Design and Analysis of a Clinical Pressure Cuff Algometer, Compatible with an fMRI Machine.

Chronic pain affects both adolescent and adult Canadians. To study the effect of social rejection on pain management in adolescents with chronic pain, an algometer can be used in conjunction with functional Magnetic Resonance Imaging (fMRI) to measure brain activity in real time. The algometer uses an automated pneumatic control system that follows a customizable pain schedule, controlling the amount of airflow in and out of a pressure cuff wrapped around a human participant's thigh. Plastic components allow compatibility with an fMRI environment. Measurable pain stimuli allow repeatable pressure schedules to be administered with a standard deviation between trials of 300 Pa (2.25 mmHg). A Failure Mode Effects Analysis was used to reduce participant, researcher and facility harm, with multiple safety features incorporated into the design. Through the analysis of medical standards and studies, the algometer is shown to be biologically safe to use on research subjects within the suggested usage parameters of a maximum pressure of 42.6 kPa (320 mmHg) and a pressure application period of up to one hour. This makes it feasible for research studies using fMRI machines.

Cognitive Reserve and Brain Maintenance: Orthogonal Concepts in Theory and Practice.

Cognitive Reserve and Brain Maintenance have traditionally been understood as complementary concepts: Brain Maintenance captures the processes underlying the structural preservation of the brain with age, and might be assessed relative to age-matched peers. Cognitive Reserve, on the other hand, refers to how cognitive processing can be performed regardless of how well brain structure has been maintained. Thus, Brain Maintenance concerns the "hardware," whereas Cognitive Reserve concerns "software," that is, brain functioning explained by factors beyond mere brain structure. We used structural brain data from 368 community-dwelling adults, age 20-80, to derive measures of Brain Maintenance and Cognitive Reserve. We found that Brain Maintenance and Cognitive were uncorrelated such that values on one measure did not imply anything about the other measure. Further, both measures were positively correlated with verbal intelligence and education, hinting at formative influences of the latter to both measures. We performed extensive split-half simulations to check our derived measures' statistical robustness. Our approach enables the out-of-sample quantification of Brain Maintenance and Cognitive Reserve for single subjects on the basis of chronological age, neuropsychological performance and structural brain measures. Future work will investigate the prognostic power of these measures with regard to future cognitive status.

The Reference Ability Neural Network Study: Life-time stability of reference-ability neural networks derived from task maps of young adults.

Analyses of large test batteries administered to individuals ranging from young to old have consistently yielded a set of latent variables representing reference abilities (RAs) that capture the majority of the variance in age-related cognitive change: Episodic Memory, Fluid Reasoning, Perceptual Processing Speed, and Vocabulary. In a previous paper (Stern et al., 2014), we introduced the Reference Ability Neural Network Study, which administers 12 cognitive neuroimaging tasks (3 for each RA) to healthy adults age 20-80 in order to derive unique neural networks underlying these 4 RAs and investigate how these networks may be affected by aging. We used a multivariate approach, linear indicator regression, to derive a unique covariance pattern or Reference Ability Neural Network (RANN) for each of the 4 RAs. The RANNs were derived from the neural task data of 64 younger adults of age 30 and below. We then prospectively applied the RANNs to fMRI data from the remaining sample of 227 adults of age 31 and above in order to classify each subject-task map into one of the 4 possible reference domains. Overall classification accuracy across subjects in the sample age 31 and above was 0.80±0.18. Classification accuracy by RA domain was also good, but variable; memory: 0.72±0.32; reasoning: 0.75±0.35; speed: 0.79±0.31; vocabulary: 0.94±0.16. Classification accuracy was not associated with cross-sectional age, suggesting that these networks, and their specificity to the respective reference domain, might remain intact throughout the age range. Higher mean brain volume was correlated with increased overall classification accuracy; better overall performance on the tasks in the scanner was also associated with classification accuracy. For the RANN network scores, we observed for each RANN that a higher score was associated with a higher corresponding classification accuracy for that reference ability. Despite the absence of behavioral performance information in the derivation of these networks, we also observed some brain-behavioral correlations, notably for the fluid-reasoning network whose network score correlated with performance on the memory and fluid-reasoning tasks. While age did not influence the expression of this RANN, the slope of the association between network score and fluid-reasoning performance was negatively associated with higher ages. These results provide support for the hypothesis that a set of specific, age-invariant neural networks underlies these four RAs, and that these networks maintain their cognitive specificity and level of intensity across age. Activation common to all 12 tasks was identified as another activation pattern resulting from a mean-contrast Partial-Least-Squares technique. This common pattern did show associations with age and some subject demographics for some of the reference domains, lending support to the overall conclusion that aspects of neural processing that are specific to any cognitive reference ability stay constant across age, while aspects that are common to all reference abilities differ across age.

Towards structured sharing of raw and derived neuroimaging data across existing resources.

Data sharing efforts increasingly contribute to the acceleration of scientific discovery. Neuroimaging data is accumulating in distributed domain-specific databases and there is currently no integrated access mechanism nor an accepted format for the critically important meta-data that is necessary for making use of the combined, available neuroimaging data. In this manuscript, we present work from the Derived Data Working Group, an open-access group sponsored by the Biomedical Informatics Research Network (BIRN) and the International Neuroimaging Coordinating Facility (INCF) focused on practical tools for distributed access to neuroimaging data. The working group develops models and tools facilitating the structured interchange of neuroimaging meta-data and is making progress towards a unified set of tools for such data and meta-data exchange. We report on the key components required for integrated access to raw and derived neuroimaging data as well as associated meta-data and provenance across neuroimaging resources. The components include (1) a structured terminology that provides semantic context to data, (2) a formal data model for neuroimaging with robust tracking of data provenance, (3) a web service-based application programming interface (API) that provides a consistent mechanism to access and query the data model, and (4) a provenance library that can be used for the extraction of provenance data by image analysts and imaging software developers. We believe that the framework and set of tools outlined in this manuscript have great potential for solving many of the issues the neuroimaging community faces when sharing raw and derived neuroimaging data across the various existing database systems for the purpose of accelerating scientific discovery.

Objective evidence of cognitive complaints in Chronic Fatigue Syndrome: a BOLD fMRI study of verbal working memory.

Individuals with Chronic Fatigue Syndrome (CFS) often have difficulties with complex auditory information processing. In a series of two Blood Oxygen Level Dependent (BOLD) functional Magnetic Resonance Imaging (fMRI) studies, we compared BOLD signal changes between Controls and individuals with CFS who had documented difficulties in complex auditory information processing (Study 1) and those who did not (Study 2) in response to performance on a simple auditory monitoring and a complex auditory information processing task (mPASAT). We hypothesized that under conditions of cognitive challenge: (1) individuals with CFS who have auditory information processing difficulties will utilize frontal and parietal brain regions to a greater extent than Controls and (2) these differences will be maintained even when objective difficulties in this domain are controlled for. Using blocked design fMRI paradigms in both studies, we first presented the auditory monitoring task followed by the mPASAT. Within and between regions of interest (ROI), group analyses were performed for both studies with statistical parametric mapping (SPM99). Findings showed that individuals with CFS are able to process challenging auditory information as accurately as Controls but utilize more extensive regions of the network associated with the verbal WM system. Individuals with CFS appear to have to exert greater effort to process auditory information as effectively as demographically similar healthy adults. Our findings provide objective evidence for the subjective experience of cognitive difficulties in individuals with CFS.

An investigation of working memory rehearsal in multiple sclerosis using fMRI.

The present study examined patterns of cerebral activation during a working memory (WM) rehearsal task in individuals diagnosed with multiple sclerosis (MS) and in healthy adults. BOLD functional magnetic resonance imaging (fMRI) was performed using a 1.5 T GE scanner to assess activation during a WM task adapted from the Sternberg paradigm (Sternberg, 1969). Participants included 8 individuals diagnosed with MS, and 5 healthy controls (HCs) matched for age and education. Task difficulty was manipulated by increasing the length of time that strings of letters were to be rehearsed. Findings revealed increased right prefrontal cortex activation and increased right temporal lobe activation in individuals diagnosed with MS compared to HCs. The potential explanations for increased right hemisphere activation in persons with MS are discussed.

Functional magnetic resonance imaging of working memory impairment after traumatic brain injury.

OBJECTIVES: To examine patterns of brain activation while performing a working memory task in persons with moderate to severe traumatic brain injury (TBI) and healthy controls. It is well established that working memory is an area of cognition that is especially vulnerable to disruption after TBI. Although much has been learned about the system of cerebral representation of working memory in healthy people, little is known about how this system is disrupted by TBI. METHODS: Functional magnetic resonance imaging (fMRI) was used to assess brain activation during a working memory task (a modified version of the paced auditory serial addition test) in nine patients with TBI and seven healthy controls. RESULTS: Patients with TBI were able to perform the task, but made significantly more errors than healthy controls. Cerebral activation in both groups was found in similar regions of the frontal, parietal, and temporal lobes, and resembled patterns of activation found in previous neuroimaging studies of working memory in healthy persons. However, compared with the healthy controls, the TBI group displayed a pattern of cerebral activation that was more regionally dispersed and more lateralised to the right hemisphere. Differences in lateralisation were particularly evident in the frontal lobes. CONCLUSIONS: Impairment of working memory in TBI seems to be associated with alterations in functional cerebral activity.

Quantitative assessment of cerebral ventricular volumes in chronic fatigue syndrome.

Previous qualitative volumetric assessment of lateral ventricular enlargement in chronic fatigue syndrome (CFS) has provided evidence for subtle structural changes in the brains of some individuals with CFS. The aim of this pilot study was to determine whether a more sensitive quantitative assessment of the lateral ventricular system would support the previous qualitative findings. In this study, we compared the total lateral ventricular volume, as well as the right and left hemisphere subcomponents in 28 participants with CFS and 15 controls. Ventricular volumes in the CFS group were larger than in control groups, a difference that approached statistical significance. Group differences in ventricular asymmetry were not observed. The results of this study provide further evidence of subtle pathophysiological changes in the brains of participants with CFS.