Production of co-speech gestures in the right hemisphere: Evidence from individuals with complete or anterior callosotomy.

INTRODUCTION: A right-hand preference for co-speech gestures in right-handed neurotypical individuals as well as the co-occurrence of speech and gesture has induced neuropsychological research to primarily target the left hemisphere when investigating co-speech gesture production. However, the substantial number of spontaneous left-hand gestures in right-handed individuals has, thus far, been unexplained. Recent studies in individuals with complete callosotomy and exclusive left hemisphere speech production show a reliable left-hand preference for co-speech gestures, indicating a right hemispheric generation. However, the findings raise the issue if the separate right hemisphere is able to also generate representational gestures. The present study challenges the proposition of a specific right hemispheric contribution to gesture production by differentiating gesture types including representational ones in individuals with complete callosotomy and by including individuals with anterior callosotomy in whom neural reorganization is less extensive. METHODS: Three right-handed individuals with complete commissurotomy (A.A., N.G., G.C.) and three right-handed individuals with anterior callosotomy (C.E., S.R., L. D), all with left hemisphere language dominance, and a matched right-handed neurotypical control group (n = 10) were examined in an experimental setting, including re-narration of a nonverbal animated cartoon and responding to intelligence questions. The participants' video-taped hand movement behavior was analyzed by two independent certified raters with the NEUROGES-ELAN system for nonverbal behavior and gesture. Unimanual right-hand and left-hand gestures were classified into eight gesture types. RESULTS: The individuals with complete and anterior callosotomy performed unimanual co-speech gestures with the left as well as the right hand, with no significant preference of one hand for gestures overall. Concerning the specific gesture types, the group with complete callosotomy showed a significant right-hand preference for pantomime gestures, which also applied to the callosotomy total group. The group with anterior callosotomy displayed a significant left-hand preference for form presentation gestures. As a trend, the callosotomy total group differed from the neurotypical group as they performed more left-hand egocentric deictic and left-hand form presentation gestures. DISCUSSION: The present study replicates the finding of a substantial left-hand use for unimanual co-speech gestures in individuals with complete callosotomy. The proposition of a right hemispheric contribution to gesture production independent from left hemispheric language production is corroborated by the finding that individuals with anterior callosotomy show a similar pattern of hand use for gestures. Representational gestures were displayed with either hand, suggesting that in particular right hemispheric spatial cognition can be directly expressed in gesture. The significant right-hand preference for pantomime gesture was outstanding and compatible with the established left hemispheric specialization for tool use praxis. The findings shed a new light on the left-hand gestures in neurotypical individuals, suggesting that these can be generated in the right hemisphere.

Biomedical Research and Informatics Living Laboratory for Innovative Advances of New Technologies in Community Mobility Rehabilitation: Protocol for Evaluation and Rehabilitation of Mobility Across Continuums of Care.

BACKGROUND: Rapid advances in technologies over the past 10 years have enabled large-scale biomedical and psychosocial rehabilitation research to improve the function and social integration of persons with physical impairments across the lifespan. The Biomedical Research and Informatics Living Laboratory for Innovative Advances of New Technologies (BRILLIANT) in community mobility rehabilitation aims to generate evidence-based research to improve rehabilitation for individuals with acquired brain injury (ABI). OBJECTIVE: This study aims to (1) identify the factors limiting or enhancing mobility in real-world community environments (public spaces, including the mall, home, and outdoors) and understand their complex interplay in individuals of all ages with ABI and (2) customize community environment mobility training by identifying, on a continuous basis, the specific rehabilitation strategies and interventions that patient subgroups benefit from most. Here, we present the research and technology plan for the BRILLIANT initiative. METHODS: A cohort of individuals, adults and children, with ABI (N=1500) will be recruited. Patients will be recruited from the acute care and rehabilitation partner centers within 4 health regions (living labs) and followed throughout the continuum of rehabilitation. Participants will also be recruited from the community. Biomedical, clinician-reported, patient-reported, and brain imaging data will be collected. Theme 1 will implement and evaluate the feasibility of collecting data across BRILLIANT living labs and conduct predictive analyses and artificial intelligence (AI) to identify mobility subgroups. Theme 2 will implement, evaluate, and identify community mobility interventions that optimize outcomes for mobility subgroups of patients with ABI. RESULTS: The biomedical infrastructure and equipment have been established across the living labs, and development of the clinician- and patient-reported outcome digital solutions is underway. Recruitment is expected to begin in May 2022. CONCLUSIONS: The program will develop and deploy a comprehensive clinical and community-based mobility-monitoring system to evaluate the factors that result in poor mobility, and develop personalized mobility interventions that are optimized for specific patient subgroups. Technology solutions will be designed to support clinicians and patients to deliver cost-effective care and the right intervention to the right person at the right time to optimize long-term functional potential and meaningful participation in the community. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/12506.

CARE frailty e-health scale: Association with incident adverse health outcomes and comparison with the Cardiovascular Health Study frailty scale in the NuAge cohort.

BACKGROUND: This study examines and compares CARE and Cardiovascular Health Study (CHS) frailty states (i.e., robust, prefrail and frail) for their association with incident adverse health outcomes, including falls, depression, cognitive and functional decline, major neurocognitive disorders, hospitalization and mortality in community-dwelling older adults living in the province of Quebec (Canada). METHODS: A subset of individuals (n = 1098) who participated in "Nutrition as a determinant of successful aging: The Quebec longitudinal study" (NuAge), which is an elderly population-based observational cohort study with 3 years of follow-up, were selected. CARE and CHS frailty states were determined using the NuAge baseline assessment. Incident falls (i.e., ≥1, ≥2 and severe falls), depression (i.e., 30-item Geriatric Depression Scale score > 10/30), decline in cognition (i.e., Modified Mini Mental State (3MS) score < 79/100) and functionality (i.e., Activity Daily Living (ADL) score ≤ 3/4 and an Instrumental Activity Daily Living (IADL) score ≤ 6/8), major neurocognitive disorders (i.e., 3MS score < 79/100 and IADL score < 6/8), hospitalization and mortality were annually recorded over a 3-year follow-up period. RESULTS: 66.8% and 23.6% of participants were classified as pre-frail and frail with CARE respectively, whereas this distribution of frailty states differed with CHS (47.9% and 8.4%). There were significant associations of CARE pre-frail and frail states with all incident adverse health outcomes, the lowest odds ratio (OR) being reported with falls and the highest with cognitive decline (OR ranging from 1.63 to 12.85 with P ≤ 0.032). All ORs of the CARE frailty states were greater than those of the CHS, except for frail participants with IADL decline (OR = 4.92 for CARE versus OR = 9.62 for CHS). CONCLUSIONS: CARE frail states were associated with incident adverse health outcomes and these associations were greater than with CHS, suggesting that the CARE scale is of clinical interest when screening for frailty and related adverse health outcomes in the elderly population.

Multi-tract multi-symptom relationships in pediatric concussion.

Background: The heterogeneity of white matter damage and symptoms in concussion has been identified as a major obstacle to therapeutic innovation. In contrast, most diffusion MRI (dMRI) studies on concussion have traditionally relied on group-comparison approaches that average out heterogeneity. To leverage, rather than average out, concussion heterogeneity, we combined dMRI and multivariate statistics to characterize multi-tract multi-symptom relationships. Methods: Using cross-sectional data from 306 previously concussed children aged 9-10 from the Adolescent Brain Cognitive Development Study, we built connectomes weighted by classical and emerging diffusion measures. These measures were combined into two informative indices, the first representing microstructural complexity, the second representing axonal density. We deployed pattern-learning algorithms to jointly decompose these connectivity features and 19 symptom measures. Results: Early multi-tract multi-symptom pairs explained the most covariance and represented broad symptom categories, such as a general problems pair, or a pair representing all cognitive symptoms, and implicated more distributed networks of white matter tracts. Further pairs represented more specific symptom combinations, such as a pair representing attention problems exclusively, and were associated with more localized white matter abnormalities. Symptom representation was not systematically related to tract representation across pairs. Sleep problems were implicated across most pairs, but were related to different connections across these pairs. Expression of multi-tract features was not driven by sociodemographic and injury-related variables, as well as by clinical subgroups defined by the presence of ADHD. Analyses performed on a replication dataset showed consistent results. Conclusions: Using a double-multivariate approach, we identified clinically-informative, cross-demographic multi-tract multi-symptom relationships. These results suggest that rather than clear one-to-one symptom-connectivity disturbances, concussions may be characterized by subtypes of symptom/connectivity relationships. The symptom/connectivity relationships identified in multi-tract multi-symptom pairs were not apparent in single-tract/single-symptom analyses. Future studies aiming to better understand connectivity/symptom relationships should take into account multi-tract multi-symptom heterogeneity. Funding: Financial support for this work came from a Vanier Canada Graduate Scholarship from the Canadian Institutes of Health Research (G.I.G.), an Ontario Graduate Scholarship (S.S.), a Restracomp Research Fellowship provided by the Hospital for Sick Children (S.S.), an Institutional Research Chair in Neuroinformatics (M.D.), as well as a Natural Sciences and Engineering Research Council CREATE grant (M.D.).

Concussions can damage networks of connections in the brain. Scientists have spent decades and millions of dollars studying concussions and potential treatments. Yet, no new treatments are available or in the pipeline. A major reason for this stagnation is that no two concussions are exactly alike. People affected by concussions may have different genetic or socioeconomic backgrounds. The nature of the injury or how its effects change over time may also vary among people with concussions. One central question facing scientists is whether there are multiple types of concussions. If so, what distinguishes them and what characteristics do they share. Some studies have looked at differences among subgroups of patients with concussions. But questions remain about whether ­ beyond differences between the patients ­ the brain injury itself differs and what impact that has on symptoms or patient trajectory. To better characterize different types of concussion, Guberman et al. analyzed diffusion magnetic resonance imaging scans from 306 nine or ten-year-old children with a previous concussion. The children were participants in the Adolescent Brain Cognitive Development Study. Using specialized statistical techniques, the researchers outlined subgroups of concussions in terms of connections and symptoms and studied how many of these subgroups each patient had. Some types of injury were linked with a category of symptoms like cognitive, mood, or physical symptoms. Some types of damage were linked with specific symptoms. Guberman et al. also found that one symptom, sleep problems, was part of many different injury subtypes. Sleep problems may occur in different patients for different reasons. For example, one patient with sleep difficulties may have experienced damage in brain regions controlling sleep and wakefulness. Another person with sleep problems may have injured parts of the brain responsible for mood and may have depression, which causes excessive sleepiness and difficulties waking up. Guberman et al. suggest a new way of thinking about concussions. If more studies confirm these concussion subgroups, scientists might use them to explore which types of therapies might be beneficial for patients with specific subgroups. Developing subgroup-targeted treatments may help scientists overcome the challenges of trying to develop therapies that work across a range of injuries. Similar disease subgrouping strategies may also help researchers study other brain diseases that may vary from patient to patient.

Noninvasive magnetic resonance imaging techniques in mild traumatic brain injury research and diagnosis.

Mild traumatic brain injury (mTBI), frequently referred to as concussion, is one of the most common neurological disorders. The underlying neural mechanisms of functional disturbances in the brains of concussed individuals remain elusive. Novel forms of brain imaging have been developed to assess patients postconcussion, including functional magnetic resonance imaging (fMRI), susceptibility-weighted imaging (SWI), diffusion MRI (dMRI), and perfusion MRI [arterial spin labeling (ASL)], but results have been mixed with a more common utilization in the research environment and a slower integration into the clinical setting. In this review, the benefits and drawbacks of the methods are described: fMRI is an effective method in the diagnosis of concussion but it is expensive and time-consuming making it difficult for regular use in everyday practice; SWI allows detection of microhemorrhages in acute and chronic phases of concussion; dMRI is primarily used for the detection of white matter abnormalities, especially axonal injury, specific for mTBI; and ASL is an alternative to the BOLD method with its ability to track cerebral blood flow alterations. Thus, the absence of a universal diagnostic neuroimaging method suggests a need for the adoption of a multimodal approach to the neuroimaging of mTBI. Taken together, these methods, with their underlying functional and structural features, can contribute from different angles to a deeper understanding of mTBI mechanisms such that a comprehensive diagnosis of mTBI becomes feasible for the clinician.

Atypical resting state functional connectivity in mild traumatic brain injury.

OBJECTIVES: This study aimed to investigate changes in three intrinsic functional connectivity networks (IFCNs; default mode network [DMN], salience network [SN], and task-positive network [TPN]) in individuals who had sustained a mild traumatic brain injury (mTBI). METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired from 27 mTBI patients with persistent postconcussive symptoms, along with 26 age- and sex-matched controls. These individuals were recruited from a Level-1 trauma center, at least 3 months after a traumatic episode. IFCNs were established based on seed-to-voxel, region-of-interest (ROI) to ROI, and independent component analyses (ICA). Subsequently, we analyzed the relationship between functional connectivity and postconcussive symptoms. RESULTS: Seed-to-voxel analysis of rs-fMRI demonstrated decreased functional connectivity in the right lateral parietal lobe, part of the DMN, and increased functional connectivity in the supramarginal gyrus, part of the SN. Our TPN showed both hypo- and hyperconnectivity dependent on seed location. Within network hypoconnectivity was observed in the visual network also using group comparison. Using an ICA, we identified altered network functional connectivity in regions within four IFCNs (sensorimotor, visual, DMN, and dorsal attentional). A significant negative correlation between dorsal attentional network connectivity and behavioral symptoms score was also found. CONCLUSIONS: Our findings indicate that rs-fMRI may be of use clinically in order to assess disrupted functional connectivity among IFCNs in mTBI patients. Improved mTBI diagnostic and prognostic information could be especially relevant for athletes looking to safely return to play, as well for individuals from the general population with persistent postconcussive symptoms months after injury, who hope to resume activity.

A Prospective, Multicenter Study to Assess the Safety and Efficacy of Translingual Neurostimulation Plus Physical Therapy for the Treatment of a Chronic Balance Deficit Due to Mild-to-Moderate Traumatic Brain Injury.

OBJECTIVES: Translingual neurostimulation (TLNS) studies indicate improved outcomes in neurodegenerative disease or spinal cord injury patients. This study was designed to assess the safety and efficacy of TLNS plus targeted physical therapy (PT) in people with a chronic balance deficit after mild-to-moderate traumatic brain injury (mmTBI). MATERIALS AND METHODS: This international, multicenter, randomized study enrolled 122 participants with a chronic balance deficit who had undergone PT following an mmTBI and had plateaued in recovery. Randomized participants received PT plus either high-frequency pulse (HFP; n = 59) or low-frequency pulse (LFP; n = 63) TLNS. The primary efficacy and safety endpoints were the proportion of sensory organization test (SOT) responders (SOT composite score improvement of ≥15 points) and fall frequency after five weeks of treatment, respectively. RESULTS: The proportion of SOT responders was significant in the HFP + PT (71.2%) and LFP + PT (63.5%) groups compared with baseline (p < 0.0005). For the pooled population, the SOT responder rate was 67.2% (p < 0.00005), and there were clinically and statistically significant improvements in SOT composite scores after two and five weeks (p < 0.0005). Both groups had reductions in falls and headache disability index scores. Mean dynamic gait index scores in both groups also significantly increased from baseline at weeks 2 and 5. CONCLUSIONS: Significant improvements in balance and gait, in addition to headaches, sleep quality, and fall frequency, were observed with TLNS plus targeted PT; in participants who had a chronic balance deficit following an mmTBI and had plateaued on prior conventional physiotherapy.

Changes in peri-calcarine cortical thickness in blindsight.

Blindsight is the ability of patients with primary visual cortex (V1) damage to process information in their clinically blind visual field in the absence of conscious awareness. In addition to those with localized V1 lesions, some patients exhibiting this phenomenon have had a cerebral hemisphere removed or disconnected from the rest of the brain for the treatment of drug-resistant epilepsy (hemispherectomy). Research into the underlying neural substrates of blindsight has long implicated the intact visual cortex in maintaining residual vision and supporting visuo-guided responses to stimuli presented ipsilaterally within the blind visual field while operating outside the geniculo-striate pathway. A recent study demonstrated functional reorganization in the dorsal visual areas of the intact hemisphere, thereby supporting its compensatory role in non-conscious vision. In this study, we used cortical thickness analysis to examine anatomical differences in the visual cortex of the intact hemisphere of three subjects with varying degrees of cortical damage and well documented blindsight: two with a right hemispherectomy (complete and partial), and one with a left V1 lesion. T1-weighted MRI data were obtained for the subjects while control data were chosen from publicly available NKI-dataset to match closely the acquisition parameters of our blindsight cases. Our results show significant increases in cortical thickness in the visual cortex of all blindsight subjects compared to healthy controls, irrespective of age-onset, etiology, and extent of the damage. Our findings add to accumulating evidence from behavioral, functional imaging, and tractography studies of cerebral compensation and reorganization.

Structural abnormalities in thalamo-prefrontal tracks revealed by high angular resolution diffusion imaging predict working memory scores in concussed children.

Because of their high prevalence, heterogeneous clinical presentation, and wide-ranging sequelae, concussions are a challenging neurological condition, especially in children. Shearing forces transmitted across the brain during concussions often result in white matter damage. The neuropathological impact of concussions has been discerned from animal studies and includes inflammation, demyelination, and axonal loss. These pathologies can overlap during the sub-acute stage of recovery. However, due to the challenges of accurately modeling complex white matter structure, these neuropathologies have not yet been differentiated in children in vivo. In the present study, we leveraged recent advances in diffusion imaging modeling, tractography, and tractometry to better understand the neuropathology underlying working memory problems in concussion. Studying a sample of 16 concussed and 46 healthy youths, we used novel tractography methods to isolate 11 working memory tracks. Along these tracks, we measured fractional anisotropy, diffusivities, track volume, apparent fiber density, and free water fraction. In three tracks connecting the right thalamus to the right dorsolateral prefrontal cortex (DLPFC), we found microstructural differences suggestive of myelin alterations. In another track connecting the left anterior-cingulate cortex with the left DLPFC, we found microstructural changes suggestive of axonal loss. Structural differences and tractography reconstructions were reproduced using test-retest analyses. White matter structure in the three thalamo-prefrontal tracks, but not the cingulo-prefrontal track, appeared to play a key role in working memory function. The present results improve understanding of working memory neuropathology in concussions, which constitutes an important step toward developing neuropathologically informed biomarkers of concussion in children.

A Prospective Study of Childhood Predictors of Traumatic Brain Injuries Sustained in Adolescence and Adulthood.

OBJECTIVE: Traumatic brain injuries (TBIs) are sustained by approximately 17% of males in the general population, many of whom subsequently present mental disorders, cognitive, and physical problems. Little is known about predictors of TBIs and how to prevent them. The present study aimed to determine whether inattention-hyperactivity and/or all externalizing problems presented by boys at age 10 predict subsequent TBIs to age 34 after taking account of previous TBIs and family social status (FSS). METHOD: 742 Canadian males were followed, prospectively, from age 6 to 34. Diagnoses of TBIs were extracted from health files, parents-reported sociodemographic and family characteristics at participants' age 6, and teachers-rated participants' behaviors at age 10. Separate logistic regression models predicted TBIs sustained from age 11 to 17 and from age 18 to 34. For each age period, two models were computed, one included previous TBIs, inattention-hyperactivity, FSS, and interaction terms, the second included previous TBIs, externalizing problems, FSS, and interaction terms. RESULTS: In models that included inattention-hyperactivity, TBIs sustained from age 11 to 17 were predicted by age 10 inattention-hyperactivity (odds ratio [OR] = 1.46, 1.05 to 2.05) and by TBIs prior to age 11 (OR = 3.50, 1.48 to 8.24); TBIs sustained from age 18 to 34 were predicted by age 10 inattention-hyperactivity (OR = 1.31, 1.01 to 170). In models that included all externalizing problems, TBIs from age 11 to 17 were predicted by prior TBIs (OR = 3.66, 1.51 to 8.39); TBIs sustained from age 18 to 34 were predicted by age 10 externalizing problems (OR = 1.45, 1.12 to 1.86). Neither FSS nor interaction terms predicted TBIs in any of the models. CONCLUSIONS: Among males, using evidence-based treatments to reduce inattention-hyperactivity and externalizing problems among boys could, potentially, decrease the risk of TBIs to age 34. Further, boys who sustain TBIs in childhood require monitoring to prevent recurrence in adolescence.

Impact of non-invasive brain stimulation on transcallosal modulation in mild traumatic brain injury: a multimodal pilot investigation.

Background: We combined performance on working memory (WM) tasks with diffusion (dMRI) and functional (fMRI) magnetic resonance imaging in young adults who had suffered a concussion to better understand the inter-hemispheric effects of unilateral repetitive transcranial magnetic stimulation (rTMS). Methods: The article is presenting pilot data on 8 symptomatic patients with persistent post-concussion symptoms for over 6 months. They received 20 sessions of rTMS over the left dorsolateral prefrontal cortex. Fractional anisotropy and mean diffusivity of the corpus callosum (CC) and fMRI measurement of blood-oxygen-level dependent signal changes during WM tasks were carried out before and after rTMS stimulation. Results: After participants had completed the rTMS sessions, we observed three main results: (1) bilateralization of activation within the WM network; (2) shift from transcallosal inhibition to transcallosal activation of the right-sided WM network via the anterior callosal fibres; and (3) shift from transcallosal activation to transcallosal inhibition of the right-sided WM network via the posterior parts of the CC. More nuanced patterns of transcallosal mediation in the region of the right-sided WM network were observed via the medial part of the CC. Conclusion: Our preliminary results encourage trends of further research supporting the use of rTMS to restore inter-hemispheric balance within the bilateral WM network in young adults with a history of concussion.

Functional reorganization of population receptive fields in a hemispherectomy patient with blindsight.

Blindsight refers to the ability of some patients with destruction of the primary visual cortex (V1) to respond to stimuli presented in their clinically blind visual field despite lack of visual awareness. Here we tested a rare and well-known patient with blindsight following hemispherectomy, DR, who has had the entire cortex in the right hemisphere removed, and in whom the right superior colliculus is the only post-chiasmatic visual structure remaining intact. Compared to more traditional cases of blindsight after damage confined to V1, the study of blindsight in hemispherectomy has offered the invaluable opportunity to examine directly two outstanding questions: the contribution of the intact hemisphere to visual processing without awareness, and the nature of plastic and compensatory changes in these remaining contralesional visual areas. Population receptive field (pRF) mapping was used to define retinotopic maps, delineate the boundaries between the visual areas, examine changes in the sizes of receptive field centres within each visual area, and their variability as a function of eccentricity. Aside from the dorsal visual areas showing blurred borders between V2d and V3d, not otherwise detected with perimetric mapping, the retinotopic maps of DR did not differ substantially from those of three matched healthy controls. Interestingly, those dorsal compartments showed a significant increase in the RF sizes toward values typical of higher-order processing cortices, while no differences were observed in the corresponding ventral visual areas. Findings showed that whereas receptive field sizes at foveal and parafoveal eccentricities (≤ 4°) were not measurably altered, the pRF size increased by ~ 270% at 4-6° of eccentricity, and the size difference reached ~ 300% between 8° and 10°. We interpret these findings to suggest that an increase in pRF sizes could be indicative of cerebral plasticity involving the retinotopic reorganization of the dorsal visual areas.

Evaluating task-based brain network activity in pediatric subjects with an mTBI: mechanisms of functional compensation are symptom-level dependent.

The diagnosis of a mild traumatic brain injury (mTBI) places large emphasis on patient-reported symptoms which has restricted our ability to evaluate patients. Task-based functional magnetic resonance imaging has the potential to act as an objective measurement of abnormal brain activity and inform clinical decision-making; however, there is little research evaluating pediatric subjects as a function of mTBI-related symptoms. The objective of this study was to evaluate the extent to which brain activity during a spatial navigation task is different between children with mTBI and a group of healthy controls (HCs) based on symptom reporting. A group of patients with mTBI (n = 27) were divided into low- and high-symptom cohorts and compared with HCs (n = 27) on a task that required participants to locate specific landmarks. No difference was found in the level of symptoms reported between patients with low-symptom participants and HCs despite the low-symptom group showing increased activity within the frontal and occipital cortices. In participants with high-symptoms, an increase in the number of reported symptoms was found relative to HCs alongside an increase in the number of active brain regions. Findings suggest that persons with an mTBI may display unique symptom-dependent patterns of altered task-related brain activity.

Are Traumatic Brain Injuries Associated With Criminality After Taking Account of Childhood Family Social Status and Disruptive Behaviors?

OBJECTIVE: The authors aimed to elucidate the links between traumatic brain injuries (TBIs) and criminal convictions in a sample of 724 Canadian males with and without criminal records followed up to age 24. METHODS: Prospectively collected data were analyzed to determine whether prior TBIs predicted subsequent criminal convictions after taking account of family social status (FSS) and childhood disruptive behaviors. At age 24, diagnoses of TBIs were extracted from health records and convictions from official criminal records. In childhood, teachers rated disruptive behaviors and parents reported FSS. RESULTS: Proportionately more individuals with offender status than nonoffender status sustained a TBI from age 18 to age 24 but not before age 18. Individuals with offender status who had sustained a TBI before and after their first conviction were similar in numbers, were raised in families of low social status, and presented high levels of disruptive behaviors from age 6 to age 12. When FSS and childhood disruptive behaviors were included in multivariable regression models, sustaining a prior TBI was not associated with an increased risk of juvenile convictions for any type of crime, for violent crimes, for convictions for any crime or violent crime from age 18 to age 24, or for a first crime or a first violent crime from age 18 to age 24. CONCLUSIONS: Among males, there was no evidence that prior TBIs were associated with an increased risk of subsequent criminal convictions from age 12 to age 24 when taking account of FSS and childhood disruptive behaviors, although these latter factors may be associated with an increased prevalence of TBIs among adult offenders.

Development, implementation and assessment of a concussion education programme for high school student-athletes.

Although experts have noted that adolescent athletes should be educated about concussions to improve their safety, there is no agreement on the most effective strategy to disseminate concussion education. The purpose of this study was to develop, implement and assess a concussion education programme. More precisely, four interactive oral presentations were delivered to high school student-athletes (N = 35, Mage = 15.94, SD = 0.34) in a large urban centre. Participants completed a questionnaire at three time-points during the season to measure changes in their knowledge (CK) and attitudes (CA) of concussions, and focus group interviews were conducted following the concussion education programme. Questionnaire data revealed participants' post-intervention CK scores were higher than their pre-intervention scores. During the focus groups, the student-athletes said they acquired CK about the role of protective equipment and symptom variability, and in terms of CA, they intended to avoid dangerous in-game collisions in the future. Our study was the first to create and deliver a concussion education intervention across multiple time-points, and to use mixed-methods in its assessment. These findings may be of interest to researchers, practitioners and stakeholders in sport who are invested in making the sport environment safer through concussion education and awareness.

Noninvasive tongue stimulation combined with intensive cognitive and physical rehabilitation induces neuroplastic changes in patients with multiple sclerosis: A multimodal neuroimaging study.

BACKGROUND: Multiple sclerosis (MS) patients have central nervous system (CNS) lesions that may impede cognitive and sensorimotor function. Few rehabilitative therapies are available. OBJECTIVES: The objective of this paper is to study effects of noninvasive tongue stimulation using the Portable Neuromodulation Stimulator (PoNS™) combined with intensive cognitive and physical rehabilitation on working memory, gait, balance and concomitant changes in the brain. METHODS: Fourteen MS patients, seven each in an active and a sham stimulation group, participated. Participants received intensive physical therapy and working memory training for 14 weeks. Functional magnetic resonance imaging (fMRI) using motor imagery and working-memory tasks were completed prior to and following therapy, as were sensory organization tests (SOT), motor performance measures, and neuropsychological assessment. RESULTS: On the SOT, the active group showed significant improvement from baseline. fMRI revealed significant blood oxygen level-dependent signal changes in the left primary motor cortex for the Active Group, while the sham group had increased activity in bilateral premotor cortices. All individuals improved on working-memory tasks, but only the active group showed increased dorsolateral prefrontal cortex activity. CONCLUSIONS: In this cohort of MS patients, the results suggest that PoNS stimulation can enhance motor performance and working memory while also driving neuroplasticity. Further studies are warranted to explore these findings.

Role of advanced neuroimaging, fluid biomarkers and genetic testing in the assessment of sport-related concussion: a systematic review.

OBJECTIVE: To conduct a systematic review of published literature on advanced neuroimaging, fluid biomarkers and genetic testing in the assessment of sport-related concussion (SRC). DATA SOURCES: Computerised searches of Medline, PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, Scopus and Cochrane Library from 1 January 2000 to 31 December 2016 were done. There were 3222 articles identified. STUDY SELECTION: In addition to medical subject heading terms, a study was included if (1) published in English, (2) represented original research, (3) involved human research, (4) pertained to SRC and (5) involved data from neuroimaging, fluid biomarkers or genetic testing collected within 6 months of injury. Ninety-eight studies qualified for review (76 neuroimaging, 16 biomarkers and 6 genetic testing). DATA EXTRACTION: Separate reviews were conducted for neuroimaging, biomarkers and genetic testing. A standardised data extraction tool was used to document study design, population, tests employed and key findings. Reviewers used a modified quality assessment of studies of diagnostic accuracy studies (QUADAS-2) tool to rate the risk of bias, and a modified Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to rate the overall level of evidence for each search. DATA SYNTHESIS: Results from the three respective reviews are compiled in separate tables and an interpretive summary of the findings is provided. CONCLUSIONS: Advanced neuroimaging, fluid biomarkers and genetic testing are important research tools, but require further validation to determine their ultimate clinical utility in the evaluation of SRC. Future research efforts should address current gaps that limit clinical translation. Ultimately, research on neurobiological and genetic aspects of SRC is predicted to have major translational significance to evidence-based approaches to clinical management of SRC, much like applied clinical research has had over the past 20 years.

The impact of symptomatic mild traumatic brain injury on complex everyday activities and the link with alterations in cerebral functioning: Exploratory case studies.

The objective of the study was to explore the neurophysiological correlates of altered functional independence using functional magnetic resonance imaging (fMRI) and event-related potentials (ERP) after a mild traumatic brain injury (mTBI). The participants consisted of three individuals with symptomatic mTBI (3.9 ± 3.6 months post-mTBI) and 12 healthy controls. The main measures used were the Instrumental Activities of Daily Living (IADL) Profile observation-based assessment; a visual externally ordered working memory task combined to event-related potentials (ERP) and fMRI recordings; neuropsychological tests; post-concussion symptoms questionnaires; and the Activities of Daily Living (ADL) Profile interview. Compared to normal controls, all three patients had difficulty with a real-world complex budgeting activity due to deficits in planning, ineffective strategy use and/or a prolonged time to detect and correct errors. Reduced activations in the right mid-dorsolateral prefrontal cortex on fMRI as well as abnormal frontal or parietal components of the ERP occurred alongside these deficits. Results of this exploratory study suggest that reduced independence in complex everyday activities in symptomatic mTBI may be at least partly explained by a decrease in brain activation in the prefrontal cortex, abnormal ERP, or slower reaction times on working memory tasks. The study presents an initial attempt at combining research in neuroscience with ecological real-world evaluation research to further our understanding of the difficulties in complex everyday activities experienced by individuals with mTBI.

Microstructural Integrity of Hippocampal Subregions Is Impaired after Mild Traumatic Brain Injury.

Mild traumatic brain injury (mTBI) affects a large number of individuals and diffusion tensor imaging can be used to investigate microstructural integrity of brain tissue after mTBI. However, results have varied considerably between studies and gray matter (GM) integrity has been largely neglected in these investigations. Given impaired working memory processing after mTBI and its possible association with Alzheimer's disease, we investigated hippocampal integrity and parcellated this structure into five subregions: subiculum, cornu ammonis (CA) 1, CA 2/3, CA 4/dentate gyrus, and stratum radiatum/lacunosum-moleculare. We also employed shape analysis of bilateral hippocampi to explore whether morphological changes had occurred due to the traumatic injury and conducted neuropsychological memory tests. The sample comprised 15 subjects with mTBI (18-55 years, nine female) and 13 age- and sex-matched healthy control subjects (19-57 years, nine female). Voxelwise analyses showed significantly increased mean diffusivity in patients, compared with controls, in the right hippocampus and three of its five subregions (family-wise error corrected p < 0.05). Additionally, results from probabilistic tractography indicated impaired CA 1 connectivity after mTBI (Benjamini-Hochberg false discovery rate [FDR] corrected p < 0.05). Shape of bilateral hippocampi did not significantly differ between groups (Benjamini-Hochberg FDR corrected p > 0.05). Subjects with mTBI reported more symptoms and performed worse in a non-standard verbal working memory task. Based on these preliminary findings, we were able to demonstrate altered diffusivity of hippocampal subregions following mTBI, indicating impaired GM microstructural integrity. These differences highlight the potential of diffusion imaging for investigation of subtle yet relevant changes in GM microstructure not detected otherwise following mTBI.

Cortical Thickness Changes and Their Relationship to Dual-Task Performance following Mild Traumatic Brain Injury in Youth.

Mild traumatic brain injury (mTBI) is common in youth, especially in those who participate in sport. Recent investigations from our group have shown that asymptomatic children and adolescents with mTBI continue to exhibit alterations in neural activity and cognitive performance compared with those without a history of mTBI. This is an intriguing finding, given that current return-to-learn and return-to-play protocols rely predominately on subjective symptom reports, which may not be sensitive enough to detect subtle injury-related changes. As a result, youth may be at greater risk for re-injury and long-term consequences if they are cleared for activity while their brains continue to be compromised. It is currently unknown whether mTBI also affects brain microstructure in the developing brain, particularly cortical thickness, and whether such changes are also related to cognitive performance. The present study examined cortical thickness in 13 asymptomatic youth (10-14 years old) who had sustained an mTBI 3-8 months prior to testing compared with 14 age-matched typically developing controls. Cortical thickness was also examined in relation to working memory performance during single and dual task paradigms. The results show that youth who had sustained an mTBI had thinner cortices in the left dorsolateral prefrontal region and right anterior and posterior inferior parietal lobes. Additionally, cortical thinning was associated with slower reaction time during the dual-task condition in the injured youth only. The results also point to a possible relationship between functional and structural alterations as a result of mTBI in youth, and lend evidence for neural changes beyond symptom resolution.