Kelvin O. Lim

Age-related decline in brain white matter anisotropy measured with spatially corrected echo-planar diffusion tensor imaging.

Echo planar (EP) diffusion tensor imaging (DTI) permits in vivo identification of the orientation and coherence of brain white matter tracts but suffers from field inhomogeneity‐induced geometric distortion. To reduce spatial distortion, polynomial warping corrections were applied and the effects tested on measures of fractional anisotropy (FA) in the genu and splenium of corpus callosum. Implementation entailed spatially warping EP images obtained without diffusion weighting (b = 0) to long‐echo T2‐weighted fast spin echo images, collected for anatomical delineation, tissue segmentation, and coregistration with the diffusion images. Using the optimal warping procedure (third‐order polynomial), the effects of age on FA and a quantitative measure of intervoxel coherence (C) in the genu, splenium, centrum semiovale, and frontal and parietal pericallosal white matter were examined in 31 healthy men (23–76 years). FA declined significantly with age in all regions except the splenium, whereas intervoxel coherence positively correlated with age in the genu. Magn Reson Med 44:259–268, 2000.

Segmentation of MR brain images into cerebrospinal fluid spaces, white and gray matter

An interactive computer method for quantifying CSF, white matter, and gray matter in magnetic resonance (MR) axial brain scans is presented. A stripping algorithm is used to remove the skull and scalp from each axial section. The images are then filtered to correct for radiofrequency inhomoge-neity image artifacts. Late echo images are subtracted from or added to early echo images to enhance fluid/tissue and gray/white tissue contrast, respectively. Thresholds for fluid/tissue and gray/white separation are set interactively. A boundary pixel locking algorithm is used to handle ambiguities due to partial voluming between the fluid and tissue compartments. The MR brain scans from five healthy, young, normal men were obtained using a standard neuroanatomical reference technique. These data were processed and percentages computed for fluid, gray matter and white matter compartments. The gray/white ratios compare favorably with those determined in a published postmortem brain study.

In vivo spectroscopic quantification of the N-acetyl moiety, creatine, and choline from large volumes of brain gray and white matter: effects of normal aging.

Volumetric proton magnetic resonance spectroscopic imaging (MRSI) was used to generate brain metabolite maps in 15 young and 19 elderly adult volunteers. All subjects also had structural MR scans, and a model, which took into account the underlying structural composition of the brain contributing to each metabolite voxel, was developed and used to estimate the concentration of the N‐acetyl‐moiety (NAc), creatine (Cr), and choline (Cho) in gray matter and white matter. NAc concentration (signal intensity per unit volume of brain) was higher in gray than white matter and did not differ between young and old subjects despite significant gray matter volume deficits in the older subjects. To the extent that NAc is an index of neuronal integrity, the available gray matter appears to be intact in these older healthy adults. Cr concentrations were much higher in gray than white matter and significantly higher in the old than young subjects. Cho concentration in gray matter was also significantly higher in old than young subjects. Independent determination of metabolite values rather than use of ratios is essential for characterizing age‐related changes in brain MRS metabolites. Magn Reson Med 41:276–284, 1999. Published 1999 Wiley‐Liss, Inc.

Age-related decline in MRI volumes of temporal lobe gray matter but not hippocampus

The effect of normal aging on the volume of the hippocampus and temporal cortex was assessed cross-sectionally with quantitative Magnetic Resonance Imaging (MRI) in 72 healthy men, spanning 5 decades of the adult age range (21 to 70 years). Neither the hippocampal nor cortical white matter volumes were significantly correlated with age. By contrast, left and right temporal lobe gray matter volumes, exclusive of the hippocampal measures, each decreased with age (p < 0.01). Volumes of temporal lobe sulcal CSF and the ventricular system (temporal horns and lateral and third ventricles) significantly increased with age. Measures of verbal and nonverbal working memory showed age-related declines and were related to enlargement of the three ventricular regions, which may be indicative of age-related atrophy of the adjacent cortex but not the hippocampus, at least up to age 70 years.

Longitudinal changes in cognition, gait, and balance in abstinent and relapsed alcoholic men: relationships to changes in brain structure.

Chronic alcoholism is associated with cognitive and motor deficits, and there is evidence for reversibility with sobriety. Alcoholic men were examined after 1 month of sobriety and 2 to 12 months later with cognitive and motor tests and magnetic resonance imaging. In this naturalistic study, 20 alcoholic participants had abstained and 22 had resumed drinking at retesting. Abstainers sustained greater improvement than relapsers on tests of delayed recall of drawings, visuospatial function, attention, gait, and balance. Shrinkage in 3rd ventricle volume across all participants significantly correlated with improvement in nonverbal short-term memory. Additional brain structure-function relationships, most involving short-term memory, were observed when analyses were restricted to alcoholic men who had maintained complete abstinence, were light relapsers for at least 3 months, or had consumed no more than 10 drinks prior to follow-up testing. Thus, alcoholic men who maintain abstinence can show substantial functional improvement that is related to improvement in brain structure condition.

Volumetric MRI assessment of temporal lobe structures in schizophrenia

This magnetic resonance imaging (MRI) study was designed to investigate whether patients with schizophrenia have focal or lateralized deficits in the volumes of temporal lobe structures. Estimated volumes of the temporal lobes, hippocampi, superior temporal gyri, lateral ventricles, third ventricle, temporal horns of the lateral ventricles, and a frontal-parietal reference area (FPRA) were quantified for each hemisphere. The schizophrenic group had less gray matter (GM) in the temporal lobes and the FPRA relative to controls. Ventricular volumes were significantly larger in the schizophrenic group, as was cerebrospinal fluid (CSF) volume for temporal lobe sulci. No significant differences in hippocampal volumes emerged between groups. The magnitude of GM deficit was not greater in the temporal lobes relative to the FPRA. These results confirm the presence of bilateral GM volume deficits of the temporal lobes in schizophrenia but do not support the hypothesis that structural changes preferentially affect the temporal lobes or the left cerebral hemisphere.

Schizophrenics have fewer and smaller P300s: A single-trial analysis

Because P300 is typically measured from an average of single trials, variations among individual trials may account for P300 amplitude reduction so often seen in patients with schizophrenia. We tested three hypotheses regarding single-trial contribution to small average P300s in schizophrenics: normal P300s are elicited on some trials and no P300s on others, all trials have consistently small P300s, or P300 latency varies over trials. Nineteen schizophrenics and 35 controls were tested on a two-tone auditory oddball event-related potential (ERP) paradigm. ERPs recorded from the parietal electrode (Pz) were subjected to a P300-screening procedure in which a 2 Hz half-sine wave template was moved across the electroencephalogram (EEG) to find the point of best fit. If, for the point of best fit, the EEG:Template covariance was greater in the signal epoch (280-600 msec) than in the noise epoch (610-930 msec), and if the EEG:Template correlation was statistically significant, the trial passed the P300-screen and was deemed to have a P300. Three types of average ERPs were constructed: Traditional Average from all good (artifact-free, correct response) trials, P300-Screen Average from all good trials that also passed the P300-screen, and Latency Adjusted Average by aligning the P300-screen trials at the latency of maximum covariance. Traditional average ERPs were significantly smaller in schizophrenics than in controls. The results of the P300-screen confirmed all three hypotheses: schizophrenics had fewer trials passing the P300-screen, smaller P300s on each trial, and P300s that were more variable in latency across trials.(ABSTRACT TRUNCATED AT 250 WORDS)

Cortical and Hippocampal Volume Deficits in Temporal Lobe Epilepsy

Summary: Purpose: To use quantitative magnetic resonance imaging (MRI) methods to examine the extent of volume abnormalities in the hippocampus and in extrahippocampal brain regions in localization‐related epilepsy of temporal lobe origin (TLE).

The relationship between P300 amplitude and regional gray matter volumes depends upon the attentional system engaged.

Event-related potentials (ERPs) and brain magnetic resonance images (MRIs) were acquired from 28 normal men, age 21-60 years. ERPs were recorded during 3 paradigms designed to elicit automatic or effortful attention, and a combination of both. MRI-derived measures of brain gray matter, white matter and cerebral spinal fluid (CSF) volumes were computed from frontal, parietal and temporal lobes. P300 amplitude correlated significantly with gray matter volumes but not with white matter or CSF volumes. Furthermore, the relationships between P300 amplitude and gray matter volumes reflected functional rather than direct topographical relationships: P300 recorded at Pz during automatically elicited attention correlated significantly with frontal but not parietal lobe gray matter volumes, P300 recorded during effortful attention correlated significantly with parietal but not frontal lobe gray matter volumes, and P300 recorded when both types of attention were invoked correlated significantly with both frontal and parietal gray matter volumes. Startle blinks, also elicited during automatic attention-engaging paradigms, were significantly correlated with frontal but not parietal lobe gray matter volumes. There was no evidence for a direct spatial relationship between P300 amplitude and the gray matter volumes underlying the recording electrode.

Auditory Oddball Deficits in Schizophrenia: An Independent Component Analysis of the fMRI Multisite Function BIRN Study

Deficits in the connectivity between brain regions have been suggested to play a major role in the pathophysiology of schizophrenia. A functional magnetic resonance imaging (fMRI) analysis of schizophrenia was implemented using independent component analysis (ICA) to identify multiple temporally cohesive, spatially distributed regions of brain activity that represent functionally connected networks. We hypothesized that functional connectivity differences would be seen in auditory networks comprised of regions such as superior temporal gyrus as well as executive networks that consisted of frontal-parietal areas. Eight networks were found to be implicated in schizophrenia during the auditory oddball paradigm. These included a bilateral temporal network containing the superior and middle temporal gyrus; a default-mode network comprised of the posterior cingulate, precuneus, and middle frontal gyrus; and multiple dorsal lateral prefrontal cortex networks that constituted various levels of between-group differences. Highly task-related sensory networks were also found. These results indicate that patients with schizophrenia show functional connectivity differences in networks related to auditory processing, executive control, and baseline functional activity. Overall, these findings support the idea that the cognitive deficits associated with schizophrenia are widespread and that a functional connectivity approach can help elucidate the neural correlates of this disorder.