Search

Kim H Tran,1,2 Andrew P McDonald,1,3 Ryan CN D’Arcy,2,3 Xiaowei Song1,2 1Clinical Research Centre, Surrey Memorial Hospital, Fraser Health Authority, Surrey, BC, Canada; 2Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC, Canada; 3Department of Medicine, University of British Columbia, Vancouver, BC, CanadaCorrespondence: Xiaowei Song 13750 96th Avenue, Surrey, BC V3V 1Z2, CanadaTel +1 604 585 5666 ext. 774 986Email xiaowei.song@fraserhealth.caAbstract: Contextual processing (or context processing; CP) is an integral component of cognition. CP allows people to manage their thoughts and actions by adjusting to surroundings. CP involves the formation of an internal representation of context in relation to the environment, maintenance of this information over a period of time, and the updating of mental representations to reflect changes in the environment. Each of these functions can be affected by aging and associated conditions. Here, we introduced contextual processing research and summarized the literature studying the impact of normal aging and neurodegeneration-related cognitive decline on CP. Through searching the PubMed, PsycINFO, and Google Scholar databases, 23 studies were retrieved that focused on the impact of aging, mild cogniitve impairment (MCI), Alzheimer’s disease (AD), and Parkinson’s disease (PD) on CP. Results indicated that CP is particularly vulnerable to aging and neurodegeneration. Older adults had a delayed onset and reduced amplitude of electrophysiological response to information detection, comparison, and execution. MCI patients demonstrated clear signs of impaired CP compared to normal aging. The only study on AD suggested a decreased proactive control in AD participants in maintaining contextual information, but seemingly intact reactive control. Studies on PD restricted to non-demented older participants, who showed limited ability to use contextual information in cognitive and motor processes, exhibiting impaired reactive control but more or less intact proactive control. These data suggest that the decline in CP with age is further impacted by accelerated aging and neurodegeneration, providing insights for improving intervention strategies. This review highlights the need for increased attention to research this important but understudied field.Keywords: Alzheimer’s disease, Parkinson’s disease, mild-cognitive impairment, aging, dementia, contextual processing, EEG-ERP, behavior

Tao Gu,1,2 Lei Lin,3 Yun Jiang,4 Juan Chen,1 Ryan CN D’Arcy,2,5,6 Min Chen,1 Xiaowei Song2,5,6 1Department of Radiology, Beijing Hospital, National Center of Gerontology, Beijing, China; 2Simon Fraser University ImageTech Laboratory, Surrey Memorial Hospital, Surrey, BC, Canada; 3Department of Acupuncture and Moxibustion, Beijing Hospital, National Centre of Gerontology, Beijing, China; 4Department of Neurology, Beijing Hospital, National Centre of Gerontology, Beijing, China; 5Department of Applied Sciences and Computing Science, Simon Fraser University, Burnaby, BC, Canada; 6Health Sciences and Innovation, Surrey Memorial Hospital, Fraser Health Authority, Surrey, BC, Canada Background: Acupuncture has been proven to be effective as an alternative therapy in treating migraine, but the pathophysiological mechanisms of the treatment remain unclear. This study investigated possible neurochemical responses to acupuncture treatment. Patients and methods: Proton magnetic resonance spectroscopy imaging was used to investigate biochemical levels pre- and post-acupuncture treatment. Participants (N=45) included subjects diagnosed with: 1) migraine without aura; 2) cervicogenic headache; and 3) healthy controls. Participants in the two patient groups received verum acupuncture using acupoints that target migraine without aura but not cervicogenic headache, while the healthy controls received a sham treatment. All participants had magnetic resonance spectroscopy scans before and after the acupuncture therapy. Levels of brain metabolites were examined in relation to clinical headache assessment scores. Results: A significant increase in N-acetylaspartate/creatine was observed in bilateral thalamus in migraine without aura after the acupuncture treatment, which was significantly correlated with the headache intensity score. Conclusion: The data demonstrate brain biochemical changes underlying the effect of acupuncture treatment of migraine. Keywords: acupuncture, metabolites, migraine, magnetic resonance spectroscopy imaging, brain, pain transmission pathways

Hui Guo,1,2 William Siu,1,3 Ryan CN D’Arcy,1,4 Sandra E Black,5,6 Lukas A Grajauskas,1,4 Sonia Singh,7,8 Yunting Zhang,2 Kenneth Rockwood,9,10 Xiaowei Song1,4,9 On behalf of The Alzheimer’s Disease Neuroimaging Initiative and the National Alzheimer’s Coordinating Center 1Health Sciences and Innovation, ImageTech Laboratory, Fraser Health Authority, Surrey, BC, Canada; 2Department of Diagnostic Imaging, Tianjin Medical University General Hospital, Tianjin, China; 3Department of Medical Imaging, Fraser Health Authority, Surrey, 4Departments of Applied Sciences and Computing Science, Simon Fraser University, Burnaby, BC, 5Department of Medicine (Neurology), 6LC Campbell Cognitive Neurology Research Unit, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre & University of Toronto, Toronto, ON, 7Department of Family Medicine, University of British Columbia, Vancouver, BC, 8Department of Research and Evaluation, Fraser Health, Surrey, BC, 9Department of Medicine (Geriatric Medicine), Dalhousie University, 10Centre for Healthcare of the Elderly, Nova Scotia Health Authority, Halifax, NS, Canada Purpose: One of the central features of brain aging is the accumulation of multiple age-related structural changes, which occur heterogeneously in individuals and can have immediate or potential clinical consequences. Each of these deficits can coexist and interact, producing both independent and additive impacts on brain health. Many of the changes can be visualized using MRI. To collectively assess whole-brain structural changes, the MRI-based Brain Atrophy and Lesion Index (BALI) has been developed. In this study, we validate this whole-brain health assessment approach using several clinical MRI examinations.Materials and methods: Data came from three independent studies: the Alzheimer’s Disease Neuroimaging Initiative Phase II (n=950; women =47.9%; age =72.7±7.4 years); the National Alzheimer’s Coordinating Center (n=722; women =55.1%; age =72.7±9.9 years); and the Tianjin Medical University General Hospital Research database on older adults (n=170; women =60.0%; age =62.9±9.3 years). The 3.0-Tesla MRI scans were evaluated using the BALI rating scheme on the basis of T1-weighted (T1WI), T2-weighted (T2WI), T2-weighted fluid-attenuated inversion recovery (T2-FLAIR), and T2*-weighted gradient-recalled echo (T2*GRE) images.Results: Atrophy and lesion changes were commonly seen in each MRI test. The BALI scores based on different sequences were highly correlated (Spearman r2>0.69; P0.29; P26.48, P

We investigated objective brain vital signs derived from event-related potentials (ERPs) for mixed martial arts (MMA) athletes and matched controls ( N  = 24). Brain vital sign scans were acquired from 9 MMA athletes and 15 age-and sex-matched controls. Our analysis specifically compared differences in brain vital signs between MMA athletes and controls at baseline. We predicted that MMA athletes would show significant differences relative to controls due to their ongoing exposure to repetitive head impacts. Participants were scanned to extract three well-established ERPs: N100 for auditory sensation; P300 for basic attention; and N400 for cognitive processing. Scans were verified using automated reports, with N100, P300, and N400 amplitudes and latencies manually identified by a blinded reviewer. Brain vital signs were compared across groups with a Kruskal-Wallis H-test for independent samples, with FDR correction for multiple comparisons. We identified significant differences between MMA athletes and controls. Specifically, there were significant N400 amplitude reductions, indicating that exposure to repetitive head impacts in MMA may be associated with changes in brain function., Competing Interests: SF, SN, and RD’A were associated with HealthTech Connex at the time of this study, which may qualify them to financially benefit from commercialization of the NeuroCatch® Platform for obtaining brain vital signs. RD’A was employed at BrainNET. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Munce, Fickling, Nijjer, Poel and D’Arcy.)

Introduction: In past work we demonstrated different patterns of white matter (WM) plasticity in females versus males associated with learning a lab-based unilateral motor skill. However, this work was completed in neurologically intact older adults. The current manuscript sought to replicate and expand upon these WM findings in two ways: (1) we investigated biological sex differences in neurologically intact young adults, and (2) participants learned a dynamic full-body balance task., Methods: 24 participants (14 female, 10 male) participated in the balance training intervention, and 28 were matched controls (16 female, 12 male). Correlational tractography was used to analyze changes in WM from pre- to post-training., Results: Both females and males demonstrated skill acquisition, yet there were significant differences in measures of WM between females and males. These data support a growing body of evidence suggesting that females exhibit increased WM neuroplasticity changes relative to males despite comparable changes in motor behavior (e.g., balance)., Discussion: The biological sex differences reported here may represent an important factor to consider in both basic research (e.g., collapsing across females and males) as well as future clinical studies of neuroplasticity associated with motor function (e.g., tailored rehabilitation approaches)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kirby, Andrushko, Boyd, Koschutnig and D’Arcy.)

Objective, rapid evaluation of cognitive function is critical for identifying situational impairment due to sleep deprivation. The present study used brain vital sign monitoring to evaluate acute changes in cognitive function for healthy adults. Thirty (30) participants were scanned using portable electroencephalography before and after either a night of regular sleep or a night of total sleep deprivation. Brain vital signs were extracted from three established event-related potential components: (1) the N100 (Auditory sensation); (2) the P300 (Basic attention); and (3) the N400 (Cognitive processing) for all time points. As predicted, the P300 amplitude was significantly reduced in the sleep deprivation group. The findings indicate that it is possible to detect situational cognitive impairment due to sleep deprivation using objective, rapid brain vital sign monitoring., Competing Interests: KJ, GP, SB, BL, JV, and RD’A are associated with HealthTech Connex and have a financial interest in the NeuroCatch Platform. JV was employed by Healthcode Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Jones, Frizzell, Fickling, Pawlowski, Brodie, Lakhani, Venter and D’Arcy.)

Introduction: Managing cognitive function in care homes is a significant challenge. Individuals in care have a variety of scores across standard clinical assessments, such as the Mini-Mental Status Exam (MMSE), and many of them have scores that fall within the range associated with dementia. A recent methodological advance, brain vital sign monitoring through auditory event-related potentials, provides an objective and sensitive physiological measurement to track abnormalities, differences, or changes in cognitive function. Taking advantage of point-of-care accessibility, the current study evaluated the methodological feasibility, the assessment of whether a particular research method can be successfully implemented, of quantitatively measuring cognition of care home residents using brain vital signs. Secondarily, the current study examined the relationship between brain vital signs, specifically the cognitive processing associated N400 component, and MMSE scores in care home residents., Materials and Methods: Brain vital signs used the established N100 (auditory sensation), P300 (basic attention), and N400 (cognitive processing) event-related potential (ERP) components. A total of 52 residents were enrolled, with all participants evaluated using the MMSE. Participants were assigned into homogeneous groups based on their MMSE scores, and were categorized into low (n = 14), medium (n = 17), and high (n = 13) MMSE groups. Both brain vital sign measures and underlying ERP waveforms were examined. Statistical analyses used partial least squares correlation (PLS) analyses in which both MMSE and age were included as factors, as well as jackknife approaches, to test for significant brain vital sign changes., Results: The current study successfully measured and analyzed standardized, quantifiable brain vital signs in a care home setting. ERP waveform data showed specific N400 changes between MMSE groups as a function of MMSE score. PLS analyses confirmed significant MMSE-related and age-related differences in the N400 amplitude ( p  < 0.05, corrected). Similarly, the jackknife approach emphasized the N400 latency difference between the low and high MMSE groups., Discussion and Conclusion: It was possible to acquire brain vital signs measures in care home residents. Additionally, the current study evaluated brain vital signs relative to MMSE in this group. The comparison revealed significant decreasing in N400 response amplitude (cognitive processing) as a function of both MMSE score and age, as well as a slowing of N400 latency. The findings indicate that objective neurophysiological measures of impairment are detectable in care home residents across the span of MMSE scores. Direct comparison to MMSE- and age-related variables represents a critical initial step ahead of future studies that will investigate relative improvements in sensitivity, validity, reliability and related advantages of brain vital sign monitoring., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Ryan D'Arcy reports financial support was provided by Canadian Frailty Network. Ryan D'Arcy reports financial support and administrative support were provided by Surrey HospitalsFoundation. Shaun Fickling reports a relationship with HealthTech Connex Inc that includes: employment. Several authors are associated with HealthTech Connex Inc., which may qualify them to financially benefit from the commercialization of a NeuroCatch® Platform capable of measuring brain vital signs., (© 2024 Published by Elsevier Ltd.)

Magnetic resonance imaging (MRI) has increasingly been used to characterize structure-function relationships during white matter neuroplasticity. Biological sex differences may be an important factor that affects patterns of neuroplasticity, and therefore impacts learning and rehabilitation. The current study examined a participant cohort before and after visuo-motor training to characterize sex differences in microstructural measures. The participants (N = 27) completed a 10-session (4 week) complex visuo-motor training task with their non-dominant hand. All participants significantly improved movement speed and their movement speed variability over the training period. White matter neuroplasticity in females and males was examined using fractional anisotropy (FA) and myelin water fraction (MWF) along the cortico-spinal tract (CST) and the corpus callosum (CC). FA values showed significant differences in the middle portion of the CST tract (nodes 38-51) across the training period. MWF showed a similar cluster in the inferior portion of the tract (nodes 18-29) but did not reach significance. Additionally, at baseline, males showed significantly higher levels of MWF measures in the middle body of the CC. Combining data from females and males would have resulted in reduced sensitivity, making it harder to detect differences in neuroplasticity. These findings offer initial insights into possible female versus male differences in white matter neuroplasticity during motor learning. This warrants investigations into specific patterns of white matter neuroplasticity for females versus males across the lifespan. Understanding biological sex-specific differences in white matter neuroplasticity may have significant implications for the interpretation of change associated with learning or rehabilitation., (© 2024. The Author(s).)

Background: Non-invasive neuromodulation using translingual neurostimulation (TLNS) has been shown to advance rehabilitation outcomes, particularly when paired with physical therapy (PT). Together with motor gains, patient-reported observations of incidental improvements in cognitive function have been noted. Both studies in healthy individuals and case reports in clinical populations have linked TLNS to improvements in attention-related cognitive processes. We investigated if the use of combined TLNS/PT would translate to changes in objective neurophysiological cognitive measures in a real-world clinical sample of patients from two separate rehabilitation clinics., Methods: Brain vital signs were derived from event-related potentials (ERPs), specifically auditory sensation (N100), basic attention (P300), and cognitive processing (N400). Additional analyses explored the attention-related N200 response given prior evidence of attention effects from TLNS/PT. The real-world patient sample included a diverse clinical group spanning from mild-to-moderate traumatic brain injury (TBI), stroke, Multiple Sclerosis (MS), Parkinson's Disease (PD), and other neurological conditions. Patient data were also acquired from a standard clinical measure of cognition for comparison., Results: Results showed significant N100 variation between baseline and endpoint following TLNS/PT treatment, with further examination showing condition-specific significant improvements in attention processing (i.e., N100 and N200). Additionally, CogBAT composite scores increased significantly from baseline to endpoint., Discussion: The current study highlighted real-world neuromodulation improvements in neurophysiological correlates of attention. Overall, the real-world findings support the concept of neuromodulation-related improvements extending beyond physical therapy to include potential attention benefits for cognitive rehabilitation., Competing Interests: SF, GP, SB, and RD’A have financial and/or business interests in HealthTech Connex, which may be affected by the research reported in this manuscript. JV was employed by company Healthcode. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kirby, Jones, Fickling, Pawlowski, Brodie, Boyd, Venter, Moser, Kalsi-Ryan, Medvedev and D’Arcy.)

Mental imagery (MI) is gaining attention as a strategy towards endogenous brain stimulation for improving motor skill. Neurofeedback (NF) is commonly used to guide MI in order to activate the relevant brain networks. The current study investigates an individualized EEG-based method for NF through broad consideration of interactions between different brain networks. We selected the change in brain functional connectivity (FC) as an objective neurophysiological measure of change in motor skill during a longitudinal physical training (PT) program. Digital tracing tasks were developed for skill training and the spatial error in tracing was used to gauge the change in skill. We used partial least squares algorithms to find the most robust contributing networks towards correlation between the resting state FC and the acquired motor skill. We used the network with the largest margin for increasing FC as the candidate for NF training while experimenting with MI during a neurofeedback training program. The participant was informed of the changes in instantaneous FC through real-time audio feedback to help guide the MI. We showed over 20% reduction in tracing error through neurofeedback training alone, without any additional PT. We also showed retention of improvement in skill for several days after the completion of neurofeedback training. Our proposed methodology shows promise for a highly individualized approach towards improvement in motor skill. Given that EEG is an accessible health and wellness technology, such a method could provide a practical complementary option towards personalized therapeutic strategies to improve motor function.

White matter (WM) neuroplasticity in the human brain has been tracked non-invasively using advanced magnetic resonance imaging techniques, with increasing evidence for improved axonal transmission efficiency as a central mechanism. The current study is the culmination of a series of studies, which characterized the structure-function relationship of WM transmission efficiency in the cortico-spinal tract (CST) during motor learning. Here, we test the hypothesis that increased transmission efficiency is linked directly to increased myelination using myelin water imaging (MWI). MWI was used to evaluate neuroplasticity-related improvements in the CST. The MWI findings were then compared to diffusion tensor imaging (DTI) results, with the secondary hypothesis that radial diffusivity (RD) would have a stronger relationship than axial diffusivity (AD) if the changes were due to increased myelination. Both MWI and RD data showed the predicted pattern of significant results, strongly supporting that increased myelination plays a central role in WM neuroplasticity., Competing Interests: Declaration of Competing Interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2022. Published by Elsevier Inc.)

Introduction: Multiple structural brain changes in Alzheimer's disease (AD) and mild cognitive impairment (MCI) have been revealed on magnetic resonance imaging (MRI). There is a fast-growing effort in applying artificial intelligence (AI) to analyze these data. Here, we review and evaluate the AI studies in brain MRI analysis with synthesis., Methods: A systematic review of the literature, spanning the years from 2009 to 2020, was completed using the PubMed database. AI studies using MRI imaging to investigate normal aging, mild cognitive impairment, and AD-dementia were retrieved for review. Bias assessment was completed using the PROBAST criteria., Results: 97 relevant studies were included in the review. The studies were typically focused on the classification of AD, MCI, and normal aging (71% of the reported studies) and the prediction of MCI conversion to AD (25%). The best performance was achieved by using the deep learning-based convolution neural network algorithms (weighted average accuracy 89%), in contrast to 76-86% using Logistic Regression, Support Vector Machines, and other AI methods., Discussion: The synthesized evidence is paramount to developing sophisticated AI approaches to reliably capture and quantify multiple subtle MRI changes in the whole brain that exemplify the complexity and heterogeneity of AD and brain aging., (Copyright © 2022. Published by Elsevier B.V.)

Magnetic resonance imaging (MRI) studies are sensitive to biological mechanisms of neuroplasticity in white matter (WM). In particular, diffusion tensor imaging (DTI) has been used to investigate structural changes. Historically, functional MRI (fMRI) neuroplasticity studies have been restricted to gray matter, as fMRI studies have only recently expanded to WM. The current study evaluated WM neuroplasticity pre-post motor training in healthy adults, focusing on motor learning in the non-dominant hand. Neuroplasticity changes were evaluated in two established WM regions-of-interest: the internal capsule and the corpus callosum. Behavioral improvements following training were greater for the non-dominant hand, which corresponded with MRI-based neuroplasticity changes in the internal capsule for DTI fractional anisotropy, fMRI hemodynamic response functions, and low-frequency oscillations (LFOs). In the corpus callosum, MRI-based neuroplasticity changes were detected in LFOs, DTI, and functional correlation tensors (FCT). Taken together, the LFO results converged as significant amplitude reductions, implicating a common underlying mechanism of optimized transmission through altered myelination. The structural and functional neuroplasticity findings open new avenues for direct WM investigations into mapping connectomes and advancing MRI clinical applications., (© 2021. The Author(s).)

Brain vital signs, measured by EEG, were used for portable, objective, neurophysiological evaluation of cognitive function in youth tackle football players. Specifically, we investigated whether previously reported pre- and post-season subconcussive changes detected in youth ice hockey players were comparably detected in football. The two objectives were to: (i) replicate previously published results showing subconcussive cognitive deficits; and (ii) the relationship between brain vital sign changes and head-impact exposure. Using a longitudinal design, 15 male football players (age 12.89 ± 0.35 years) were tested pre- and post-season, with none having a concussion diagnosis during the season. Peak latencies and amplitudes were quantified for Auditory sensation (N100), Basic attention (P300) and Cognitive processing (N400). Regression analyses tested the relationships between these brain vital signs and exposure to head impacts through both number of impacts sustained, and total sessions (practices and games) participated. The results demonstrated significant pre/post differences in N400 latencies, with ∼70 ms delay ( P  < 0.01), replicating prior findings. Regression analysis also showed significant linear relationships between brain vital signs changes and head impact exposure based on accelerometer data and games/practices played (highest R  = 0.863, P < 0.001 for overall sessions). Number of head impacts in youth football (age 12-14 years) findings corresponded most closely with prior Junior-A ice hockey (age 16-21 years) findings, suggesting comparable contact levels at younger ages in football. The predictive relationship of brain vital signs provided a notable complement to instrumented accelerometers, with a direct physiological measure of potential individual exposure to subconcussive impacts., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: Electroencephalography (EEG)-derived event-related potentials (ERPs) provide information about a variety of brain functions, but often suffer from low inherent signal-to-noise ratio (SNR). To overcome the low SNR, techniques that pool data from multiple sensors have been applied. However, such pooling implicitly assumes that the SNR among sensors is equal, which is not necessarily valid. This study presents a novel approach for signal pooling that accounts for differential SNR among sensors., Methods: The new technique involves pooling together signals from multiple EEG channels weighted by their respective SNRs relative to the overall SNR of all channels. We compared ERP responses derived using this new technique with those derived using both individual channels as well as traditional averaged-based channel pooling. The outcomes were evaluated in both simulated data and real data from healthy adult volunteers (n = 37). Responses corresponding to a range of ERP components indexing auditory sensation (N100), attention (P300) and language processing (N400) were evaluated., Results: Simulation results demonstrate that, compared to traditional pooling technique, the new SNR-weighted channel pooling technique improved ERP response effect size in cases of unequal noise among channels ( p 's < 0.001). Similarly, results from real-world experimental data showed that the new technique resulted in significantly greater ERP effect sizes compared to either traditional pooling or individual channel approach for all three ERP components ( p 's < 0.001). Furthermore, the new channel pooling approach also resulted in larger ERP signal amplitudes as well as greater differences among experimental conditions ( p 's < 0.001)., Conclusion: These results suggest that the new technique improves the capture of ERP responses relative to traditional techniques. As such, SNR-weighted channel pooling can further enable widespread applications of ERP techniques, especially those that require rapid assessments in noisy out-of-laboratory environments.

The size of our pupils changes continuously in response to variations in ambient light levels, a process known as the pupillary light reflex (PLR). The PLR is not a simple reflex as its function is modulated by cognitive brain function and any long-term changes in brain function secondary to injury should cause a change in the parameters of the PLR. We performed a retrospective clinical review of the PLR of our patients using the BrightLamp Reflex iPhone app. The PLR variables of latency, maximum pupil diameter (MaxPD), minimum pupil diameter (MinPD), maximum constriction velocity (MCV), and the 75% recovery time (75% PRT) were associated with significant differences between subjects who had suffered a concussion and those that had not. There were also significant differences in PLR metrics over the life span and between genders and those subjects with and without symptoms. The differences in PLR metrics are modulated not only by concussion history but also by gender and whether or not the person has symptoms associated with a head injury. A concussive injury to the brain is associated with changes in the PLR that persist over the life span, representing biomarkers that might be used in clinical diagnosis, treatment, and decision making.

COVID-19 is increasingly being linked to brain health impacts. The emerging situation is consistent with evidence of immunological injury to the brain, which has been described as a resulting "brain fog." The situation need not be medicalized but rather clinically managed in terms of improving resilience for an over-stressed nervous system. Pre-existing comparisons include managing post-concussion syndromes and/or brain fog. The objective evaluation of changes in cognitive functioning will be an important clinical starting point, which is being accelerated through pandemic digital health innovations. Pre-morbid brain health can significantly optimize risk factors and existing clinical frameworks provide useful guidance in managing over-stressed COVID-19 nervous systems., Competing Interests: RD is the inventor of the NeuroCatch Platform medical device and qualifies for financial benefit from commercialization. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 D'Arcy, Sandhu, Marshall and Besemann.)

Background: Prior concussion studies have shown that objective neurophysiological measures are sensitive to detecting concussive and subconcussive impairments in youth ice-hockey. These studies monitored brain vital signs at rink-side using a within-subjects design to demonstrate significant changes from pre-season baseline scans. However, practical clinical implementation must overcome inherent challenges related to any dependence on a baseline. This requires establishing the start of normative reference data sets. Methods: The current study collected specific reference data for N = 58 elite, youth, male ice-hockey players and compared these with a general reference dataset from N = 135 of males and females across the lifespan. The elite hockey players were recruited to a select training camp through CAA Hockey, a management agency for players drafted to leagues such as the National Hockey League (NHL). The statistical analysis included a test-retest comparison to establish reliability, and a multivariate analysis of covariance to evaluate differences in brain vital signs between groups with age as a covariate. Findings: Test-retest assessments for brain vital signs evoked potentials showed moderate-to-good reliability (Cronbach's Alpha > 0.7, Intraclass correlation coefficient > 0.5) in five out of six measures. The multivariate analysis of covariance showed no overall effect for group ( p = 0.105), and a significant effect of age as a covariate was observed ( p < 0.001). Adjusting for the effect of age, a significant difference was observed in the measure of N100 latency ( p = 0.022) between elite hockey players and the heterogeneous control group. Interpretation: The findings support the concept that normative physiological data can be used in brain vital signs evaluation in athletes, and should additionally be stratified for age, skill level, and experience. These can be combined with general norms and/or individual baseline assessments where appropriate and/or possible. The current results allow for brain vital sign evaluation independent of baseline assessment, therefore enabling objective neurophysiological evaluation of concussion management and cognitive performance optimization in ice-hockey., Competing Interests: SF, NC, GPw, TF, BL, and RD’A are associated with HealthTech Connex and have a financial interest in the NeuroCatch Platform. FC is the founder of the Carrick Institute, but had no financial interest in the NeuroCatch Platform. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Carrick, Pagnacco, Azzolino, Hunfalvay, Oggero, Frizzell, Smith, Pawlowski, Campbell, Fickling, Lakhani and D’Arcy.)

The brain vital signs framework is a portable, objective, neurophysiological evaluation of brain function at point-of-care. We investigated brain vital signs at pre- and post-season for age 14 or under (Bantam) and age 16-20 (Junior-A) male ice hockey players to (i) further investigate previously published brain vital sign results showing subconcussive cognitive deficits and (ii) validate these findings through comparison with head-impact data obtained from instrumented accelerometers. With a longitudinal study design, 23 male ice hockey players in Bantam ( n  = 13; age 13.63 ± 0.62) and Tier II Junior-A ( n  = 10; age 18.62 ± 0.86) divisions were assessed at pre- and post-season. None were diagnosed with a concussion during the season. Cognitive evoked potential measures of Auditory sensation (N100), Basic attention (P300) and Cognitive processing (N400) were analysed as changes in peak amplitudes and latencies (six standard scores total). A regression analysis examined the relationship between brain vital signs and the number of head impacts received during the study season. Significant pre/post differences in brain vital signs were detected for both groups. Bantam and Junior-A players also differed in number of head impacts (Bantam: 32.92 ± 17.68; Junior-A: 195.00 ± 61.08; P  < 0.001). Importantly, the regression model demonstrated a significant linear relationship between changes in brain vital signs and total head impacts received ( R  = 0.799, P  = 0.007), with clear differences between the Bantam and Junior-A groups. In the absence of a clinically diagnosed concussion, the brain vital sign changes appear to have demonstrated the compounding effects of repetitive subconcussive impacts. The findings underscored the importance of an objective physiological measure of brain function along the spectrum of concussive impacts., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Purpose/objective(s): Gliomas are uniformly fatal brain tumours with significant neurological and quality of life detriment to patients. Improvement in outcomes has remained largely unchanged in nearly 20 years. MRI (magnetic resonance imaging) is often used in diagnosis and management. Machine learning analyses of large-scale MRI data are pivotal in advancing the diagnosis, management and improve outcomes in neuro-oncology. A common challenge to robust machine learning approaches is the lack of large 'ground truth' datasets in supervised learning for building classification and prediction models. The creation of these datasets relies on human-expert input and is time-consuming and subjective error-prone, limiting effective machine learning applications. Simulation of mechanistic aspects such as geometry, location and physical properties of brain tumours can generate large-scale ground-truth datasets allowing for comparison of analysis techniques in clinical applications. We aimed to develop a transparent and convenient method for building 'ground truth' presentations of simulated glioma lesions on anatomical MRI., Materials/methods: The simulation workflow was created using the Feature Manipulation Engine (FME®), a data integration platform specializing in the spatial data processing. By compiling and integrating FME's functions to read, integrate, transform, validate, save, and display MRI data, and experimenting with ways to manipulate the parameters concerning location, size, shape, and signal intensity with the presentations of glioma, we were able to generate simulated appearances of high-grade gliomas on gadolinium-based high-resolution 3D T1-weighted MRI (1 mm 3 ). Data of patients with canonical high-grade tumours were used as real-world tumours for validating the accuracy of the simulation. Twenty raters who are experienced with brain tumour interpretation on MRI independently completed a survey, designed to distinguish simulated and real-world brain tumours. Sensitivity and specificity were calculated for assessing the performance of the approach with the binary classification of simulated vs real-world tumours. Correlation and regression were used in run time analysis, assessing the software toolset's efficiency in producing different numbers of simulated lesions. Differences in the group means were examined using the non-parametric Kruskal-Wallis test., Results: The simulation method was developed as an interpretable and useful workflow for the easy creation of tumour simulations and incorporation into 3D MRI. A linear increase in the running time and memory usage was observed with an increasing number of generated lesions. The respondents' accuracy rate ranged between 33.3 and 83.3 %. The sensitivity and specificity were low for a human expert to differentiate simulated lesions from real gliomas (0.43 and 0.58) or vice versa (0.65 and 0.62). The mean scores ranking the real-world gliomas did not differ between the simulated and real tumours., Conclusion: The reliable and user-friendly software method can allow for robust simulation of high-grade glioma on MRI. Ongoing research efforts include optimizing the workflow for generating glioma datasets as well as adapting it to simulating additional MRI brain changes., (Copyright © 2020. Published by Elsevier B.V.)

Background: Adopting a better understanding of how both older adults and health care providers view the community management of frailty is necessary for improving home health, especially facing the coronavirus disease 2019 (COVID-19) pandemic. We conducted a qualitative focus group study to assess how both older adults and health care providers view frailty and virtual health care in home health., Methods: Two focus groups enrolled home-living older adults and health care professionals, respectively (n = 15). Questions targeting the use of virtual / telehealth technologies in-home care for frail older adults were administered at audio-recorded group interviews. Transcribed discussions were coded and analyzed using NVivo software., Results: The older adult group emphasized the autonomy related to increasing frailty and social isolation and the need for transparent dissemination of health care planning. They were optimistic about remote technology-based supports and suggested that telehealth / health-monitoring/tracking were in high demand. Health care professionals emphasized the importance of a holistic biopsychosocial approach to frailty management. They highlighted the need for standardized early assessment and management of frailty., Conclusions: The integrated perspectives provided an updated understanding of what older adults and practitioners value in home-living supports. This knowledge is helpful to advancing virtual home care, providing better care for frail individuals with complex health care needs., Competing Interests: Nothing to disclose., (© 2021 The Authors. Aging Medicine published by Beijing Hospital and John Wiley & Sons Australia, Ltd.)

Background: In a recent high-profile case study, we used functional magnetic resonance imaging (fMRI) to monitor improvements in motor function related to neuroplasticity following rehabilitation for severe traumatic brain injury (TBI). The findings demonstrated that motor function improvements can occur years beyond current established limits. The current study extends the functional imaging investigation to characterize neuromodulation effects on neuroplasticity to further push the limits., Methods: Canadian Soldier Captain (retired) Trevor Greene (TG) survived a severe open-TBI when attacked with an axe during a 2006 combat tour in Afghanistan. TG has since continued intensive daily rehabilitation to recover motor function, experiencing an extended plateau using conventional physical therapy. To overcome this plateau, we paired translingual neurostimulation (TLNS) with the continuing rehabilitation program., Results: Combining TLNS with rehabilitation resulted in demonstrable clinical improvements along with corresponding changes in movement evoked electro-encephalography (EEG) activity. High-density magneto-encephalography (MEG) characterized cortical activation changes in corresponding beta frequency range (27 Hz). MEG activation changes corresponded with reduced interhemispheric inhibition in the post-central gyri regions together with increased right superior/middle frontal activation suggesting large scale network level changes., Conclusions: The findings provide valuable insight into the potential importance of non-invasive neuromodulation to enhance neuroplasticity mechanisms for recovery beyond the perceived limits of rehabilitation.

Numerous studies have noted the importance of white matter changes in motor learning, but existing literature only focuses on structural and microstructural MRI changes, as there are limited tools available for in vivo investigations of white matter function. One method that has gained recent prominence is the application of blood oxygen level dependent (BOLD) fMRI to white matter, with high-field scanners now being able to better detect the smaller hemodynamic changes present in this tissue type compared to those in the gray matter. However, fMRI techniques have yet to be applied to investigations of neuroplastic change with motor learning in white matter. White matter function represents an unexplored component of neuroplasticity and is essential for gaining a complete understanding of learning-based changes occurring throughout the whole brain. Twelve healthy, right-handed participants completed fine motor and gross motor tasks with both hands, using an MRI compatible computer mouse. Using a crossover design along with a prior analysis approach to establish WM activation, participants received a baseline scan followed by 2 weeks of training, returning for a midpoint and endpoint scan. The motor tasks were designed to be selectively difficult for the left hand, leading to a training effect only in that condition. Analysis targeted the comparison and detection of training-associated right vs left hand changes. A statistically significant improvement in motor task score was only noted for the left-hand motor condition. A corresponding change in the temporal characteristics of the white matter hemodynamic response was shown within only the right corticospinal tract. The hemodynamic response exhibited a reduction in the dispersion characteristics after the training period. To our knowledge, this is the first report of MRI detectable functional neuroplasticity in white matter, suggesting that modifications in temporal characteristics of white matter hemodynamics may underlie functional neuroplasticity in this tissue., (Copyright © 2020 Frizzell, Grajauskas, Liu, Ghosh Hajra, Song and D’Arcy.)

Objective: The ability to measure event-related potentials (ERPs) as practical, portable brain vital signs is limited by the physical locations of electrodes. Standard electrode locations embedded within the hair result in challenges to obtaining quality signals in a rapid manner. Moreover, these sites require electrode gel, which can be inconvenient. As electrical activity in the brain is spatially volume distributed, it should be possible to predict ERPs from distant sensor locations at easily accessible mastoid and forehead scalp regions., Methods: An artificial neural network was trained on ERP signals recorded from below hairline electrode locations (Tp9, Tp10, Af7, Af8 referenced to Fp1, Fp2) to predict signals recorded at the ideal Cz location., Results: The model resulted in mean improvements in intraclass correlation coefficient relative to control for all stimulus types (Standard Tones: +9.74%, Deviant Tones: +3.23%, Congruent Words: +15.25%, Incongruent Words: +25.43%) and decreases in RMS Error (Standard Tones: -26.72%, Deviant Tones: -17.80%, Congruent Words: -28.78%, Incongruent Words: -29.61%) compared to the individual distant channels. Measured vs predicted ERP amplitudes were highly and significantly correlated with control for the N100 (R = 0.5, p adj < 0.05), P300 (R = 0.75, p adj < 0.01), and N400 (R = 0.75, p adj < 0.01) ERPs., Conclusion: ERP waveforms at distant channels can be combined using a neural network autoencoder to model the control channel features with better precision than those at individual distant channels. This is the first demonstration of feasibility of predicting evoked potentials and brain vital signs using signals recorded from more distant, practical locations., Significance: This solves a key engineering challenge for applications that require portability, comfort, and speed of measurement as design priorities for measurement of event-related potentials across a range of individuals, settings, and circumstances.

Background : Neuromodulation through translingual neurostimulation (TLNS) has been shown to initiate long-lasting processes of neuronal reorganization with a variety of outcomes (i.e., neuroplasticity). Non-invasive TLNS is increasingly accessible through the Portable Neuromodulation Stimulator (PoNS ® ), a medical device that delivers electrical stimulation to the tongue to activate the trigeminal (V) and facial (VII) cranial nerves. Anecdotal reports from previous clinical studies have suggested incidental improvements in cognitive function. To objectively explore this observation, we examined TLNS-related effects on the semantic N400 brain vital sign cognitive response during cognitive skills training in healthy individuals. Methods : Thirty-seven healthy volunteers were randomized to receive simultaneous TLNS (treatment) or no TLNS (control) while undergoing cognitive skills training. Cognitive training was conducted for two 20-min sessions (morning and afternoon/evening) over 3 consecutive days. Brain vital signs were evaluated at baseline, Day 1, and Day 3. Analyses focused on cognitive processing as measured by N400 changes in amplitude and latency. Results : Over the 3-day course of cognitive training, the N400 amplitude decreased significantly in the control group due to habituation ( p = 0.028). In contrast, there was no significant change in the TLNS treatment group. Conclusion : TLNS led to a sustained N400 response during cognitive skills training, as measured by the brain's vital signs framework. The study findings suggest differential learning effects due to neuromodulation, consistent with increased attention and cognitive vigilance., (Copyright © 2020 Smith, Livingstone, Fickling, Tannouri, Campbell, Lakhani, Danilov, Sackier and D’Arcy.)

Using a longitudinal case study design, we have tracked the recovery of motor function following severe traumatic brain injury (TBI) through a multimodal neuroimaging approach. In 2006, Canadian Soldier Captain (retired) Trevor Greene (TG) was attacked with an axe to the head while on tour in Afghanistan. TG continues intensive daily rehabilitation, which recently included the integration of physical therapy (PT) with neuromodulation using translingual neurostimulation (TLNS) to facilitate neuroplasticity. Recent findings with PT + TLNS demonstrated that recovery of motor function occurred beyond conventional time limits, currently extending past 14-years post-injury. To investigate whether PT + TLNS similarly resulted in associated cognitive function improvements, we examined event-related potentials (ERPs) with the brain vital signs framework. In parallel with motor function improvements, brain vital signs detected significant increases in basic attention (as measured by P300 response amplitude) and cognitive processing (as measured by contextual N400 response amplitude). These objective cognitive improvements corresponded with TG's self-reported improvements, including a noteworthy and consistent reduction in ongoing symptoms of post-traumatic stress disorder (PTSD). The findings provide valuable insight into the potential importance of non-invasive neuromodulation in cognitive rehabilitation, in addition to initial indications for physical rehabilitation., (Copyright © 2020 Fickling, Greene, Greene, Frehlick, Campbell, Etheridge, Smith, Bollinger, Danilov, Rizzotti, Livingstone, Lakhani and D’Arcy.)

Introduction: Previous studies have shown that simulation is an acceptable method of training in nursing education. The objectives of this study were to determine the effectiveness of tablet-based simulation in learning neurosurgical instruments and to assess whether skills learnt in the simulation environment are transferred to a real clinical task and retained over time., Methods: A randomised controlled trial was conducted. Perioperative nurses completed three consecutive sessions of a simulation. Group A performed simulation tasks prior to identifying real instruments, whereas Group B (control group) was asked to identify real instruments prior to the simulation tasks. Both groups were reassessed for knowledge recall after 1 week., Results: Ninety-three nurses completed the study. Participants in Group A, who had received tablet-based simulation, were 23% quicker in identifying real instruments and did so with better accuracy (93.2% vs 80.6%, p<0.0001) than Group B. Furthermore, the simulation-based learning was retained at 7 days with 97.8% correct instrument recognition in Group A and 96.2% in Group B while maintaining both speed and accuracy., Conclusion: This is the first study to assess the effectiveness of tablet-based simulation training for instrument recognition by perioperative nurses. Our results demonstrate that instrument knowledge acquired through tablet-based simulation training results in improved identification and retained recognition of real instruments., Competing Interests: Competing interests: DBC and RCND are members of the medical advisory board and stock option holders with Conquer Experience. The authors have no financial relationships with Conquer Experience that may have influenced the submitted work; specifically, the authors did not receive research funding or financial compensation from Conquer Experience for this study. Furthermore, study conception, study design, acquisition of data, statistical analysis, interpretation and drafting of the manuscript were performed independently by the research team without participation from Conquer Experience. No one from Conquer Experience has seen, or participated in, any part of the writing of the manuscript., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Blink-related oscillations (BROs) are a recently discovered neurophysiological response associated with spontaneous blinking, distinct from the well-known oculomotor and visual suppression effects. BROs strongly activate the bilateral precuneus along with other cortical regions involved in visuospatial processing and associative episodic memory, and are believed to represent environmental monitoring processes that occur following blink-induced visual interruptions. Although these responses have been reported across multiple imaging modalities under both resting and cognitive loading conditions, it is yet unknown whether these responses also exist under external sensory stimulation conditions. To address this, we investigated BRO responses in healthy adults using 64-channel electroencephalography (EEG), while participants underwent passive external auditory and visual stimulation. Our results showed that BRO responses are present under both auditory and visual stimulation conditions (p ​< ​0.05), with similar temporal and spectral features compared to rest. However, visual stimulation did result in decreased BRO amplitude compared to auditory and resting conditions (p ​< ​0.05), suggesting decreased neuronal resources for processing blink-related information in the visual but not auditory environment. There were also additional pre-blink spectral changes in the visual condition compared to rest (p ​< ​0.05), which suggest that passive visual stimulation induces neural preparatory processes occurring in anticipation of the upcoming blink event. Together, these findings provide new and compelling evidence that blink-related neural processes are modulated not only by the internal cognitive loading due to simultaneous task demands, but also by competing external sensory requirements. This highlights the link between blinking and cognition, and further demonstrates the importance of BROs as a new window into brain function., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Blink-related oscillations derived from electroencephalography (EEG) have recently emerged as an important measure of awareness. Combined with portable EEG hardware with low-density electrode arrays, this neural marker may crucially augment the existing bedside assessments of consciousness in unresponsive patients. Nonetheless, the close relationship between signal characteristics of the neural response of interest and blink-induced oculomotor artifacts poses particular challenges when measuring blink-related oscillations using a point-of-care platform. This study presents a novel denoising approach based on time-frequency (TF) filtering that exploits the differential temporal and spectral features to isolate the neural response from ocular artifact in a low-density array., Methods: We investigated the effectiveness of the TF filtering technique using 64-channel EEG data collected in healthy adults, with focal analysis of the Pz and POz channels., Results: TF filtering showed comparable performance in denoising the signal relative to the established gold-standard independent component analysis approach, with strong similarities in morphological characteristics as measured by intraclass correlations (p < 0.001), extent of artifact rejection based on the ocular contamination index (p < 0.006), as well as time- and frequency-domain signal capture (p < 0.05). Results are robust at the individual and group levels, and are crucially validated using raw data from only four electrodes comprising Pz, POz, Fp2, and T7., Conclusion: These results demonstrate for the first time that TF filtering enables the successful capture and isolation of the blink-related oscillations response using a four-electrode array., Significance: This significantly advances the translation of the blink-related oscillations marker to a point-of-care platform for eventual bedside applications.

Despite past controversies, increasing evidence has led to acceptance that white matter activity is detectable using functional magnetic resonance imaging (fMRI). In spite of this, advanced analytic methods continue to be published that reinforce a historic bias against white matter activation by using it as a nuisance regressor. It is important that contemporary analyses overcome this blind spot in whole brain functional imaging, both to ensure that newly developed noise regression techniques are accurate, and to ensure that white matter, a vital and understudied part of the brain, is not ignored in functional neuroimaging studies., (Copyright © 2019 Grajauskas, Frizzell, Song and D’Arcy.)

Background: Despite growing evidence of a critical link between neuromodulation technologies and neuroplastic recovery, the underlying mechanisms of these technologies remain elusive., Objective: To investigate physiological evidence of central nervous system (CNS) changes in humans during translingual neurostimulation (TLNS)., Methods: We used high-density electroencephalography (EEG) to measure changes in resting brain activity before, during, and after high frequency (HF) and low frequency (LF) TLNS., Results: Wavelet power analysis around Cz and microstate analysis revealed significant changes after 20 min of stimulation compared to baseline. A secondary effect of exposure order was also identified, indicating a differential neuromodulatory influence of HF TLNS relative to LF TLNS on alpha and theta signal power., Conclusions: These results further our understanding of the effects of TLNS on underlying resting brain activity, which in the long-term may contribute to the critical link between clinical effect and changes in brain activity.

Autism Spectrum Disorder (ASD) is an increasingly common developmental disorder that affects 1 in 59 children. Despite this high prevalence of ASD, knowledge regarding the biological basis of its associated cognitive difficulties remains scant. In this study, we aimed to identify altered neurophysiological responses underlying inhibitory control and emotion processing difficulties in ASD, together with their associations with age and various domains of cognitive and social function. This was accomplished by assessing electroencephalographic recordings during an emotional go/nogo task alongside parent rating scales of behavior. Event related potential (ERP) N200 component amplitudes were reduced in children with ASD compared to typically developing (TD) children. No group differences were found, however, for task performance, P300 amplitude or latency, or N170 amplitude or latency, suggesting that individuals with ASD may only present conflict monitoring abnormalities, as reflected by the reduced N200 component, compared to TD individuals. Consistent with previous findings, increased age correlated with improved task performance scores and reduced N200 amplitude in the TD group, indicating that as these children develop, their neural systems become more efficient. These associations were not identified in the ASD group. Results also showed significant associations between increased N200 amplitudes and improved executive control abilities and decreased autism traits in TD children only. The newly discovered findings of decreased brain activation in children with ASD, alongside differences in correlations with age compared to TD children, provide a potential neurophysiological indicator of atypical development of inhibitory control mechanisms in these individuals.

Blink-related oscillations (BROs) have been linked with environmental monitoring processes associated with blinking, with cortical activations in the bilateral precuneus. Although BROs have been described under resting and passive fixation conditions, little is known about their characteristics under cognitive loading. To address this, we investigated BRO effects during both mental arithmetic (MA) and passive fixation (PF) tasks using magnetoencephalography (n =20), while maintaining the same sensory environment in both tasks. Our results confirmed the presence of BRO effects in both MA and PF tasks, with similar characteristics including blink-related increase in global field power and blink-related activation of the bilateral precuneus. In addition, cognitive loading due to MA also modulated BRO effects by decreasing BRO-induced cortical activations in key brain regions including the bilateral anterior precuneus. Interestingly, blinking during MA-but not PF-activated regions of the ventral attention network (i.e., right supramarginal gyrus and inferior frontal gyrus), suggesting possible recruitment of these areas for blink processing under cognitive loading conditions. Time-frequency analysis revealed a consistent pattern of BRO-related effects in the precuneus in both tasks, but with task-related functional segregation within the anterior and posterior subregions. Based on these findings, we postulate a potential neurocognitive mechanism for blink processing in the precuneus. This study is the first investigation of BRO effects under cognitive loading, and our results provide compelling new evidence for the important cognitive implications of blink-related processing in the human brain., (© 2018 Wiley Periodicals, Inc.)

There is a growing demand for objective evaluations of concussion. We developed a portable evoked potential framework to extract 'brain vital signs' using electroencephalography. Brain vital signs were derived from well established evoked responses representing auditory sensation (N100), basic attention (P300), and cognitive processing (N400) amplitudes and latencies, converted to normative metrics (six total). The study evaluated whether concussion-related neurophysiological impairments were detected over the duration of ice hockey seasons using brain vital signs. Forty-seven Tier III, Junior A, male ice hockey players were monitored over two seasons. Twelve sustained concussions after baseline testing then completed post-injury and return-to-play assessments. Twenty-three were not diagnosed with a concussion during the season and completed both baseline and post-season testing. Scores were evaluated using a repeated-measures analysis of variance with post hoc two-tailed paired t-tests. Concussion resulted in significantly increased amplitude and delayed latency scores for all six brain vital signs (P < 0.0001). Importantly, significant changes at return-to-play were also detected in basic attention (P300) amplitude, indicating persistent subclinical impairment. In the non-concussed group, there was also a significant change between baseline and post-season (P = 0.0047), with specific decreases in cognitive processing (N400) speed (P = 0.011) and overall total score (P = 0.002).

Objective: The ability to orient with respect to the current context (e.g. current time or location) is crucial for daily functioning, and is used to measure overall cognitive health across many frontline clinical assessments. However, these tests are often hampered by their reliance on verbal probes (e.g. 'What city are we in?') in evaluating orientation. Objective, physiology-based measures of orientation processing are needed, but no such measures are currently in existence. We report the initial development of potential brainwave-based markers of orientation processing as characterized using electroencephlography (EEG) and magnetoencephalography (MEG)., Approach: An auditory stimulus sequence embedded with words corresponding to orientation-relevant (i.e. related to the 'here and now') and orientation-irrelevant (i.e. unrelated to the current context) conditions was used to elicit orientation processing responses. EEG/MEG data, in concert with clinical assessments, were collected from 29 healthy adults. Analysis at sensor and source levels identified and characterized neural signals related to orientation processing., Main Results: Orientation-irrelevant stimuli elicited increased negative amplitude in EEG-derived event-related potential (ERP) waveforms during the 390-570 ms window (p  <  0.05), with cortical activations across the left frontal, temporal, and parietal regions. These effects are consistent with the well-known N400 response to semantic incongruence. In contrast, ERP responses to orientation-relevant stimuli exhibited increased positive amplitude during the same interval (p  <  0.05), with activations across the bilateral temporal and parietal regions. Importantly, these differential responses were robust at the individual level, with machine-learning classification showing high accuracy (89%), sensitivity (0.88) and specificity (0.90)., Significance: This is the first demonstration of a neurotechnology platform that elicits, captures, and evaluates electrophysiological markers of orientation processing. We demonstrate neural responses to orientation stimuli that are validated across EEG and MEG modalities and robust at the individual level. The extraction of physiology-based markers through this technique may enable improved objective brain functional evaluation in clinical applications.

The critical need for rapid objective, physiological evaluation of brain function at point-of-care has led to the emergence of brain vital signs-a framework encompassing a portable electroencephalography (EEG) and an automated, quick test protocol. This framework enables access to well-established event-related potential (ERP) markers, which are specific to sensory, attention, and cognitive functions in both healthy and patient populations. However, all our applications to-date have used auditory stimulation, which have highlighted application challenges in persons with hearing impairments (e.g., aging, seniors, dementia). Consequently, it has become important to translate brain vital signs into a visual sensory modality. Therefore, the objectives of this study were to: 1) demonstrate the feasibility of visual brain vital signs; and 2) compare and normalize results from visual and auditory brain vital signs. Data were collected from 34 healthy adults (33 ± 13 years) using a 64-channel EEG system. Visual and auditory sequences were kept as comparable as possible to elicit the N100, P300, and N400 responses. Visual brain vital signs were elicited successfully for all three responses across the group (N100: F = 29.8380, p < 0.001; P300: F = 138.8442, p < 0.0001; N400: F = 6.8476, p = 0.01). Initial auditory-visual comparisons across the three components showed attention processing (P300) was found to be the most transferrable across modalities, with no group-level differences and correlated peak amplitudes (rho = 0.7, p = 0.0001) across individuals. Auditory P300 latencies were shorter than visual ( p < 0.0001) but normalization and correlation ( r = 0.5, p = 0.0033) implied a potential systematic difference across modalities. Reduced auditory N400 amplitudes compared to visual ( p = 0.0061) paired with normalization and correlation across individuals ( r = 0.6, p = 0.0012), also revealed potential systematic modality differences between reading and listening language comprehension. This study provides an initial understanding of the relationship between the visual and auditory sequences, while importantly establishing a visual sequence within the brain vital signs framework. With both auditory and visual stimulation capabilities available, it is possible to broaden applications across the lifespan.

Advances in MRI technology have significantly contributed to our ability to understand the process of brain ageing, allowing us to track and assess changes that occur during normal ageing and neurological conditions. This paper focuses on reviewing structural changes of the ageing brain that are commonly seen using MRI, summarizing the pathophysiology, prevalence, and neuroanatomical distribution of changes including atrophy, lacunes, white matter lesions, and dilated perivascular spaces. We also review the clinically accessible methodology for assessing these MRI-based changes, covering visual rating scales, as well computer-aided and fully automated methods. Subsequently, we consider novel assessment methods designed to evaluate changes across the whole brain, and finally discuss new directions in this field of research., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Survivors of severe brain injury may remain in a decreased state of conscious awareness for an extended period of time. Clinical scales are used to describe levels of consciousness but rely on behavioural responses, precipitating misdiagnosis. We have previously utilized event-related potentials (ERPs) to circumvent reliance on behavioural responses. However, practical implementation barriers limit the clinical utility of ERP assessment at point-of-care (POC). To address this challenge, we developed the Halifax Consciousness Scanner (HCS)-a rapid, semi-automated electroencephalography system. The current study evaluated: (i) HCS feasibility in sub-acute, POC settings nationwide; (ii) ERP P300 responses in patients with acquired brain injury versus healthy controls; and (iii) correlations within and between clinical measures and P300 latencies. We assessed 28 patients with severe, chronic impairments from brain injuries and contrasted the results with healthy control data ( n  = 100). Correlational analyses examined relationships between P300 latencies and the commonly used clinical scales. P300 latencies were significantly delayed in patients compared to healthy controls ( P  < 0.05). Clinical assessment scores were significantly inter-correlated and correlated significantly with P300 latencies ( P  < 0.05). In sub-acute and chronic care settings, the HCS provided a physiological measure of neurocognitive processing at POC for patients with severe acquired brain injury, including those with disorders of consciousness.

Cognitive decline with aging and dementia is especially poignant with regard to the executive functioning that is necessary for activities of daily independent living. The relationship between age-related neurodegeneration in the prefrontal cortex and executive functioning has been uniquely investigated using task-phase functional magnetic resonance imaging (fMRI) to detect brain activity in response to stimuli; however, a comprehensive list of task designs that have been implemented to task-phase fMRI is absent in the literature. The purpose of this review was to recognize what methods have been used to study executive functions with aging and dementia in fMRI tasks, and to describe and categorize them. The following cognitive subdomains were emphasized: cognitive flexibility, planning and decision-making, working memory, cognitive control/inhibition, semantic processing, attention and concentration, emotional functioning, and multitasking. Over 30 different task-phase fMRI designs were found to have been implemented in the literature, all adopted from standard neuropsychological assessments. Cognitive set-shifting and decision-making tasks were particularly well studied in regard to age-related neurodegeneration, while emotional functioning and multitasking designs were found to be the least utilized. Summarizing the information on which tasks have shown the greatest usability will assist in the future design and implementation of effective fMRI experiments targeting executive functioning., Competing Interests: The authors have no conflict of interests to declare., (© 2018 The Authors. Aging Medicine published by Beijing Hospital and John Wiley & Sons Australia, Ltd.)

Background: For nearly four decades, the N400 has been an important brainwave marker of semantic processing. It can be recorded non-invasively from the scalp using electrical and/or magnetic sensors, but largely within the restricted domain of research laboratories specialized to run specific N400 experiments. However, there is increasing evidence of significant clinical utility for the N400 in neurological evaluation, particularly at the individual level. To enable clinical applications, we recently reported a rapid evaluation framework known as "brain vital signs" that successfully incorporated the N400 response as one of the core components for cognitive function evaluation. The current study characterized the rapidly evoked N400 response to demonstrate that it shares consistent features with traditional N400 responses acquired in research laboratory settings-thereby enabling its translation into brain vital signs applications., Methods: Data were collected from 17 healthy individuals using magnetoencephalography (MEG) and electroencephalography (EEG), with analysis of sensor-level effects as well as evaluation of brain sources. Individual-level N400 responses were classified using machine learning to determine the percentage of participants in whom the response was successfully detected., Results: The N400 response was observed in both M/EEG modalities showing significant differences to incongruent versus congruent condition in the expected time range (p < 0.05). Also as expected, N400-related brain activity was observed in the temporal and inferior frontal cortical regions, with typical left-hemispheric asymmetry. Classification robustly confirmed the N400 effect at the individual level with high accuracy (89%), sensitivity (0.88) and specificity (0.90)., Conclusion: The brain vital sign N400 characteristics were highly consistent with features of the previously reported N400 responses acquired using traditional laboratory-based experiments. These results provide important evidence supporting clinical translation of the rapidly acquired N400 response as a potential tool for assessments of higher cognitive functions.

There have been many attempts to assess the elements of age- and dementia- related neurodegenerative changes in the brain using MRI; however, traditionally assessments focus only on single deficit. Over the past few years, our group has worked to create and validate the Brain Atrophy and Lesion Index (BALI) as an MRI-based whole-brain structural degeneration rating scale. The BALI can be used for applications in aging and dementia across the entire brain and can be applied to common clinical MR images. As a whole-brain structural health assessment, the BALI gives a more representative picture of how the brain ages. During the aging process, multiple elements of degeneration accumulate and interact to overwhelm repair processes and cause high-level failure in the function of the brain. To reflect this process, the BALI combines the assessment of several neurodegeneration changes into one scale. The BALI evaluation can be performed quickly and has been validated for use by non-neuroradiology expert raters trained with the method. This review gives a brief overview of the content of the BALI; covers the development, refinement, and application of the method; and provides insights about future development and clinical implementation of MRI-based whole-brain health assessment in aging and dementia., Competing Interests: The authors declare that no conflicts of interest exist with this work., (© 2018 The Authors. Aging Medicine published by Beijing Hospital and John Wiley & Sons Australia, Ltd.)

Introduction: Haemorrhagic stroke is of significant healthcare concern due to its association with high mortality and lasting impact on the survivors' quality of life. Treatment decisions and clinical outcomes depend strongly on the size, spread and location of the haematoma. Non-contrast CT (NCCT) is the primary neuroimaging modality for haematoma assessment in haemorrhagic stroke diagnosis. Current procedures do not allow convenient NCCT-based haemorrhage volume calculation in clinical settings, while research-based approaches are yet to be tested for clinical utility; there is a demonstrated need for developing effective solutions. The project under review investigates the development of an automatic NCCT-based haematoma computation tool in support of accurate quantification of haematoma volumes., Methods and Analysis: Several existing research methods for haematoma volume estimation are studied. Selected methods are tested using NCCT images of patients diagnosed with acute haemorrhagic stroke. For inter-rater and intrarater reliability evaluation, different raters will analyse haemorrhage volumes independently. The efficiency with respect to time of haematoma volume assessments will be examined to compare with the results from routine clinical evaluations and planimetry assessment that are known to be more accurate. The project will target the development of an enhanced solution by adapting existing methods and integrating machine learning algorithms. NCCT-based information of brain haemorrhage (eg, size, volume, location) and other relevant information (eg, age, sex, risk factor, comorbidities) will be used in relation to clinical outcomes with future project development. Validity and reliability of the solution will be examined for potential clinical utility., Ethics and Dissemination: The project including procedures for deidentification of NCCT data has been ethically approved. The study involves secondary use of existing data and does not require new consent of participation. The team consists of clinical neuroimaging scientists, computing scientists and clinical professionals in neurology and neuroradiology and includes patient representatives. Research outputs will be disseminated following knowledge translation plans towards improving stroke patient care. Significant findings will be published in scientific journals. Anticipated deliverables include computer solutions for improved clinical assessment of haematoma using NCCT., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Detection of functional magnetic resonance imaging (fMRI) activation in white matter has been increasingly reported despite historically being controversial. Much of the development work to-date has used high-field 4 T MRI and specialized pulse sequences. In the current study, we utilized conventional 3 T MRI and a commonly applied gradient-echo-planar imaging sequence to evaluate white matter (WM) fMRI sensitivity within a common framework. Functional WM activity was replicated in target regions of interest within the corpus callosum, at the group and individual levels. As expected there was a reduction in overall WM activation sensitivity. Individual analyses revealed that 8 of the 13 individuals showed white matter activation, showing a lower percentage of individuals with WM activation detected. Importantly, WM activation results were sensitive to analyses that applied alternate hemodynamic response functions, with an increase in the group level cluster when hemodynamic response function (HRF) onset slope was reduced. The findings supported the growing evidence that WM activation is detectable, with activation levels are closer to thresholds used for routine 3T MRI studies. Optimization factors, such as the HRF model, appear to be important to further enhance the characterization of WM activity in fMRI., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Spontaneous blinking occurs 15-20 times per minute. Although blinking has often been associated with its physiological role of corneal lubrication, there is now increasing behavioral evidence suggesting that blinks are also modulated by cognitive processes such as attention and information processing. Recent low-density electroencephalography (EEG) studies have reported so-called blink-related oscillations (BROs) associated with spontaneous blinking at rest. Delta-band (0.5-4 Hz) BROs are thought to originate from the precuneus region involved in environmental monitoring and awareness, with potential clinical utility in evaluation of disorders of consciousness. However, the neural mechanisms of BROs have not been elucidated. Using magnetoencephalography (MEG), we characterized delta-band BROs in 36 healthy individuals while controlling for background brain activity. Results showed that, compared to pre-blink baseline, delta-band BROs resulted in increased global field power ( p < 0.001) and time-frequency spectral power ( p < 0.05) at the sensor level, peaking at ~250 ms post-blink maximum. Source localization showed that spontaneous blinks activated the bilateral precuneus ( p < 0.05 FWE), and source activity within the precuneus was also consistent with sensor-space results. Crucially, these effects were only observed in the blink condition and were absent in the control condition, demonstrating that results were due to spontaneous blinks rather than as part of the inherent brain activity. The current study represents the first MEG examination of BROs. Our findings suggest that spontaneous blinks activate the precuneus regions consistent with environmental monitoring and awareness, and provide important neuroimaging support for the cognitive role of spontaneous blinks.