshold (1 cm) for conventional tES electrodes (∼35 cm2) to achieve reliable tES sessions suggested in the literature. Averaged Variability was 5.2%, with F4 electrode location as the least consistent placement. Conclusions These methods provide objective feedback for experimenters on their performance in placing tES electrodes. Applications of these methods can be used to monitor electrode locations in tES studies of a larger cohort using F3/F4 montage and other conventional electrode arrangements. Future studies may include co-registering the landmark locations with imaging-derived head models to quantify the effects of electrode accuracy/drift on predicted field distributions in the brain. Highlights • Inaccurate electrode placements may affect observed tES outcomes. • We proposed new methods to monitor accurate and consistent tES electrode location. • Our methods were proved useful to detect electrode drift in tES participants. • Our methods can be used as quality control for more reliable tES studies. [ABSTRACT FROM AUTHOR]

Background Adults over age 65 represent the fastest growing population in the US. Decline in cognitive abilities is a hallmark of advanced age and is associated with loss of independence and dementia risk. There is a pressing need to develop effective interventions for slowing or reversing the cognitive aging process. While certain forms of cognitive training have shown promise in this area, effects only sometimes transfer to neuropsychological tests within or outside the trained domain. This paper describes a NIA-funded Phase III adaptive multisite randomized clinical trial, examining whether transcranial direct current stimulation (tDCS) of frontal cortices enhances neurocognitive outcomes achieved from cognitive training in older adults experiencing age-related cognitive decline: the Augmenting Cognitive Training in Older Adults study (ACT). Methods ACT will enroll 360 participants aged 65 to 89 with age-related cognitive decline, but not dementia. Participants will undergo cognitive training intervention or education training-control combined with tDCS or sham tDCS control. Cognitive training employs a suite of eight adaptive training tasks focused on attention/speed of processing and working memory from Posit Science BrainHQ. Training control involves exposure to educational nature/history videos and related content questions of the same interval/duration as the cognitive training. Participants are assessed at baseline, after training (12 weeks), and 12-month follow-up on our primary outcome measure, NIH Toolbox Fluid Cognition Composite Score, as well as a comprehensive neurocognitive, functional, clinical and multimodal neuroimaging battery. Significance The findings from this study have the potential to significantly enhance efforts to ameliorate cognitive aging and slow dementia. [ABSTRACT FROM AUTHOR]

We present device standards for low-power non-invasive electrical brain stimulation devices classified as limited output transcranial electrical stimulation (tES). Emerging applications of limited output tES to modulate brain function span techniques to stimulate brain or nerve structures, including transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), and transcranial pulsed current stimulation (tPCS), have engendered discussion on how access to technology should be regulated. In regards to legal regulations and manufacturing standards for comparable technologies, a comprehensive framework already exists, including quality systems (QS), risk management, and (inter)national electrotechnical standards (IEC). In Part 1, relevant statutes are described for medical and wellness application. While agencies overseeing medical devices have broad jurisdiction, enforcement typically focuses on those devices with medical claims or posing significant risk. Consumer protections regarding responsible marketing and manufacture apply regardless. In Part 2 of this paper, we classify the electrical output performance of devices cleared by the United States Food and Drug Administration (FDA) including over-the-counter (OTC) and prescription electrostimulation devices, devices available for therapeutic or cosmetic purposes, and devices indicated for stimulation of the body or head. Examples include iontophoresis devices, powered muscle stimulators (PMS), cranial electrotherapy stimulation (CES), and transcutaneous electrical nerve stimulation (TENS) devices. Spanning over 13 FDA product codes, more than 1200 electrical stimulators have been cleared for marketing since 1977. The output characteristics of conventional tDCS, tACS, and tPCS techniques are well below those of most FDA cleared devices, including devices that are available OTC and those intended for stimulation on the head. This engineering analysis demonstrates that with regard to output performance and standing regulation, the availability of tDCS, tACS, or tPCS to the public would not introduce risk, provided such devices are responsibly manufactured and legally marketed. In Part 3, we develop voluntary manufacturer guidance for limited output tES that is aligned with current regulatory standards. Based on established medical engineering and scientific principles, we outline a robust and transparent technical framework for ensuring limited output tES devices are designed to minimize risks, while also supporting access and innovation. Alongside applicable medical and government activities, this voluntary industry standard (LOTES-2017) further serves an important role in supporting informed decisions by the public. [ABSTRACT FROM AUTHOR]

Background There has been increased interest in the potential use of transcranial direct current stimulation (tDCS) as treatment for multiple conditions including depression, pain, and cognitive impairment. However, few studies account for the possible influence of comorbid medications when conducting tDCS research. Objective/Hypothesis This literature review was conducted to examine what is currently known about the impact of medications on tDCS, provide recommendations for future research practices, and highlight areas where more research is needed. Methods Key terms were searched in PubMed and Web of Science to identify studies that examine the impact of medication on tDCS effects in adults. Relevant papers' reference lists were also reviewed for thoroughness. Studies examined the effects of medication on 1 mA tDCS delivered to M1 (motor) and orbit/supraorbital (SO) area. All studies measured the effects of tDCS via MEP TMS paradigm. Results Results of the literature review suggest multiple classes of medications, including sodium and calcium channel blockers, and medications that influence various neurotransmitter systems (GABA, dopamine, serotonin, etc.) may all impact tDCS effects on tissue excitability. Conclusions Research to date suggests multiple classes of medications may impact tDCS effects. These results highlight the importance of documenting medication use in research subjects and carefully considering what types of medications should be allowed into tDCS trials. Many questions still remain regarding the exact mechanisms of action for tDCS and how various parameters (medication dosages, tDCS stimulation intensity, etc.) may further impact the effects of medications on tDCS. [ABSTRACT FROM AUTHOR]

Background Previous studies indicate that transcranial direct current stimulation (tDCS) with anode over motor cortex (M1) and cathode over contralateral supraorbital region (SO) may be effective in reducing pain, but these studies are limited in number and have not focused on older adults with osteoarthritis (OA). Objective To evaluate the preliminary efficacy and safety of M1-SO applied tDCS on clinical pain severity and mobility performance in adults with knee OA pain. Methods Forty 50- to 70-year-old community-dwelling participants with knee OA were randomly assigned to receive five daily sessions of 2 mA tDCS for 20 min (n = 20) or sham tDCS (n = 20). We measured clinical pain severity via Numeric Rating Scale, Western Ontario and McMaster Universities Osteoarthritis Index, and Short-Form McGill Pain Questionnaire. In addition, we measured mobility performance using the 6-Minute Walk Test and the Short Physical Performance Battery. Moreover, we obtained a sensation/safety questionnaire and measured cognition changes using the PROMIS-Applied Cognition-Abilities-Short Form 8a. Results Active tDCS over M1-SO significantly reduced Numeric Rating Scale of pain compared to sham tDCS after completion of the five daily sessions, and remained up to three weeks. No other measures were significantly different from sham. Participants tolerated tDCS over M1-SO well without serious adverse effects or cognition changes. Conclusion Although not consistent in all pain measurements, our findings demonstrate promising clinical efficacy for reduction in pain perception for older adults with knee OA. Trial registration ClinicalTrials.gov Identifier NCT02512393 . [ABSTRACT FROM AUTHOR]

Background Conventional transcranial direct current stimulation (tDCS) methods involve application of weak electrical current through electrodes encased in saline-soaked sponges affixed to the head using elastic straps. In the absence of careful preparation, electrodes can drift from their original location over the course of a tDCS session. Objective The current paper investigates the influence of electrode drift on distribution of electric fields generated by conventional tDCS. Methods MRI-derived finite element models of electric fields produced by tDCS were used to investigate the influence of incremental drift in electrodes for two of the most common electrode montages used in the literature: M1/SO (motor to contralateral supraorbital) and F3/F4 (bilateral frontal). Based on these models, we extracted predicted current intensity from 20 representative structures in the brain. Results Results from separate RM-ANOVAs for M1/SO and F3/F4 montages demonstrated that 5% incremental drift in electrode position significantly changed the distribution of current delivered by tDCS to the human brain ( F ' s > 8.6, P ' s < 0.001). Pairwise comparisons demonstrated that as little as 5% drift was able to produce significant differences in current intensity in structures distributed across the brain ( P ' s < 0.03). Conclusions Drift in electrode position during a session of tDCS produces significant alteration in the intensity of stimulation delivered to the brain. Elimination of this source of variability will facilitate replication and interpretation of tDCS findings. Furthermore, measurement and statistically accounting for drift may prove important for better characterizing the effects of tDCS on the human brain and behavior. [ABSTRACT FROM AUTHOR]

Abstract: There is a growing interest both in identifying the neural mechanisms of magnitude estimation and in identifying forms of bias that can explain aspects of behavioral syndromes like unilateral neglect. Magnitude estimation is associated with activation of temporo-parietal cortex in both cerebral hemispheres of normal subjects; however, it is unclear if and how left hemisphere lesions bias magnitude estimation because the infrequency of neglect and the presence of aphasia in these subjects confound examination. In contrast, we examined magnitude estimation using 12 different types of sensory stimuli that spanned five sensory domains in two patients with very different clinical presentations following unilateral left hemisphere stroke. One patient had neglect sub-acutely without aphasia. The other had aphasia chronically after a temporo-parietal lesion but not neglect. The neglect patient was re-examined 48h after being treated with modafinil (Provigil) for decreased arousal. Both patients demonstrated bias in magnitude estimation relative to normal subjects (n =83). Alertness improved in the neglect patient after taking modafinil. His neglect also resolved and his magnitude estimates more closely resembled those of normal subjects. This is the first evidence, to our knowledge, that left hemisphere injury can bias magnitude estimation in a manner similar but not identical to that associated with right hemisphere injury. [Copyright &y& Elsevier]

Abstract: Mark VW, Oberheu AM, Henderson C, Woods AJ. Ballism after stroke responds to standard physical therapeutic interventions. Arch Phys Med Rehabil 2005;86: 1226–33. Objective: To report the effects of noninvasive standard physical therapy (PT) interventions on an involuntary movement disorder after stroke. Design: Single case with clinical follow-up over 2 years. Setting: Inpatient stroke and rehabilitation services and outpatient clinic. Participant: A man with acute bilateral ballism after unilateral subthalamic infarction. Interventions: Rhythmic coordinated bilateral limb movements and firm tactile stimulation to the hand. Main Outcome Measures: We had not anticipated that dyskinesia itself would specifically improve during treatment. Consequently, we used qualitative clinical observations, including review of videotaped performance, and self-reported limb control. Hypotheses concerning treatment effects were developed after data collection. Results: Involuntary movements recurrently improved within treatment sessions. Conclusions: PT may improve dyskinesia after stroke. The benefit may be adjunctive or alternative to current invasive treatments of movement disorders after brain injury and merits confirmation. The improvements are consistent with current research indicating that (1) intact cortical, subcortical, cerebellar, and spinal areas interact to generate bilateral rhythmic limb movements that can overcome dyskinesia and (2) tactile stimulation can improve motor deficits associated with basal ganglia disorders. Finally, because functional activities assessments improved our evaluation of ballism, these should be routinely used along with conventional neurologic examination to assess involuntary movement disorders. [Copyright &y& Elsevier]

Knee osteoarthritis (OA) is a leading cause of late life pain and disability, and non-Hispanic black (NHB) adults experience greater OA-related pain and disability than non-Hispanic whites (NHWs). Recent evidence implicates psychosocial stress, cognitive-attentional processes, and altered central pain processing as contributors to greater OA-related pain and disability among NHBs. To address these ethnic/race disparities, this clinical trial will test whether a mindfulness intervention (Breathing and Attention Training, BAT) combined with transcranial direct current stimulation (tDCS) will enhance pain modulatory balance and pain-related brain function, reduce clinical pain, and attenuate ethnic differences therein, among NHBs and NHWs with knee OA. Participants will complete assessments of clinical pain, function, psychosocial measures, and quantitative sensory testing (QST), including mechanical temporal summation and conditioned pain modulation. Neuroimaging will be performed to examine pain-related brain structure and function. Then, participants will be randomized to one of four groups created by crossing two BAT conditions (Real vs. Sham) with two tDCS conditions (Real vs. Sham). Participants will then undergo five treatment sessions during which the assigned BAT and tDCS interventions will be delivered concurrently for 20 min over one week. After the fifth intervention session, participants will undergo assessments of clinical pain and function, QST and neuroimaging identical to the pretreatment measures, and monthly follow-up assessments of pain will be conducted for three months. This will be the first study to determine whether mindfulness and tDCS treatments will show additive or synergistic effects when combined, and whether treatment effects differ across ethnic/race groups. [ABSTRACT FROM AUTHOR]

The expression of microRNA (miRNA) is influenced by ongoing biological processes, including aging, and has begun to play a role in the measurement of neurodegenerative processes in central nervous system. The purpose of this study is to utilize machine learning approaches to determine whether miRNA can be utilized as a blood-based biomarker of cognitive aging. A random forest regression combining miRNA with biological (brain volume), clinical (comorbid conditions), and demographic variables in 115 typically aging older adults explained the greatest level of variance in cognitive performance compared to the other machine learning models explored. Three miRNA (miR-140-5p, miR-197-3p, and miR-501-3p) were top-ranked predictors of multiple cognitive outcomes (Fluid, Crystallized, and Overall Cognition) and past studies of these miRNA link them to cellular senescence, inflammatory signals for atherosclerotic formation, and potential development of neurodegenerative disorders (e.g., Alzheimer's disease). Several novel miRNAs were also linked to age and multiple cognitive functions, findings which together warrant further exploration linking these miRNAs to brain-derived metrics of neurodegeneration in typically aging older adults. [ABSTRACT FROM AUTHOR]

To address the rising prevalence of Alzheimer's disease and related dementias, effective interventions that can be widely disseminated are warranted. The Preventing Alzheimer's with Cognitive Training study (PACT) investigates a commercially available computerized cognitive training program targeting improved Useful Field of View Training (UFOVT) performance. The primary goal is to test the effectiveness of UFOVT to reduce incidence of clinically defined mild cognitive impairment (MCI) or dementia with a secondary objective to examine if effects are moderated by plasma β-amyloid level or apolipoprotein E e4 (APOE e4) allele status. This multisite study utilizes a randomized, controlled experimental design with blinded assessors and investigators. Individuals who are 65 years of age and older are recruited from the community. Eligible participants who demonstrate intact cognitive status (Montreal Cognitive Assessment score > 25) are randomized and asked to complete 45 sessions of either a commercially available computerized-cognitive training program (UFOVT) or computerized games across 2.5 years. After three years, participants are screened for cognitive decline. For those demonstrating decline or who are part of a random subsample, a comprehensive neuropsychological assessment is completed. Those who perform below a pre-specified level are asked to complete a clinical evaluation, including an MRI, to ascertain clinical diagnosis of normal cognition, MCI, or dementia. Participants are asked to provide blood samples for analyses of Alzheimer's disease related biomarkers. The PACT study addresses the rapidly increasing prevalence of dementia. Computerized cognitive training may provide a non-pharmaceutical option for reducing incidence of MCI or dementia to improve public health. Registration: The PACT study is registered at http://Clinicaltrials.gov NCT03848312 [ABSTRACT FROM AUTHOR]

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. 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. 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). 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. • Somatosensory information is crucial to neural control of walking. • Older adults experience impairments in tactile somatosensation of the feet. • To compensate, older adults may rely on executive control processes during walking. • Results show an association between poor sensation and higher prefrontal activity. • Poor sensation was also associated with poorer walking and balance performance. [ABSTRACT FROM AUTHOR]