Accelerated Aging after Traumatic Brain Injury: An ENIGMA Multi-Cohort Mega-Analysis.

OBJECTIVE: The long-term consequences of traumatic brain injury (TBI) on brain structure remain uncertain. Given evidence that a single significant brain injury event increases the risk of dementia, brain-age estimation could provide a novel and efficient indexing of the long-term consequences of TBI. Brain-age procedures use predictive modeling to calculate brain-age scores for an individual using structural magnetic resonance imaging (MRI) data. Complicated mild, moderate, and severe TBI (cmsTBI) is associated with a higher predicted age difference (PAD), but the progression of PAD over time remains unclear. We sought to examine whether PAD increases as a function of time since injury (TSI) and if injury severity and sex interacted to influence this progression. METHODS: Through the ENIGMA Adult Moderate and Severe (AMS)-TBI working group, we examine the largest TBI sample to date (n = 343), along with controls, for a total sample size of n = 540, to replicate and extend prior findings in the study of TBI brain age. Cross-sectional T1w-MRI data were aggregated across 7 cohorts, and brain age was established using a similar brain age algorithm to prior work in TBI. RESULTS: Findings show that PAD widens with longer TSI, and there was evidence for differences between sexes in PAD, with men showing more advanced brain age. We did not find strong evidence supporting a link between PAD and cognitive performance. INTERPRETATION: This work provides evidence that changes in brain structure after cmsTBI are dynamic, with an initial period of change, followed by relative stability in brain morphometry, eventually leading to further changes in the decades after a single cmsTBI. ANN NEUROL 2024;96:365-377.

An Examination of Positive and Negative Outcomes During the COVID-19 Pandemic Among Persons With Multiple Sclerosis.

IMPORTANCE: This study provides information to clinicians about how persons with MS coped in both positive and negative ways during a potentially traumatic experience (the coronavirus disease 2019 [COVID-19] pandemic), which will help clinicians to provide better services to this population in the face of stressful events. OBJECTIVE: To describe both positive and negative outcomes among persons with multiple sclerosis (MS) and to examine whether resilience and social support were related to positive and negative outcomes during the peak of the pandemic. DESIGN: An online survey administered during the COVID-19 pandemic. PARTICIPANTS: Participants were 74 individuals with MS and 104 healthy controls (HCs) recruited through social media and community support groups. OUTCOMES AND MEASURES: The survey included questionnaires that assessed both positive and negative responses to the pandemic, including benefit finding, loneliness, and distress. Resilience and social support were also assessed. RESULTS: Differences were noted between persons with MS and HCs on negative but not positive outcomes. Better social support and resilience were related to positive outcomes. CONCLUSIONS AND RELEVANCE: Both persons with MS and HCs were similar in benefit finding and stress management. However, negative outcomes were worse in the MS group. Our findings shed light on the importance of individuals with MS adopting a positive outlook to help during times of adversity. What This Article Adds: Among persons with disabilities such as multiple sclerosis, finding benefits during stressful times can be a potential coping mechanism. Furthermore, resilience and social support should be taken into account to moderate the effects of adverse events.

Development and Psychometric Properties of Self-Reported Job Interview Skills and Job Interview Anxiety for Autistic Transition-Age Youth.

BACKGROUND: The study of job interview training is an emerging area among transition-age autistic youth who face significant challenges when navigating job interviews. The autism field has limited measures that have undergone rigorous psychometric evaluation. OBJECTIVE: We sought to evaluate the psychometric properties of adapted self-report measures assessing job interview skills and job interview anxiety. METHODS: As part of two parent randomized controlled trials, eighty-five transition-age autistic youth completed measures related to the strength of their job interview skills and their level of job interview anxiety. We conducted classical test theory analyses, exploratory and confirmatory factor analyses, and Rasch model analytic and calibration analyses. Pearson correlations were used to establish concurrent, divergent, and criterion validity by correlating these scales with measures of social differences, depressive symptoms, behaviors, neuropsychological functioning, and work history. RESULTS: Our analyses yielded two brief and reliable scales: Measure of Job Interview Skills (MOJO-iSkills) and Measure of Job Interview Anxiety (MOJO-iAnxiety), which demonstrated initial concurrent, divergent, and criterion validities when correlated with measures of depressive symptoms, social differences, internalizing and externalizing behavior, and work history. CONCLUSIONS: This study presents initial evidence that MOJO-iSkills and MOJO-iAnxiety have acceptable psychometric properties supporting they can be used to reliably and validly assess job interview skills and interview anxiety.

Healthcare Disruptions and Use of Telehealth Services Among People With Multiple Sclerosis During the COVID-19 Pandemic.

OBJECTIVE: The current study examined health care disruptions and use of telehealth services among people with multiple sclerosis (pwMS) during the COVID-19 pandemic. DESIGN: Cross-sectional survey. SETTING: General community. PARTICIPANTS: Participants (N=163) included 70 pwMS and 93 healthy controls (HCs). The majority of respondents were from the United States (88%). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Rates of health care disruptions (eg, missing/canceling appointments, experiencing delays) and telehealth use for MS and non-MS medical care and mental health care. RESULTS: In this U.S. majority, predominantly White, and high socioeconomic status sample, 38% to 50% of pwMS reported experiencing disruptions in their MS and non-MS medical care and 20% to 33% reported disruptions in their mental health care; this was significantly lower than the rates observed among HCs. Compared with HCs, pwMS were more likely to use telehealth than in-person services, especially for mental health care. The majority of pwMS and HCs reported being satisfied with telehealth services. Individuals with higher degrees of functional limitation experienced more health care disruptions and were more likely to use telehealth services than individuals with lower degrees of functional limitation. CONCLUSIONS: Despite high health care disruption rates, pwMS frequently used and were highly satisfied with telehealth services during the COVID-19 pandemic. Due to physical limitations commonly observed in the MS population that may preclude travel, telehealth services should be continued even after resolution of the pandemic to expand access and reduce health care disparities.

The impact of the COVID-19 pandemic on engagement in activities of daily living in persons with acquired brain injury.

PRIMARY OBJECTIVES: This study examined (a) the impact of coronavirus disease-2019 (COVID-19) pandemic on engagement in activity participation in persons with acquired brain injury (ABI); and (b) whether changes in activity participation during the pandemic were associated participants' health-related quality of life (HRQoL). RESEARCH DESIGN: Exploratory online survey study. METHODS: Eighty-seven respondents with ABI and 98 healthy adults (HA) participated in this study. Engagement in activity participation during COVID-19 was calculated as a percentage of the activities participants performed before the pandemic. MAIN RESULTS: Participants with ABI modified their activities less than HA in order to maintain level of engagement in activity participation. They stopped performing more activities during the pandemic compared to HA and compared to their pre-pandemic engagement. Both groups continued to do similar percentage of activities without modifications compared to before the pandemic. Better HRQoL in both groups was predicted by a larger percentage of activities continued and fewer activities stopped. CONCLUSION: Results emphasize the importance of addressing activity participation changes during situations where there are disruptions of the individual's habits and routines in order to minimize negative consequences of such changes.

Independent contributions of social cognition and depression to functional status after moderate or severe traumatic brain injury.

Impairments in cognitive processing related to social understanding and communication (i.e., "social cognition") are well documented after moderate or severe traumatic brain injury (TBI) and can contribute to negative functional outcome. Depression is also a common feature of TBI with detrimental functional consequences. We evaluated relationships between social cognition, depression symptom severity, and functional status in individuals with chronic TBI (>1 year post injury; n = 25) and healthy controls (n = 30) using objective tests of social cognition as well as self-reported depression (Beck Depression Inventory-II) and functional status (Functional Behavior Profile). Results revealed significant relationships between depression and functional status across the sample, and relationships between social cognition and functional status specific to TBI. In the TBI group only, social cognition significantly predicted both overall and social functional status above and beyond depression. Group differences in functional status were independently mediated by social cognition and, especially, depression. Our findings suggest that social cognitive impairments and depression are distinct, functionally relevant TBI sequelae. Interventions to improve social functioning in this population may be most effective when contextualized within treatments for emotional disturbances.

Social Cognition in Individuals with Progressive Multiple Sclerosis: A Pilot Study Using TASIT-S.

OBJECTIVE: Individuals with multiple sclerosis (MS) can have difficulty on tasks requiring social cognition, including Theory of Mind (ToM) and facial affect recognition. However, most research on social cognition in MS has focused on Relapsing-Remitting MS; less is known about deficits in individuals with progressive MS. This pilot study examined the social cognitive abilities of individuals with progressive MS on a dynamic social cognition task: The Awareness of Social Inference Test - Short Form (TASIT-S). METHODS: Fifteen individuals with progressive MS and 17 healthy controls performed TASIT-S, which includes 3 subtests assessing facial affect recognition and ToM. RESULTS: The MS group was impaired on all subtests of TASIT-S, including Emotion Evaluation, Social Inference - Minimal, and Social Inference - Enriched, which examine facial affect recognition and ToM. Deficits on TASIT-S were significantly correlated with several cognitive abilities including working memory, learning memory, and verbal IQ. CONCLUSIONS: Our findings suggest individuals with progressive MS were impaired across multiple social cognition domains as assessed by the TASIT-S. Furthermore, social cognitive abilities were related to cognitive abilities such as visuospatial memory and executive abilities. Results are discussed in terms of social cognition deficits in MS and how they relate to cognitive abilities.

The Neural Mechanisms Underlying Processing Speed Deficits in Individuals Who Have Sustained a Spinal Cord Injury: A Pilot Study.

Our objective was to determine differences in brain activation during a processing-speed task in individuals with SCI compared to a group of age-matched healthy controls and to a group of older healthy controls. Ten individuals with cervical SCI (C3-C5), 10 age-matched healthy controls and 10 older healthy controls participated in a cross-sectional study in which performance on neuropsychological tests of processing speed and brain activation were the main outcome measures. The brain areas used by the individuals with SCI during the processing-speed task differed significantly from the age-matched healthy controls, but were similar to the older control cohort, and included activation in frontal, parietal and hippocampal areas. This suggests that individuals with SCI may compensate for processing-speed deficits by relying on brain regions that classically support control cognitive processes such as executive control and memory.

Postdecisional Processing Delays in Metacognitive Monitoring After Traumatic Brain Injury.

OBJECTIVE: To document the process by which metacognitive judgments ("online" monitoring of one's own cognitive performance during task completion) are made after traumatic brain injury (TBI). PARTICIPANTS: Sixteen community-dwelling adults with moderate to severe TBI and 16 matched healthy controls. DESIGN: Prospective, cross-sectional design. MEASURES: Metacognitive retrospective confidence judgments and reaction times were collected as participants performed a metamemory task. RESULTS: Adults with TBI did not differ from healthy peers in metacognitive accuracy; however, they took significantly longer to make retrospective confidence judgments. Retrospective confidence judgment reaction times were not consistently correlated to measures of processing speed in either sample. CONCLUSIONS: Adults with TBI engage in different postdecisional processes to make metacognitive judgments compared with healthy controls. Findings suggest that reaction times may be an important dimension of metacognition to assess clinically after TBI.

Progressive resistance exercise training and changes in resting-state functional connectivity of the caudate in persons with multiple sclerosis and severe fatigue: A proof-of-concept study.

Fatigue is one of the most disabling symptoms of multiple sclerosis (MS). While progressive resistance training (PRT) has been shown to reduce fatigue in persons with MS, it is not clear why these reductions occur. One hypothesis is that PRT may induce functional changes to the caudate, a region highly implicated in MS fatigue. The aim of the current study was to study the effects of PRT on overall fatigue impact and resting-state functional connectivity of the caudate in persons with MS reporting severe fatigue. Participants were semi-randomly assigned to either a 16-week home-based PRT (n = 5) or stretching control (n = 5) condition. Both groups demonstrated reductions in overall fatigue impact (main effect of time: F = .84, d = .65). Significant group × time interactions were found, with the PRT group demonstrating post-training increases in functional connectivity between the caudate and left inferior parietal (F = 66.0, p < .001), bilateral frontal (both p < .001), and right insula (F = 21.8, p = .002) regions compared to the stretching group. Furthermore, greater post-training increases in functional connectivity between the caudate and left inferior parietal region were associated with greater decreases in cognitive fatigue (r = -.52) specifically. This study provides initial evidence for the caudate as a potential neural substrate for the beneficial effects of PRT on fatigue in persons with MS.

Cognitive but Not Affective Theory of Mind Deficits in Progressive MS.

OBJECTIVE: Social cognitive deficits are an important consequence of multiple sclerosis (MS), yet our understanding of how these deficits manifest in progressive MS is currently limited. To this end, we examined theory of mind (ToM) ability in a sample of individuals with progressive MS using an ecologically valid virtual assessment tool that allows for delineation of cognitive ToM (inferring thoughts and intentions of others) from affective ToM (inferring emotions of others). METHODS & RESULTS: We compared 15 individuals with progressive MS and 15 healthy controls on their ToM ability using the Virtual Assessment of Mentalising Ability. We found that, relative to healthy controls, participants with progressive MS were impaired in cognitive ToM, but not in affective ToM. Furthermore, we found that the MS participants' deficits in cognitive ToM were mediated by their general cognitive ability such that poor cognitive ToM ability in MS was explained by poor performance on tests of memory and processing speed. CONCLUSIONS: Our findings demonstrate that ToM deficits in progressive MS may be limited to cognitive ToM, while affective ToM is conserved. This could be attributable to the MS-related deficits in general cognitive ability, which appear to negatively affect only the cognitive component of ToM.

Community Integration in Traumatic Brain Injury: The Contributing Factor of Affect Recognition Deficits.

OBJECTIVE: Individuals with traumatic brain injury (TBI) can experience social isolation, which is damaging to well-being and counterproductive to successful rehabilitation. It has been proposed that social cognitive deficits that commonly result from TBI may contribute to weakened social integration. However, the consequences of specific social cognitive deficits in TBI are still being delineated. The current work sought to better characterize the relationship between community integration and facial affect recognition (FAR) in TBI. PARTICIPANTS AND METHODS: A total of 27 participants with moderate to severe TBI and 30 healthy controls (HCs) completed two tests of FAR, which employed either static photographic stimuli or dynamic video stimuli (The Awareness of Social Inference Test). The Community Integration Questionnaire was also administered to participants. RESULTS: Participants with TBI were significantly impaired on both the static and dynamic FAR measures, yet the deficits were most pronounced within the dynamic task. Furthermore, participants with TBI reported lower community integration compared with HCs. FAR was positively associated with community integration in both groups, such that participants with proficient affect recognition skills were better integrated into their communities. CONCLUSIONS: FAR deficits may contribute to the lack of community integration often observed in TBI; thus, interventions designed to improve FAR may be beneficial to this population's ability to successfully reintegrate into society.

Longitudinal examination of the relationship between changes in white matter organization and cognitive outcome in chronic TBI.

Background and Objective: Changes in cerebral white matter organization have been documented in acute phases of recovery from traumatic brain injury (TBI). However, little is known about reorganization processes in more chronic stages of recovery. The current study identified changes in white matter organization in chronic cases of TBI, and determined the relationship between structural changes and cognitive functioning. Methods: 15 adults with moderate to severe TBI and eight healthy controls completed neuropsychological testing and diffusion tensor imaging (DTI) scanning. Participants returned 3 years from the initial session to complete identical neuropsychological tests and scans. Results: Adults with TBI were found to have significantly reduced fractional anisotropy (FA), a metric of white matter organization, compared to healthy participants at baseline and also at 3-year follow-up. Within the sample of adults with TBI, increases in FA were observed over time. Importantly, increases in FA in the TBI sample were also correlated with improvements in cognitive performance. Conclusions: This study provides evidence of a dynamic process of white matter change occurring beyond the initial phases of recovery after moderate to severe TBI. The observed relationship between structural reorganization and changes in cognitive performance has implications for rehabilitation potential in more chronic phases of recovery.

A randomized controlled trial to treat impaired learning and memory in multiple sclerosis: The self-GEN trial.

BACKGROUND: Difficulties in learning and memory are among the most persistent and frequently reported cognitive symptoms in individuals with multiple sclerosis (MS). OBJECTIVE: To examine the efficacy of the self-generation learning program ( self-GEN trial) that consist of behavioral intervention sessions, teaching self-generation technique while using metacognitive strategies to improve learning and memory abilities in persons with MS. Additionally, the treatment aimed to address generalization of the treatment to activities of daily living. METHODS: This double-blind, placebo-controlled, randomized clinical trial included 35 participants with clinically definite MS, 19 in the treatment group and 16 in the placebo control group. Participants completed a baseline neuropsychological assessment, including questionnaires assessing everyday memory and a repeat assessment immediately post-treatment. RESULTS: The treatment group showed significantly improved learning and memory, self-regulation, and metacognition relative to the placebo post-treatment. Similar results were noted on measures of depression, functional status, and quality of life (QOL). CONCLUSION: This study provides initial Class I evidence that the self-GEN behavioral intervention improves memory, self-regulation, functional status, affective symptomatology, and QOL in patients with MS.

Fronto-striatal network activation leads to less fatigue in multiple sclerosis.

BACKGROUND: The fronto-striatal network has been implicated in both fatigue, a common multiple sclerosis (MS) symptom, and goal attainment, which has been shown to reduce fatigue in healthy individuals. OBJECTIVES: To investigate whether stimulation of the fronto-striatal network through goal attainment (potential monetary gain) leads to fatigue reduction in MS and healthy control (HC) participants. METHODS: In all, 14 healthy and 19 MS participants performed a gambling task during functional magnetic resonance imaging (fMRI). Participants were presented with an opportunity to receive monetary reward during the outcome condition of the task but not during the no outcome condition. Self-reported fatigue measures were obtained after each condition and outside of the scanner. Structural alterations were also examined. RESULTS: A significant decrease in fatigue was observed after the outcome condition compared to the no outcome condition in both groups. Significantly greater activation was observed in the ventral striatum in association with the outcome condition compared to the no outcome condition in both groups. Ventromedial prefrontal cortex showed significantly greater activation during the no outcome condition compared to the outcome condition with greater difference between conditions in the HC group. CONCLUSION: This is the first functional neuroimaging study showing that stimulation of the fronto-striatal network through goal attainment leads to decreased on-task fatigue in MS and healthy participants.

Information processing speed in multiple sclerosis: Past, present, and future.

BACKGROUND: Information processing speed (IPS) is a prevalent cognitive impairment in multiple sclerosis (MS). OBJECTIVES: This review aims to summarize the methods applied to assess IPS in MS and its theoretical conceptualization. A PubMed search was performed to select articles published between 1 January 2004 and 31 December 2013, resulting in 157 articles included. RESULTS: The majority (54%) of studies assessed IPS with heterogeneous samples (several disease courses). Studies often report controlling for presence of other neurological disorders (60.5%), age (58.6%), education (51.6%), alcohol history (47.8%), or use of steroids (39.5%). Potential confounding variables, such as recent relapses (50.3%), history of developmental disorders (19.1%), and visual problems (29.9%), were often neglected. Assessments used to study IPS were heterogeneous (ranging from simple to complex tasks) among the studies under review, with 62 different tasks used. Only 9.6% of articles defined the construct of IPS and 22.3% discussed IPS in relation to a theoretical model. FUTURE DIRECTIONS: The challenges for the upcoming decade include clarification of the definition of IPS as well as its theoretical conceptualization and a consensus on assessment. Based on the results obtained, we propose a new theoretical model, the tri-factor model of IPS.

Changes in activity participation following traumatic brain injury.

Traumatic brain injury (TBI) often results in impairments in cognitive skills as well as depression. As a result of these changes in cognition and mood, individuals with TBI may reduce their levels of participation and often report reduced health-related quality of life (HrQOL). The current study compares levels of past and present activity participation between healthy participants and persons with TBI using a client-centred approach in measurement. We additionally examine the relationship between activity participation, emotional functioning and HrQOL in persons with TBI. Fifty-two individuals with TBI who live in the community and 30 healthy age-matched controls performed a battery of cognitive tests and rated their affective symptomatology and activity participation (using the Activity Card Sort Test). Participants with TBI reported significantly lower current activity participation compared to controls. Current levels of activity and participation in the TBI sample were significantly related to age, time since injury, and HrQOL. Additionally, depressive symptomatology was significantly associated with HrQOL, but not with activity participation. Following TBI, levels of activity participation are reduced in most aspects of life, but more profoundly in social activities, high demand leisure activities and household activities. Additionally, high levels of depressive symptoms are associated with negative reports of HrQOL, regardless of current levels of activity participation.

Dynamic Assessment of Social Cognition in Individuals with Multiple Sclerosis: A Pilot Study.

It has recently been reported that individuals with multiple sclerosis (MS) are impaired on tasks requiring emotional processing and social cognition, including tasks of Theory of Mind (ToM) and facial affect recognition. The current pilot study examined the ability of individuals with MS to understand and interpret lies and sarcasm using a dynamic task: The Awareness of Social Inference Test (TASIT). Fifteen individuals with MS and 15 healthy controls (HCs) performed the Social Inference-Enriched subtest of the TASIT, in which they viewed video-taped social interactions in which lies and sarcasm are presented. Additionally, tests of cognition were also administered to better understand the relationship between specific cognitive abilities and the ability to understand lies and sarcasm. The MS group showed impairments in the ability to interpret and understand lies and sarcasm relative to HCs. These impairments were correlated with several cognitive abilities including processing speed, working memory, learning and memory, and premorbid IQ. The results indicate that the TASIT is a sensitive measure of social cognition in individuals with MS. Furthermore, performance on the TASIT was related to cognitive abilities. Results are discussed in terms of social cognition deficits in MS and how they relate to cognitive abilities. (JINS, 2016, 22, 83-88).

Awareness of Subjective Fatigue After Moderate to Severe Traumatic Brain Injury.

OBJECTIVE: As measurements of subjective fatigue after traumatic brain injury (TBI) rely on self-assessment, deficits in self-awareness after TBI may distort subjective fatigue reports. This study investigates awareness of subjective fatigue after TBI using self- and informant reports. PARTICIPANTS: Fourteen adults with moderate to severe TBI and 7 healthy controls (HCs). MEASURES: Modified Fatigue Impact Scale (MFIS) and battery of cognitive and emotional tests. Informants completed an "other-report," rating their perception of participant's fatigue. Subjective fatigue awareness was defined as discrepancy between self- and other-MFIS scores. RESULTS: Adults with TBI showed greater discrepancies between self- and other-MFIS scores than did HCs. Negative relations were found between fatigue awareness and symptoms of depression, but there were no relationships between fatigue awareness and cognitive performance. CONCLUSIONS: Results indicate that adults with TBI have poorer awareness of subjective fatigue than HCs. Correlations between subjective fatigue awareness and depression support existing literature implicating strong emotional components in the experience of subjective fatigue postinjury. Findings suggest cautious interpretation of subjective fatigue, as responses may not reflect fatigue symptoms exclusively.

Functional magnetic resonance imaging movers and shakers: does subject-movement cause sampling bias?

Head movement during functional magnetic resonance imaging (fMRI) degrades data quality. The effects of small movements can be ameliorated during data postprocessing, but data associated with severe movement is frequently discarded. In discarding these data, it is often assumed that head-movement is a source of random error, and that data can be discarded from subjects with severe movement without biasing the sample. We tested this assumption by examining whether head movement was related to task difficulty and cognitive status among persons with multiple sclerosis (MS). Thirty-four persons with MS were scanned while performing a working memory task with three levels of difficulty (the N-back task). Maximum movement (angle, shift) was estimated for each difficulty level. Cognitive status was assessed by combining performance on a working memory and processing speed task. An interaction was found between task difficulty and cognitive status (high vs. low cognitive ability): there was a linear increase in movement as task difficulty increased that was larger among subjects with lower cognitive ability. Analyses of the signal-to-noise ratio (SNR) confirmed that increases in movement degraded data quality. Similar, though far smaller, effects were found in a cohort of healthy control (HC) subjects. Therefore, discarding data with severe movement artifact may bias MS samples such that only those with less-severe cognitive impairment are included in the analyses. However, even if such data are not discarded outright, subjects who move more (MS and HC) will contribute less to the group-level results because of degraded SNR.