Neuropsychological patterns in magnetic resonance imaging-defined subgroups of patients with degenerative dementia.

We hypothesized that specific neuropsychological deficits were associated with specific patterns of atrophy. A magnetic resonance imaging volumetric study and a neuropsychological protocol were obtained for patients with several frontotemporal lobar dementia phenotypes including a social/dysexecutive (SOC/EXEC, n = 17), progressive nonfluent aphasia (n = 9), semantic dementia (n = 7), corticobasal syndrome (n = 9), and Alzheimer's disease (n = 21). Blinded to testing results, patients were partitioned according to pattern of predominant cortical atrophy; our partitioning algorithm had been derived using seriation, a hierarchical classification technique. Neuropsychological test scores were regressed versus these atrophy patterns as fixed effects using the covariate total atrophy as marker for disease severity. The results showed the model accounted for substantial variance. Furthermore, the "large-scale networks" associated with each neuropsychological test conformed well to the known literature. For example, bilateral prefrontal cortical atrophy was exclusively associated with SOC/EXEC dysfunction. The neuropsychological principle of "double dissociation" was supported not just by such active associations but also by the "silence" of locations not previously implicated by the literature. We conclude that classifying patients with degenerative dementia by specific pattern of cortical atrophy has the potential to predict individual patterns of cognitive deficits.

Race differences in the age at diagnosis among medicaid-eligible children with autism.

OBJECTIVE: To examine racial differences in the age at which Medicaid-eligible children first receive an autistic disorder (AD) diagnosis and to examine time in mental health treatment until an AD diagnosis was received. METHOD: Philadelphia Medicaid specialty mental health claims identified 406 children who received services in 1999 for AD. Claims from 1993-1999 were used to identify the date of first mental health visit, first receipt of AD diagnosis, and number of visits occurring between those dates. Linear regression was used to examine the relationship among race, age at first diagnosis of AD, time in mental health treatment, and number of visits until the diagnosis was made. RESULTS: On average, white children received the AD diagnosis at 6.3 years of age, compared with 7.9 years for black children (p <.001). White children entered the mental health system at an earlier age (6.0 versus 7.1 years, p =.005); however, after adjusting for age, sex, and time eligible for Medicaid, black children required more time in treatment before receiving the diagnosis. CONCLUSIONS: Important disparities exist in the early detection and treatment of autism. These disparities may be the result of differences in help-seeking, advocacy and support, and clinician behaviors.

Integrating postprocessed functional MR images with picture archiving and communication systems.

We describe a method of converting postprocessed functional MR images to the Digital Imaging and Communications in Medicine (DICOM) standard and sending these DICOM images directly into any picture archiving and communication system (PACS) or stand-alone DICOM database. This method provides system-wide access and archiving of previously research-only applications, it permits the clinical review of postprocessed data on DICOM-compliant workstations, and it can be used to move functional MR data onto intraoperative neuronavigational workstations for surgical guidance. The procedure can be used with any MR postprocessed dataset, and it can be extended to other imaging modalities.

Prelude to passion: limbic activation by "unseen" drug and sexual cues.

BACKGROUND: The human brain responds to recognizable signals for sex and for rewarding drugs of abuse by activation of limbic reward circuitry. Does the brain respond in similar way to such reward signals even when they are "unseen", i.e., presented in a way that prevents their conscious recognition? Can the brain response to "unseen" reward cues predict the future affective response to recognizable versions of such cues, revealing a link between affective/motivational processes inside and outside awareness? METHODOLOGY/PRINCIPAL FINDINGS: We exploited the fast temporal resolution of event-related functional magnetic resonance imaging (fMRI) to test the brain response to "unseen" (backward-masked) cocaine, sexual, aversive and neutral cues of 33 milliseconds duration in male cocaine patients (n = 22). Two days after scanning, the affective valence for visible versions of each cue type was determined using an affective bias (priming) task. We demonstrate, for the first time, limbic brain activation by "unseen" drug and sexual cues of only 33 msec duration. Importantly, increased activity in an large interconnected ventral pallidum/amygdala cluster to the "unseen" cocaine cues strongly predicted future positive affect to visible versions of the same cues in subsequent off-magnet testing, pointing both to the functional significance of the rapid brain response, and to shared brain substrates for appetitive motivation within and outside awareness. CONCLUSIONS/SIGNIFICANCE: These findings represent the first evidence that brain reward circuitry responds to drug and sexual cues presented outside awareness. The results underscore the sensitivity of the brain to "unseen" reward signals and may represent the brain's primordial signature for desire. The limbic brain response to reward cues outside awareness may represent a potential vulnerability in disorders (e.g., the addictions) for whom poorly-controlled appetitive motivation is a central feature.

Comparison of quantitative perfusion imaging using arterial spin labeling at 1.5 and 4.0 Tesla.

High-field arterial spin labeling (ASL) perfusion MRI is appealing because it provides not only increased signal-to-noise ratio (SNR), but also advantages in terms of labeling due to the increased relaxation time T(1) of labeled blood. In the present study, we provide a theoretical framework for the dependence of the ASL signal on the static field strength, followed by experimental validation in which a multislice pulsed ASL (PASL) technique was carried out at 4T and compared with PASL and continuous ASL (CASL) techniques at 1.5T, both in the resting state and during motor activation. The resting-state data showed an SNR ratio of 2.3:1.4:1 in the gray matter and a contrast-to-noise ratio (CNR) of 2.7:1.1:1 between the gray and white matter for the difference perfusion images acquired using 4T PASL, 1.5T CASL, and 1.5T PASL, respectively. However, the functional data acquired using 4T PASL did not show significantly improved sensitivity to motor cortex activation compared with the 1.5T functional data, with reduced fractional perfusion signal change and increased intersubject variability. Possible reasons for these experimental results, including susceptibility effects and physiological noise, are discussed.

Relapsing-remitting multiple sclerosis and whole-brain N-acetylaspartate measurement: evidence for different clinical cohorts initial observations.

PURPOSE: To quantify the rate of concentration decline of neuronal marker N-acetylaspartate (NAA) in the entire brain of patients with relapsing-remitting multiple sclerosis (MS) in relation to healthy age-matched control subjects. MATERIALS AND METHODS: Whole-brain NAA (WBNAA) concentration was quantified in 49 patients with relapsing-remitting MS by using magnetic resonance (MR) imaging and proton MR spectroscopy. It was statistically analyzed by using Spearman rank correlation coefficients to test the intragroup relationship between WBNAA and Expanded Disability Status Scale (EDSS) score and Mann-Whitney analyses to test for differences between subgroups' EDSS scores versus previously published WBNAA values for healthy subjects, disease duration, and age. RESULTS: Analyses indicated three subgroups of WBNAA dynamics: Ten patients' conditions were "stable," exhibiting an insignificant change of about 0% (0.02/14.37) per year of clinically definite disease duration (P =.54); 27 patients showed "moderate" decline, -2.8% (-0.34/12.18) per year (P <.01); and 12 patients experienced "rapid" decline, -27.9% (-3.39/12.14) per year (P <.01). No correlation was found between WBNAA deficit, EDSS score, and age. CONCLUSION: Ascertaining an individual's NAA concentration dynamics might enable early forecast of disease course, reflect disease severity and thus influence treatment decisions, and improve clinical trial efficiency by allowing selection of candidates on the basis of WBNAA dynamics in addition to clinical status.