In vivo evidence of differential frontal cortex metabolic abnormalities in progressive and relapsing-remitting multiple sclerosis.

The pathophysiology of progressive multiple sclerosis remains elusive, significantly limiting available disease-modifying therapies. Proton MRS (1 H-MRS) enables in vivo measurement of small molecules implicated in multiple sclerosis, but its application to key metabolites glutamate, γ-aminobutyric acid (GABA), and glutathione has been sparse. We employed, at 7 T, a previously validated 1 H-MRS protocol to measure glutamate, GABA, and glutathione, as well as glutamine, N-acetyl aspartate, choline, and myoinositol, in the frontal cortex of individuals with relapsing-remitting (N = 26) or progressive (N = 21) multiple sclerosis or healthy control adults (N = 25) in a cross-sectional analysis. Only individuals with progressive multiple sclerosis demonstrated reduced glutamate (F2,65 = 3.424, p = 0.04; 12.40 ± 0.62 mM versus control 13.17 ± 0.95 mM, p = 0.03) but not glutamine (F2,65 = 0.352, p = 0.7; 4.71 ± 0.35 mM versus control 4.84 ± 0.42 mM), reduced GABA (F2,65 = 3.89, p = 0.03; 1.29 ± 0.23 mM versus control 1.47 ± 0.25 mM, p = 0.05), and possibly reduced glutathione (F2,65 = 0.352, p = 0.056; 2.23 ± 0.46 mM versus control 2.51 ± 0.48 mM, p < 0.1). As a group, multiple sclerosis patients demonstrated significant negative correlations between disease duration and glutamate or GABA (ρ = -0.4, p = 0.02) but not glutamine or glutathione. Alone, only relapsing-remitting multiple sclerosis patients exhibited a significant negative correlation between disease duration and GABA (ρ = -0.5, p = 0.03). Taken together, these results indicate that frontal cortex metabolism is differentially disturbed in progressive and relapsing-remitting multiple sclerosis.

Prognosticating brain tumor patient survival after laser thermotherapy: Comparison between neuroradiological reading and semi-quantitative analysis of MRI data.

BACKGROUND AND PURPOSE: Given increasing interest in laser interstitial thermotherapy (LITT) to treat brain tumor patients, we explored if examining multiple MRI contrasts per brain tumor patient undergoing surgery can impact predictive accuracy of survival post-LITT. MATERIALS AND METHODS: MRI contrasts included fluid-attenuated inversion recovery (FLAIR), T1 pre-gadolinium (T1pre), T1 post-gadolinium (T1Gd), T2, diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC), susceptibility weighted images (SWI), and magnetization-prepared rapid gradient-echo (MPRAGE). The latter was used for MRI data registration across preoperative to postoperative scans. Two ROIs were identified by thresholding preoperative FLAIR (large ROI) and T1Gd (small ROI) images. For each MRI contrast, a numerical score was assigned based on changing image intensity of both ROIs (vs. a normal ROI) from preoperative to postoperative stages. The fully-quantitative method was based on changing image intensity across scans at different stages without any human intervention, whereas the semi-quantitative method was based on subjective criteria of cumulative trends across scans at different stages. A fully-quantitative/semi-quantitative score per patient was obtained by averaging scores for each MRI contrast. A standard neuroradiological reading score per patient was obtained from radiological interpretation of MRI data. Scores from all 3 methods per patient were compared against patient survival, and re-examined for comorbidity and pathology effects. RESULTS: Patient survival correlated best with semi-quantitative scores obtained from T1Gd, ADC, and T2 data, and these correlations improved when biopsy and comorbidity were included. CONCLUSION: These results suggest interfacing neuroradiological readings with semi-quantitative image analysis can improve predictive accuracy of patient survival.

Randomized, Sham-Controlled Trial of Real-Time Functional Magnetic Resonance Imaging Neurofeedback for Tics in Adolescents With Tourette Syndrome.

BACKGROUND: Activity in the supplementary motor area (SMA) has been associated with tics in Tourette syndrome (TS). The aim of this study was to test a novel intervention-real-time functional magnetic resonance imaging neurofeedback from the SMA-for reduction of tics in adolescents with TS. METHODS: Twenty-one adolescents with TS were enrolled in a double-blind, randomized, sham-controlled, crossover study involving two sessions of neurofeedback from their SMA. The primary outcome measure of tic severity was the Yale Global Tic Severity Scale administered by an independent evaluator before and after each arm. The secondary outcome was control over the SMA assessed in neuroimaging scans, in which subjects were cued to increase/decrease activity in SMA without receiving feedback. RESULTS: All 21 subjects completed both arms of the study and all assessments. Participants had significantly greater reduction of tics on the Yale Global Tic Severity Scale after real neurofeedback as compared with the sham control (p < .05). Mean Yale Global Tic Severity Scale Total Tic score decreased from 25.2 ± 4.6 at baseline to 19.9 ± 5.7 at end point in the neurofeedback condition and from 24.8 ± 8.1 to 23.3 ± 8.5 in the sham control condition. The 3.8-point difference is clinically meaningful and corresponds to an effect size of 0.59. However, there were no differences in changes on the secondary measure of control over the SMA. CONCLUSIONS: This first randomized controlled trial of real-time functional magnetic resonance imaging neurofeedback in adolescents with TS suggests that this neurofeedback intervention may be helpful for improving tic symptoms. However, no effects were found in terms of change in control over the SMA, the hypothesized mechanism of action.

Neural correlates of stress-induced and cue-induced drug craving: influences of sex and cocaine dependence.

OBJECTIVE: Although stress and drug cue exposure each increase drug craving and contribute to relapse in cocaine dependence, no previous research has directly examined the neural correlates of stress-induced and drug cue-induced craving in cocaine-dependent women and men relative to comparison subjects. METHOD: Functional MRI was used to assess responses to individualized scripts for stress, drug/alcohol cue and neutral-relaxing-imagery conditions in 30 abstinent cocaine-dependent individuals (16 women, 14 men) and 36 healthy recreational-drinking comparison subjects (18 women, 18 men). RESULTS: Significant three-way interactions between diagnostic group, sex, and script condition were observed in multiple brain regions including the striatum, insula, and anterior and posterior cingulate. Within women, group-by-condition interactions were observed involving these regions and were attributable to relatively increased regional activations in cocaine-dependent women during the stress and, to a lesser extent, neutral-relaxing conditions. Within men, group main effects were observed involving these same regions, with cocaine-dependent men demonstrating relatively increased activation across conditions, with the main contributions from the drug and neutral-relaxing conditions. In men and women, subjective drug-induced craving measures correlated positively with corticostriatal-limbic activations. CONCLUSIONS: In cocaine dependence, corticostriatal-limbic hyperactivity appears to be linked to stress cues in women, drug cues in men, and neutral-relaxing conditions in both. These findings suggest that sex should be taken into account in the selection of therapies in the treatment of addiction, particularly those targeting stress reduction.

Unification of sentence processing via ear and eye: an fMRI study.

We present new evidence based on fMRI for the existence and neural architecture of an abstract supramodal language system that can integrate linguistic inputs arising from different modalities such that speech and print each activate a common code. Working with sentence material, our aim was to find out where the putative supramodal system is located and how it responds to comprehension challenges. To probe these questions we examined BOLD activity in experienced readers while they performed a semantic categorization task with matched written or spoken sentences that were either well-formed or contained anomalies of syntactic form or pragmatic content. On whole-brain scans, both anomalies increased net activity over non-anomalous baseline sentences, chiefly at left frontal and temporal regions of heteromodal cortex. The anomaly-sensitive sites correspond approximately to those that previous studies (Michael et al., 2001; Constable et al., 2004) have found to be sensitive to other differences in sentence complexity (object relative minus subject relative). Regions of interest (ROIs) were defined by peak response to anomaly averaging over modality conditions. Each anomaly-sensitive ROI showed the same pattern of response across sentence types in each modality. Voxel-by-voxel exploration over the whole brain based on a cosine similarity measure of common function confirmed the specificity of supramodal zones.

Differentiation of speech and nonspeech processing within primary auditory cortex.

Primary auditory cortex (PAC), located in Heschl's gyrus (HG), is the earliest cortical level at which sounds are processed. Standard theories of speech perception assume that signal components are given a representation in PAC which are then matched to speech templates in auditory association cortex. An alternative holds that speech activates a specialized system in cortex that does not use the primitives of PAC. Functional magnetic resonance imaging revealed different brain activation patterns in listening to speech and nonspeech sounds across different levels of complexity. Sensitivity to speech was observed in association cortex, as expected. Further, activation in HG increased with increasing levels of complexity with added fundamentals for both nonspeech and speech stimuli, but only for nonspeech when separate sources (release bursts/fricative noises or their nonspeech analogs) were added. These results are consistent with the existence of a specialized speech system which bypasses more typical processes at the earliest cortical level.

Neural activity associated with stress-induced cocaine craving: a functional magnetic resonance imaging study.

OBJECTIVE: Stress is known to increase cocaine craving and relapse risk in cocaine dependence. Identifying neural activity associated with stress and stress-induced cocaine craving is important in understanding the neurobiology of cocaine craving and relapse. METHOD: Blood oxygenation level dependent (BOLD) signal changes were assessed in a functional magnetic resonance imaging (fMRI) session with healthy controls and treatment-engaged, abstinent, cocaine-dependent individuals (patients) as they participated in brief guided imagery and recall of three personal stress and three personal neutral situations. RESULTS: During stress, patients showed significantly less BOLD activation than controls in specific frontal and para-limbic regions, such as the anterior cingulate (AC) region, left hippocampal/parahippocampal region, right fusiform gyrus, and the right postcentral gyrus. On the other hand, patients had increased activity in the caudate and dorsal striatum region during stress, activation that was significantly associated with stress-induced cocaine craving ratings. CONCLUSIONS: Patients failed to activate AC and related circuits during stress, regions associated with control, and regulation of emotion and distress states. Instead, they exhibited greater craving-related activation in the dorsal striatum, a region related to reward pathways and part of the obsessive-compulsive circuitry. Such functional alterations in stress processing may underlie the stress-related vulnerability to cocaine relapse often observed in cocaine-dependent individuals in early recovery.