Multiple sclerosis-related white matter microstructural change alters the BOLD hemodynamic response.

Multiple sclerosis (MS) results in inflammatory damage to white matter microstructure. Prior research using blood-oxygen-level dependent (BOLD) imaging indicates MS-related alterations to brain function. What is currently unknown is the extent to which white matter microstructural damage influences BOLD signal in MS. Here we assessed changes in parameters of the BOLD hemodynamic response function (HRF) in patients with relapsing-remitting MS compared to healthy controls. We also used diffusion tensor imaging to assess whether MS-related changes to the BOLD-HRF were affected by changes in white matter microstructural integrity. Our results showed MS-related reductions in BOLD-HRF peak amplitude. These MS-related amplitude decreases were influenced by individual differences in white matter microstructural integrity. Other MS-related factors including altered reaction time, limited spatial extent of BOLD activity, elevated lesion burden, or lesion proximity to regions of interest were not mediators of group differences in BOLD-HRF amplitude. Results are discussed in terms of functional hyperemic mechanisms and implications for analysis of BOLD signal differences.

The efficiency of fMRI region of interest analysis methods for detecting group differences.

BACKGROUND: Using a standard space brain template is an efficient way of determining region-of-interest (ROI) boundaries for functional magnetic resonance imaging (fMRI) data analyses. However, ROIs based on landmarks on subject-specific (i.e., native space) brain surfaces are anatomically accurate and probably best reflect the regional blood oxygen level dependent (BOLD) response for the individual. Unfortunately, accurate native space ROIs are often time-intensive to delineate even when using automated methods. NEW METHOD: We compared analyses of group differences when using standard versus native space ROIs using both volume and surface-based analyses. Collegiate and military-veteran participants completed a button press task and a digit-symbol verification task during fMRI acquisition. Data were analyzed within ROIs representing left and right motor and prefrontal cortices, in native and standard space. Volume and surface-based analysis results were also compared using both functional (i.e., percent signal change) and structural (i.e., voxel or node count) approaches. RESULTS AND COMPARISON WITH EXISTING METHOD(S): Results suggest that transformation into standard space can affect the outcome of structural and functional analyses (inflating/minimizing differences, based on cortical geography), and these transformations can affect conclusions regarding group differences with volumetric data. CONCLUSIONS: Caution is advised when applying standard space ROIs to volumetric fMRI data. However, volumetric analyses show group differences and are appropriate in circumstances when time is limited. Surface-based analyses using functional ROIs generated the greatest group differences and were less susceptible to differences between native and standard space. We conclude that surface-based analyses are preferable with adequate time and computing resources.

Central Executive Dysfunction and Deferred Prefrontal Processing in Veterans with Gulf War Illness.

Gulf War Illness is associated with toxic exposure to cholinergic disruptive chemicals. The cholinergic system has been shown to mediate the central executive of working memory (WM). The current work proposes that impairment of the cholinergic system in Gulf War Illness patients (GWIPs) leads to behavioral and neural deficits of the central executive of WM. A large sample of GWIPs and matched controls (MCs) underwent functional magnetic resonance imaging during a varied-load working memory task. Compared to MCs, GWIPs showed a greater decline in performance as WM-demand increased. Functional imaging suggested that GWIPs evinced separate processing strategies, deferring prefrontal cortex activity from encoding to retrieval for high demand conditions. Greater activity during high-demand encoding predicted greater WM performance. Behavioral data suggest that WM executive strategies are impaired in GWIPs. Functional data further support this hypothesis and suggest that GWIPs utilize less effective strategies during high-demand WM.

Auditory memory distortion for spoken prose.

Observers often remember a scene as containing information that was not presented but that would have likely been located just beyond the observed boundaries of the scene. This effect is called boundary extension (BE; e.g., Intraub & Richardson, 1989). Previous studies have observed BE in memory for visual and haptic stimuli, and the present experiments examined whether BE occurred in memory for auditory stimuli (prose, music). Experiments 1 and 2 varied the amount of auditory content to be remembered. BE was not observed, but when auditory targets contained more content, boundary restriction (BR) occurred. Experiment 3 presented auditory stimuli with less content and BR also occurred. In Experiment 4, white noise was added to stimuli with less content to equalize the durations of auditory stimuli, and BR still occurred. Experiments 5 and 6 presented trained stories and popular music, and BR still occurred. This latter finding ruled out the hypothesis that the lack of BE in Experiments 1-4 reflected a lack of familiarity with the stimuli. Overall, memory for auditory content exhibited BR rather than BE, and this pattern was stronger if auditory stimuli contained more content. Implications for the understanding of general perceptual processing and directions for future research are discussed.