Faculty Bibliography

Compromised white matter (WM) integrity in inferior frontal WM has been related to impulsivity in men with schizophrenia. However, these relationships may be more widespread. Fractional anisotropy (FA) derived from diffusion tensor imaging of 25 men with schizophrenia was transformed into Talairach space. Correlations between FA and impulsiveness were examined on a voxelwise basis. We found negative correlations between FA and impulsivity in inferior frontal WM, anterior cingulate, caudate, insula, and inferior parietal lobule. Positive correlations were obtained in the left postcentral gyrus, right superior/middle temporal gyrus, and bilateral fusiform gyrus. These areas may comprise a fronto-temporo-limbic circuit that modulates impulsivity. The voxelwise correlation method can serve as a hypothesis-generation method for relating target behaviors to their underlying neural networks

Despite its potential advantages for fMRI analysis, fuzzy C-means (FCM) clustering suffers from limitations such as the need for a priori knowledge of the number of clusters, and unknown statistical significance and instability of the results. We propose a randomization-based method to control the false-positive rate and estimate statistical significance of the FCM results. Using this novel approach, we develop an fMRI activation detection method. The ability of the method in controlling the false-positive rate is shown by analysis of false positives in activation maps of resting-state fMRI data. Controlling the false-positive rate in FCM allows comparison of different fuzzy clustering methods, using different feature spaces, to other fMRI detection methods. In this article, using simulation and real fMRI data, we compare a novel feature space that takes the variability of the hemodynamic response function into account (HRF-based feature space) to the conventional cross-correlation analysis and FCM using the cross-correlation feature space. In both cases, the HRF-based feature space provides a greater sensitivity compared to the cross-correlation feature space and conventional cross-correlation analysis. Application of the proposed method to finger-tapping fMRI data, using HRF-based feature space, detected activation in sub-cortical regions, whereas both of the FCM with cross-correlation feature space and the conventional cross-correlation method failed to detect them

The cerebral deposition of amyloid beta-peptide, a central event in Alzheimer's disease (AD) pathogenesis, begins several years before the onset of clinical symptoms. Noninvasive detection of AD pathology at this initial stage would facilitate intervention and enhance treatment success. In this study, high-field MRI was used to detect changes in regional brain MR relaxation times in three types of mice: 1). transgenic mice (PS/APP) carrying both mutant genes for amyloid precursor protein (APP) and presenilin (PS), which have high levels and clear accumulation of beta-amyloid in several brain regions, starting from 10 weeks of age; 2). transgenic mice (PS) carrying only a mutant gene for presenilin (PS), which show subtly elevated levels of Abeta-peptide without beta-amyloid deposition; and 3). nontransgenic (NTg) littermates as controls. The transverse relaxation time T(2), an intrinsic MR parameter thought to reflect impaired cell physiology, was significantly reduced in the hippocampus, cingulate, and retrosplenial cortex, but not the corpus callosum, of PS-APP mice compared to NTg. No differences in T(1) values or proton density were detected between any groups of mice. These results indicate that T(2) may be a sensitive marker of abnormalities in this transgenic mouse model of AD

Attending to rare stimuli interspersed among repetitive frequent stimuli produces a positive scalp potential at 300 to 600 ms after the target stimulus onset; this potential is known as the P300 wave. Although there is clear evidence of low visual P300 in subjects at high risk (HR) for developing alcoholism, the functional neuroanatomical correlates have not been studied. Functional and high-resolution anatomical magnetic resonance images were collected during the performance of a visual oddball task, from six control (low risk-LR) subjects with high P300s and eight HR subjects with low P300s. All the HR subjects were offspring of male alcoholics. The data were analyzed using a randomization-based statistical method that accounts for multiple comparisons, requires no assumptions about the noise structure of the data, and does not require spatial or temporal smoothing. Target counts showed that all subjects performed the task comparably. Analysis of the functional magnetic resonance imaging (fMRI) data revealed two areas with significantly lower activation in the HR group when compared to the LR group: the bilateral inferior parietal lobule (BA 40), and the bilateral inferior frontal gyrus (BA 44). Inferior parietal lobule showed significantly lower activation in the HR group in contrast to the LR group, and inferior frontal gyrus was not activated in the HR group but was only activated in the LR group. This finding indicates that a dysfunctional frontoparietal circuit may underlie the low P300 responses seen in HR subjects. This perhaps implies a deficiency in the rehearsal component of the working memory system