Concussion is a major health concern, associated with short-term deficits in physical function, emotion and cognition, along with negative long-term health outcomes. However, we remain in the early ...stages of characterizing MRI markers of concussion, particularly during the first week post-injury when symptoms are most severe. In this study, 52 varsity athletes were scanned using Magnetic Resonance Imaging (MRI), including 26 athletes with acute concussion (scanned 1-7 days post-injury) and 26 matched control athletes. A comprehensive set of functional and structural MRI measures were analyzed, including cerebral blood flow (CBF) and global functional connectivity (Gconn) of grey matter, along with fractional anisotropy (FA) and mean diffusivity (MD) of white matter. An analysis comparing acutely concussed athletes and controls showed limited evidence for reliable mean effects of acute concussion, with only MD showing spatially extensive differences between groups. We subsequently demonstrated that the number of days post-injury explained a significant proportion of inter-subject variability in MRI markers of acutely concussed athletes. Athletes scanned at early acute injury (1-3 days) had elevated CBF and Gconn and reduced FA, but those scanned at late acute injury (5-7 days) had the opposite response. In contrast, MD showed a more complex, spatially-dependent relationship with days post-injury. These novel findings highlight the variability of MRI markers during the acute phase of concussion and the critical importance of considering the acute injury time interval, which has significant implications for studies relating acute MRI data to concussion outcomes.
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.
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
functional magnetic resonance imaging (fMRI), and self-reported symptoms were recorded.
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.
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.
Aneurysmal subarachnoid hemorrhage (aSAH) is associated with significant mortality rates, and most survivors experience significant cognitive deficits across multiple domains, including executive ...function. It is critical to determine the neural basis for executive deficits in aSAH, in order to better understand and improve patient outcomes. This study is the first examination of resting-state functional Magnetic Resonance Imaging in a group of aSAH patients, used to characterize changes in functional connectivity of the frontoparietal network. We scanned 14 aSAH patients and 14 healthy controls, and divided patients into "impaired" and "unimpaired" groups based on a composite executive function score. Impaired patients exhibited significantly lower quality of life and neuropsychological impairment relative to controls, across multiple domains. Seed-based functional connectivity analysis demonstrated that unimpaired patients were not significantly different from controls, but impaired patients had increased frontoparietal connectivity. Patients evidenced increased frontoparietal connectivity as a function of decreased executive function and decreased mood (i.e. quality of life). In addition, T1 morphometric analysis demonstrated that these changes are not attributable to local cortical atrophy among aSAH patients. These results establish significant, reliable changes in the endogenous brain dynamics of aSAH patients, that are related to cognitive and mood outcomes.
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.
Concussion is associated with significant symptoms within hours to days post-injury, including disturbances in physical function, cognition, sleep and emotion. However, little is known about how ...subjective impairments correlate with objective measures of cerebrovascular function following brain injury. This study examined the relationship between symptoms and cerebral blood flow (CBF) in individuals following sport-related concussion. Seventy university level athletes had CBF measured using Arterial Spin Labelling (ASL), including 35 with acute concussion and 35 matched controls and their symptoms were assessed using the Sport Concussion Assessment Tool 3 (SCAT3). For concussed athletes, greater total symptom severity was associated with elevated posterior cortical CBF, although mean CBF was not significantly different from matched controls (
= 0.46). Examining symptom clusters, athletes reporting greater cognitive symptoms also had lower frontal and subcortical CBF, relative to athletes with greater somatic symptoms. The "cognitive" and "somatic" subgroups also exhibited significant differences in CBF relative to controls (
≤ 0.026). This study demonstrates objective CBF correlates of symptoms in recently concussed athletes and shows that specific symptom clusters may have distinct patterns of altered CBF, significantly extending our understanding of the neurobiology of concussion and traumatic brain injury.
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.
To administer the CDT naturalistically to a healthy older aging population in an MRI environment, and characterize the brain activity associated with test completion.
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.
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,
< 0.001); the clock hand drawing (R3) component (rho = -0.50,
< 0.005); and the total clock (rho = -0.62,
< 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.
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.
A variety of preprocessing techniques are available to correct subject-dependant artifacts in fMRI, caused by head motion and physiological noise. Although it has been established that the chosen ...preprocessing steps (or "pipeline") may significantly affect fMRI results, it is not well understood how preprocessing choices interact with other parts of the fMRI experimental design. In this study, we examine how two experimental factors interact with preprocessing: between-subject heterogeneity, and strength of task contrast. Two levels of cognitive contrast were examined in an fMRI adaptation of the Trail-Making Test, with data from young, healthy adults. The importance of standard preprocessing with motion correction, physiological noise correction, motion parameter regression and temporal detrending were examined for the two task contrasts. We also tested subspace estimation using Principal Component Analysis (PCA), and Independent Component Analysis (ICA). Results were obtained for Penalized Discriminant Analysis, and model performance quantified with reproducibility (R) and prediction metrics (P). Simulation methods were also used to test for potential biases from individual-subject optimization. Our results demonstrate that (1) individual pipeline optimization is not significantly more biased than fixed preprocessing. In addition, (2) when applying a fixed pipeline across all subjects, the task contrast significantly affects pipeline performance; in particular, the effects of PCA and ICA models vary with contrast, and are not by themselves optimal preprocessing steps. Also, (3) selecting the optimal pipeline for each subject improves within-subject (P,R) and between-subject overlap, with the weaker cognitive contrast being more sensitive to pipeline optimization. These results demonstrate that sensitivity of fMRI results is influenced not only by preprocessing choices, but also by interactions with other experimental design factors. This paper outlines a quantitative procedure to denoise data that would otherwise be discarded due to artifact; this is particularly relevant for weak signal contrasts in single-subject, small-sample and clinical datasets.
There is growing evidence that fluctuations in brain activity may exhibit scale-free ("fractal") dynamics. Scale-free signals follow a spectral-power curve of the form P(f ) ∝ f(-β), where spectral ...power decreases in a power-law fashion with increasing frequency. In this study, we demonstrated that fractal scaling of BOLD fMRI signal is consistently suppressed for different sources of cognitive effort. Decreases in the Hurst exponent (H), which quantifies scale-free signal, was related to three different sources of cognitive effort/task engagement: 1) task difficulty, 2) task novelty, and 3) aging effects. These results were consistently observed across multiple datasets and task paradigms. We also demonstrated that estimates of H are robust across a range of time-window sizes. H was also compared to alternative metrics of BOLD variability (SDBOLD) and global connectivity (Gconn), with effort-related decreases in H producing similar decreases in SDBOLD and Gconn. These results indicate a potential global brain phenomenon that unites research from different fields and indicates that fractal scaling may be a highly sensitive metric for indexing cognitive effort/task engagement.
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.
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.
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.
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.
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.
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