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Introduction: Post-acute COVID syndrome (PACS) is a growing concern, given its impact on mental health and quality of life. However, its effects on cerebral white matter remain poorly understood, particularly in non-hospitalized cohorts. The goals of this cross-sectional, observational study were to examine (1) whether PACS was associated with distinct alterations in white matter microstructure, compared to symptom-matched non-COVID viral infection; and (2) whether microstructural alterations correlated with indices of post-COVID emotional health., Methods: Data were collected for 54 symptomatic individuals who tested positive for COVID-19 (mean age 41 ± 12 yrs., 36 female) and 14 controls who tested negative for COVID-19 (mean age 41 ± 14 yrs., 8 female), with both groups assessed an average of 4-5 months after COVID testing. Diffusion magnetic resonance imaging data were collected, and emotional health was assessed via the NIH emotion toolbox, with summary scores indexing social satisfaction, well-being and negative affect., Results: Despite similar symptoms, the COVID-19 group had reduced mean and axial diffusivity, along with increased mean kurtosis and neurite dispersion, in deep white matter. After adjusting for social satisfaction, higher levels of negative affect in the COVID-19 group were also correlated with increased mean kurtosis and reduced free water in white matter., Discussion: These results provide preliminary evidence that indices of white matter microstructure distinguish PACS from symptomatic non-COVID infection. Moreover, white matter effects seen in PACS correlate with the severity of emotional sequelae, providing novel insights into this highly prevalent disorder., 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 Churchill, Roudaia, Chen, Sekuler, Gao, Masellis, Lam, Cheng, Heyn, Black, MacIntosh, Graham and Schweizer.)

Post-acute COVID syndrome (PACS) is a global health concern and is often associated with debilitating symptoms. Post-COVID fatigue is a particularly frequent and troubling issue, and its underlying mechanisms remain incompletely understood. One potential contributor is micropathological injury of subcortical and brainstem structures, as has been identified in other patient populations. Texture-based analysis (TA) may be used to measure such changes in anatomical MRI data. The present study develops a methodology of voxel-wise TA mapping in subcortical and brainstem regions, which is then applied to T1-weighted MRI data from a cohort of 48 individuals who had PACS (32 with and 16 without ongoing fatigue symptoms) and 15 controls who had cold and flu-like symptoms but tested negative for COVID-19. Both groups were assessed an average of 4-5 months post-infection. There were no significant differences between PACS and control groups, but significant differences were observed within the PACS groups, between those with and without fatigue symptoms. This included reduced texture energy and increased entropy, along with reduced texture correlation, cluster shade and profile in the putamen, pallidum, thalamus and brainstem. These findings provide new insights into the neurophysiological mechanisms that underlie PACS, with altered tissue texture as a potential biomarker of this debilitating condition., Competing Interests: Declaration of Competing Interest The authors report no disclosures relevant to the manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: To investigate whether a history of traumatic brain injury (TBI) is associated with greater long-term grey-matter loss in patients with mild cognitive impairment (MCI)., Methods: 85 patients with MCI were identified, including 26 with a previous history of traumatic brain injury (MCI[TBI-]) and 59 without (MCI[TBI+]). Cortical thickness was evaluated by segmenting T1-weighted MRI scans acquired longitudinally over a 2-year period. Bayesian multilevel modelling was used to evaluate group differences in baseline cortical thickness and longitudinal change, as well as group differences in neuropsychological measures of executive function., Results: At baseline, the MCI[TBI+] group had less grey matter within right entorhinal, left medial orbitofrontal and inferior temporal cortex areas bilaterally. Longitudinally, the MCI[TBI+] group also exhibited greater longitudinal declines in left rostral middle frontal, the left caudal middle frontal and left lateral orbitofrontal areas sover the span of 2 years (median = 1-2%, 90%HDI [-0.01%: -0.001%], probability of direction (PD) = 90-99%). The MCI[TBI+] group also displayed greater longitudinal declines in Trail-Making-Test (TMT)-derived ratio (median: 0.737%, 90%HDI: [0.229%: 1.31%], PD = 98.8%) and differences scores (median: 20.6%, 90%HDI: [-5.17%: 43.2%], PD = 91.7%)., Conclusions: Our findings support the notion that patients with MCI and a history of TBI are at risk of accelerated neurodegeneration, displaying greatest evidence for cortical atrophy within the left middle frontal and lateral orbitofrontal frontal cortex. Importantly, these results suggest that long-term TBI-mediated atrophy is more pronounced in areas vulnerable to TBI-related mechanical injury, highlighting their potential relevance for diagnostic forms of intervention in TBI., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Optical tracking of head pose via fiducial markers has been proven to enable effective correction of motion artifacts in the brain during magnetic resonance imaging but remains difficult to implement in the clinic due to lengthy calibration and set up times. Advances in deep learning for markerless head pose estimation have yet to be applied to this problem because of the sub-millimetre spatial resolution required for motion correction. In the present work, two optical tracking systems are described for the development and training of a neural network: one marker-based system (a testing platform for measuring ground truth head pose) with high tracking fidelity to act as the training labels, and one markerless deep-learning-based system using images of the markerless head as input to the network. The markerless system has the potential to overcome issues of marker occlusion, insufficient rigid attachment of the marker, lengthy calibration times, and unequal performance across degrees of freedom (DOF), all of which hamper the adoption of marker-based solutions in the clinic. Detail is provided on the development of a custom moiré-enhanced fiducial marker for use as ground truth and on the calibration procedure for both optical tracking systems. Additionally, the development of a synthetic head pose dataset is described for the proof of concept and initial pre-training of a simple convolutional neural network. Results indicate that the ground truth system has been sufficiently calibrated and can track head pose with an error of <1 mm and <1°. Tracking data of a healthy, adult participant are shown. Pre-training results show that the average root-mean-squared error across the 6 DOF is 0.13 and 0.36 (mm or degrees) on a head model included and excluded from the training dataset, respectively. Overall, this work indicates excellent feasibility of the deep-learning-based approach and will enable future work in training and testing on a real dataset in the MRI environment.

This study aimed to investigate the clinical stratification of amyotrophic lateral sclerosis (ALS) patients in relation to in vivo cerebral degeneration. One hundred forty-nine ALS patients and one hundred forty-four healthy controls (HCs) were recruited from the Canadian ALS Neuroimaging Consortium (CALSNIC). Texture analysis was performed on T1-weighted scans to extract the texture feature "autocorrelation" (autoc), an imaging biomarker of cerebral degeneration. Patients were stratified at baseline into early and advanced disease stages based on criteria adapted from ALS clinical trials and the King's College staging system, as well as into slow and fast progressors (disease progression rates, DPR). Patients had increased autoc in the internal capsule. These changes extended beyond the internal capsule in early-stage patients (clinical trial-based criteria), fast progressors, and in advanced-stage patients (King's staging criteria). Longitudinal increases in autoc were observed in the postcentral gyrus, corticospinal tract, posterior cingulate cortex, and putamen; whereas decreases were observed in corpus callosum, caudate, central opercular cortex, and frontotemporal areas. Both longitudinal increases and decreases of autoc were observed in non-overlapping regions within insula and precentral gyrus. Within-criteria comparisons of autoc revealed more pronounced changes at baseline and longitudinally in early- (clinical trial-based criteria) and advanced-stage (King's staging criteria) patients and fast progressors. In summary, comparative patterns of baseline and longitudinal progression in cerebral degeneration are dependent on sub-group selection criteria, with clinical trial-based stratification insufficiently characterizing disease stage based on pathological cerebral burden., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Driving is the preferred mode of transportation for adults across the healthy age span. However, motor vehicle crashes are among the leading causes of injury and death, especially for older adults, and under distracted driving conditions. Understanding the neuroanatomical basis of driving may inform interventions that minimize crashes. This exploratory study examined the neuroanatomical correlates of undistracted and distracted simulated straight driving., Methods: One-hundred-and-thirty-eight participants (40.6% female) aged 17-85 years old (mean and SD = 58.1 ± 19.9 years) performed a simulated driving task involving straight driving and turns at intersections in a city environment using a steering wheel and foot pedals. During some straight driving segments, participants responded to auditory questions to simulate distracted driving. Anatomical T1-weighted MRI was used to quantify grey matter volume and cortical thickness for five brain regions: the middle frontal gyrus (MFG), precentral gyrus (PG), superior temporal cortex (STC), posterior parietal cortex (PPC), and cerebellum. Partial correlations controlling for age and sex were used to explore relationships between neuroanatomical measures and straight driving behavior, including speed, acceleration, lane position, heading angle, and time speeding or off-center. Effects of interest were noted at an unadjusted p -value threshold of 0.05., Results: Distracted driving was associated with changes in most measures of straight driving performance. Greater volume and cortical thickness in the PPC and cerebellum were associated with reduced variability in lane position and heading angle during distracted straight driving. Cortical thickness of the MFG, PG, PPC, and STC were associated with speed and acceleration, often in an age-dependent manner., Conclusion: Posterior regions were correlated with lane maintenance whereas anterior and posterior regions were correlated with speed and acceleration, especially during distracted driving. The regions involved and their role in straight driving may change with age, particularly during distracted driving as observed in older adults. Further studies should investigate the relationship between distracted driving and the aging brain to inform driving interventions., 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 Guan, Churchill, Fischer, Graham and Schweizer.)

Previous studies have shown that the left hemisphere dominates motor function, often observed through homotopic activation measurements. Using a functional connectivity approach, this study investigated the lateralization of the sensorimotor cortex during handwriting and drawing, two complex visuomotor tasks with varying contextual demands. We found that both left- and right-lateralized connectivity in the primary motor cortex (M1), dorsal premotor cortex (PMd), somatosensory cortex, and visual regions were evident in adults (males and females), primarily in an interhemispheric integrative fashion. Critically, these lateralization tendencies remained highly invariant across task contexts, representing a task-invariant neural architecture for encoding fundamental motor programs consistently implemented in different task contexts. Additionally, the PMd exhibited a slight variation in lateralization degree between task contexts, reflecting the ability of the high-order motor system to adapt to varying task demands. However, connectivity-based lateralization of the sensorimotor cortex was not detected in 10-year-old children (males and females), suggesting that the maturation of connectivity-based lateralization requires prolonged development. In summary, this study demonstrates both task-invariant and task-sensitive connectivity lateralization in sensorimotor cortices that support the resilience and adaptability of skilled visuomotor performance. These findings align with the hierarchical organization of the motor system and underscore the significance of the functional connectivity-based approach in studying functional lateralization., (Copyright © 2024 the authors.)

Background: There has been little direct examination of how traumatic brain injury (TBI) affects the rate of neurodegeneration for individuals with Alzheimer's disease (AD)., Methods: The study examined 89 cognitively normal adults (65 with and 24 without prior TBI) and 65 with AD (16 with and 49 without prior TBI). Cortical thickness was quantified from T1-weighted MRI scans at baseline and follow-up (mean interval 33.4 months). Partial least squares analysis was used to evaluate the effects of AD and TBI history on the longitudinal change in cortical thickness., Results: Significant group effects were identified throughout the frontal and temporal cortices. Comparison of the AD groups to their control cohorts showed greater relative atrophy for the AD cohort with prior TBI., Conclusion: These results indicate that a history of TBI exacerbates longitudinal declines in cortical thickness among AD patients, providing new insights into the shared pathomechanisms between these neurological conditions., Competing Interests: On behalf of all authors, the corresponding author states that there is no conflict of interest.

Objective: The corticospinal tract (CST) reveals progressive microstructural alterations in ALS measurable by DTI. The aim of this study was to evaluate fractional anisotropy (FA) along the CST as a longitudinal marker of disease progression in ALS., Methods: The study cohort consisted of 114 patients with ALS and 110 healthy controls from the second prospective, longitudinal, multicentre study of the Canadian ALS Neuroimaging Consortium (CALSNIC-2). DTI and clinical data from a harmonized protocol across 7 centres were collected. Thirty-nine ALS patients and 61 controls completed baseline and two follow-up visits and were included for longitudinal analyses. Whole brain-based spatial statistics and hypothesis-guided tract-of-interest analyses were performed for cross-sectional and longitudinal analyses., Results: FA was reduced at baseline and longitudinally in the CST, mid-corpus callosum (CC), frontal lobe, and other ALS-related tracts, with alterations most evident in the CST and mid-CC. CST and pontine FA correlated with functional impairment (ALSFRS-R), upper motor neuron function, and clinical disease progression rate. Reduction in FA was largely located in the upper CST; however, the longitudinal decline was greatest in the lower CST. Effect sizes were dependent on region, resulting in study group sizes between 17 and 31 per group over a 9-month interval. Cross-sectional effect sizes were maximal in the upper CST; whereas, longitudinal effect sizes were maximal in mid-callosal tracts., Conclusions: Progressive microstructural alterations in ALS are most prominent in the CST and CC. DTI can provide a biomarker of cerebral degeneration in ALS, with longitudinal changes in white matter demonstrable over a reasonable observation period, with a feasible number of participants, and within a multicentre framework., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Traumatic brain injury (TBI) is associated with an accelerated course of dementia, although biological relationships are incompletely understood., Methods: The study examined 1124 participants, including 343 with Alzheimer disease (AD), 127 with AD with TBI, 266 cognitively normal adults with TBI, and 388 cognitively normal adults without TBI. Cortical thickness was quantified from T1-weighted magnetic resonance imaging data. Multiple linear regression was used to determine the interaction between AD and TBI on cortical thickness., Results: Among those with AD, TBI was associated with an earlier age of AD onset but, counterintuitively, less cortical thinning in frontotemporal regions relative to non-AD controls., Discussion: AD with TBI represents a distinct group from AD, likely with distinct pathologic contributions beyond gray matter loss. This finding has important implications for the diagnosis and treatment of AD in the presence of TBI and indicates that models of AD, aging, and neural loss should account for TBI history., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Post-acute coronavirus disease 2019 (COVID-19) syndrome (PACS) is a growing concern, with headache being a particularly debilitating symptom with high prevalence. The long-term effects of COVID-19 and post-COVID headache on brain function remain poorly understood, particularly among non-hospitalized individuals. This study focused on the power-law scaling behavior of functional brain dynamics, indexed by the Hurst exponent (H). This measure is suppressed during physiological and psychological distress and was thus hypothesized to be reduced in individuals with post-COVID syndrome, with greatest reductions among those with persistent headache., Methods: Resting-state blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging data were collected for 57 individuals who had COVID-19 (32 with no headache, 14 with ongoing headache, 11 recovered) and 17 controls who had cold and flu-like symptoms but  tested negative for COVID-19. Individuals were assessed an average of 4-5 months after COVID testing, in a cross-sectional, observational study design., Results: No significant differences in H values were found between non-headache COVID-19 and control groups., while those with ongoing headache had significantly reduced H values, and those who had recovered from headache had elevated H values, relative to non-headache groups. Effects were greatest in temporal, sensorimotor, and insular brain regions. Reduced H in these regions was also associated with decreased BOLD activity and local functional connectivity., Conclusions: These findings provide new insights into the neurophysiological mechanisms that underlie persistent post-COVID headache, with reduced BOLD scaling as a potential biomarker that is specific to this debilitating condition., (© 2023 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Background: Parallel radiofrequency transmission (pTx) remains a promising technology for addressing high-field magnetic resonance imaging (MRI) challenges, particularly regarding the safety of patients with implanted deep brain stimulation (DBS) devices. Radiofrequency (RF) shim optimization methods utilizing pTx technology have shown the potential to minimize induced RF heating effects at the electrode tips of DBS devices at 3 T., Purpose: Research pTx system implementations often involve the combination of custom and commercial hardware that are integrated onto an existing MRI system. As a result, system characterization is important to ensure implant-friendly safe imaging conditions are satisfied for the operating range of the hardware., Methods: Utilizing electromagnetic and thermal simulations, the impact of system uncertainty is studied for the proposed 4- and 8-channel pTx system setup and its associated "safe mode" for DBS applications., Results: Electromagnetic simulations indicated that instrumentation errors can affect the overall electric field strength experienced at the DBS lead tip, and a worst-case system uncertainty analysis predicted temperature elevations of +1.5°C in the 4-channel setup and +0.9°C in the 8-channel setup., Conclusions: In conclusion, system uncertainty can impact the precision of pTx RF inputs which in the worst-case, may lead to an unsafe imaging scenario and the proposed 8-channel setup may provide more robustness and thus, safer conditions for MRI of DBS patients., (© 2023 American Association of Physicists in Medicine.)

Amyotrophic Lateral Sclerosis (ALS) is a complex neurodegenerative disorder characterized by motor neuron degeneration. Significant research has begun to establish brain magnetic resonance imaging (MRI) as a potential biomarker to diagnose and monitor the state of the disease. Deep learning has emerged as a prominent class of machine learning algorithms in computer vision and has shown successful applications in various medical image analysis tasks. However, deep learning methods applied to neuroimaging have not achieved superior performance in classifying ALS patients from healthy controls due to insignificant structural changes correlated with pathological features. Thus, a critical challenge in deep models is to identify discriminative features from limited training data. To address this challenge, this study introduces a framework called SF 2 Former, which leverages the power of the vision transformer architecture to distinguish ALS subjects from the control group by exploiting the long-range relationships among image features. Additionally, spatial and frequency domain information is combined to enhance the network's performance, as MRI scans are initially captured in the frequency domain and then converted to the spatial domain. The proposed framework is trained using a series of consecutive coronal slices and utilizes pre-trained weights from ImageNet through transfer learning. Finally, a majority voting scheme is employed on the coronal slices of each subject to generate the final classification decision. The proposed architecture is extensively evaluated with multi-modal neuroimaging data (i.e., T1-weighted, R2*, FLAIR) using two well-organized versions of the Canadian ALS Neuroimaging Consortium (CALSNIC) multi-center datasets. The experimental results demonstrate the superiority of the proposed strategy in terms of classification accuracy compared to several popular deep learning-based techniques., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Clinical neuroimaging studies often investigate group differences between patients and controls, yet multivariate imaging features may enable individual-level classification. This study aims to classify youth with bipolar disorder (BD) versus healthy youth using grey matter cerebral blood flow (CBF) data analyzed with logistic regressions., Methods: Using a 3 Tesla magnetic resonance imaging (MRI) system, we collected pseudo-continuous, arterial spin-labelling, resting-state functional MRI (rfMRI) and T 1 -weighted images from youth with BD and healthy controls. We used 3 logistic regression models to classify youth with BD versus controls, controlling for age and sex, using mean grey matter CBF as a single explanatory variable, quantitative CBF features based on principal component analysis (PCA) or relative (intensity-normalized) CBF features based on PCA. We also carried out a comparison analysis using rfMRI data., Results: The study included 46 patients with BD (mean age 17 yr, standard deviation [SD] 1 yr; 25 females) and 49 healthy controls (mean age 16 yr, SD 2 yr; 24 females). Global mean CBF and multivariate quantitative CBF offered similar classification performance that was above chance. The association between CBF images and the feature map was not significantly different between groups ( p = 0.13); however, the multivariate classifier identified regions with lower CBF among patients with BD (Δ CBF = -2.94 mL/100 g/min; permutation test p = 0047). Classification performance decreased when considering rfMRI data., Limitations: We cannot comment on which CBF principal component is most relevant to the classification. Participants may have had various mood states, comorbidities, demographics and medication records., Conclusion: Brain CBF features can classify youth with BD versus healthy controls with above-chance accuracy using logistic regression. A global CBF feature may offer similar classification performance to distinct multivariate CBF features., Competing Interests: Competing interests: Bradley MacIntosh reports funding from the Brain and Behavior Research Foundation. Benjamin Goldstein is chair of the Pediatric Task Force and Vascular Task Force with the International Society for Bipolar Disorders. He holds the RBC Investments Chair in children’s mental health and developmental psychopathology. No other competing interests were declared., (© 2023 CMA Impact Inc. or its licensors.)

Background: Neurological symptoms associated with coronavirus disease 2019 (COVID-19), such as fatigue and smell/taste changes, persist beyond infection. However, little is known of brain physiology in the post-COVID-19 timeframe., Purpose: To determine whether adults who experienced flu-like symptoms due to COVID-19 would exhibit cerebral blood flow (CBF) alterations in the weeks/months beyond infection, relative to controls who experienced flu-like symptoms but tested negative for COVID-19., Study Type: Prospective observational., Population: A total of 39 adults who previously self-isolated at home due to COVID-19 (41.9 ± 12.6 years of age, 59% female, 116.5 ± 62.2 days since positive diagnosis) and 11 controls who experienced flu-like symptoms but had a negative COVID-19 diagnosis (41.5 ± 13.4 years of age, 55% female, 112.1 ± 59.5 since negative diagnosis)., Field Strength and Sequences: A 3.0 T; T1-weighted magnetization-prepared rapid gradient and echo-planar turbo gradient-spin echo arterial spin labeling sequences., Assessment: Arterial spin labeling was used to estimate CBF. A self-reported questionnaire assessed symptoms, including ongoing fatigue. CBF was compared between COVID-19 and control groups and between those with (n = 11) and without self-reported ongoing fatigue (n = 28) within the COVID-19 group., Statistical Tests: Between-group and within-group comparisons of CBF were performed in a voxel-wise manner, controlling for age and sex, at a family-wise error rate of 0.05., Results: Relative to controls, the COVID-19 group exhibited significantly decreased CBF in subcortical regions including the thalamus, orbitofrontal cortex, and basal ganglia (maximum cluster size = 6012 voxels and maximum t-statistic = 5.21). Within the COVID-19 group, significant CBF differences in occipital and parietal regions were observed between those with and without self-reported on-going fatigue., Data Conclusion: These cross-sectional data revealed regional CBF decreases in the COVID-19 group, suggesting the relevance of brain physiology in the post-COVID-19 timeframe. This research may help elucidate the heterogeneous symptoms of the post-COVID-19 condition., Evidence Level: 2., Technical Efficacy: Stage 3., (© 2022 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

There has been growing attention on the effect of COVID-19 on white-matter microstructure, especially among those that self-isolated after being infected. There is also immense scientific interest and potential clinical utility to evaluate the sensitivity of single-shell diffusion magnetic resonance imaging (MRI) methods for detecting such effects. In this work, the performances of three single-shell-compatible diffusion MRI modeling methods are compared for detecting the effect of COVID-19, including diffusion-tensor imaging, diffusion-tensor decomposition of orthogonal moments and correlated diffusion imaging. Imaging was performed on self-isolated patients at the study initiation and 3-month follow-up, along with age- and sex-matched controls. We demonstrate through simulations and experimental data that correlated diffusion imaging is associated with far greater sensitivity, being the only one of the three single-shell methods to demonstrate COVID-19-related brain effects. Results suggest less restricted diffusion in the frontal lobe in COVID-19 patients, but also more restricted diffusion in the cerebellar white matter, in agreement with several existing studies highlighting the vulnerability of the cerebellum to COVID-19 infection. These results, taken together with the simulation results, suggest that a significant proportion of COVID-19 related white-matter microstructural pathology manifests as a change in tissue diffusivity. Interestingly, different b-values also confer different sensitivities to the effects. No significant difference was observed in patients at the 3-month follow-up, likely due to the limited size of the follow-up cohort. To summarize, correlated diffusion imaging is shown to be a viable single-shell diffusion analysis approach that allows us to uncover opposing patterns of diffusion changes in the frontal and cerebellar regions of COVID-19 patients, suggesting the two regions react differently to viral infection., (© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

The mechanisms for regulating cerebral blood flow (CBF) are highly sensitive to traumatic brain injury (TBI). The perfusion imaging technique may be used to assess CBF and identify perfusion abnormalities following a TBI. Studies have identified CBF disturbances across the injury severity spectrum and correlations with both acute and long-term indices of clinical outcome. Although not yet widely used in the clinical context, this is an important area of ongoing research., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Intraoperative adverse events lead to patient injury and death, and are increasing. Early warning systems (EWSs) have been used to detect patient deterioration and save lives. However, few studies have used EWSs to monitor surgical performance and caution about imminent technical errors. Previous (non-surgical) research has investigated neural activity to predict future motor errors using electroencephalography (EEG). The present proof-of-concept cohort study investigates whether EEG could predict technical errors in surgery., Methods: In a large academic hospital, three surgical fellows performed 12 elective laparoscopic general surgeries. Audiovisual data of the operating room and the surgeon's neural activity were recorded. Technical errors and epochs of good surgical performance were coded into events. Neural activity was observed 40 s prior and 10 s after errors and good events to determine how far in advance errors were detected. A hierarchical regression model was used to account for possible clustering within surgeons. This prospective, proof-of-concept, cohort study was conducted from July to November 2021, with a pilot period from February to March 2020 used to optimize the technique of data capture and included participants who were blinded from study hypotheses., Results: Forty-five technical errors, mainly due to too little force or distance (n = 39), and 27 good surgical events were coded during grasping and dissection. Neural activity representing error monitoring (p = .008) and motor uncertainty (p = .034) was detected 17 s prior to errors, but not prior to good surgical performance., Conclusions: These results show that distinct neural signatures are predictive of technical error in laparoscopic surgery. If replicated with low false-alarm rates, an EEG-based EWS of technical errors could be used to improve individualized surgical training by flagging imminent unsafe actions-before errors occur and cause patient harm., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: The long-term impact of COVID-19 on brain function remains poorly understood, despite growing concern surrounding post-acute COVID-19 syndrome (PACS). The goal of this cross-sectional, observational study was to determine whether there are significant alterations in resting brain function among non-hospitalized individuals with PACS, compared to symptomatic individuals with non-COVID infection., Methods: Data were collected for 51 individuals who tested positive for COVID-19 (mean age 41±12 yrs., 34 female) and 15 controls who had cold and flu-like symptoms but tested negative for COVID-19 (mean age 41±14 yrs., 9 female), with both groups assessed an average of 4-5 months after COVID testing. None of the participants had prior neurologic, psychiatric, or cardiovascular illness. Resting brain function was assessed via functional magnetic resonance imaging (fMRI), and self-reported symptoms were recorded., Results: Individuals with COVID-19 had lower temporal and subcortical functional connectivity relative to controls. A greater number of ongoing post-COVID symptoms was also associated with altered functional connectivity between temporal, parietal, occipital and subcortical regions., Discussion: These results provide preliminary evidence that patterns of functional connectivity distinguish PACS from non-COVID infection and correlate with the severity of clinical outcome, providing novel insights into this highly prevalent disorder., Competing Interests: SB reports payments for contract research to her institution from GE Healthcare, Eli Lilly and Company, Biogen, Genentech, Optina Diagnostics, and Roche; consulting fees and payments related to an advisory board from Roche; and payments related to an advisory board, a speaker panel, talks, and an educational session from Biogen. There were peer-reviewed grants to her institution from the Ontario Brain Institute, Canadian Institutes of Health Research, Leducq Foundation, Heart and Stroke Foundation of Canada, National Institutes of Health, Alzheimer’s Drug Discovery Foundation, Brain Canada, Weston Brain Institute, Canadian Partnership for Stroke Recovery, Canadian Foundation for Innovation, Focused Ultrasound Foundation, Alzheimer’s Association US, Department of National Defense, Montreal Medical International Kuwait, Queen’s University, Compute Canada Resources for Research Groups, CANARIE, and Networks of Centres of Excellence of Canada. She has participated on a data safety monitoring board or advisory board for the Conference Board of Canada, World Dementia Council, and University of Rochester. She has contributed to the mission and scientific leadership of the Small Vessel VCID Biomarker Validation Consortium, National Institute of Neurological Disorders and Stroke. 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 Churchill, Roudaia, Chen, Gilboa, Sekuler, Ji, Gao, Lin, Jegatheesan, Masellis, Goubran, Rabin, Lam, Cheng, Fowler, Heyn, Black, MacIntosh, Graham and Schweizer.)

Objective: To examine the roles of the default mode network (DMN) and executive control network (ECN) in prolonged recovery after mild traumatic brain injury (mTBI), and relationships with indices of white matter microstructural injury., Methods: Seventeen mTBI patients with persistent symptoms were imaged an average of 21.5 months post-injury, along with 23 healthy controls. Resting-state functional magnetic resonance imaging (rs-fMRI) was used to evaluate functional connectivity (FC) of the DMN and ECN. Diffusion tensor imaging (DTI) quantified fractional anisotropy, along with mean, axial and radial diffusivity of white matter tracts., Results: Compared to controls, patients with mTBI had increased functional connectivity of the DMN and ECN to brain regions implicated in salience and frontoparietal networks, and increased white matter diffusivity within the cerebrum and brainstem. Among the patients, FC was correlated with better neurocognitive test scores, while diffusivity was correlated with more severe self-reported symptoms. The FC and diffusivity values within abnormal brain regions were not significantly correlated., Conclusion: For female mTBI patients with prolonged symptoms, hyper-connectivity may represent a compensatory response that helps to mitigate the effects of mTBI on cognition. These effects are unrelated to indices of microstructural injury, which are correlated with symptom severity, suggesting that rs-fMRI and DTI may capture distinct aspects of pathophysiology.

Background: There is evidence of alterations in mitochondrial energy metabolism and cerebral blood flow (CBF) in adults and youth with bipolar disorder (BD). Brain thermoregulation is based on the balance of heat-producing metabolism and heat-dissipating mechanisms, including CBF., Objective: To examine brain temperature, and its relation to CBF, in relation to BD and mood symptom severity in youth., Methods: This study included 25 youth participants (age 17.4 ± 1.7 years; 13 BD, 12 control group (CG)). Magnetic resonance spectroscopy data were acquired to obtain brain temperature in the left anterior cingulate cortex (ACC) and the left precuneus. Regional estimates of CBF were provided by arterial spin labeling imaging. Analyses used general linear regression models, covarying for age, sex, and psychiatric medications., Results: Brain temperature was significantly higher in BD compared to CG in the precuneus. A higher ratio of brain temperature to CBF was significantly associated with greater depression symptom severity in both the ACC and precuneus within BD. Analyses examining the relationship of brain temperature or CBF with depression severity score did not reveal any significant finding in the ACC or the precuneus., Conclusion: The current study provides preliminary evidence of increased brain temperature in youth with BD, in whom reduced thermoregulatory capacity is putatively associated with depression symptom severity. Evaluation of brain temperature and CBF in conjunction may provide valuable insight beyond what can be gleaned by either metric alone. Larger prospective studies are warranted to further evaluate brain temperature and its association with CBF concerning BD., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The ballistocardiogram (BCG), the induced electric potentials by the head motion originating from heartbeats, is a prominent source of noise in electroencephalography (EEG) data during magnetic resonance imaging (MRI). Although methods have been proposed to suppress the BCG artifact, more work considering the variability of cardiac cycles and head motion across time and subjects is needed to provide highly robust correction. Here, a method called "dynamic modeling of heartbeats" (DMH) is proposed to reduce BCG artifacts in EEG data recorded inside an MRI system. The DMH method models BCG artifacts by combining EEG points at time instants with similar dynamics. The modeled BCG artifact is then subtracted from the EEG recording to suppress the BCG artifact. Performance of DMH was tested and specifically compared with the Optimal Basis Set (OBS) method on EEG data recorded inside a 3T MRI system with either no MRI acquisition (Inside-MRI), echo-planar imaging (EPI-EEG), or fast MRI acquisition using simultaneous multi-slice and inverse imaging methods (SMS-InI-EEG). In a steady-state visual evoked response (SSVEP) paradigm, the 15-Hz oscillatory neuronal activity at the visual cortex after DMH processing was about 130% of that achieved by OBS processing for Inside-MRI, SMS-InI-EEG, and EPI-EEG conditions. The DMH method is computationally efficient for suppressing BCG artifacts and in the future may help to improve the quality of EEG data recorded in high-field MRI systems for neuroscientific and clinical applications., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Alcohol use disorder (AUD) is a highly prevalent, often refractory, medical illness. The symptoms of AUD are driven by dysfunction in several neurocircuits centered on the nucleus accumbens (NAc). Case reports and animal studies suggest NAc-DBS may be an effective harm-reduction treatment in severe AUD. Six patients with severe, refractory AUD underwent NAc-DBS. Safety metrics and clinical outcomes were recorded. Positron emission tomography (FDG-PET) was used to measure glucose metabolism in the NAc at baseline and 6 months. Functional magnetic resonance imaging (fMRI) was used to characterize postoperative changes in NAc functional connectivity to the rest of the brain, as well as NAc and dorsal striatal reactivity to alcoholic visual cues. This study was registered with ClinicalTrials.gov, NCT03660124. All patients experienced a reduction in craving. There was a significant reduction in alcohol consumption, alcohol-related compulsivity, and anxiety at 12 months. There was no significant change in depression. FDG-PET analysis demonstrated reduced NAc metabolism by 6 months, which correlated with improvements in compulsive drinking behaviors. Clinical improvement correlated with reduced functional connectivity between the NAc and the visual association cortex. Active DBS was associated with reduced activation of the dorsal striatum during passive viewing of alcohol-containing pictures. NAc-DBS is feasible and safe in patients with severe, otherwise refractory AUD. It is associated with a reduction in cravings and addictive behavior. A potential mechanism underlying this process is a down-regulation of the NAc, a disruption of its functional connectivity to the visual association cortex, and interference of cue-elicited dorsal striatum reactivity. Trial Registration NCT03660124 ( www.clinicaltrials.gov )., (© 2022. Crown.)

Abundant behavioral studies have demonstrated high comorbidity of reading and handwriting difficulties in developmental dyslexia (DD), a neurological condition characterized by unexpectedly low reading ability despite adequate nonverbal intelligence and typical schooling. The neural correlates of handwriting deficits remain largely unknown; however, as well as the extent that handwriting deficits share common neural bases with reading deficits in DD. The present work used functional magnetic resonance imaging to examine brain activity during handwriting and reading tasks in Chinese dyslexic children (n = 18) and age-matched controls (n = 23). Compared to controls, dyslexic children exhibited reduced activation during handwriting tasks in brain regions supporting sensory-motor processing (including supplementary motor area and postcentral gyrus) and visual-orthography processing (including bilateral precuneus and right cuneus). Among these regions, the left supplementary motor area and the right precuneus also showed a trend of reduced activation during reading tasks in dyslexics. Moreover, increased activation was found in the left inferior frontal gyrus and anterior cingulate cortex in dyslexics, which may reflect more efforts of executive control to compensate for the impairments of motor and visual-orthographic processing. Finally, dyslexic children exhibited aberrant functional connectivity among brain areas for cognitive control and sensory-motor processes during handwriting tasks. Together, these findings suggest that handwriting deficits in DD are associated with functional abnormalities of multiple brain regions implicated in motor execution, visual-orthographic processing, and cognitive control, providing important implications for the diagnosis and treatment of dyslexia., (© 2021 The Authors. Developmental Science published by John Wiley & Sons Ltd.)

Background: Increasing evidence implicates oxidative stress (OS) in Alzheimer disease (AD) and mild cognitive impairment (MCI). Depletion of the brain antioxidant glutathione (GSH) may be important in OS-mediated neurodegeneration, though studies of post-mortem brain GSH changes in AD have been inconclusive. Recent in vivo measurements of the brain and blood GSH may shed light on GSH changes earlier in the disease., Aim: To quantitatively review in vivo GSH in AD and MCI compared to healthy controls (HC) using meta-analyses., Method: Studies with in vivo brain or blood GSH levels in MCI or AD with a HC group were identified using MEDLINE, PsychInfo, and Embase (1947-June 2020). Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated for outcomes using random effects models. Outcome measures included brain GSH (Meshcher-Garwood Point Resolved Spectroscopy (MEGA-PRESS) versus non-MEGA-PRESS) and blood GSH (intracellular versus extracellular) in AD and MCI. The Q statistic and Egger's test were used to assess heterogeneity and risk of publication bias, respectively., Results: For brain GSH, 4 AD (AD=135, HC=223) and 4 MCI (MCI=213, HC=211) studies were included. For blood GSH, 26 AD (AD=1203, HC=1135) and 7 MCI (MCI=434, HC=408) studies were included. Brain GSH overall did not differ in AD or MCI compared to HC; however, the subgroup of studies using MEGA-PRESS reported lower brain GSH in AD (SMD [95%CI] -1.45 [-1.83, -1.06], p<0.001) and MCI (-1.15 [-1.71, -0.59], z=4.0, p<0.001). AD had lower intracellular and extracellular blood GSH overall (-0.87 [-1. 30, -0.44], z=3.96, p<0.001). In a subgroup analysis, intracellular GSH was lower in MCI (-0.66 [-1.11, -0.21], p=0.025). Heterogeneity was observed throughout (I 2 >85%) and not fully accounted by subgroup analysis. Egger's test indicated risk of publication bias., Conclusion: Blood intracellular GSH decrease is seen in MCI, while both intra- and extracellular decreases were seen in AD. Brain GSH is decreased in AD and MCI in subgroup analysis. Potential bias and heterogeneity suggest the need for measurement standardization and additional studies to explore sources of heterogeneity., (© 2022. The Author(s).)

Concussion is associated with acute disturbances in brain function and behavior, with potential long-term effects on brain health. However, it is presently unclear whether there are sex differences in acute and long-term brain recovery. In this study, magnetic resonance imaging (MRI) was used to scan 61 participants with sport-related concussion (30 male, 31 female) longitudinally at acute injury, medical clearance to return to play (RTP), and 1-year post-RTP. A large cohort of 167 controls (80 male, 87 female) was also imaged. Each MRI session assessed cerebral blood flow (CBF), along with white matter fractional anisotropy (FA) and mean diffusivity (MD). For concussed athletes, the parameters were converted to difference scores relative to matched control subgroups, and partial least squares modeled the main and sex-specific effects of concussion. Although male and female athletes did not differ in acute symptoms or time to RTP , all MRI measures showed significant sex differences during recovery. Males had greater reductions in occipital-parietal CBF (mean difference and 95%CI: 9.97 ml/100 g/min, [4.84, 15.12] ml/100 g/min, z = 3.73) and increases in callosal MD (9.07 × 10 -5 , [-14.14, -3.60] × 10 -5 , z = -3.46), with greatest effects at 1-year post-RTP. In contrast, females had greater reductions in FA of the corona radiata (16.50 × 10 -3 , [-22.38, -11.08] × 10 -3 , z = -5.60), with greatest effects at RTP. These findings provide new insights into how the brain recovers after a concussion, showing sex differences in both the acute and chronic phases of injury., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Background: The detailed extent of neuroinvasion or deleterious brain changes resulting from COVID-19 and their time courses remain to be determined in relation to "long-haul" COVID-19 symptoms. Our objective is to determine whether there are alterations in functional brain imaging measures among people with COVID-19 after hospital discharge or self-isolation., Methods: This paper describes a protocol for NeuroCOVID-19, a longitudinal observational study of adults aged 20-75 years at Sunnybrook Health Sciences Centre in Toronto, Ontario, that began in April 2020. We aim to recruit 240 adults, 60 per group: people who contracted COVID-19 and were admitted to hospital (group 1), people who contracted COVID-19 and self-isolated (group 2), people who experienced influenza-like symptoms at acute presentation but tested negative for COVID-19 and self-isolated (group 3, control) and healthy people (group 4, control). Participants are excluded based on premorbid neurologic or severe psychiatric illness, unstable cardiovascular disease, and magnetic resonance imaging (MRI) contraindications. Initial and 3-month follow-up assessments include multiparametric brain MRI and electroencephalography. Sensation and cognition are assessed alongside neuropsychiatric assessments and symptom self-reports. We will test the data from the initial and follow-up assessments for group differences based on 3 outcome measures: MRI cerebral blood flow, MRI resting state fractional amplitude of low-frequency fluctuation and electroencephalography spectral power., Interpretation: If neurophysiologic alterations are detected in the COVID-19 groups in our NeuroCOVID-19 study, this information could inform future research regarding interventions for long-haul COVID-19. The study results will be disseminated to scientists, clinicians and COVID-19 survivors, as well as the public and private sectors to provide context on how brain measures relate to lingering symptoms., Competing Interests: Competing interests: Sandra Black reports payments for contract research to her institution from GE Healthcare, Eli Lilly and Company, Biogen, Genentech, Optina Diagnostics and Roche; consulting fees and payments related to an advisory board from Roche; and payments related to an advisory board, a speaker panel, talks and an educational session from Biogen. There were peer-reviewed grants to her institution from the Ontario Brain Institute, Canadian Institutes of Health Research, Leducq Foundation, Heart and Stroke Foundation of Canada, National Institutes of Health, Alzheimer’s Drug Discovery Foundation, Brain Canada, Weston Brain Institute, Canadian Partnership for Stroke Recovery, Canadian Foundation for Innovation, Focused Ultrasound Foundation, Alzheimer’s Association US, Department of National Defence, Montreal Medical International – Kuwait, Queen’s University, Compute Canada Resources for Research Groups, CANARIE and Networks of Centres of Excellence of Canada. She has participated on a data safety monitoring board or advisory board for the Conference Board of Canada, World Dementia Council and University of Rochester. She has contributed to the mission and scientific leadership of the Small Vessel VCID Biomarker Validation Consortium, National Institute of Neurological Disorders and Stroke. No other competing interests were declared., (© 2021 CMA Joule Inc. or its licensors.)

Concussion is a major health concern, making it critical to identify factors that influence risk and resilience. The salience network (SN) likely plays a key role in concussion risk, given its roles in orienting attention, functional adaptability, and interoceptive awareness. The SN's functions are thought to be mediated through causal control of other networks, including the default mode network (DMN) and executive control network (ECN). It was therefore hypothesized that the SN of at-risk individuals would have altered functional and structural connectivity with the DMN and ECN. For this prospective study, 167 university athletes had baseline clinical assessments and magnetic resonance imaging scans and were monitored for the rest of their varsity career, with any concussions recorded. Athletes concussed in the same season as imaging (CSS; n  = 17) and those concussed in later seasons (CLS; n  = 15) were matched to controls that were not concussed after imaging. Functional connectivity and white matter fractional anisotropy (FA) were compared between concussed and control groups. Prior to injury, CSS athletes had significantly elevated total symptom severity scores, elevated SN-DMN functional connectivity and reduced FA of connecting white matter tracts, whereas CLS athletes showed no significant clinical or imaging effects. These findings provide new insights into the neurobiology of concussion risk and resilience, as indices of SN-DMN network connectivity are associated with short-term but not long-term concussion risk.

Background and Objectives: To test the hypothesis that a history of concussion (HOC) causes greater disturbances in cerebral blood flow (CBF) and white matter microstructure of midline brain structures after subsequent concussions, during the acute and chronic phases of recovery., Methods: In this longitudinal MRI study, 61 athletes with uncomplicated concussion (36 with HOC) were imaged at the acute phase of injury (1-7 days after injury), the subacute phase (8-14 days), medical clearance to return to play (RTP), 1 month after RTP, and 1 year after RTP. A normative group of 167 controls (73 with HOC) were also imaged. Each session assessed CBF of the cingulate cortex, along with fractional anisotropy (FA) and mean diffusivity (MD) of the corpus callosum. Linear mixed models tested for interactions of HOC with time since injury. The Sport Concussion Assessment Tool (SCAT) was also used to evaluate effects of HOC on symptoms, cognition, and balance., Results: Athletes with HOC had significantly greater declines in midcingulate CBF subacutely ( z = -3.29, p = 0.002) and greater declines in posterior cingulate CBF at 1 year after RTP ( z = -2.42, p = 0.007). No significant effects of HOC were seen for FA, whereas athletes with HOC had higher MD of the splenium at RTP ( z = 2.54, p = 0.008). These effects were seen in the absence of significant differences in SCAT domains (| z | ≤ 1.14, p ≥ 0.256) or time to RTP ( z = 0.23, p = 0.818)., Discussion: Results indicate subacute and chronic effects of HOC on cingulate CBF and callosal microstructure in the absence of differences in clinical indices. These findings provide new insights into physiologic brain recovery after concussion, with cumulative effects of repeated injury detected among young, healthy athletes., (© 2021 American Academy of Neurology.)

Magnetic resonance fingerprinting (MRF) is a quantitative MRI (qMRI) framework that provides simultaneous estimates of multiple relaxation parameters as well as metrics of field inhomogeneity in a single acquisition. However, current challenges exist in the forms of (1) scan time; (2) need for custom image reconstruction; (3) large dictionary sizes; (4) long dictionary-matching time. This study aims to introduce a novel streamlined magnetic-resonance fingerprinting (sMRF) framework based on a single-shot echo-planar imaging (EPI) sequence to simultaneously estimate tissue T1, T2, and T2* with integrated B1 + correction. Encouraged by recent work on EPI-based MRF, we developed a method that combines spin-echo EPI with gradient-echo EPI to achieve T2 in addition to T1 and T2* quantification. To this design, we add simultaneous multi-slice (SMS) acceleration to enable full-brain coverage in a few minutes. Moreover, in the parameter-estimation step, we use deep learning to train a deep neural network (DNN) to accelerate the estimation process by orders of magnitude. Notably, due to the high image quality of the EPI scans, the training process can rely simply on Bloch-simulated data. The DNN also removes the need for storing large dictionaries. Phantom scans along with in-vivo multi-slice scans from seven healthy volunteers were acquired with resolutions of 1.1×1.1×3 mm 3 and 1.7×1.7×3 mm 3 , and the results were validated against ground truth measurements. Excellent correspondence was found between our T1, T2, and T2* estimates and results obtained from standard approaches. In the phantom scan, a strong linear relationship (R = 1-1.04, R 2 >0.96) was found for all parameter estimates, with a particularly high agreement for T2 estimation (R 2 >0.99). Similar findings are reported for the in-vivo human data for all of our parameter estimates. Incorporation of DNN results in a reduction of parameter estimation time on the order of 1000 x and a reduction in storage requirements on the order of 2500 x while achieving highly similar results as conventional dictionary matching (%differences of 7.4 ± 0.4%, 3.6 ± 0.3% and 6.0 ± 0.4% error in T1, T2, and T2* estimation). Thus, sMRF has the potential to be the method of choice for future MRF studies by providing ease of implementation, fast whole-brain coverage, and ultra-fast T1/T2/T2* estimation., Competing Interests: Declarations of Competing Interest Mahdi Khajehim holds a US patent application regarding the sMRF approach described in this manuscript (Publication Number: WO/2020/206553)., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate progressive cerebral degeneration in amyotrophic lateral sclerosis (ALS) by assessing alterations in N -acetylaspartate (NAA) ratios in the motor and prefrontal cortex within clinical subgroups of ALS., Methods: Seventy-six patients with ALS and 59 healthy controls were enrolled in a prospective, longitudinal, multicenter study in the Canadian ALS Neuroimaging Consortium. Participants underwent serial clinical evaluations and magnetic resonance spectroscopy at baseline and 4 and 8 months using a harmonized protocol across 5 centers. NAA ratios were quantified in the motor cortex and prefrontal cortex. Patients were stratified into subgroups based on disease progression rate, upper motor neuron (UMN) signs, and cognitive status. Linear mixed models were used for baseline and longitudinal comparisons of NAA metabolite ratios., Results: Patients with ALS had reduced NAA ratios in the motor cortex at baseline ( p < 0.001). Ratios were lower in those with more rapid disease progression and greater UMN signs ( p < 0.05). A longitudinal decline in NAA ratios was observed in the motor cortex in the rapidly progressing ( p < 0.01) and high UMN burden ( p < 0.01) cohorts. The severity of UMN signs did not change significantly over time. NAA ratios were reduced in the prefrontal cortex only in cognitively impaired patients ( p < 0.05 ) ; prefrontal cortex metabolites did not change over time., Conclusions: Progressive degeneration of the motor cortex in ALS is associated with more aggressive clinical presentations. These findings provide biological evidence of variable spatial and temporal cerebral degeneration linked to the disease heterogeneity of ALS. The use of standardized imaging protocols may have a role in clinical trials for patient selection or subgrouping., Classification of Evidence: This study provides Class II evidence that MRS NAA metabolite ratios of the motor cortex are associated with more rapid disease progression and greater UMN signs in patients with ALS., Trial Registration Information: ClinicalTrials.gov Identifier: NCT02405182., (© 2021 American Academy of Neurology.)

Introduction: Driving motor vehicles is a complex task that depends heavily on how visual stimuli are received and subsequently processed by the brain. The potential impact of distraction on driving performance is well known and poses a safety concern - especially for individuals with cognitive impairments who may be clinically unfit to drive. The present study is the first to combine functional magnetic resonance imaging (fMRI) and eye-tracking during simulated driving with distraction, providing oculomotor metrics to enhance scientific understanding of the brain activity that supports driving performance., Materials and Methods: As initial work, twelve healthy young, right-handed participants performed turns ranging in complexity, including simple right and left turns without oncoming traffic, and left turns with oncoming traffic. Distraction was introduced as an auditory task during straight driving, and during left turns with oncoming traffic. Eye-tracking data were recorded during fMRI to characterize fixations, saccades, pupil diameter and blink rate., Results: Brain activation maps for right turns, left turns without oncoming traffic, left turns with oncoming traffic, and the distraction conditions were largely consistent with previous literature reporting the neural correlates of simulated driving. When the effects of distraction were evaluated for left turns with oncoming traffic, increased activation was observed in areas involved in executive function (e.g., middle and inferior frontal gyri) as well as decreased activation in the posterior brain (e.g., middle and superior occipital gyri). Whereas driving performance remained mostly unchanged (e.g., turn speed, time to turn, collisions), the oculomotor measures showed that distraction resulted in more consistent gaze at oncoming traffic in a small area of the visual scene; less time spent gazing at off-road targets (e.g., speedometer, rear-view mirror); more time spent performing saccadic eye movements; and decreased blink rate., Conclusion: Oculomotor behavior modulated with driving task complexity and distraction in a manner consistent with the brain activation features revealed by fMRI. The results suggest that eye-tracking technology should be included in future fMRI studies of simulated driving behavior in targeted populations, such as the elderly and individuals with cognitive complaints - ultimately toward developing better technology to assess and enhance fitness to drive., 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 © 2021 Yuen, Tam, Churchill, Schweizer and Graham.)

The Trail Making Test (TMT) is widely used to probe brain function and is performed with pen and paper, involving Parts A (linking numbers) and B (alternating between linking numbers and letters). The relationship between TMT performance and the underlying brain activity remains to be characterized in detail. Accordingly, sixteen healthy young adults performed the TMT using a touch-sensitive tablet to capture enhanced performance metrics, such as the speed of linking movements, during simultaneous electroencephalography (EEG). Linking and non-linking periods were derived as estimates of the time spent executing and preparing movements, respectively. The seconds per link (SPL) was also used to quantify TMT performance. A strong effect of TMT Part A and B was observed on the SPL value as expected (Part B showing increased SPL value); whereas the EEG results indicated robust effects of linking and non-linking periods in multiple frequency bands, and effects consistent with the underlying cognitive demands of the test., 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 © 2021 Lin, Tam, Churchill, Lin, MacIntosh, Schweizer and Graham.)

Cognitive impairment is now recognized in a subset of patients with amyotrophic lateral sclerosis (ALS). The objective of the study was to identify group differences and neuroanatomical correlates of the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) in participants ALS. Fifty-three ALS patients and 43 healthy controls recruited as a part of our multicentre study (CALSNIC) were administered the ECAS and underwent an MRI scan. Voxel-based morphometry and tract based spatial statistics (TBSS) was performed to identify structural changes and associations with impaired ECAS scores. Lower performance in the ECAS verbal fluency and executive domains were noted in ALS patients as compared to controls (p < 0.01). Extensive white matter degeneration was noted in the corticospinal tract in all ALS patients, while ALS patients with impaired verbal fluency or executive domains (ALS-exi, n = 22), displayed additional degeneration in the corpus callosum, cingulum and superior longitudinal fasciculus as compared to controls (p < 0.05, TFCE corrected). Mild grey matter changes and associations with ECAS verbal fluency or executive performance were noted at lenient statistical thresholds (p < 0.001, uncorrected). Executive impairment was detected using the ECAS in our multicentre sample of Canadian ALS patients. White matter degeneration in motor regions was revealed in ALS patients with extensive spread to frontal regions in the ALS-exi sub-group. Mild associations between ECAS verbal fluency, executive function scores and MRI metrics suggest that reduced performance may be associated with widespread structural integrity., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Concussion is associated with significant functional disturbances in the first week post-injury. Computerized neurocognitive testing tools have become widely adopted in concussion management, to identify specific domains of impairment and obtain more objective measures of recovery. Reaction time (RT) slowing is a common sequela of concussion, however, the functional brain networks that underlie RT performance remain under-studied in both healthy and concussed athletic cohorts. This study used blood-oxygenation-level-dependent function magnetic resonance imaging (BOLD fMRI) to evaluate resting brain function of 45 university-level athletes with concussion in the first week post-injury, along with a control cohort of 102 athletes without recent concussion. We evaluated the main effects of concussion and RT on functional connectivity, along with concussion × RT interactions, using multivariate analysis techniques. Concussion was associated with reduced connectivity throughout the brain, whereas RT slowing was associated with elevated connectivity in parietal and temporal regions, for both control and concussed groups. For the concussed group, RT slowing was also associated with disrupted connectivity between fronto-insular and default mode networks. For concussed athletes, the brain networks associated with slower post-injury RT also showed similar but non-significant associations with longitudinal changes in RT performance relative to pre-injury baseline. These study findings provide new insights into the effects of concussion on neurocognitive function and suggest the presence of functional brain networks that are specific to concussion-related RT slowing., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Concussion is associated with acute cognitive impairments, with declines in processing speed and reaction time being common. In the clinical setting, these issues are identified via symptom assessments and neurocognitive test (NCT) batteries. Practice guidelines recommend integrating both symptoms and NCTs into clinical decision-making, but correlations between these measures are often poor. This suggests that many patients experience difficulties in the self-appraisal of cognitive issues. It is presently unclear what neural mechanisms give rise to appraisal mismatch after a concussion. One promising target is the insula, which regulates aspects of cognition, particularly interoception and self-monitoring. The present study tested the hypothesis that appraisal mismatch is due to altered functional connectivity of the insula to frontal and midline structures, with hypo-connectivity leading to under-reporting of cognitive issues and hyper-connectivity leading to over-reporting. Data were collected from 59 acutely concussed individuals and 136 normative controls, including symptom assessments, NCTs and magnetic resonance imaging (MRI) data. Analysis of resting-state functional MRI supported the hypothesis, identifying insular networks that were associated with appraisal mismatch in concussed athletes that included frontal, sensorimotor, and cingulate connections. Subsequent analysis of diffusion tensor imaging also determined that symptom over-reporting was associated with reduced fractional anisotropy and increased mean diffusivity of posterior white matter. These findings provide new insights into the mechanisms of cognitive appraisal mismatch after a concussion. They are of particular interest given the central role of symptom assessments in the diagnosis and clinical management of concussion., 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 © 2021 Churchill, Hutchison, Graham and Schweizer.)

High-performance university athletes experience frequent exertion, resulting in disrupted biological homeostasis, but it is unclear to what extent brain physiology is affected. We examined whether athletes without overtraining symptoms show signs of increased neurophysiological stress over the course of a single athletic season, and whether the effects are modified by demographic factors of age, sex and concussion history, and sport-related factors of contact exposure and season length. Fifty-three university-level athletes were recruited from multiple sports at a single institution and followed longitudinally from beginning of season (BOS) to end of season (EOS) and 1 month afterwards, with a subset followed up at the subsequent beginning of season. MRI was used to comprehensively assess white matter (WM) diffusivity, cerebral blood flow (CBF), and brain activity, while overtraining symptoms were assessed with Hooper's Index (HI). Although athletes did not report increased HI scores, they showed significantly increased white matter diffusivity and decreased CBF at EOS and 1 month afterwards, with recovery at follow-up. Global brain activity was not significantly altered though, highlighting the ability of the brain to adapt to exercise-related stressors. Male athletes had greater white matter diffusivity at EOS, but female athletes had greater declines in CBF at 1 month afterwards. Post-season changes in MRI measures were not related to change in HI score, age, concussion history, contact exposure, or length of athletic season. Hence, the brain shows substantial but reversible neurophysiological changes due to season play in the absence of overtraining symptoms, with effects that are sex-dependent but otherwise insensitive to demographic variations. These findings provide new insights into the effects of training and competitive play on brain health., 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 © 2021 Churchill, Hutchison, Graham and Schweizer.)

There is a growing body of literature using functional MRI to study the acute and long-term effects of concussion on functional brain networks. To date, studies have largely focused on changes in pairwise connectivity strength between brain regions. Less is known about how concussion affects whole-brain network topology, particularly the "small-world" organization which facilitates efficient communication at both local and global scales. The present study addressed this knowledge gap by measuring local and global efficiency of 26 concussed athletes at acute injury, return to play (RTP) and one year post-RTP, along with a cohort of 167 athletic controls. On average, concussed athletes showed no alterations in local efficiency but had elevated global efficiency at acute injury, which had resolved by RTP. Athletes with atypically long recovery, however, had reduced global efficiency at 1 year post-RTP, suggesting long-term functional abnormalities for this subgroup. Analyses of nodal efficiency further indicated that global network changes were driven by high-efficiency visual and sensorimotor regions and low-efficiency frontal and subcortical regions. This study provides evidence that concussion causes subtle acute and long-term changes in the small-world organization of the brain, with effects that are related to the clinical profile of recovery.

Background: Deep brain stimulation (DBS) is a standard of care treatment for multiple neurologic disorders. Although 3-tesla (3T) magnetic resonance imaging (MRI) has become the gold-standard modality for structural and functional imaging, most centers refrain from 3T imaging in patients with DBS devices in place because of safety concerns. 3T MRI could be used not only for structural imaging, but also for functional MRI to study the effects of DBS on neurocircuitry and optimize programming., Objective: To use an anthropomorphic phantom design to perform temperature and voltage safety testing on an activated DBS device during 3T imaging., Methods: An anthropomorphic 3D-printed human phantom was constructed and used to perform temperature and voltage testing on a DBS device during 3T MRI. Based on the phantom assessment, a cohort study was conducted in which 6 human patients underwent MRI with their DBS device in an activated (ON) state., Results: During the phantom study, temperature rises were under 2°C during all sequences, with the DBS in both the deactivated and activated states. Radiofrequency pulses from the MRI appeared to modulate the electrical discharge from the DBS, resulting in slight fluctuations of voltage amplitude. Six human subjects underwent MRI with their DBS in an activated state without any serious adverse events. One patient experienced stimulation-related side effects during T1-MPRAGE scanning with the DBS in an ON state because of radiofrequency-induced modulation of voltage amplitude., Conclusion: Following careful phantom-based safety testing, 3T structural and functional MRI can be safely performed in subjects with activated deep brain stimulators., (Copyright © 2020 by the Congress of Neurological Surgeons.)

Functional magnetic resonance imaging (fMRI) is a powerful modality to study brain activity. To approximate naturalistic writing and drawing behaviours inside the scanner, many fMRI-compatible tablet technologies have been developed. The digitizing feature of the tablets also allows examination of behavioural kinematics with greater detail than using paper. With enhanced ecological validity, tablet devices have advanced the fields of neuropsychological tests, neurosurgery, and neurolinguistics. Specifically, tablet devices have been used to adopt many traditional paper-based writing and drawing neuropsychological tests for fMRI. In functional neurosurgery, tablet technologies have enabled intra-operative brain mapping during awake craniotomy in brain tumour patients, as well as quantitative tremor assessment for treatment outcome monitoring. Tablet devices also play an important role in identifying the neural correlates of writing in the healthy and diseased brain. The fMRI-compatible tablets provide an excellent platform to support naturalistic motor responses and examine detailed behavioural kinematics.