Publications by Year: 2008

BACKGROUND: Alcoholism-related deficits in cognition and emotion point toward frontal and limbic dysfunction, particularly in the right hemisphere. Prefrontal and anterior cingulate cortices are involved in cognitive and emotional functions and play critical roles in the oversight of the limbic reward system. In the present study, we examined the integrity of white matter tracts that are critical to frontal and limbic connectivity. METHODS: Diffusion tensor magnetic resonance imaging (DT-MRI) was used to assess functional anisotropy (FA), a measure of white matter integrity, in 15 abstinent long-term chronic alcoholic and 15 demographically equivalent control men. Voxel-based and region-based analyses of group FA differences were applied to these scans. RESULTS: Alcoholic subjects had diminished frontal lobe FA in the right superior longitudinal fascicles II and III, orbitofrontal cortex white matter, and cingulum bundle, but not in corresponding left hemisphere regions. These right frontal and cingulum white matter regional FA measures provided 97% correct group discrimination. Working Memory scores positively correlated with superior longitudinal fascicle III FA measures in control subjects only. CONCLUSIONS: The findings demonstrate white matter microstructure deficits in abstinent alcoholic men in several right hemisphere tracts connecting prefrontal and limbic systems. These white matter deficits may contribute to underlying dysfunction in memory, emotion, and reward response in alcoholism.

CONTEXT: Previous studies have reported hypofunction, structural abnormalities, and biochemical abnormalities of the dorsal anterior midcingulate cortex (daMCC) in attention-deficit/hyperactivity disorder (ADHD). Stimulant medications are effective treatments for ADHD, but their neural effects have not been fully characterized. OBJECTIVE: To determine whether the methylphenidate hydrochloride osmotic-release oral system (OROS) would increase functional magnetic resonance imaging (fMRI) activation, compared with placebo, in the daMCC and other frontoparietal regions subserving attention during the Multi-Source Interference Task (MSIT). DESIGN: Randomized, placebo-controlled, 6-week, before-after fMRI study. SETTING: Academic medical center ambulatory clinic.

OBJECTIVE: The limbic structures in early-onset schizophrenia-spectrum illness (SZ) and bipolar disorder (BPD) were studied to discern patterns associated with diagnosis and sex. METHODS: Thirty-five youths with DSM-IV BPD without psychosis, 19 with BPD with psychosis, 20 with SZ, and 29 healthy controls (HC), similar in age (6-17 years) and sex, underwent structured and clinical interviews, neurological examination, and cognitive testing. Structural magnetic resonance images (MRIs) were acquired on a 1.5 Tesla, General Electric Signa Scanner. Differences in subcortical brain volumes, including the amygdala and hippocampus, were evaluated using two-way (diagnosis, sex) univariate analyses covarying for total cerebral volume and age. RESULTS: Youth with SZ and BPD showed no differences in amygdala and hippocampal volumes. However, boys with SZ had smallest left amygdala and girls with BPD had the smallest left hippocampal volumes. In exploratory analyses, SZ showed reduced thalamic volumes bilaterally and both BPD groups had larger right nucleus accumbens (NA) volumes relative to HC. CONCLUSION: There were no limbic volumetric differences between BPD and SZ. However, there were diagnosis-by-sex interactions in the amygdala and hippocampus, structures that are rich in sex hormone receptors. In addition, smaller thalamus was associated with SZ while larger right NA volumes were most related to BPD. This study underscores the importance of assessing diagnostic effects and sex effects on the brain in future studies and provides evidence that boys and girls with SZ and BPD may have differential patterns of neuropathology associated with disease expression.

Attention-deficit/hyperactivity disorder (ADHD) is hypothesized to be due, in part, to structural defects in brain networks influencing cognitive, affective, and motor behaviors. Although the current literature on fiber tracts is limited in ADHD, gray matter abnormalities suggest that white matter (WM) connections may be altered selectively in neural systems. A prior study (Ashtari et al. 2005), using diffusion tensor magnetic resonance imaging (DT-MRI), showed alterations within the frontal and cerebellar WM in children and adolescents with ADHD. In this study of adults with childhood ADHD, we hypothesized that fiber pathways subserving attention and executive functions (EFs) would be altered. To this end, the cingulum bundle (CB) and superior longitudinal fascicle II (SLF II) were investigated in vivo in 12 adults with childhood ADHD and 17 demographically comparable unaffected controls using DT-MRI. Relative to controls, the fractional anisotropy (FA) values were significantly smaller in both regions of interest in the right hemisphere, in contrast to a control region (the fornix), indicating an alteration of anatomical connections within the attention and EF cerebral systems in adults with childhood ADHD. The demonstration of FA abnormalities in the CB and SLF II in adults with childhood ADHD provides further support for persistent structural abnormalities into adulthood.

OBJECTIVE: This study aimed to explore the potential of in vivo q-space imaging in the differentiation between different cerebral water components. MATERIALS AND METHODS: Diffusion-weighted imaging was performed in six directions with 32 equally spaced q values and a maximum b value of 6600 s/mm(2). The shape of the signal-attenuation curve and the displacement propagator were examined and compared with a normal distribution using the kurtosis parameter. Maps displaying kurtosis, fast and slow components of the apparent diffusion coefficients, fractional anisotropy and directional diffusion were calculated. The displacement propagator was further described by the full width at half and at tenth maximum and by the probability density of zero displacement P(0). Three healthy volunteers and three patients with previously diagnosed multiple sclerosis (MS) were examined. RESULTS: Simulations indicated that the kurtosis of a signal-attenuation curve can determine if more than one water component is present and that care must be taken to select an appropriate threshold. It was possible to distinguish MS plaques in both signal and diffusional kurtosis maps, and in one patient, plaques of different degree of demyelinization showed different behavior. DISCUSSION: Our results indicate that in vivo q-space analysis is a potential tool for the assessment of different cerebral water components, and it might extend the diagnostic interpretation of data from diffusion magnetic resonance imaging.