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Transcranial direct current stimulation (tDCS) is an emerging treatment for major depression. We recruited participants with moderate-to-severe major depressive episodes for an observational clinical trial using Soterix Medical's tDCS telehealth platform as a standard of care. The acute intervention consisted of 28 sessions (5 sessions/week, 6 weeks) of the left anodal dorsolateral prefrontal cortex (DLPFC) tDCS (2.0 mA × 30 min) followed by a tapering phase of weekly sessions for 4 weeks (weeks 7-10). The n = 16 completing participants had a significant reduction in depressive symptoms by week 2 of treatment [Montgomery-Åsberg Depression Rating Scale (MADRS), Baseline: 28.00 ± 4.35 vs. Week 2: 17.12 ± 5.32, p < 0.001] with continual improvement across each biweekly timepoint. Acute intervention responder and remission rates were 75 and 63% and 88 and 81% following the taper period (week 10).

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OBJECTIVE: At the time of multiple sclerosis (MS) diagnosis, identifying those at risk for poorer health-related quality of life and emotional well-being can be a critical consideration for treatment planning. This study aimed to test whether adverse childhood experiences predict MS patients' health-related quality of life and emotional functioning at time of diagnosis and initial course of disease. METHODS: We recruited patients at the time of new MS diagnosis to complete self-report surveys at baseline and a one-year follow-up. Questionnaires included the Adverse Childhood Experiences (ACEs), as well as the MS Knowledge Questionnaire (MSKQ), the 36-Item Short Form Health Survey (SF-36), and Self-Management Screening (SeMaS). RESULTS: A total of n = 31 participants recently diagnosed with relapsing remitting MS (median EDSS = 1.0, age M = 33.84 ± 8.4 years) completed the study measures. The ACEs significantly predicted health-related quality of life (SF-36) at baseline (Adjusted R 2 = 0.18, p = 0.011) and follow-up (Adjusted R 2 = 0.12, p = 0.03), baseline scores on the SeMaS Depression scale (Adjusted R 2 = 0.19, p = 0.008), as well as follow-up scores on the SeMaS Anxiety (Adjusted R 2 = 0.19, p = 0.014) and SeMaS Depression (Adjusted R 2 = 0.14, p = 0.036) scales. Importantly, increased ACEs scores were predictive of increased anxiety at the one-year follow-up assessment, compared to baseline. CONCLUSIONS: Childhood adversity predicts health-related quality of life and emotional well-being at time of MS diagnosis and over the initial course of the disease. Measured using a brief screening inventory (ACEs), routine administration may be useful for identifying patients in need of increased supportive services.

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OBJECTIVE: Cognitive deficits following a traumatic brain injury (TBI) are a leading cause of disability in young adults and there is a critical need for novel approaches to improve cognitive outcomes in TBI survivors. Transcranial direct current stimulation (tDCS) paired with cognitive remediation has emerged as a viable, cost-effective, noninvasive approach for treating cognitive impairments in a wide variety of neurological conditions. Here, we report the first case study utilizing remotely supervised tDCS (RS-tDCS) protocol paired with cognitive remediation in a 29-year-old man with persisting cognitive and emotional sequelae following TBI. METHOD: Neuropsychological measures were administered before and after the patient completed 20 daily sessions of RS-tDCS (2.0 mA × 20 minutes, left anodal dorsolateral prefrontal cortex montage). During the daily stimulation period, he completed adaptive cognitive training. All treatment procedures were delivered at home and monitored in real time via videoconference with a study technician. RESULTS: Following 20 RS-tDCS and cognitive training sessions, he had significant improvements (>1 SD) on tests of attention and working memory, semantic fluency, and information processing speed. Mood was also improved. CONCLUSIONS: This is the first demonstration of at-home telerehabilitation with RS-tDCS and cognitive training to improve cognitive outcomes following TBI.

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Background: Cognitive impairment is a common feature of multiple sclerosis (MS). A semi-structured interview, including informant input, can characterize the experience of individuals living with MS and cognitive involvement. Objective: We administered the Cognitive Assessment Interview (CAI), a patient- and informant-based semi-structured interview, to characterize the experience of cognitive impairments in those living with MS. Methods: Trained raters administered the CAI to a sample of MS participants and their informants enrolled for a trial of cognitive remediation. Cognitive impairments on the CAI were characterized and compared to those captured by neuropsychological and self-report measures. Results: A total of n = 109 MS participants (mean age = 50.3 ± 12.2) and their available informants (n = 71) were interviewed. Participants reported experiencing processing speed (90/106, 85%), working memory (87/109, 80%), and learning and memory (79/109, 72%) problems most commonly. CAI-based ratings were moderately correlated with a self-report measure (Multiple Sclerosis Neuropsychological Screening Questionnaire, r s = 0.52, p < 0.001) and only mildly correlated with objective neuropsychological measures specific to executive functions (r s = 0.21, p = 0.029). For those with informant interviews, ratings were overall consistent, suggesting that the CAI is valid even in cases in which an informant is unavailable and the interview is conducted with the patient alone (as is often the case in clinical and research settings). Conclusions: The CAI provides a semi-structured interview to characterize the experience of cognitive impairment in MS, with findings representing real-world functioning, adding valuable information to both self-report measures and neuropsychological assessment.

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BACKGROUND: The Symbol Digit Modalities Test (SDMT) is the gold standard for cognitive screening in multiple sclerosis (MS). OBJECTIVE: Due to the recent COVID-19 pandemic and the increased need for virtual clinical visits, we examined the reliability of remote administration of the SDMT vs. standard in-person administration to individuals with MS. METHODS: Pearson's correlation analysis was performed between SDMT scores on the in-person and remote administrations. RESULTS: For n = 132 participants, remote and in-person SDMT scores were strongly correlated (r = .80, p = .000). CONCLUSION: Remote administration of the SDMT is a reliable cognitive screening approach in MS.

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BACKGROUND: Cognitive impairment due to multiple sclerosis (MS) is common and often limits occupational functioning, contributes to disability, and reduces quality of life. Early detection of cognitive involvement in MS is critical for treatment planning and intervention, and frequent, regular cognitive monitoring may provide insight into subtle changes in disease progression. OBJECTIVE: To compare the sensitivity and specificity of clinical, computer-based and experimental measures to early cognitive involvement in MS. METHODS: Cognitive functioning was compared in MS participants early in the disease course to matched healthy controls using conventional, computer-based and functional assessments: the Brief International Cognitive Assessment in MS (BICAMS); the computer-based Cogstate Brief Battery (CBB); the Attention Network Test-Interaction (ANT-I), including intra-individual variability; and the Test of Everyday Cognitive Ability (TECA), a functional measure of instrumental activities of daily living. RESULTS: MS participants (n = 25, mean disease duration= 5.82 ± 3.65 years) and demographically matched healthy controls (n = 29) completed the cognitive assessments. The Cogstate measure of choice reaction time (AUC = 0.73, p = .004), intra-individual variability on the ANT-I (AUC = 0.79, p = .001), and TECA (AUC = 0.78, p = .001) scores were the most sensitive and specific markers of cognitive involvement in MS. CONCLUSIONS: Brief, repeatable, computer-based measures of reaction time and variability detect early MS associated cognitive involvement.

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Autism spectrum disorder (ASD) is a pervasive neurodevelopmental condition, affecting cognition and behavior throughout the life span. With recent advances in neuroimaging techniques and analytical approaches, a considerable effort has been directed toward identifying the neuroanatomical underpinnings of ASD. While gray-matter abnormalities have been found throughout cortical, subcortical, and cerebellar regions of affected individuals, there is currently little consistency across findings, partly due to small sample-sizes and great heterogeneity among participants in previous studies. Here, we report voxel-based morphometry of structural magnetic resonance images in a relatively large sample of high-functioning adults with ASD (n = 66) and matched typically-developing controls (n = 66) drawn from multiple studies. We found decreased gray-matter volume in posterior brain regions, including the posterior hippocampus and cuneus, as well as increased gray-matter volume in frontal brain regions, including the medial prefrontal cortex, superior and inferior frontal gyri, and middle temporal gyrus in individuals with ASD. We discuss our results in relation to findings obtained in previous studies, as well as their potential clinical implications.

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Accumulating evidence suggests that autonomic signals and their cortical representations are closely linked to emotional processes, and that related abnormalities could lead to social deficits. Although socio-emotional impairments are a defining feature of autism spectrum disorder (ASD), empirical evidence directly supporting the link between autonomic, cortical, and socio-emotional abnormalities in ASD is still lacking. In this study, we examined autonomic arousal indexed by skin conductance responses (SCR), concurrent cortical responses measured by functional magnetic resonance imaging, and effective brain connectivity estimated by dynamic causal modeling in seventeen unmedicated high-functioning adults with ASD and seventeen matched controls while they performed an empathy-for-pain task. Compared to controls, adults with ASD showed enhanced SCR related to empathetic pain, along with increased neural activity in the anterior insular cortex, although their behavioral empathetic pain discriminability was reduced and overall SCR was decreased. ASD individuals also showed enhanced correlation between SCR and neural activities in the anterior insular cortex. Importantly, significant group differences in effective brain connectivity were limited to greater reduction in the negative intrinsic connectivity of the anterior insular cortex in the ASD group, indicating a failure in attenuating anterior insular responses to empathetic pain. These results suggest that aberrant interoceptive precision, as indexed by abnormalities in autonomic activity and its central representations, may underlie empathy deficits in ASD.

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Autism spectrum disorders are associated with social and emotional deficits, the aetiology of which are not well understood. A growing consensus is that the autonomic nervous system serves a key role in emotional processes, by providing physiological signals essential to subjective states. We hypothesized that altered autonomic processing is related to the socio-emotional deficits in autism spectrum disorders. Here, we investigated the relationship between non-specific skin conductance response, an objective index of sympathetic neural activity, and brain fluctuations during rest in high-functioning adults with autism spectrum disorder relative to neurotypical controls. Compared with control participants, individuals with autism spectrum disorder showed less skin conductance responses overall. They also showed weaker correlations between skin conductance responses and frontal brain regions, including the anterior cingulate and anterior insular cortices. Additionally, skin conductance responses were found to have less contribution to default mode network connectivity in individuals with autism spectrum disorders relative to controls. These results suggest that autonomic processing is altered in autism spectrum disorders, which may be related to the abnormal socio-emotional behaviours that characterize this condition.

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Although possible sources and functions of the resting-state networks (RSNs) of the brain have been proposed, most evidence relies on circular logic and reverse inference. We propose that autonomic arousal provides an objective index of psychophysiological states during rest that may also function as a driving source of the activity and connectivity of RSNs. Recording blood oxygenation level-dependent (BOLD) signal using functional magnetic resonance imaging and skin conductance simultaneously during rest in human subjects, we found that the spontaneous fluctuations of BOLD signals in key nodes of RSNs are associated with changes in nonspecific skin conductance response, a sensitive psychophysiological index of autonomic arousal. Our findings provide evidence of an important role for the autonomic nervous system to the spontaneous activity of the brain during "rest."

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Exposure to Bisphenol-A (BPA), an endocrine disruptor used in plastics, occurs in the United States on a daily basis. Recent studies suggest exposure during development causes memory deficits later in life; however, the ramifications of exposure in adulthood are unclear. We examined the effects of acute BPA administration (40 µg/kg) on memory and synaptic plasticity in adult male rats. BPA significantly impaired both visual and spatial memory and decreased dendritic spine density on pyramidal cells in CA1 and the medial prefrontal cortex (mPFC). Additionally, BPA significantly decreased PSD-95, a synaptic marker, in the hippocampus and increased cytosolic pCREB, a transcription factor, in mPFC. Together, these findings show that a single dose of BPA, below the USEPA reference safe daily limit of 50 µg/kg/day, may block the formation of new memories by interfering with neural plasticity processes in the adult brain.

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