The Toronto Concussion Study: a prospective investigation of characteristics in a cohort of adults from the general population seeking care following acute concussion, 2016-2020.

Purpose: There is limited research regarding the characteristics of those from the general population who seek care following acute concussion. Methods: To address this gap, a large cohort of 473 adults diagnosed with an acute concussion (female participants = 287; male participants = 186) was followed using objective measures prospectively over 16 weeks beginning at a mean of 5.1 days post-injury. Results: Falls were the most common mechanism of injury (MOI) (n = 137, 29.0%), followed by sports-related recreation (n = 119, 25.2%). Male participants were more likely to be injured playing recreational sports or in a violence-related incident; female participants were more likely to be injured by falling. Post-traumatic amnesia (PTA) was reported by 80 participants (16.9 %), and loss of consciousness (LOC) was reported by 110 (23.3%). In total, 54 participants (11.4%) reported both PTA and LOC. Male participants had significantly higher rates of PTA and LOC after their injury compared to their female counterparts. Higher initial symptom burden was associated with a longer duration of recovery for both male and female participants. Female participants had more symptoms and higher severity of symptoms at presentation compared to male participants. Female participants were identified to have a longer recovery duration, with a mean survival time of 6.50 weeks compared to 5.45 weeks in male participants (p < 0.0001). A relatively high proportion of female and male participants in this study reported premorbid diagnoses of depression and anxiety compared to general population characteristics. Conclusion: Although premorbid diagnoses of depression and/or anxiety were associated with higher symptom burden at the initial visit, the duration of symptoms was not directly associated with a pre-injury history of psychological/psychiatric disturbance. This cohort of adults, from the general population, seeking care for their acute concussion attained clinical and functional recovery over a period of 4-12 weeks.

Revisiting the ICHD-3 criteria for headache attributed to mild traumatic injury to the head: Insights from the Toronto Concussion Study Analysis of Acute Headaches Following Concussion.

BACKGROUND: There is limited prospective data on the prevalence, timing of onset, and characteristics of acute headache following concussion/mild traumatic brain injury. METHODS: Adults diagnosed with concussion (arising from injuries not related to work or motor vehicle accidents) were recruited from emergency departments and seen within one week post injury wherein they completed questionnaires assessing demographic variables, pre-injury headache history, post-injury headache history, and the Sport Concussion Assessment Tool (SCAT-3) symptom checklist, the Sleep and Concussion Questionnaire (SCQ) and mood/anxiety on the Brief Symptom Inventory (BSI). RESULTS: A total of 302 participants (59% female) were enrolled (mean age 33.6 years) and almost all (92%) endorsed post-traumatic headache (PTH) with 94% endorsing headache onset within 24 hours of injury. Headache location was not correlated with site of injury. Most participants (84%) experienced daily headache. Headache quality was pressure/squeezing in 69% and throbbing/pulsing type in 22%. Associated symptoms included: photophobia (74%), phonophobia (72%) and nausea (55%). SCAT-3 symptom scores, Brief Symptom Inventory and Sleep and Concussion Questionnaire scores were significantly higher in those endorsing acute PTH. No significant differences were found in week 1 acute PTH by sex, history of migraine, pre-injury headache frequency, anxiety, or depression, nor presence/absence of post-traumatic amnesia and self-reported loss of consciousness. CONCLUSIONS: This study highlights the very high incidence of acute PTH following concussion, the timing of onset and characteristics of acute PTH, the associated psychological and sleep disturbances and notes that the current ICHD-3 criteria for headaches attributed to mild traumatic injury to the head are reasonable, the interval between injury and headache onset should not be extended beyond seven days and could, potentially, be shorted to allow for greater diagnostic precision.

The Toronto Concussion Study: Sense of smell is not associated with concussion severity or recovery.

OBJECTIVE: To examine sense of smell as a biomarker for both severity and duration of post-concussion symptoms. METHODS: Participants were recruited prospectively from an outpatient concussion clinic. Sense of smell was assessed using the University of Pennsylvania Smell Identification Test (UPSIT) within 7 days, and 4, 8 - or 16-weeks post-injury. UPSIT normative data were used as normal controls. The main outcomes were: symptom severity on the Sport Concussion Assessment Tool 3 (SCAT3) symptom inventory and time to physician-declared recovery. RESULTS: A total of 167 participants (mean age 32.9 [SD, 12.2] years, 59% female [n = 99]) were classified at 1 week post injury as follows: severe hyposmia in 5 (3%), moderate hyposmia in 10 (6%), mild hyposmia in 48 (29%), and normosmia in 104 (62%) individuals. A convenience sample of 81 individuals with concussion were tested at follow-up. Acute impairment of sense of smell following concussion was not associated with symptom severity on the SCAT3 or time to recovery. Sense of smell was stable from baseline to follow-up in this population. CONCLUSION: This study provides evidence that routine testing of sense of smell in individuals with concussion is not warranted as a biomarker for severity of concussion and concussion recovery.

Can Sport Concussion Assessment Tool (SCAT) Symptom Scores Be Converted to Rivermead Post-concussion Symptoms Questionnaire (RPQ) Scores and Vice Versa? Findings From the Toronto Concussion Study.

Background: The Rivermead Post-Concussion Symptoms Questionnaire (RPQ) and the Sports Concussion Assessment Tool (SCAT) are widely used self-report tools assessing the type, number, and severity of concussion symptoms. There are overlapping symptoms and domains, though they are scored differently. The SCAT consists of 22 questions with a 7-point Likert scale for a total possible score 132. The RPQ has 16 questions and a 5-point Likert scale for a total of 64 possible points. Being able to convert between the two scores would facilitate comparison of results in the concussion literature. Objectives: To develop equations to convert scores on the SCAT to the RPQ and vice versa. Methods: Adults (17-85 years) diagnosed with a concussion at a referring emergency department were seen in the Hull-Ellis Concussion and Research Clinic, a rapid access concussion clinic at Toronto Rehab-University Health Network (UHN) Toronto Canada, within 7 days of injury. The RPQ and SCAT symptom checklists as well as demographic questionnaires were administered to all participants at Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16. Results: 215 participants had 1,168 matched RPQ and SCAT assessments. Total scores of the RPQ and the SCAT had a rho = 0.91 (p < 0.001); correlations were lower for sub-scores of specific symptom domains (range 0.74-0.87, p < 0.001 for all domain comparisons). An equation was derived to calculate SCAT scores using the number and severity of symptoms on the RPQ. Estimated scores were within 3 points of the observed total score on the SCAT. A second equation was derived to calculate the RPQ from the proportion weighted total score of the SCAT. This equation estimated corresponding scores within 3 points of the observed score on the RPQ. Conclusions: The RPQ and SCAT symptom checklists total scores are highly correlated and can be used to estimate the total score on the corresponding assessment. The symptom subdomains are also strongly correlated between the 2 scales however not as strongly correlated as the total score. The equations will enable researchers and clinicians to quickly convert between the scales and to directly compare concussion research findings.

MCADNNet: Recognizing Stages of Cognitive Impairment through Efficient Convolutional fMRI and MRI Neural Network Topology Models.

Mild cognitive impairment (MCI) represents the intermediate stage between normal cerebral aging and dementia associated with Alzheimer's disease (AD). Early diagnosis of MCI and AD through artificial intelligence has captured considerable scholarly interest; researchers hope to develop therapies capable of slowing or halting these processes. We developed a state-of-the-art deep learning algorithm based on an optimized convolutional neural network (CNN) topology called MCADNNet that simultaneously recognizes MCI, AD, and normally aging brains in adults over the age of 75 years, using structural and functional magnetic resonance imaging (fMRI) data. Following highly detailed preprocessing, four-dimensional (4D) fMRI and 3D MRI were decomposed to create 2D images using a lossless transformation, which enables maximum preservation of data details. The samples were shuffled and subject-level training and testing datasets were completely independent. The optimized MCADNNet was trained and extracted invariant and hierarchical features through convolutional layers followed by multi-classification in the last layer using a softmax layer. A decision-making algorithm was also designed to stabilize the outcome of the trained models. To measure the performance of classification, the accuracy rates for various pipelines were calculated before and after applying the decision-making algorithm. Accuracy rates of 99.77% 0.36% and 97.5% 1.16% were achieved for MRI and fMRI pipelines, respectively, after applying the decision-making algorithm. In conclusion, a cutting-edge and optimized topology called MCADNNet was designed and preceded a preprocessing pipeline; this was followed by a decision-making step that yielded the highest performance achieved for simultaneous classification of the three cohorts examined.

Self-reported Balance Disturbance and Performance-Based Balance Impairment After Concussion in the General Population.

OBJECTIVE: To characterize the prevalence of, and relationship between, self-reported balance disturbance and performance-based balance impairment in the general population with concussion. SETTING: Rehabilitation hospital outpatient concussion clinic. PARTICIPANTS: One hundred six individuals with concussion (49 males, mean age = 32.4; SD = 11.5 years), mean (SD) = 5 (1.8) days postinjury. DESIGN: Cross-sectional observational study. MAIN MEASURES: SCAT3 Symptoms Subscale, Balance Error Scoring System, modified Balance Error Scoring System, and center-of-pressure root-mean-square amplitude and velocity in eyes open and closed conditions. RESULTS: The majority of participants reported balance or dizziness symptoms (54% and 63%, respectively) and demonstrated balance impairment on the Balance Error Scoring System and modified Balance Error Scoring System (66% and 58%, respectively). The prevalence of balance impairment across center-of-pressure measures varied from 32% to 48%. There was no effect of balance or dizziness symptom severity on any of the balance measures (F2,103 = 1.02; P = .44) and (F2,103 = 1.45; P = .10), respectively. There was poor agreement between self-report of balance/dizziness symptoms and identified balance impairment across all balance measures (all κ ≤ 0.26 and κ ≤ 0.20, respectively). CONCLUSIONS: There was no clear relationship between the subjective experience of balance disturbance and objective measures of balance impairment in the general population. These results have implications for clinical evaluation of postconcussive deficits and determination of recovery.

Changes in Resting-State Connectivity following Melody-Based Therapy in a Patient with Aphasia.

Melody-based treatments for patients with aphasia rely on the notion of preserved musical abilities in the RH, following left hemisphere damage. However, despite evidence for their effectiveness, the role of the RH is still an open question. We measured changes in resting-state functional connectivity following melody-based intervention, to identify lateralization of treatment-related changes. A patient with aphasia due to left frontal and temporal hemorrhages following traumatic brain injuries (TBI) more than three years earlier received 48 sessions of melody-based intervention. Behavioral measures improved and were maintained at the 8-week posttreatment follow-up. Resting-state fMRI data collected before and after treatment showed an increase in connectivity between motor speech control areas (bilateral supplementary motor areas and insulae) and RH language areas (inferior frontal gyrus pars triangularis and pars opercularis). This change, which was specific for the RH, was greater than changes in a baseline interval measured before treatment. No changes in RH connectivity were found in a matched control TBI patient scanned at the same intervals. These results are compatible with a compensatory role for RH language areas following melody-based intervention. They further suggest that this therapy intervenes at the level of the interface between language areas and speech motor control areas necessary for language production.

Age differences in the functional interactions among the default, frontoparietal control, and dorsal attention networks.

Older adults typically show weaker functional connectivity (FC) within brain networks compared with young adults, but stronger functional connections between networks. Our primary aim here was to use a graph theoretical approach to identify age differences in the FC of 3 networks-default mode network (DMN), dorsal attention network, and frontoparietal control (FPC)-during rest and task conditions and test the hypothesis that age differences in the FPC would influence age differences in the other networks, consistent with its role as a cognitive "switch." At rest, older adults showed lower clustering values compared with the young, and both groups showed more between-network connections involving the FPC than the other 2 networks, but this difference was greater in the older adults. Connectivity within the DMN was reduced in older compared with younger adults. Consistent with our hypothesis, between-network connections of the FPC at rest predicted the age-related reduction in connectivity within the DMN. There was no age difference in within-network FC during the task (after removing the specific task effect), but between-network connections were greater in older adults than in young adults for the FPC and dorsal attention network. In addition, age reductions were found in almost all the graph metrics during the task condition, including clustering and modularity. Finally, age differences in between-network connectivity of the FPC during both rest and task predicted cognitive performance. These findings provide additional evidence of less within-network but greater between-network FC in older adults during rest but also show that these age differences can be altered by the residual influence of task demands on background connectivity. Our results also support a role for the FPC as the regulator of other brain networks in the service of cognition. Critically, the link between age differences in inter-network connections of the FPC and DMN connectivity, and the link between FPC connectivity and performance, support the hypothesis that FC of the FPC influences the expression of age differences in other networks, as well as differences in cognitive function.

The Associative Memory Deficit in Aging Is Related to Reduced Selectivity of Brain Activity during Encoding.

Human aging is characterized by reductions in the ability to remember associations between items, despite intact memory for single items. Older adults also show less selectivity in task-related brain activity, such that patterns of activation become less distinct across multiple experimental tasks. This reduced selectivity or dedifferentiation has been found for episodic memory, which is often reduced in older adults, but not for semantic memory, which is maintained with age. We used fMRI to investigate whether there is a specific reduction in selectivity of brain activity during associative encoding in older adults, but not during item encoding, and whether this reduction predicts associative memory performance. Healthy young and older adults were scanned while performing an incidental encoding task for pictures of objects and houses under item or associative instructions. An old/new recognition test was administered outside the scanner. We used agnostic canonical variates analysis and split-half resampling to detect whole-brain patterns of activation that predicted item versus associative encoding for stimuli that were later correctly recognized. Older adults had poorer memory for associations than did younger adults, whereas item memory was comparable across groups. Associative encoding trials, but not item encoding trials, were predicted less successfully in older compared with young adults, indicating less distinct patterns of associative-related activity in the older group. Importantly, higher probability of predicting associative encoding trials was related to better associative memory after accounting for age and performance on a battery of neuropsychological tests. These results provide evidence that neural distinctiveness at encoding supports associative memory and that a specific reduction of selectivity in neural recruitment underlies age differences in associative memory.

Rehospitalization After Traumatic Brain Injury: A Population-Based Study.

OBJECTIVE: To examine, from a Canadian population-based perspective, the incidence and etiology of long-term hospital utilization among persons living with traumatic brain injury (TBI) by age and sex. DESIGN: Retrospective cohort study. SETTING: Acute care hospitals. PARTICIPANTS: Index cases of TBI (N=29,269) were identified from the Discharge Abstract Database for fiscal years 2002/2003 through 2009/2010 and were followed-up until 36 months after injury. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Rehospitalization was defined as admission to an acute care facility that occurred up to 36 months after index injury. Diagnoses associated with subsequent rehospitalization were examined by age and sex. RESULTS: Of the patients with TBI, 35.5% (n=10,390) were subsequently hospitalized during the 3-year follow-up period. Multivariable logistic regression (controlling for index admission hospital) identified men, older age, mechanism of injury being a fall, greater injury severity, rural residence, greater comorbidity, and psychiatric comorbidity to be significant predictors of rehospitalization in a 3-year period postinjury. The most common causes for rehospitalization differed by age and sex. CONCLUSIONS: Rehospitalization after TBI is common. Factors associated with rehospitalization can inform long-term postdischarge planning. Findings also support examining causes for rehospitalization by age and sex.

Inter-individual differences in the experience of negative emotion predict variations in functional brain architecture.

Current evidence suggests that two spatially distinct neuroanatomical networks, the dorsal attention network (DAN) and the default mode network (DMN), support externally and internally oriented cognition, respectively, and are functionally regulated by a third, frontoparietal control network (FPC). Interactions among these networks contribute to normal variations in cognitive functioning and to the aberrant affective profiles present in certain clinical conditions, such as major depression. Nevertheless, their links to non-clinical variations in affective functioning are still poorly understood. To address this issue, we used fMRI to measure the intrinsic functional interactions among these networks in a sample of predominantly younger women (N=162) from the Human Connectome Project. Consistent with the previously documented dichotomous motivational orientations (i.e., withdrawal versus approach) associated with sadness versus anger, we hypothesized that greater sadness would predict greater DMN (rather than DAN) functional dominance, whereas greater anger would predict the opposite. Overall, there was evidence of greater DAN (rather than DMN) functional dominance, but this pattern was modulated by current experience of specific negative emotions, as well as subclinical depressive and anxiety symptoms. Thus, greater levels of currently experienced sadness and subclinical depression independently predicted weaker DAN functional dominance (i.e., weaker DAN-FPC functional connectivity), likely reflecting reduced goal-directed attention towards the external perceptual environment. Complementarily, greater levels of currently experienced anger and subclinical anxiety predicted greater DAN functional dominance (i.e., greater DAN-FPC functional connectivity and, for anxiety only, also weaker DMN-FPC coupling). Our findings suggest that distinct affective states and subclinical mood symptoms have dissociable neural signatures, reflective of the symbiotic relationship between cognitive processes and emotional states.

Age differences in the default network at rest and the relation to self-referential processing.

Older adults show a 'positivity bias' in tasks involving emotion and self-referential processing. A critical network that is involved in self-referencing and shows age-related decline is the default network (DN). The purpose of the current study was to investigate age differences in pre- and post-task DN functional connectivity (FC) and signal variability, and to examine whether they are predictive of the positivity bias in self-referencing. We measured FC and within-subject variability of the DN in resting-state scans preceding and following tasks involving personality judgements on the self and a close other. Older adults endorsed more positive traits than younger adults on both tasks. FC was weaker post-task in older vs younger adults, and younger adults had greater variability than older adults in DN nodes. Younger adults with higher post-task DN variability had more negative self-ratings. For both age groups, greater FC in the DN was associated with more negative self-ratings. Neither FC nor variability was related to other ratings, despite the potential for self-processing when making other judgements. Our findings suggest that ageing leads to reduced FC and variability in the DN, which is most apparent after task, and may be one mechanism underlying the positive bias with age.

Age differences in the intrinsic functional connectivity of default network subsystems.

Recent work suggests that the default mode network (DMN) includes two core regions, the ventromedial prefrontal cortex and posterior cingulate cortex (PCC), and several unique subsystems that are functionally distinct. These include a medial temporal lobe (MTL) subsystem, active during remembering and future projection, and a dorsomedial prefrontal cortex (dmPFC) subsystem, active during self-reference. The PCC has been further subdivided into ventral (vPCC) and dorsal (dPCC) regions that are more strongly connected with the DMN and cognitive control networks, respectively. The goal of this study was to examine age differences in resting state functional connectivity within these subsystems. After applying a rigorous procedure to reduce the effects of head motion, we used a multivariate technique to identify both common and unique patterns of functional connectivity in the MTL vs. the dmPFC, and in vPCC vs. dPCC. All four areas had robust functional connectivity with other DMN regions, and each also showed distinct connectivity patterns in both age groups. Young and older adults had equivalent functional connectivity in the MTL subsystem. Older adults showed weaker connectivity in the vPCC and dmPFC subsystems, particularly with other DMN areas, but stronger connectivity than younger adults in the dPCC subsystem, which included areas involved in cognitive control. Our data provide evidence for distinct subsystems involving DMN nodes, which are maintained with age. Nevertheless, there are age differences in the strength of functional connectivity within these subsystems, supporting prior evidence that DMN connectivity is particularly vulnerable to age, whereas connectivity involving cognitive control regions is relatively maintained. These results suggest an age difference in the integrated activity among brain networks that can have implications for cognition in older adults.

Hospitalizations and emergency department visits for TBI in Ontario.

OBJECTIVE: The aim of this study was to determine the number of annual hospitalizations and overall episodes of care that involve a traumatic brain injury (TBI) by age and gender in the province of Ontario. To provide a more accurate assessment of the prevalence of TBI, episodes of care included visits to the emergency department (ED), as well as admissions to hospital. Mechanisms of injury for overall episodes were also investigated. METHODS: Traumatic brain injury cases from fiscal years 2002/03-2006/07 were identified by means of ICD-10 codes. Data were collected from the National Ambulatory Care Reporting System and the Discharge Abstract Database. RESULTS: The rate of hospitalization was highest for elderly persons over 75 years-of-age. Males generally had higher rates for both hospitalizations and episodes of care than did females. The inclusion of ED visits to hospitalizations had the greatest impact on the rates of TBI in the youngest age groups. Episodes of care for TBI were greatest in youth under the age of 14 and elderly over the age of 85. Falls (41.6%) and being struck by or against an object (31.1%) were the most frequent causes for a TBI. CONCLUSIONS: The study provides estimates for TBI from the only Canadian province that has systematically captured ED visits in a national registry. It shows the importance of tracking ED visits, in addition to hospitalizations, to capture the burden of TBI on the health care system. Prevention strategies should include information on ED visits, particularly for those at younger ages.

The social zebrafish: behavioral responses to conspecific, heterospecific, and computer animated fish.

Zebrafish has been in the forefront of developmental biology and genetics, but only recently has interest in their behavior increased. Zebrafish are small and prolific, which lends this species to high throughput screening applications. A typical feature of zebrafish is its propensity to aggregate in groups, a behavior known as shoaling. Thus, zebrafish has been proposed as a possible model organism appropriate for the analysis of the genetics of vertebrate social behavior. However, shoaling behavior is not well characterized in zebrafish. Here, using a recently developed software application, we first investigate how zebrafish respond to conspecific and heterospecific fish species that differ in coloration and/or shoaling tendencies. We found that zebrafish shoaled with their own species but not with two heterospecific species, one of which was a shoaling the other a non-shoaling species. In addition, we have started the analysis of visual stimuli that zebrafish may utilize to determine whether to shoal with a fish or not. We systematically modified the color, the location, the pattern, and the body shape of computer animated zebrafish images and presented them to experimental zebrafish. The subjects responded differentially to some of these stimuli showing preference for yellow and avoidance of elongated zebrafish images. Our results suggest that computerized stimulus presentation and automated behavioral quantification of zebrafish responses are feasible, which in turn implies that high throughput forward genetic mutation or drug screening will be possible in the analysis of social behavior with this model organism.