Faculty Bibliography

INTRODUCTION/BACKGROUND:Cannabis use is rising in the United States. Up to 30 % of individuals who use cannabis develop cannabis use disorder (CUD), for which there are no FDA-approved treatments. This randomized controlled trial (RCT) evaluated the feasibility and efficacy of a novel, one-month telehealth intervention of remotely supervised tDCS (RS-tDCS) paired with mindfulness meditation. This home-based telehealth intervention was evaluated in a cohort of women with multiple sclerosis (MS), a vulnerable subpopulation of adults with high rates of CUD. METHODS:The intervention included 20 home-based RS-tDCS sessions targeting the left DLPFC, delivering 2.0mA for 20minutes, paired with guided mindfulness meditation. Sessions were conducted 5 days per week for four weeks. Fifty-two women with MS and CUD (age: 44 ± 10 years) consented to participate; 47 were randomized 2:1 to active or sham tDCS. Feasibility was assessed via retention and adherence, while preliminary efficacy was measured by cannabis use, withdrawal symptoms, and MS-related symptom scales. RESULTS:Of 47 randomized participants (31 active, 16 sham), 39 (83 %) completed the intervention. The active tDCS group showed significant reductions in weekly cannabis use (Daily Sessions, Frequency, Age of Onset, and Quantity of Cannabis Use Inventory, DFAQ-CU: 5.3 ± 2.4 vs. 3.9 ± 2.7 days, p = 0.014) and withdrawal symptoms (CWS: p < 0.001). A trend toward reduced MS-related symptoms was observed (SymptoMScreen: p = 0.031). Cognitive performance improvement at the end of the intervention was significant in the active group (p = 0.011 vs. p = 0.172), supporting functional benefits of reduced cannabis use. CONCLUSIONS:This pilot RCT supports the feasibility and preliminary efficacy of telehealth tDCS in a medical subpopulation. Studying women with MS highlights its potential for large-scale RCTs and clinical use.

OBJECTIVE:The application of transcranial direct current stimulation (tDCS) at home for the treatment of depression and other neuropsychiatric disorders presents both significant opportunities and inherent challenges. Ensuring safety and maintaining high-quality stimulation are paramount for the efficacy and safety of at-home tDCS. This study investigates tDCS quality based on its technical parameters as well as safety of at-home and in-clinic tDCS applications comparing the data from two randomized controlled trials in patients with major depressive disorder. METHODS:We analyzed 229 active stimulation sessions from the HomeDC study (at-home tDCS) and 835 sessions from the DepressionDC study (in-clinic tDCS). Notably, five adverse events (skin lesions) were reported exclusively in the at-home cohort, highlighting the critical need for enhanced safety protocols in unsupervised environments. RESULTS:= .097). The at-home tDCS sessions exhibited higher impedance variability (M = 837, SD = 328) compared to in-clinic sessions (M = 579, SD = 309). Furthermore, at-home tDCS sessions resulting in adverse events (AEs) were associated with significantly higher average impedances than sessions without such issues. CONCLUSION/CONCLUSIONS:The study demonstrates that monitoring the technical parameters of at-home tDCS used in this study is essential. However, it may be not sufficient for ensuring safety and promptly detecting or preventing adverse events. Quality control protocols including digital training and monitoring techniques should be systematically developed and tested for a reliable and safe application of at-home tDCS therapies.

More than half of individuals with multiple sclerosis (MS) use cannabis, with up to 20 % at risk of cannabis use disorder (CUD). While some individuals with MS report symptom relief from cannabis use, particularly for pain, sleep, and mood, there is limited support for its evidence-based therapeutic use. In contrast, long-term use has been associated with poorer cognitive and emotional functioning, fatigue, and reduced quality of life. Although reducing or stopping cannabis use has shown benefits, there is a lack of accessible interventions. We recruited nationally for a pilot study of a remotely supervised home-based intervention to reduce cannabis use among women with MS and CUD. The trial response provided critical insights into cannabis use patterns and the significant demand for accessible, effective interventions, highlighting an urgent unmet need within the MS community.

BACKGROUND:Childhood environmental factors back to the prenatal environment can contribute to MS risk. Childhood adversity, which causes biological, behavioral, and epigenetic changes that can be passed down through families, has been understudied in MS. Here, we emphasize the need to understand the role that intergenerational adversity may play among families affected by MS. OBJECTIVE:To evaluate the frequency and types of adverse childhood experiences among parents of children with MS. METHODS:Individuals with pediatric MS (n = 68) were enrolled in a longitudinal study of cognition. At enrollment, the patient and one caregiver or parent completed questionnaires. As the pediatric participants were under age 18 at time of enrollment, one parent completed the Adverse Childhood Experiences (ACEs, a 10-item self-report measure) about the parents' own childhood. Results from the ACE questionnaire among parents of pediatric healthy controls (n = 96) and adults in a national cohort are also reported for comparison. RESULTS:Over half of pediatric MS parents reported at least one ACE exposure. Of parents that did have ACE exposures, the exposures were broad in terms of abuse, neglect, and household dysfunction. Over 10 % of parents reported total ACE scores of 7 or above. CONCLUSION/CONCLUSIONS:Over half of pediatric MS parents experienced some degree of childhood adversity. The impact of intergenerational adversity on the development of pediatric onset MS warrants further study.

Depression is a common and debilitating disorder affecting millions. First-line treatments fail to achieve remission in about one-third of patients, highlighting a critical treatment need. Transcranial direct current stimulation (tDCS) has emerged as a novel treatment for depression. Therefore, the aim of this review was to provide a comprehensive overview of the last decade of tDCS trials for depression and propose future research directions. To compile studies of the past decade, we conducted a systematic review and meta-analysis of randomized clinical trials (RCTs) of tDCS for depression. A total of 21 RCTs were included, presenting a moderate effect for active tDCS compared to placebo. We also provided a description of study designs, stimulation parameters, and patients' characteristics. Following, we proposed possible strategies to enhance clinical effectiveness and reduce variability in results, including 1) optimization/personalization of tDCS via spatial and temporal target localization; 2) optimized methodological strategies, including home-based, accelerated tDCS protocols and novel trial designs; and 3) investigate patient profile to identify features that can predict treatment response. In conclusion, tDCS holds promise as a treatment for depression, but variability in trial parameters and outcomes underscores the need for its further optimization. Refining and standardizing protocols may enhance its effectiveness.

Fatigue is a common and often debilitating feature of multiple sclerosis (MS) that lacks reliably effective treatment options for most patients. Transcranial direct current stimulation (tDCS), a safe and well-tolerated type of noninvasive brain stimulation, is a low-cost and home-based approach with the potential to reduce fatigue in MS. We conducted a double-blind, sham-controlled, randomized clinical trial to compare active vs. low-dose (sham) tDCS paired with computer-based cognitive training, delivered as a home-based intervention, to reduce MS-related fatigue. Participants with MS-related fatigue, but without depression, were stratified by neurologic disability using the Extended Disability Status Scale (EDSS) and randomized to complete 30 daily sessions over six weeks of either active or sham tDCS paired with online cognitive training (BrainHQ). The primary outcome was the change in PROMIS Fatigue score from baseline to the end of the intervention. A total of 117 participants were randomized, with 92% completing all treatment sessions. Both groups showed significant reductions in fatigue, with no significant difference between them. This suggests that tDCS does not provide any additional benefit over cognitive training alone in reducing fatigue, but confirms the feasibility and tolerance of this home-based intervention.

BACKGROUND/OBJECTIVES/UNASSIGNED:Primary progressive aphasia (PPA) is managed with speech-language therapy (SLT) to slow language decline. Pairing transcranial direct current stimulation (tDCS) with SLT can enhance its effects. However, further research is needed to confirm these findings and guide its clinical use. We evaluated the feasibility of providing an intervention combining tDCS with SLT as a home-based and remotely supervised intervention. METHODS/UNASSIGNED:Participants with confirmed PPA who had word-finding difficulties were recruited for an open-label observational study. The intervention consisted of 20 daily sessions over 1 month, each with 45-min of personalized word retrieval training. During the first 30-min, participants received tDCS over the left inferior frontal gyrus (anode F7, cathode O1) at 2.0 mA. Language measures were remotely administered at baseline and intervention end. RESULTS/UNASSIGNED:= 0.016) from baseline to intervention end. CONCLUSIONS/UNASSIGNED:Our case series demonstrates that home-based tDCS added to SLT is feasible for patients with PPA. However, larger controlled studies are required to confirm its effectiveness in slowing language decline and to fully determine the benefits of this approach. This approach not only facilitates broader access to participation but also enables the extended treatment necessary to evaluate its clinical benefits, moving this treatment closer to clinical availability as a telehealth treatment.

BACKGROUND/UNASSIGNED:Many individuals with progressive multiple sclerosis (PMS) are challenged by reduced manual dexterity and limited rehabilitation options. Transcranial direct current stimulation (tDCS) during motor training can improve rehabilitation outcomes. We developed a protocol for remotely supervising tDCS to deliver sessions of stimulation paired with training at home. OBJECTIVE/UNASSIGNED:This study evaluated the effectiveness of at-home tDCS paired with manual dexterity training for individuals with PMS. METHODS/UNASSIGNED:Sixty-five right-hand dominant participants with PMS and hand impairment were randomized to receive either active or sham M1-SO tDCS paired with manual dexterity training over 4 weeks. Clinical outcomes were measured by the changes in Nine-Hole Peg Test (9-HPT) and Dellon-Modified-Moberg-Pick-Up Test (DMMPUT). RESULTS/UNASSIGNED:= 0.04). CONCLUSION/UNASSIGNED:At-home tDCS paired with manual dexterity training is effective for individuals with PMS, with M1-SO tDCS enhancing training outcomes and offering a promising intervention for improving and preserving hand dexterity.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Psychosocial adversity and stress, known to predispose adults to neurodegenerative and inflammatory immune disorders, are widespread among children who experience socioeconomic disadvantage, and the associated neurotoxicity and proinflammatory profile may predispose these children to multiple sclerosis (MS). We sought to determine associations of socioeconomic disadvantage and psychosocial adversity with odds of pediatric-onset MS (POMS), age at POMS onset, and POMS disease activity. METHODS:This case-control study used data collected across 17 sites in the United States by the Environmental and Genetic Risk Factors for Pediatric Multiple Sclerosis Study. Cases (n = 381) were youth aged 3-21 years diagnosed with POMS or a clinically isolated demyelinating syndrome indicating high risk of MS. Frequency-matched controls (n = 611) aged 3-21 years were recruited from the same institutions. Prenatal and postnatal adversity and postnatal socioeconomic factors were assessed using retrospective questionnaires and zip code data. The primary outcome was MS diagnosis. Secondary outcomes were age at onset, relapse rate, and Expanded Disability Status Scale (EDSS). Predictors were maternal education, maternal prenatal stress events, child separation from caregivers during infancy and childhood, parental death during childhood, and childhood neighborhood disadvantage. RESULTS:= 0.025). There were no associations of the socioeconomic variables with age at onset, relapse rate, or EDSS, or of prenatal or postnatal adverse events with risk of POMS, age at onset, relapse rate, or EDSS. DISCUSSION/CONCLUSIONS:Low socioeconomic status at the neighborhood level may increase the risk of POMS while high parental education may be protective against POMS. Although we did not find associations of other evaluated prenatal or postnatal adversities with POMS, future research should explore such associations further by assessing a broader range of stressful childhood experiences.