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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.)

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.)

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.)

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.)

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.)

Neuroimaging has identified significant disturbances in cerebrovascular reactivity (CVR) in the early symptomatic phase of sport-related concussion. However, less is known about how whole-brain alterations in CVR evolve after concussion and whether they remain present beyond medical clearance to return to play (RTP). In the present study, CVR was evaluated using blood-oxygenation-level-dependent functional magnetic resonance imaging (BOLD fMRI) during a respiratory challenge. Imaging data were collected for 110 university-level athletes, including 39 concussed athletes and 71 athletic controls. The concussed athletes were imaged at the acute phase of injury (1-7 days post-injury), the subacute phase (8-14 days post-injury), medical clearance to RTP, 1 month post-RTP, and 1 year post-RTP. Enhanced negative BOLD response to controlled breathing was seen at acute injury, with attenuation of the effect mainly occurring by 1 year post-RTP. Secondary analyses showed that greater symptom severity and prolonged recovery were associated with enhanced BOLD response in the acute phase of injury, but a more attenuated BOLD response in the subacute phase. This study provides novel information characterizing the CVR response after concussion and shows CVR to be a sensitive technique for evaluating long-term brain recovery., (Copyright © 2020 Churchill, Hutchison, Graham and Schweizer.)

Resting state functional magnetic resonance imaging (rs-fMRI) has become an indispensable tool in neuroscience research. Despite this, rs-fMRI signals are easily contaminated by artifacts arising from movement of the head during data collection. The artifacts can be problematic even for motions on the millimeter scale, with complex spatiotemporal properties that can lead to substantial errors in functional connectivity estimates. Effective correction methods must be employed, therefore, to distinguish true functional networks from motion-related noise. Research over the last three decades has produced numerous correction methods, many of which must be applied in combination to achieve satisfactory data quality. Subject instruction, training, and mild restraints are helpful at the outset, but usually insufficient. Improvements come from applying multiple motion correction algorithms retrospectively after rs-fMRI data are collected, although residual artifacts can still remain in cases of elevated motion, which are especially prevalent in patient populations. Although not commonly adopted at present, "real-time" correction methods are emerging that can be combined with retrospective methods and that promise better correction and increased rs-fMRI signal sensitivity. While the search for the ideal motion correction protocol continues, rs-fMRI research will benefit from good disclosure practices, such as: (1) reporting motion-related quality control metrics to provide better comparison between studies; and (2) including motion covariates in group-level analyses to limit the extent of motion-related confounds when studying group differences.

The Letter Cancellation Task (LCT) is a widely used pen-and-paper probe of attention in clinical and research settings. Despite its popularity, the neural correlates of the task are not well understood. The present study uses functional magnetic resonance imaging (fMRI) and specialized tablet technology to identify the neural correlates of the LCT in 32 healthy older adults between 50-85 years of age, and further investigates the effect of healthy aging on performance. Subjects performed the LCT in its standard pen-and-paper administration and with the tablet during fMRI. Performance on the tablet was significantly slower than on pen-and-paper, with both response modes showing slower performance as a function of age. Across all ages, bilateral brain activation was observed in the cerebellum, superior temporal lobe, precentral gyrus, frontal gyrus, and occipital and parietal areas. Increasing age correlated with reduced brain activity in the supplementary motor area, middle occipital gyrus, medial and inferior frontal gyrus, cerebellum and putamen. Better LCT performance was correlated with increased activity in the middle frontal gyrus, and reduced activity in the cerebellum. The brain regions activated are associated with visuospatial attention and motor control, and are consistent with the neural correlates of LCT performance previously identified in lesion studies.

Importance: The clock-drawing test (CDT) is an important neurocognitive assessment tool, widely used as a screening test for dementia. Behavioral performance on the test has been studied extensively, but there is scant literature on the underlying neural correlates. Purpose: To administer the CDT naturalistically to a healthy older aging population in an MRI environment, and characterize the brain activity associated with test completion. Main Outcome and Measure: Blood-oxygen-level dependent (BOLD) functional MRI was conducted as participants completed the CDT using novel tablet technology. Brain activity during CDT performance was contrasted to rest periods of visual fixation. Performance on the CDT was evaluated using a standardized scoring system (Rouleau score) and time to test completion. To assess convergent validity, performance during fMRI was compared to performance on a standard paper version of the task, administered in a psychometric testing room. Results: Study findings are reported for 33 cognitively healthy older participants aged 52-85. Activation was observed in the bilateral frontal, occipital and parietal lobes as well as the supplementary motor area and precentral gyri. Increased age was significantly correlated with Rouleau scores on the clock number drawing (R2) component (rho = -0.55, p < 0.001); the clock hand drawing (R3) component (rho = -0.50, p < 0.005); and the total clock (rho = -0.62, p < 0.001). Increased age was also associated with decreased activity in the bilateral parietal and occipital lobes as well as the right temporal lobe and right motor areas. Conclusion and Relevance: This imaging study characterizes the brain activity underlying performance of the CDT in a healthy older aging population using the most naturalistic version of the task to date. The results suggest that the functions of the occipital and parietal lobe are significantly altered by the normal aging process, which may lead to performance decrements.

Handwriting is a complex human activity that engages a blend of cognitive and visual motor skills. Current understanding of the neural correlates of handwriting has largely come from lesion studies of patients with impaired handwriting. Task-based fMRI studies would be useful to supplement this work. To address concerns over ecological validity, previously we developed a fMRI-compatible, computerized tablet system for writing and drawing including visual feedback of hand position and an augmented reality display. The purpose of the present work is to use the tablet system in proof-of-concept to characterize brain activity associated with clinically relevant handwriting tasks, originally developed to characterize handwriting impairments in Alzheimer's disease patients. As a prelude to undertaking fMRI studies of patients, imaging was performed of twelve young healthy subjects who copied sentences, phone numbers, and grocery lists using the fMRI-compatible tablet. Activation maps for all handwriting tasks consisted of a distributed network of regions in reasonable agreement with previous studies of handwriting performance. In addition, differences in brain activity were observed between the test subcomponents consistent with different demands of neural processing for successful task performance, as identified by investigating three quantitative behavioral metrics (writing speed, stylus contact force and stylus in air time). This study provides baseline behavioral and brain activity results for fMRI studies that adopt this handwriting test to characterize patients with brain impairments.

The Trail Making Test (TMT) is widely used for assessing executive function, frontal lobe abilities, and visual motor skills. Part A of this pen-and-paper test (TMT-A) involves linking numbers randomly distributed in space, in ascending order. Part B (TMT-B) alternates between linking numbers and letters. TMT-B is more demanding than TMT-A, but the mental processing that supports the performance of this test remains incompletely understood. Functional MRI (fMRI) may help to clarify the relationship between TMT performance and brain activity, but providing an environment that supports real-world pen-and-paper interactions during fMRI is challenging. Previously, an fMRI-compatible tablet system was developed for writing and drawing with two modes of interaction: the original cursor-based, proprioceptive approach, and a new mode involving augmented reality to provide visual feedback of hand position (VFHP) for enhanced user interaction. This study characterizes the use of the tablet during fMRI of young healthy adults ( n = 22), with half of the subjects performing TMT with VFHP and the other half performing TMT without VFHP. Activation maps for both TMT-A and TMT-B performance showed considerable overlap between the two tablet modes, and no statistically differences in brain activity were detected when contrasting TMT-B vs. TMT-A for the two tablet modes. Behavioral results also showed no statistically different interaction effects for TMT-B vs. TMT-A for the two tablet modes. Tablet-based TMT scores showed reasonable convergent validity with those obtained by administering the standard pen-and-paper TMT to the same subjects. Overall, the results suggest that despite the slightly different mechanisms involved for the two modes of tablet interaction, both are suitable for use in fMRI studies involving TMT performance. This study provides information for using tablet-based TMT methods appropriately in future fMRI studies involving patients and healthy individuals.

There is growing concern about how participation in contact sports affects the brain. Retrospective evidence suggests that contact sports are associated with long-term negative health outcomes. However, much of the research to date has focused on former athletes with significant health problems. Less is known about the health of current athletes in contact and collision sports who have not reported significant medical issues. In this cross-sectional study, advanced magnetic resonance imaging (MRI) was used to evaluate multiple aspects of brain physiology in three groups of athletes participating in non-contact sports ( N  = 20), contact sports ( N  = 22), and collision sports ( N  = 23). Diffusion tensor imaging was used to assess white matter microstructure based on measures of fractional anisotropy (FA) and mean diffusivity (MD); resting-state functional MRI was used to evaluate global functional connectivity; single-voxel spectroscopy was used to compare ratios of neural metabolites, including N -acetyl aspartate (NAA), creatine (Cr), choline, and myo-inositol. Multivariate analysis revealed structural, functional, and metabolic measures that reliably differentiated between sport groups. The collision group had significantly elevated FA and reduced MD in white matter, compared to both contact and non-contact groups. In contrast, the collision group showed significant reductions in functional connectivity and the NAA/Cr metabolite ratio, relative to only the non-contact group, while the contact group overlapped with both non-contact and collision groups. For brain regions associated with contact sport participation, athletes with a history of concussion also showed greater alterations in FA and functional connectivity, indicating a potential cumulative effect of both contact exposure and concussion history on brain physiology. These findings indicate persistent differences in brain physiology for athletes participating in contact and collision sports, which should be considered in future studies of concussion and subconcussive impacts.

For a significant percentage of subjects, with chronic traumatic brain injury (TBI), who report persisting cognitive impairment and functional loss, the diagnosis is often impeded by the fact that routine neuroimaging often does not reveal any abnormalities. In this paper, we used diffusion tensor imaging (DTI) to investigate the apparently normal white matter (as assessed by routine magnetic resonance imaging) in the brains of 19 subjects with sub-acute (9) and chronic (10) TBI. We also assessed memory, executive function, and visual-motor coordination in these subjects. Using a voxel-wise approach, we investigated if parameters of diffusion were significantly different between TBI subjects and 17 healthy controls (HC), who were demographically matched to the TBI group. We also investigated if changes in DTI parameters were associated with neuropsychological performance in either group. Our results indicate significantly increased mean and axial diffusivity (MD and AD, respectively) values in widespread brain locations in TBI subjects, while controlling for age, sex, and time since injury. HC performed significantly better than the TBI subjects on tests of memory and executive function, indicating the persisting functional loss in chronic TBI. We found no correlation between diffusion parameters and performance on test of executive function in either group. We found negative correlation between FA and composite memory scores, and positive correlation between RD and visuomotor coordination test scores, in various tracts in both groups. Our study suggests that changes in MD and AD can indicate persisting micro-structure abnormalities in normal-appearing white matter in the brains of subjects with chronic TBI. Our results also suggest that FA in major white matter tracts is correlated with memory in health and in disease, alike; larger and longitudinal studies are needed to discern potential differences in these correlations in the two groups.

Object: Preoperative functional magnetic resonance imaging (fMRI) remains a promising method to aid in the surgical management of patients diagnosed with brain tumors. For patients that are candidates for awake craniotomies, surgical decisions can potentially be improved by fMRI but this depends on the level of concordance between preoperative brain maps and the maps provided by the gold standard intraoperative method, direct cortical stimulation (DCS). There have been numerous studies of the concordance between fMRI and DCS using sensitivity and specificity measures, however the results are variable across studies and the key factors influencing variability are not well understood. Thus, the present work addresses the influence of technical factors on fMRI and DCS concordance. Methods: Motor and language mapping data were collected for a group of glioma patients ( n = 14) who underwent both preoperative fMRI and intraoperative DCS in an awake craniotomy procedure for tumor removal. Normative fMRI data were also acquired in a healthy control group ( n = 12). The fMRI and DCS mapping data were co-registered; true positive (TP), true negative (TN), false positive (FP), and false negative (FN) occurrences were tabulated over the exposed brain surface. Sensitivity and specificity were measured for the total group, and for the motor and language sub-groups. The influence of grid placement, fMRI statistical thresholding, and task standardization were assessed. Correlations between proportions of agreement and error were also carefully scrutinized to evaluate concordance in more detail. Results: Concordance was significantly better for motor vs. language mapping. There was an inverse relationship between TP and TN with increasing statistical threshold, and FP dominated the total error. Sensitivity and specificity were reduced when tasks were not standardized across fMRI and DCS. Conclusions: Although the agreement between fMRI and DCS is good, variability is introduced by technical factors that can diminish the quality of patient data. Neurosurgeons should evaluate the usefulness of fMRI data while considering that (a) discordance arises primarily from FP fMRI results; (b) there is an inherent trade-off between sensitivity and specificity with fMRI statistical threshold; and, ((c) best results are achieved using batteries of tasks that are standardized across both mapping methods.)

Neuropsychological tests behavioral tasks that very commonly involve handwriting and drawing are widely used in the clinic to detect abnormal brain function. Functional magnetic resonance imaging (fMRI) may be useful in increasing the specificity of such tests. However, performing complex pen-and-paper tests during fMRI involves engineering challenges. Previously, we developed an fMRI-compatible, computerized tablet system to address this issue. However, the tablet did not include visual feedback of hand position (VFHP), a human factors component that may be important for fMRI of certain patient populations. A real-time system was thus developed to provide VFHP and integrated with the tablet in an augmented reality display. The effectiveness of the system was initially tested in young healthy adults who performed various handwriting tasks in front of a computer display with and without VFHP. Pilot fMRI of writing tasks were performed by two representative individuals with and without VFHP. Quantitative analysis of the behavioral results indicated improved writing performance with VFHP. The pilot fMRI results suggest that writing with VFHP requires less neural resources compared to the without VFHP condition, to maintain similar behavior. Thus, the tablet system with VFHP is recommended for future fMRI studies involving patients with impaired brain function and where ecologically valid behavior is important.

Neuropsychological tests of verbal fluency are very widely used to characterize impaired cognitive function. For clinical neuroscience studies and potential medical applications, measuring the brain activity that underlies such tests with functional magnetic resonance imaging (fMRI) is of significant interest-but a challenging proposition because overt speech can cause signal artifacts, which tend to worsen as the duration of speech tasks becomes longer. In a novel approach, we present the group brain activity of 12 subjects who performed a self-paced written version of phonemic fluency using fMRI-compatible tablet technology that recorded responses and provided task-related feedback on a projection screen display, over long-duration task blocks (60 s). As predicted, we observed robust activation in the left anterior inferior and medial frontal gyri, consistent with previously reported results of verbal fluency tasks which established the role of these areas in strategic word retrieval. In addition, the number of words produced in the late phase (last 30 s) of written phonemic fluency was significantly less (p < 0.05) than the number produced in the early phase (first 30 s). Activation during the late phase vs. the early phase was also assessed from the first 20 s and last 20 s of task performance, which eliminated the possibility that the sluggish hemodynamic response from the early phase would affect the activation estimates of the late phase. The last 20 s produced greater activation maps covering extended areas in bilateral precuneus, cuneus, middle temporal gyrus, insula, middle frontal gyrus and cingulate gyrus. Among these areas, greater activation was observed in the bilateral middle frontal gyrus (Brodmann area BA 9) and cingulate gyrus (BA 24, 32) likely as part of the initiation, maintenance, and shifting of attentional resources. Consistent with previous pertinent fMRI literature involving overt and covert verbal responses, these findings highlight the promise and practicality of fMRI of written phonemic fluency.

Sport-related concussions are now recognized as a major public health concern: the number of participants in sport and recreation is growing, possibly playing their games faster, and there is heightened public awareness of injuries to some high-profile athletes. However, many clinicians still rely on subjective symptom reports for the clinical determination of recovery. Relying on subjective symptom reports can be problematic, as it has been shown that some concussed athletes may downplay their symptoms. The use of neuropsychological (NP) testing has enabled clinicians to measure the effects and extent of impairment following concussion more precisely, providing more objective metrics for determining recovery. Nevertheless, there is a remaining concern that brain abnormalities may exist beyond the point at which individuals achieve recovery in self-reported symptoms and cognition measured by NP testing. Our understanding of brain recovery after concussion is important, not only from a neuroscience perspective, but also from the perspective of clinical decision-making for safe return-to-play. A number of advanced neuroimaging tools, including blood oxygen level dependent functional magnetic resonance imaging (fMRI), have independently yielded early information on abnormal brain functioning. In the two cases presented in this article, we report contrasting brain activation patterns and recovery profiles using fMRI. Importantly, fMRI was conducted using adapted versions of the most sensitive computerized NP tests administered in our current clinical practice to determine impairments and recovery after sport-related concussion. One of the cases is consistent with the concept of lagging brain recovery.

Planar electrodes are increasingly used in therapeutic neural stimulation techniques such as functional electrical stimulation, epidural spinal cord stimulation (ESCS), and cortical stimulation. Recently, optimized electrode geometries have been shown to increase the efficiency of neural stimulation by increasing the variation of current density on the electrode surface. In the present work, a new family of modified fractal electrode geometries is developed to enhance the efficiency of neural stimulation. It is shown that a promising approach in increasing the neural activation function is to increase the "edginess" of the electrode surface, a concept that is explained and quantified by fractal mathematics. Rigorous finite element simulations were performed to compute electric potential produced by proposed modified fractal geometries. The activation of 256 model axons positioned around the electrodes was then quantified, showing that modified fractal geometries required a 22% less input power while maintaining the same level of neural activation. Preliminary in vivo experiments investigating muscle evoked potentials due to median nerve stimulation showed encouraging results, supporting the feasibility of increasing neural stimulation efficiency using modified fractal geometries.

The global burden of stroke continues to grow. Although stroke prevention strategies (e.g., medications, diet, and exercise) can contribute to risk reduction, options for acute interventions (e.g., thrombolytic therapy for ischemic stroke) are limited to the minority of patients. The remaining patients are often left with profound neurological disabilities that substantially impact quality of life, economic productivity, and increase caregiver burden. In the last decade, however, the future outlook for such patients has been tempered by movement toward the view that the brain is capable of reorganizing after injury. Many now view brain recovery after stroke as an area of scientific research with large potential for therapeutic advances, far into the future (Broderick and William, 2004). As a probe of brain anatomy, function and physiology, magnetic resonance imaging (MRI) is a non-invasive and highly versatile modality that promises to play a particularly important role in such research. Here we provide a basic review of MRI physical principles and applications for assessing stroke, looking toward the future role MRI may play in improving stroke rehabilitation methods and stroke recovery.

Introduction: Non-invasive measurements of brain activity have an important role to play in understanding driving ability. The current study aimed to identify the neural underpinnings of human driving behavior by visualizing the areas of the brain involved in driving under different levels of demand, such as driving while distracted or making left turns at busy intersections., Materials and Methods: To capture brain activity during driving, we placed a driving simulator with a fully functional steering wheel and pedals in a 3.0 Tesla functional magnetic resonance imaging (fMRI) system. To identify the brain areas involved while performing different real-world driving maneuvers, participants completed tasks ranging from simple (right turns) to more complex (left turns at busy intersections). To assess the effects of driving while distracted, participants were asked to perform an auditory task while driving analogous to speaking on a hands-free device and driving., Results: A widely distributed brain network was identified, especially when making left turns at busy intersections compared to more simple driving tasks. During distracted driving, brain activation shifted dramatically from the posterior, visual and spatial areas to the prefrontal cortex., Conclusions: Our findings suggest that the distracted brain sacrificed areas in the posterior brain important for visual attention and alertness to recruit enough brain resources to perform a secondary, cognitive task. The present findings offer important new insights into the scientific understanding of the neuro-cognitive mechanisms of driving behavior and lay down an important foundation for future clinical research.

A functional magnetic resonance imaging (fMRI)-compatible fiber-optic bend sensor was investigated to assess whether the device could be used effectively to monitor opening and closing of the jaw during an fMRI experiment at 3 T. In contrast to surface electromyography, a bend sensor fixed to the chin of the participant is fast and easy to use and is not affected by strong electromagnetic fields. Bend sensor recordings are characterized by high validity (compared with concurrent video recordings of mouth opening) and high reliability (comparing two independent measurements). The results of this study indicate that a bend sensor is able to record the opening and closing of the jaw associated with different overt speech conditions (producing the utterances /a/, /pa/, /pataka/) and the opening of the mouth without speech production. Data post-processing such as filtering was not necessary. There are several potential applications for bend sensor recordings of speech-related jaw movements. First, bend sensor recordings are a valuable tool to assess behavioral performance, such as response latencies, accuracies, and completion times, which is particularly important in children, seniors, or patients with various neurological or psychiatric conditions. Second, the timing information provided by bend sensor data may improve the predicted hemodynamic response that is used for fMRI analysis based on the general linear model (GLM). Third, bend sensor recordings may be included in GLM analyses not for statistical contrast purposes, but as a covariate of no interest, accounting for part of the data variance to model fMRI artifacts due to motion outside the field of view.