Faculty Bibliography

OBJECTIVES/OBJECTIVE:When administered in repeated daily doses, transcranial direct current stimulation (tDCS) directed to the prefrontal cortex has cumulative efficacy for the treatment of depression. Depression can be marked by altered processing of emotionally salient information. An acute marker of response to tDCS may be measured as an immediate change in emotional information processing. Using an easily administered web-based task, we tested immediate changes in emotional information processing in acute response to tDCS in participants with and without depression. MATERIALS AND METHODS/METHODS:We enrolled n = 21 women with mild-to-moderate depression and n = 20 controls without depression to complete a web-based visual search task before and after 30 minutes of tDCS directed to the prefrontal cortex. The timed task required participants to identify a target face among arrays showing sad, neutral, or mixed (distractor) expressions. RESULTS:At baseline, as predicted, the participants with depression differed from those without in emotional processing speed (mean z score difference -0.66 ± 0.27, p = 0.022) and accuracy in identifying sad stimuli (error rate: 4.4% vs 1.8%, p = 0.039). In response to tDCS, the participants with depression became significantly faster on the distractor condition (pre- vs post-tDCS z scores: -0.45 ± 0.65 vs -0.85 ± 0.65, p = 0.009), suggesting a specific reduction in bias toward negative emotional information. In response to tDCS, the depressed group also had significant improvements in self-reported mood (increased happy, decreased sad and anxious mood). CONCLUSIONS:Participants with depression vs those without were differentiated by their performance of the visual search task at baseline and in response to tDCS. Given that measurable effects on depression scales may require weeks of tDCS treatments, acute change in emotional information processing can serve as an easily obtainable marker of depression and its response to tDCS. CLINICAL TRIAL REGISTRATION/BACKGROUND:The Clinicaltrials.gov registration number for the study is NCT05188248.

BACKGROUND:Post-acute sequelae of SARS-CoV-2 infection (PASC) symptoms have broad impact, and may affect individuals regardless of COVID-19 severity, socioeconomic status, race, ethnicity, or age. A prominent PASC symptom is cognitive dysfunction, colloquially referred to as "brain fog" and characterized by declines in short-term memory, attention, and concentration. Cognitive dysfunction can severely impair quality of life by impairing daily functional skills and preventing timely return to work. METHODS:RECOVER-NEURO is a prospective, multi-center, multi-arm, phase 2, randomized, active-comparator design investigating 3 interventions: (1) BrainHQ is an interactive, online cognitive training program; (2) PASC-Cognitive Recovery is a cognitive rehabilitation program specifically designed to target frequently reported challenges among individuals with brain fog; (3) transcranial direct current stimulation (tDCS) is a noninvasive form of mild electrical brain stimulation. The interventions will be combined to establish 5 arms: (1) BrainHQ; (2) BrainHQ + PASC-Cognitive Recovery; (3) BrainHQ + tDCS-active; (4) BrainHQ + tDCS-sham; and (5) Active Comparator. The interventions will occur for 10 weeks. Assessments will be completed at baseline and at the end of intervention and will include cognitive testing and patient-reported surveys. All study activities can be delivered in Spanish and English. DISCUSSION/CONCLUSIONS:This study is designed to test whether cognitive dysfunction symptoms can be alleviated by the use of pragmatic and established interventions with different mechanisms of action and with prior evidence of improving cognitive function in patients with neurocognitive disorder. If successful, results will provide beneficial treatments for PASC-related cognitive dysfunction. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov NCT05965739. Registered on July 25, 2023.

BACKGROUND/UNASSIGNED:Cognitive decline in multiple sclerosis (MS) is common, but unpredictable, and increases with disease duration. As such, early detection of cognitive decline may improve the effectiveness of interventions. To that end, the Symbol Digit Modalities Test (SDMT) is effective in detecting slow processing speed as it relates to cognitive impairment, and intraindividual variability (IIV) observed in trials assessing continuous reaction time (RT) may be a useful indicator of early cognitive changes. Here, we will assess cognitive IIV changes in adults with early MS. METHODS/UNASSIGNED:Adults with relapsing-remitting MS (RRMS), <11 years since diagnosis, were recruited nationally. Baseline and two-year follow-up assessments included Brief International Cognitive Assessment in MS (BICAMS) and Cogstate computerized tests. Intraindividual variability in RT was calculated from psychomotor tasks and data were age-normalized. RESULTS/UNASSIGNED:= 0.05) compared to the lower SDMT group, with no significant RT or BICAMS changes. CONCLUSIONS/UNASSIGNED:In early MS, higher SDMT performance at baseline is associated with less cognitive variability but may indicate susceptibility to increased variability over time, highlighting the importance of monitoring IIV for early cognitive changes.

INTRODUCTION/UNASSIGNED:Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique with simultaneous (during stimulation) and cumulative effects (after repeated sessions) on blood flow and neuronal metabolism. These effects remain mostly unclear especially in multiple sclerosis (MS). This work aims to elucidate brain metabolic and hemodynamic underpinnings of tDCS and its potential therapeutic impact in MS patients using quantitative tDCS-MRI. METHODS/UNASSIGNED:) were obtained at pre-tDCS, during-tDCS and post-tDCS. RESULTS/UNASSIGNED:and CBF in pre-tDCS follow up, reaching the magnitudes measured at baseline during-tDCS. DISCUSSION/UNASSIGNED:TDCS induces an acute surge in metabolic activity persisting immediately after the stimulation is removed. Moreover, treatment composed of repeated tDCS-aCT paired sessions contributes to establishing long-lasting increases in neuronal activity.

BACKGROUND/UNASSIGNED:Autonomic nervous system (ANS) dysfunction is frequently seen in people living with multiple sclerosis (MS). Heart rate variability (HRV) is an easy and objective index for evaluating ANS functioning, and it has been previously used to explore the association between ANS and the experience of symptom burden in other chronic diseases. Given ANS functioning can be influenced by physical and psychological factors, this study investigated whether emotional distress and/or the presence of ANS dysfunction is associated with symptom severity in people living with MS. METHODS/UNASSIGNED:Participants with MS and healthy controls (HC) with no history of cardiac conditions were recruited to self-collect HR data sampled from a chest strap HR monitor (PolarH10). Short-term HR signal was collected for five minutes, and time and frequency HRV analyses were performed and compared between groups. HRV values were then compared to self-reported distress (Kessler Psychological Distress Scale) and MS participants' self-reported measures of symptom burden (SymptoMScreen). RESULTS/UNASSIGNED:= 0.007). A significant mediation effect was also observed, with emotional distress fully mediating the association between HRV and symptom burden. CONCLUSIONS/UNASSIGNED:These findings suggest the potential for ANS dysfunction, as measured by HRV (i.e., lower value of HF power), to be utilized as an objective marker of symptom burden in people living with MS. Moreover, it is apparent that the relationship between HRV and symptom burden is mediated by emotional distress.

OBJECTIVES:Intra-individual variability (IIV), measured across repeated response times (RT) during continuous psychomotor tasks, is an early marker of cognitive change in the context of neurodegeneration. To advance IIV towards broader application in clinical research, we evaluated IIV from a commercial cognitive testing platform and compared it to the calculation approaches used in experimental cognitive studies. METHODS:-transformed standard deviation or "LSD"). We calculated IIV from the raw RTs using coefficient of variation (CoV), regression-based, and ex-Gaussian methods. The IIV from each calculation was then compared by rank across participants. RESULTS:A total of n = 120 participants with MS aged 20-72 (Mean ± SD, 48.99 ± 12.09) completed the baseline cognitive measures. For each task, the interclass correlation coefficient was generated. Each ICC showed that LSD, CoV, ex-Gaussian, and regression methods clustered strongly (Average ICC for DET: 0.95 with 95% CI [0.93, 0.96]; Average ICC for IDN: 0.92 with 95% CI [0.88 to 0.93]; Average ICC for ONB: 0.93 with 95% CI [0.90 to 0.94]). Correlational analyses indicated the strongest correlation between LSD and CoV for all tasks (rs ≥ 0.94). CONCLUSION:The LSD was consistent with research-based methods for IIV calculations. These findings support the use of LSD for the future measurement of IIV for clinical studies.

Abstract Background: Loss of hand dexterity is disabling and reduces quality of life. People living with progressive forms of MS have marked neurologic disabilities but limited rehabilitation options. Transcranial direct current stimulation (tDCS) is a method of noninvasive brain stimulation in which stimulation delivered during motor training can strengthen outcomes. We have established a remotely supervised tDCS (RS-tDCS) protocol that delivers multiple stimulation sessions paired with training to participants at home.
Objective(s): To evaluate a blinded randomized sham-controlled clinical trial of active vs. sham tDCS paired with manual dexterity training for people with progressive MS.
Method(s): We recruited right-hand dominant individuals with progressive MS and hand dexterity impairment. Participants completed 20 sessions of daily (M-F) manual dexterity and were randomized to either active (2.0 mA) or sham primary motor cortex (M1-SO) tDCS. Manual dexterity was measured with the Nine-Hole Peg Test (9HPT) and Dellon-Modified Moberg Pick-Up test (MMPUT) at baseline and study end and transformed to normative z-scores for comparison.
Result(s): Participants were n=60 with primary (32%) or secondary (68%) progressive MS (52% female, ages 37-72 years, and a median Expanded Disability Status Scale (EDSS) score of 5.0 [1.5-7.5]). The intervention was safe and well tolerated, with n=59/60 (98%) completing 18/20 daily sessions. Combining hands and tasks, the full group improved following the manual dexterity training (mean z-score improvement 1.64+/-9.53, p=0.016). Active tDCS led to greater improvement (mean z-score improvement 4.51+/-8.78, p=0.001). Analyzing those with right- or left-hand impairment at baseline, the active tDCS group had significant improvement on the 9HPT (Right: p=0.036, Left: p=0.028) and trended towards significant improvement for the MMPUT (Right: p=0.071, Left: p=0.079).
Conclusion(s): At-home manual dexterity training paired with tDCS is a safe, tolerable, and feasible intervention for people with progressive MS and hand impairment. Training outcomes are augmented with simultaneous M1-SO tDCS. Research Category and Technology and Methods Clinical Research: 9. Transcranial Direct Current Stimulation (tDCS) Keywords: tDCS, motor training, multiple sclerosis, teleintervention
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Abstract Objectives: Evaluate feasibility and preliminary efficacy of remotely supervised transcranial Direct Current Stimulation (RS-tDCS) interventions for persistent post-traumatic headache (PPTH) secondary to mild TBI (mTBI).
Method(s): Veterans with PPTH completed a 28-day baseline observation of headache days and received either active or sham RS-tDCS paired with mindfulness meditation. This 4-week intervention of 20-minutes daily (M-F) RS-tDCS (anodal stimulation dlPFC) was monitored via VA Video Connect. Feasibility was determined by the number of participants completing >=80% of the intervention. Efficacy was measured by changes in number of moderate/severe headache days from baseline period to the end of treatment phase, and 4-week post-treatment follow-up. Secondary endpoints included total number of headache days, acute pain medication use, as well as headache- and mTBI-related disability.
Result(s): Twenty-six veterans (46.6+/-8.7 years) with PPTH completed baseline observations and were randomized to either active (n=13) or sham (n=13) treatment groups. A total of 22/25 (88%) participants fully completed either active (10/12) or sham (12/13) interventions (p=.0.59). Within-group analyses reveled significant reductions in moderate/severe headache days in the active (p=0.04) but not sham (p=0.54) groups. This resulted in a trend towards significant reductions in moderate/severe headache days in the active vs. sham groups (p = 0.07). Active participants also demonstrated a reduction in total number of headache days during treatment (p=0.04) where the sham group did not (p=0.70). There is statistically significant reduction in total number of headache days during treatment for active vs. sham participants (p=0.03). No significant differences were maintained during the 4-week post-treatment follow-up (p's>0.05).
Conclusion(s): RS-tDCS treatment feasible with high adherence and effective for veterans with PPTH. Findings suggest that active RS-tDCS via dlPFC reduce headache frequency and improve clinical outcomes. A larger phase II study is warranted to confirm these findings and inform evaluation for clinical use. Research Category and Technology and Methods Clinical Research: 9. Transcranial Direct Current Stimulation (tDCS) Keywords: tDCS, Persistent Post-traumatic headache, Veterans, mTBI
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