Nancy Madigan

Speed of information processing in traumatic brain injury: modality-specific factors.

Objective: To assess speed of information processing by two serial addition tests (one visual, one auditory) in individuals with moderate-to-severe traumatic brain injuries (TBIs) and in a healthy, normal control group (NC). The tasks were designed to equate and control for accuracy of performance across the TBI and NC groups, thus allowing for quantification of information processing speed. Design: Performance across groups and tasks were compared using 2 × 2 repeated measure analyses of variance (ANOVAs). In addition, each individuals processing speed was used to adjust rate of stimulus presentation on a subsequent “rehabilitation” trial to determine further whether this adjustment equated accuracy of performance. Setting: Rehabilitation hospital. Patients: 22 outpatients with moderate-to-severe TBI (6 women, 16 men; mean age = 34.6 years; duration of loss of consciousness = 22.6 days) and 20 age- and education-matched healthy controls. Results: Processing speed was slower in TBI subjects, relative to controls and was significantly related to measures of executive functioning for those with TBI. Relative to controls, speed of processing in the TBI group was disproportionately slower when information was presented in the auditory, relative to the visual, modality. Conclusions: Speed of information processing is a major impairment in those with TBI when unconfounded by performance accuracy. The modality-specific impairment observed in the TBI group may, in part, be due to a greater within-modality interference effect created by the auditory version of the task. By manipulating information at a pace customized for an individual through compensatory strategies and environmental modifications, information-processing performance of TBI participants can be enhanced significantly.

Relationships among Facial, Prosodic, and Lexical Channels of Emotional Perceptual Processing

This study was designed to address the issue of whether there is a general processor for the perception of emotion or whether there are separate processors. We examined the relationships among three channels of emotional communication in 100 healthy right-handed adult males and females. The channels were facial, prosodic/intonational, and lexical/verbal; both identification and discrimination tasks of emotional perception were utilised. Statistical analyses controlled for nonemotional perceptual factors and subject characteristics (i.e. demographic and general cognitive). For identification, multiple significant correlations were found among the channels. For discrimination, fewer correlations were significant. Overall, these results provide support for the notion of a general processor for emotional perceptual identification in normal adult subjects.

Contribution of cortical lesion subtypes at 7T MRI to physical and cognitive performance in MS

Objectives: Evaluate cross-sectionally the contribution of focal cortical lesion (CL) subtypes at ultra-high-field MRI and traditional MRI metrics of brain damage to neurologic disability and cognitive performance in a heterogeneous multiple sclerosis (MS) cohort. Methods: Thirty-four patients with early or established disease including clinically isolated syndrome, relapsing-remitting MS, and secondary progressive MS were scanned on a human 7-tesla (7T) (Siemens) scanner to acquire fast low-angle shot (FLASH) T2*-weighted images for characterization of white matter and deep gray matter lesion volume, and CL types. Patients also underwent anatomical 3T MRI for cortical thickness estimation, and neuropsychological testing within 1 week of the 7T scan. Twenty-seven patient scans were acceptable for further analysis. Neurologic disability was measured using the Expanded Disability Status Scale. Results: Type III-IV CLs had the strongest relationship to physical disability (ρ = 0.670, p < 0.0001). White matter lesion volume and type I CLs are each significantly associated with 6 of 11 neuropsychological test variables. Type III-IV CLs significantly correlate with 4 of 11 neuropsychological test variables whereas type II CLs, deep gray matter lesion volume, and cortical thickness metrics are less frequently associated with cognitive performance. Conclusions: Leukocortical (type I) and subpial (III-IV) CLs identified on 7T FLASH-T2* sequences are potential cortical biomarkers of cognitive and neurologic status in MS.

The neuroinflammatory component of gray matter pathology in multiple sclerosis

In multiple sclerosis (MS), using simultaneous magnetic resonance–positron emission tomography (MR‐PET) imaging with 11C‐PBR28, we quantified expression of the 18kDa translocator protein (TSPO), a marker of activated microglia/macrophages, in cortex, cortical lesions, deep gray matter (GM), white matter (WM) lesions, and normal‐appearing WM (NAWM) to investigate the in vivo pathological and clinical relevance of neuroinflammation.

Quantitative oxygen extraction fraction from 7-Tesla MRI phase: reproducibility and application in multiple sclerosis.

Quantitative oxygen extraction fraction (OEF) in cortical veins was studied in patients with multiple sclerosis (MS) and healthy subjects via magnetic resonance imaging (MRI) phase images at 7 Tesla (7 T). Flow-compensated, three-dimensional gradient-echo scans were acquired for absolute OEF quantification in 23 patients with MS and 14 age-matched controls. In patients, we collected T2∗-weighted images for characterization of white matter, deep gray matter, and cortical lesions, and also assessed cognitive function. Variability of OEF across readers and scan sessions was evaluated in a subset of volunteers. OEF was averaged from 2 to 3 pial veins in the sensorimotor, parietal, and prefrontal cortical regions for each subject (total of ∼10 vessels). We observed good reproducibility of mean OEF, with intraobserver coefficient of variation (COV)=2.1%, interobserver COV=5.2%, and scan—rescan COV=5.9%. Patients exhibited a 3.4% reduction in cortical OEF relative to controls (P=0.0025), which was not different across brain regions. Although oxygenation did not relate with measures of structural tissue damage, mean OEF correlated with a global measure of information processing speed. These findings suggest that cortical OEF from 7-T MRI phase is a reproducible metabolic biomarker that may be sensitive to different pathologic processes than structural MRI in patients with MS.

Development of procedures for rating posed emotional expressions across facial, prosodic, and lexical channels.

A number of rating systems are available to evaluate emotional communication in a single modality. The main purpose of this study was to develop procedures to train human raters to evaluate posed expressions of emotion across three different channels of communication, i.e., facial, prosodic/intonational, and lexical/verbal. These procedures were used to evaluate posed emotional expressions produced by individuals with unilateral brain lesions from stroke. Posers in this preliminary report were two right brain-damaged, two left brain-damaged, and two normal control right-handed adults who were marched on demographic and neurological factors. Eight emotional expressions, both positive and negative, were produced in three channels and rated for intensity, pleasantness, and category accuracy. 15 normal adults served as raters, five per channel. The rating procedures were comparable across channels, with analogous properties, and yielded substantial interrater agreement. In this small sample of posers, it was observed that the expressions of the right brain-damaged group were rated as the least accurate and those of the left brain-damaged group as the most intense. When patterns of individual performance across the channels were examined, performance was quiet consistent for the normal controls yet variable for the right brain-damaged persons. These observations are in keeping with the notion that patients with right hemisphere pathology have difficulty in emotional communication. In summary, these findings suggest that comparison of emotional expressions across multiple channels is feasible.

The association between intra- and juxta-cortical pathology and cognitive impairment in multiple sclerosis by quantitative T2* mapping at 7 T MRI

Using quantitative T2* at 7 Tesla (T) magnetic resonance imaging, we investigated whether impairment in selective cognitive functions in multiple sclerosis (MS) can be explained by pathology in specific areas and/or layers of the cortex. Thirty-one MS patients underwent neuropsychological evaluation, acquisition of 7 T multi-echo T2* gradient-echo sequences, and 3 T anatomical images for cortical surfaces reconstruction. Seventeen age-matched healthy subjects served as controls. Cortical T2* maps were sampled at various depths throughout the cortex and juxtacortex. Relation between T2*, neuropsychological scores and a cognitive index (CI), calculated from a principal component analysis on the whole battery, was tested by a general linear model. Cognitive impairment correlated with T2* increase, independently from white matter lesions and cortical thickness, in cortical areas highly relevant for cognition belonging to the default-mode network (p < 0.05 corrected). Dysfunction in different cognitive functions correlated with longer T2* in selective cortical regions, most of which showed longer T2* relative to controls. For most tests, this association was strongest in deeper cortical layers. Executive dysfunction, however, was mainly related with pathology in juxtameningeal cortex. T2* explained up to 20% of the variance of the CI, independently of conventional imaging metrics (adjusted-R2: 52–67%, p < 5.10− 4). Location of pathology across the cortical width and mantle showed selective correlation with impairment in differing cognitive domains. These findings may guide studies at lower field strength designed to develop surrogate markers of cognitive impairment in MS.

Is the Relationship between Cortical and White Matter Pathologic Changes in Multiple Sclerosis Spatially Specific? A Multimodal 7-T and 3-T MR Imaging Study with Surface and Tract-based Analysis

PURPOSE To investigate in vivo the spatial specificity of the interdependence between intracortical and white matter (WM) pathologic changes as function of cortical depth and distance from the cortex in multiple sclerosis (MS), and their independent contribution to physical and cognitive disability. MATERIALS AND METHODS This study was institutional review board-approved and participants gave written informed consent. In 34 MS patients and 17 age-matched control participants, 7-T quantitative T2* maps, 3-T T1-weighted anatomic images for cortical surface reconstruction, and 3-T diffusion tensor images (DTI) were obtained. Cortical quantitative T2* maps were sampled at 25%, 50%, 75% depth from pial surface. Tracts of interest were reconstructed by using probabilistic tractography. The relationship between DTI metrics voxelwise of the tracts and cortical integrity in the projection cortex was tested by using multilinear regression models. RESULTS In MS, DTI abnormal findings along tracts correlated with quantitative T2* changes (suggestive of iron and myelin loss) at each depth of the cortical projection area (P < .01, corrected). This association, however, was not spatially specific because abnormal findings in WM tracts also related to cortical pathologic changes outside of the projection cortex of the tract (P < .001). Expanded Disability Status Scale pyramidal score was predicted by axial diffusivity along the corticospinal tract (β = 4.6 × 10(3); P < .001), Symbol Digit Modalities Test score by radial diffusivity along the cingulum (β = -4.3 × 10(4); P < .01), and T2* in the cingulum cortical projection at 25% depth (β = -1.7; P < .05). CONCLUSION Intracortical and WM injury are concomitant pathologic processes in MS, which are not uniquely distributed according to a tract-cortex-specific pattern; their association may reflect a common stage-dependent mechanism.

Hedonic Ratings of Odors as a Function of Odor Sequence in Older Adults

Pleasant and unpleasant odors were presented to 20 subjects in two same-valence blocks, i.e., all pleasant ones first, all unpleasant ones second, or vice versa, and in alternation. Hedonic ratings increased for the second block of odors which followed the first block of oppositely valenced odors. Alternation did not appear to affect hedonic ratings. These findings suggest that presentation of odors can alter hedonic ratings, producing a contrast effect when odors are given in a blocked fashion.

Heterogeneous pathological processes account for thalamic degeneration in multiple sclerosis: Insights from 7 T imaging

Background: Thalamic degeneration impacts multiple sclerosis (MS) prognosis. Objective: To investigate heterogeneous thalamic pathology, its correlation with white matter (WM), cortical lesions and thickness, and as function of distance from cerebrospinal fluid (CSF). Methods: In 41 MS subjects and 17 controls, using 3 and 7 T imaging, we tested for (1) differences in thalamic volume and quantitative T2* (q-T2*) (2) globally and (3) within concentric bands originating from the CSF/thalamus interface; (4) the relation between thalamic, cortical, and WM metrics; and (5) the contribution of magnetic resonance imaging (MRI) metrics to clinical scores. We also assessed MS thalamic lesion distribution as a function of distance from CSF. Results: Thalamic lesions were mainly located next to the ventricles. Thalamic volume was decreased in MS versus controls (p < 10−2); global q-T2* was longer in secondary progressive multiple sclerosis (SPMS) only (p < 10−2), indicating myelin and/or iron loss. Thalamic atrophy and longer q-T2* correlated with WM lesion volume (p < 0.01). In relapsing-remitting MS, q-T2* thalamic abnormalities were located next to the WM (p < 0.01 (uncorrected), p = 0.09 (corrected)), while they were homogeneously distributed in SPMS. Cortical MRI metrics were the strongest predictors of clinical outcome. Conclusion: Heterogeneous pathological processes affect the thalamus in MS. While focal lesions are likely mainly driven by CSF-mediated factors, overall thalamic degeneration develops in association with WM lesions.