Adaptive Thresholding for Improving Sensitivity in Single-Trial Simultaneous EEG/fMRI

A common approach used to fuse simultaneously recorded EEG and fMRI is to correlate trial-by-trial variability in the EEG, or variability of components derived therefrom, with the blood oxygenation level dependent response. When this correlation is done using the conventional univariate approach, for example with the general linear model, there is the usual problem of correcting the statistics for multiple comparisons. Cluster thresholding is often used as the correction of choice, though in many cases it is utilized in an ad hoc way, for example by employing the same cluster thresholds for both traditional regressors (stimulus or behaviorally derived) and EEG-derived regressors. In this paper we describe a resampling procedure that takes into account the a priori statistics of the trial-to-trial variability of the EEG-derived regressors in a way that trades off cluster size and maximum voxel Z-score to properly correct for multiple comparisons. We show that this data adaptive procedure improves sensitivity for smaller clusters of activation, without sacrificing the specificity of the results. Our results suggest that extra care is needed in correcting statistics when the regressor model is derived from noisy and/or uncertain measurements, as is the case for regressors constructed from single-trial variations in the EEG

Neuroimmune Signaling In The Regulation of Cocaine and Opioid Seeking Behaviors

The abuse of cocaine and opioids is a major public health threat, yet, to date, therapies aimed at treating these disorders have limited efficacy. Preventing relapse is a major goal in the treatment of individuals that meet the criteria for a substance use disorder. Much research has been directed at understanding neuroadaptations that underlie the uncontrollable bouts of craving that often precipitate relapse. However, a dearth of studies has investigated the potential role of neuroimmune signaling in relapse. Toll-like receptor 4 (TLR4) is a pattern recognition receptor expressed on immune cells that has been indicated in ligating cocaine and opioids and initiating signal transduction of inflammatory cytokine pathways. Recognition of these drugs by TLR4 results in the induction of an innate immune response within the mesolimbic dopamine system. In turn, this mesolimbic dopamine response has been indicated to alter dopamine signaling and contribute to the reinforcing effects of drugs of abuse. However, it is unknown whether TLR4 effects may extend to drug-seeking behavior characteristic of drug-relapse. To investigate this question, the studies outlined here employ rodent self-administration models of cocaine and opioid relapse-like behavior to investigate the potential role of neuroimmune signaling. TLR4 antagonists applied into the VTA and NAc Shell, but not NAc Core, were found to reduce cocaine-seeking behavior. Conversely, the TLR4 agonist LPS administered into the VTA moderately induced drug-seeking. Manipulating pro-inflammatory and anti-inflammatory signaling in the NAc Core had no clear interpretable effect on incubation of cocaine craving. Oxycodone self-administration was reduced in the incubation of craving model following systemic administration of the glia inhibitor Ibudilast throughout the course of withdrawal. Reduction in incubation of oxycodone drug-seeking of the Ibudilast group was accompanied by a decrease in expression of the astrocyte gliosis marker GFAP. However, Ibudilast also reduced self-administration of sucrose, complicating the interpretation of specificity of Ibudilast&rsquo;s behavioral effects. Together, these data indicate a role of neuroimmune signaling in drug-seeking behaviors for cocaine and oxycodone.</p

Multivariate and Univariate Analysis of Continuous Arterial Spin Labeling Perfusion MRI in Alzheimer's Disease

Continuous arterial spin labeling (CASL) magnetic resonance imaging (MRI) was combined with multivariate analysis for detection of an Alzheimer's disease (AD)-related cerebral blood flow (CBF) covariance pattern. Whole-brain resting CBF maps were obtained using spin echo, echo planar imaging (SE-EPI) CASL in patients with mild AD (n=12, age=70.7+/-8.7 years, 7 males, modified Mini-Mental State Examination (mMMS)=38.7/57+/-11.1) and age-matched healthy controls (HC) (n=20; age=72.1+/-6.5 years, 8 males). A covariance pattern for which the mean expression was significantly higher (P<0.0005) in AD than in HC was identified containing posterior cingulate, superior temporal, parahippocampal, and fusiform gyri, as well as thalamus, insula, and hippocampus. The results from this analysis were supplemented with those from the more standard, region of interest (ROI) and voxelwise, univariate techniques. All ROIs (17/hemisphere) showed significant decrease in CBF in AD (P<0.001 for all ROIs, alphacorrected=0.05). The area under the ROC curve for discriminating AD versus HC was 0.97 and 0.94 for covariance pattern and gray matter ROI, respectively. Fewer areas of depressed CBF in AD were detected using voxelwise analysis (corrected, P<0.05). These areas were superior temporal, cingulate, middle temporal, fusiform gyri, as well as inferior parietal lobule and precuneus. When tested on extensive split-half analysis to map out the replicability of both multivariate and univariate approaches, the expression of the pattern from multivariate analysis was superior to that of the univariat

An Event-Related fMRI Study of the Neurobehavioral Impact of Sleep Deprivation on Performance of a Delayed-Match-to-Sample Task

Eighteen subjects (ages 18-35) underwent event-related functional magnetic resonance imaging (efMRI) while performing a delayed-match-to-sample (DMS) task before and immediately after 48 h of sustained wakefulness. The DMS trial events were: a 3-s study period of either a one-, three-, or six-letter visual array; a 7-s retention interval; and a 3-s probe period, where a button press indicated whether the probe letter was in the study array. Ordinal Trend Canonical Variates Analysis (OrT CVA) was applied to the data from the probe period for trials with six-letter study lists prior to and immediately following sleep deprivation to find an activation pattern whose expression decreased with sleep deprivation in as many subjects as possible, while being present in both conditions. The first principal component of the OrT analysis identified a covariance pattern whose expression decreased as a function of sleep deprivation in 17 of 18 subjects (p<0.001). While overall expression of the pattern showed a systematic decrease with sleep deprivation, the brain regions that make up the pattern show covarying increases and decreases in activation. Regions that decreased their activation were noted in the parietal (BA 7 and 40), temporal (BA 37, 38 and 39) and occipital (BA 18 and 19) lobes; regions that increased their activation were noted in the cerebellum, basal ganglia, thalamus and the anterior cingulate gyrus (BA 32). The reduction in pattern expression with sleep deprivation for each subject was related to the change in performance on the DMS task. Subject decreases in pattern expression were correlated with reductions in recognition accuracy (p<0.05), increased intra-individual variability in reaction time (p<0.005) and increased lapsing (p<0.005)

A Common Neural Network for Cognitive Reserve in Verbal and Object Working Memory in Young but Not Old

Epidemiologic evidence suggests that cognitive reserve (CR) mitigates the effects of aging on cognitive function. The goal of this study was to see whether a common neural mechanism for CR could be demonstrated in brain imaging data acquired during the performance of 2 tasks with differing cognitive processing demands. Young and elder subjects were scanned with functional magnetic resonance imaging (fMRI) while performing a delayed item response task that used either letters (40 young, 18 old) or shapes (24 young, 21 old). Difficulty or load was manipulated by varying the number of stimuli that were presented for encoding. Load-dependent fMRI signal corresponding to each trial component (stimulus presentation, retention delay, and probe) and task (letter or shape) was regressed onto 2 putative CR variables. Canonical variates analysis was applied to the resulting maps of regression coefficients, separately for each trial component, to summarize the imaging data--CR relationships. There was a latent brain pattern noted in the stimulus presentation phase that manifested similar relationships between load-related encoding activation and CR variables across the letter and shape tasks in the young but not the elder age group. This spatial pattern could represent a general neural instantiation of CR that is affected by the aging process

An event-related fMRI study of the neural networks underlying repetition suppression and reaction time priming in implicit visual memory

Unfamiliar line drawings were presented to subjects three times during BOLD fMRI scanning. A set of brain areas was detected in which the effect of stimulus repetition on the evoked fMRI response depended on whether or not the drawing could be conceived as a coherent three-dimensional structure. Differential repetition effects were found in the neural response to drawings of both structurally possible and impossible objects. This differential effect of repetition was related to the amount of reaction time priming on the concurrent task involving decisions about three-dimensional structure in the possible but not in the impossible objects. These results point to different neurophysiological processing mechanisms for structurally possible and impossible images and demonstrate neural plasticity that predicts behavioral priming for structurally possible images

White Matter Hyperintensities and Cognition: Testing the Reserve Hypothesis

OBJECTIVE: White matter hyperintensities (WMH), visualized on T2-weighted MRI, are thought to reflect small-vessel vascular disease. Much like other markers of brain disease, the association between WMH and cognition is imperfect. The concept of reserve may account for this imperfect relationship. The purpose of this study was to test the reserve hypothesis in the association between WMH severity and cognition. We hypothesized that individuals with higher amounts of reserve would be able to tolerate greater amounts of pathology than those with lower reserve. METHODS: Neurologically healthy older adults (n=717) from a community-based study received structural MRI, neuropsychological assessment, and evaluation of reserve. WMH volume was quantified algorithmically. We derived latent constructs representing four neuropsychological domains, a measure of cognitive reserve, and a measure of brain reserve. Measures of cognitive and brain reserve consisted of psychosocial (e.g., education) and anthropometric (e.g., craniometry) variables, respectively. RESULTS: Increased WMH volume was associated with poorer cognition and higher cognitive and brain reserve were associated with better cognition. Controlling for speed/executive function or for language function, those with higher estimates of cognitive reserve had significantly greater degrees of WMH volume, particularly among women. Controlling for cognitive functioning across all domains, individuals with higher estimates of brain reserve had significantly greater WMH volume. CONCLUSIONS: For any given level of cognitive function, those with higher reserve had more pathology in the form of WMH, suggesting that they are better able to cope with pathology than those with lower reserve. Both brain reserve and cognitive reserve appear to mitigate the impact of pathology on cognition

Reduction in Cerebral Blood Flow in Areas Appearing as White Matter Hyperintensities on Magnetic Resonance Imaging

The purpose of this study was to examine cerebral blood flow (CBF) as measured by arterial spin labeling (ASL) in tissue classified as white matter hyperintensities (WMH), normal appearing white matter, and grey matter. Seventeen healthy older adults received structural and ASL MRI. Cerebral blood flow was derived for three tissue types: WMH, normal appearing white matter, and grey matter. Cerebral blood flow was lower in WMH areas relative to normal appearing white matter, which in turn, was lower than grey matter. Regions with consistently lower CBF across individuals were more likely to appear as WMH. Results are consistent with an emerging literature linking diminished regional perfusion with the risk of developing WMH

Feedback on feedback: eliciting learners’ responses to written feedback through student-generated screencasts

Despite the potential benefits of assignment feedback, learners often fail to use it effectively. This study examines the ways in which adult distance learners engage with written feedback on one of their assignments. Participants were 10 undergraduates studying Spanish at the Open University, UK. Their responses to feedback were elicited by means of student-generated screencast (Jing®) recordings in which students talked through the feedback written by their tutors. The recordings were analysed in terms of the students’ cognitive, affective and metacognitive responses to the tutors’ feedback. Results show that, while students do engage with tutor feedback and make active efforts to integrate it, they sometimes use ineffective strategies, especially when tutor and student make different assumptions about the role of feedback. The richness of the data obtained from the Feedback on feedback (F on F) method suggests that it has the potential to promote much needed feedback dialogue between students and tutors