Can quantitative susceptibility mapping help diagnose and predict recovery of concussion in children? An A-CAP study.

BACKGROUND: Quantitative susceptibility mapping (QSM) is an MRI technique that is a potential biomarker for concussion. We performed QSM in children following concussion or orthopaedic injury (OI), to assess QSM performance as a diagnostic and prognostic biomarker. METHODS: Children aged 8-17 years with either concussion (N=255) or OI (N=116) were recruited from four Canadian paediatric emergency departments and underwent QSM postacutely (2-33 days postinjury) using 3 Tesla MRI. QSM Z-scores within nine regions of interest (ROI) were compared between groups. QSM Z-scores were also compared with the 5P score, the current clinical benchmark for predicting persistent postconcussion symptoms (PPCS), at 4 weeks postinjury, with PPCS defined using reliable change methods based on both participant and parent reports. RESULTS: Concussion and OI groups did not differ significantly in QSM Z-scores for any ROI. Higher QSM Z-scores within frontal white matter (WM) independently predicted PPCS based on parent ratings of cognitive symptoms (p=0.001). The combination of frontal WM QSM Z-score and 5P score was better at predicting PPCS than 5P score alone (p=0.004). The area under the curve was 0.72 (95% CI 0.63 to 0.81) for frontal WM susceptibility, 0.69 (95% CI 0.59 to 0.79) for the 5P score and 0.74 (95% CI 0.65 to 0.83) for both. CONCLUSION: The findings suggest that QSM is a potential MRI biomarker that can help predict PPCS in children with concussion, over and above the current clinical benchmark, and thereby aid in clinical management. They also suggest a frontal lobe substrate for PPCS, highlighting the potential for QSM to clarify the neurophysiology of paediatric concussion.

Cerebral Amyloid Angiopathy Is Associated With Executive Dysfunction and Mild Cognitive Impairment.

BACKGROUND AND PURPOSE: Autopsy studies suggest that cerebral amyloid angiopathy (CAA) is associated with cognitive impairment and risk for dementia. We analyzed neuropsychological test data from a prospective cohort study of patients with CAA to identify the prevalence of cognitive impairment and its associations with brain magnetic resonance imaging features and the apolipoprotein E genotype. METHODS: Data were analyzed from 34 CAA, 16 Alzheimer's disease, 69 mild cognitive impairment, and 27 ischemic stroke participants. Neuropsychological test results were expressed as z scores in relation to normative data provided by the test manuals and then grouped into domains of memory, executive function, and processing speed. RESULTS: Mean test scores in CAA participants were significantly lower than norms for memory (-0.44±1.03; P=0.02), executive function (-1.14±1.07; P<0.001), and processing speed (-1.06±1.12; P<0.001). Twenty-seven CAA participants (79%) had mild cognitive impairment based on low cognitive performance accompanied by cognitive concerns. CAA participants had similarly low executive function scores as Alzheimer's disease, but relatively preserved memory. CAA participants' scores were lower than those of ischemic stroke controls for executive function and processing speed. Lower processing speed scores in CAA were associated with higher magnetic resonance imaging white matter hyperintensity volume. There were no associations with the apolipoprotein E ε4 allele. CONCLUSIONS: Mild cognitive impairment is very prevalent in CAA. The overall cognitive profile of CAA is more similar to that seen in vascular cognitive impairment rather than Alzheimer's disease. White matter ischemic lesions may underlie some of the impaired processing speed in CAA.

Reliability of functional magnetic resonance imaging activation during working memory in a multi-site study: analysis from the North American Prodrome Longitudinal Study.

Multi-site neuroimaging studies offer an efficient means to study brain functioning in large samples of individuals with rare conditions; however, they present new challenges given that aggregating data across sites introduces additional variability into measures of interest. Assessing the reliability of brain activation across study sites and comparing statistical methods for pooling functional data are critical to ensuring the validity of aggregating data across sites. The current study used two samples of healthy individuals to assess the feasibility and reliability of aggregating multi-site functional magnetic resonance imaging (fMRI) data from a Sternberg-style verbal working memory task. Participants were recruited as part of the North American Prodrome Longitudinal Study (NAPLS), which comprises eight fMRI scanning sites across the United States and Canada. In the first study sample (n=8), one participant from each home site traveled to each of the sites and was scanned while completing the task on two consecutive days. Reliability was examined using generalizability theory. Results indicated that blood oxygen level-dependent (BOLD) signal was reproducible across sites and was highly reliable, or generalizable, across scanning sites and testing days for core working memory ROIs (generalizability ICCs=0.81 for left dorsolateral prefrontal cortex, 0.95 for left superior parietal cortex). In the second study sample (n=154), two statistical methods for aggregating fMRI data across sites for all healthy individuals recruited as control participants in the NAPLS study were compared. Control participants were scanned on one occasion at the site from which they were recruited. Results from the image-based meta-analysis (IBMA) method and mixed effects model with site covariance method both showed robust activation in expected regions (i.e. dorsolateral prefrontal cortex, anterior cingulate cortex, supplementary motor cortex, superior parietal cortex, inferior temporal cortex, cerebellum, thalamus, basal ganglia). Quantification of the similarity of group maps from these methods confirmed a very high (96%) degree of spatial overlap in results. Thus, brain activation during working memory function was reliable across the NAPLS sites and both the IBMA and mixed effects model with site covariance methods appear to be valid approaches for aggregating data across sites. These findings indicate that multi-site functional neuroimaging can offer a reliable means to increase power and generalizability of results when investigating brain function in rare populations and support the multi-site investigation of working memory function in the NAPLS study, in particular.

The question shapes the answer: the neural correlates of task differences reveal dynamic semantic processing.

Task effects in semantic processing were investigated by contrasting the neural activation associated with two semantic categorization tasks (SCT) using event-related fMRI. The two SCTs involved different decision categories: is it an animal? vs. is it a concrete thing? Participants completed both tasks and, across participants, the same core set of items were presented in both tasks. Results showed task differences in the neural activation associated with these items: in the animal SCT there was greater activation in a number of frontal and temporal regions, including left superior and middle temporal gyri, while in the concrete SCT there was greater activation in left medial frontal gyrus and bilaterally in the precentral gyri. These results are interpreted as evidence of top-down modulation of semantic processing; participants make adjustments to optimize performance in a given task and these adjustments have consequences for the activation observed.

Is undiagnosed synaesthesia a confounding factor in the interpretation of MRI images?

Synaesthesia is a condition in which stimulation of a sensory modality evokes another sensation in the same or a different sensory modality. Currently, synaesthesia is considered a neurological condition that involves crosstalk between brain regions. Given the numerous anatomical and functional connections within the brain, it is possible that undiagnosed synaesthesia may influence the results of functional magnetic resonance imaging (fMRI) studies or even structural MRI. In this paper, we investigated the currently available literature to determine if and how the sensations invoked by synaesthesia could impact fMRI and structural MRI. Our investigation found that synaesthesia can have a profound impact on fMRI studies of sensory and cognitive functions, and there is evidence to suggest structural connections in the brain are also altered. Given the low prevalence of synaesthesia, the likelihood of synaesthesia being a confounding factor in fMRI studies of patient groups is small; however, determining the presence of synaesthesia is important for investigating individual patients.