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Biomedical subjects

K O Lim

Publications and source records attributed to K O Lim.

At least 19 recordsLinked to original sources

Cognitive and motor impairments are related to gray matter volume deficits in schizophrenia.

This study examined whether the neuropsychological deficits observed in patients with schizophrenia were related to cortical gray matter volume deficits in these patients. All subjects were men and included 34 patients with DSM-III-R Schizophrenia and 47 age-matched healthy controls. Subjects received a battery of 21 tests, assessing four different functional domains: executive functions, short-term memory and production, declarative memory, and motor ability. MRI volumes were corrected for normal variation in head size and age, and neuropsychological test scores were corrected for normal variation in age. The schizophrenic group had significantly smaller cortical gray matter volumes (p < .05) and lower test scores in all functional domain than the control group (p = .0001). Within the schizophrenic group, lower scores in each domain were significantly correlated with smaller total cortical gray matter volumes; however, no predictable relationships were observed between neuropsychological test performance and the volumes of specific cortical regions.

Adult

Brain dysmorphology in adults with congenital rubella plus schizophrenialike symptoms.

Brain morphology was quantified with magnetic resonance imaging (MRI) in adult patients with congenital rubella who also had schizophrenialike symptoms. MRIs were compared with those of adult early-onset schizophrenic patients without congenital rubella and age-matched healthy control subjects. The rubella patients had significantly smaller intracranial volumes and shorter stature than the schizophrenic patients or the controls; however, both patient groups had smaller cortical gray matter, but not white matter, volumes than the control group, even when the MRI volumes were corrected for head size and age. In addition, both patient groups showed significant enlargement of the lateral ventricles but not cortical sulci when compared with expected values of normal adults of the same age and head size. Overall, the pattern of dysmorphology was identical in the rubella and the schizophrenic groups. The observations in the rubella group are consistent with a developmental lesion that limits full brain growth, with the small intracranial volume due at least in part to a severe cortical gray matter volume deficit. Thus, the brain dysmorphology of congenital rubella may provide an instance of prenatal viral infection that models the schizophrenic pattern and provides indirect support for a developmental hypothesis of the neuropathogenesis of schizophrenia.

Adult

Longitudinal volumetric computed tomographic analysis of regional brain changes in normal aging and Alzheimer's disease.

OBJECTIVE: This study used a semiautomated image analysis technique to quantify the rate and regional pattern of cerebrospinal fluid (CSF) volume changes in the computed tomographic brain examinations of healthy adults and patients with Alzheimer's disease (AD). DESIGN: Longitudinal, within-subject design, with statistical correction for longitudinal method error (eg, head repositioning effects). SETTING: Palo Alto (Calif) Department of Veterans Affairs Medical Center. PATIENTS AND OTHER PARTICIPANTS: The 41 patients with AD were recruited from the Geriatric Psychiatry Research Unit and the National Institute of Mental Health Clinical Research Center of the Palo Alto Department of Veterans Affairs Medical Center. The 35 healthy control subjects were recruited from the local community. MAIN OUTCOME MEASURES: Cerebrospinal fluid volumes estimated from computed tomographic scans. RESULTS: Even after accounting for an estimate of method error (eg, head positioning effects) across computed tomographic examinations, the patients with AD showed greater annual CSF volume increases than did the control group. This CSF volume enlargement was not uniform across brain regions of interest; rather, the patients with AD showed disproportionate volume increases in the ventricular system and the sylvian fissures. Greater CSF volume changes in the patients with AD were significantly associated with greater cognitive decline on the Mini-Mental State Examination. Furthermore, younger patients with AD showed more rapid progression on computed tomographic scans than did older patients. CONCLUSIONS: The rate of CSF volume enlargement is region specific, with the most marked annual rate of change occurring in the ventricular system and the sylvian fissures. In addition, younger patients show more rapid progression in the ventricular and frontal sulcal brain regions of interest than do older patients.

Aged

Anterior hippocampal volume deficits in nonamnesic, aging chronic alcoholics.

Magnetic resonance imaging was used to quantify the volume of the hippocampus in 47 men with chronic alcoholism and 72 healthy male control subjects. The subjects ranged in age from 21 to 70 years, thus permitting a test of whether older alcoholics suffer greater brain tissue volume reduction than do younger ones. Comparison brain regions included temporal lobe gray matter, white matter, and cerebrospinal fluid, as well as measures of the lateral ventricles, third ventricle, and temporal horns. The results of this cross-sectional study showed that the anterior, but not the posterior, portions of the hippocampus in both hemispheres were significantly smaller in the alcoholic than the healthy control group. Furthermore, the bilateral anterior hippocampal volume loss was greater in older than younger alcoholics. Despite the hippocampal volume deficit, these alcoholics did not demonstrate an explicit memory impairment; furthermore, memory test scores did not correlate significantly with hippocampal volumes. In the alcoholics, the age-related volume loss, which was over and above that expected in normal aging, was also evident in the temporal cortex and white matter. Likewise, alcoholic ventricular enlargement was age-related. Analysis of covariance revealed that the anterior hippocampal deficit persisted after accounting for the temporal lobe gray matter volume deficit. Multiple regression analysis revealed that the age-related brain volume abnormalities observed in the alcoholics could not be attributed to duration of alcoholism or total lifetime consumption of alcohol.

Adult

Longitudinal changes in magnetic resonance imaging brain volumes in abstinent and relapsed alcoholics.

Chronic alcoholism is associated with smaller volumes of cortical gray matter and white matter and a complementary increase in brain cerebrospinal fluid (CSF) volumes, relative to age norms. This longitudinal study quantified the extent of brain volume changes associated with abstinence and drinking at three time points in chronic alcoholics. We obtained magnetic resonance imaging (MRI) on 58 alcoholic men after an average of 12 days (MRI-1) and 32 days (MRI-2) of sobriety. In addition, 58 healthy control subjects were scanned at a comparable interval. At MRI-3, 11 controls and 39 alcoholics were rescanned, 2-12 months after MRI-2; 19 alcoholics had abstained, and 20 had resumed drinking. Axial MRI slices were segmented into cortical gray matter, white matter, and CSF and summed over seven slices; lateral and third ventricular volumes were also estimated. MRI volume changes were corrected using an estimate of interscan measurement error caused by head positioning differences, and then divided by the interval to yield rates of change (slopes). From MRI-1 to MRI-2, the alcoholic group showed declines in CSF volumes of the lateral ventricles and posterior cortical sulci, and a trend toward an increase in anterior cortical gray matter volume relative to the control group. From MRI-2 to MRI-3, third ventricular volumes decreased in the abstainers relative to the relapsers and controls; cortical white matter volume decreased in the relapsers. In the relapsers, lifetime consumption of alcohol (as of MRI-1) predicted later vulnerability to white matter volume decline and third ventricular enlargement with resumption of drinking. These data suggest that improvement in cortical gray matter, sulcal, and lateral ventricular volumes occur early in the course of abstinence, and that improvement in third ventricular volume appears later with continued abstinence.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

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.

Adult

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)

Adult

A quantitative magnetic resonance imaging study of changes in brain morphology from infancy to late adulthood.

OBJECTIVE: To model in vivo the dynamic interrelations of head size, gray matter, white matter, and cerebrospinal fluid (CSF) volumes from infancy to old age using magnetic resonance imaging (MRI). DESIGN: Cross-sectional, between-subjects using an age-regression model. SETTING: A Veterans Affairs medical center and community hospitals. PARTICIPANTS: There were 88 male and female subjects aged 3 months to 30 years whose clinical MRI film had been read as normal and 73 healthy male volunteers aged 21 to 70 years who had an MRI performed specifically for this study. MAIN OUTCOME MEASURES: These MRI data were quantified using a semiautomated computer technique for segmenting images into gray matter, white matter, and CSF compartments. The cortex was defined geometrically as the outer 45% on each analyzed slice, and the volumes of cortical white matter, gray matter, and CSF were computed. Subcortical (ventricular) CSF volume was computed for the inner 55% of each analyzed slice. RESULTS: In the younger sample, intracranial volume increased by about 300 mL from 3 months to 10 years. The same patterns of change in volume of each compartment across the age range were seen in both sexes: cortical gray matter volume peaked around age 4 years and decreased thereafter; cortical white matter volume increased steadily until about age 20 years; cortical and ventricular CSF volumes remained constant. In the older sample, brain volumes were statistically adjusted for normal variation in head size through a regression procedure and revealed the following pattern: cortical gray matter volume decreased curvilin-early, showing an average volume loss of 0.7 mL/y, while cortical white matter volume remained constant during the five decades; complementary to the cortical gray matter decrease, cortical CSF volume increased by 0.6 mL/y and ventricular volumes increased by 0.3 mL/y. CONCLUSIONS: These patterns of growth and change seen in vivo with MRI are largely consistent with neuropathological studies, as well as animal models of development, and may reflect neuronal progressive and regressive processes, including cell growth, myelination, cell death, and atrophy.

Adolescent

Short TE phosphorus spectroscopy using a spin-echo pulse.

In vivo phosphorus spectroscopy requires very short acquisition delays in order to capture the signal from components with short transverse relaxation times (T2). The echo time typical of standard slice selective spin-echo pulses are too long for this application, so hard pulse, free induction decay (FID) acquisitions have frequently been used instead. With FID, however, there is an interval between the time of coherence and data acquisition (acquisition delay), with resulting baseline distortions. In this paper we describe the design of a new short TE, slice-selective, composite spin-echo pulse with echo times as short as 2.5 ms. With a long TR, fully relaxed, multislice spectra can be collected. This technique will be useful for assessing in vivo, changes in brain phospholipid activity associated with psychiatric and neurological diseases.

Brain

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.

Adult

Effect of suturing on the mechanical properties of bovine pericardium--implications for cardiac valve bioprosthesis.

In the fabrication of a bioprosthetic heart valve from bovine pericardial tissues, the tissues are subjected to suturing. The stress-strain response of sutured as well as unsutured strips of this tissue were examined. The stress-strain response was determined using a tensile-testing machine. It was found that suturing weakens the tissue in that sutured strips are more extensible, exhibit a lower stress at rupture and a lower final elastic modulus. In addition, it was also found that the bigger the suture/needle size used the greater the decrease in tissue strength. In all, tissue strength was observed to decrease by 22 to 59% in this study. The weakening of the tissue is attributed to the puncture holes created by the surgeon's needle which create regions of weakness. This response of bovine pericardial tissue to suturing should be given due consideration in the fabrication of a bioprosthetic heart valve using this tissue.

Animals

Greater abnormalities of brain cerebrospinal fluid volumes in younger than in older patients with Alzheimer's disease.

OBJECTIVE: This study used a semiautomated analysis technique to quantify differences in regional brain cerebrospinal fluid volumes observed with computed tomography between healthy adults and patients with Alzheimer's disease (AD). DESIGN: Cross-sectional, between-subject design, using an age-regression model. SETTING: Palo Alto (Calif) Department of Veterans Affairs Medical Center. PATIENTS AND OTHER PARTICIPANTS: The 117 patients with probable or definite AD were recruited from the Geriatric Psychiatry Research Unit and National Institute of Mental Health Clinical Research Center of the Palo Alto Department of Veterans Affairs Medical Center. The 114 healthy volunteers were recruited from the local community. MAIN OUTCOME MEASURES: Cerebrospinal fluid volumes estimated from computed tomographic scans and neuropsychological test scores. RESULTS: The computed tomographic estimates of ventricular and sulcal cerebrospinal fluid volumes increased significantly in all sampled brain regions in normal aging and were vastly larger in AD than in normal aging. Furthermore, younger patients with AD had significantly greater cerebrospinal fluid volume enlargement than did older patients with AD compared with healthy controls of their age. When the AD group was divided on the basis of reported age at symptom onset, patients in the early-onset group (onset before age 65 years) were quantitatively more abnormal than and showed a different pattern of abnormality from the patients in the late-onset group. This onset difference was also evident in neuropsychological test performance. CONCLUSIONS: This cross-sectional study revealed a number of converging findings that suggested greater abnormality in the early-onset than in the late-onset group of patients with AD. The possibility remains, however, that the two onset groups represent different stages along a continuum of pathologic changes.

Adult

Increase in brain cerebrospinal fluid volume is greater in older than in younger alcoholic patients: a replication study and CT/MRI comparison.

This cross-sectional study used a semi-automated analysis technique to quantify regional brain cerebrospinal fluid (CSF) volumes derived from computed tomography (CT) in 84 healthy men ranging from 21 to 82 years of age and 28 patients meeting Research Diagnostic Criteria for alcohol dependence. The goals were to replicate an earlier CT study of an independent sample of alcoholic and control subjects (Pfefferbaum et al., 1988a; Zipursky et al., 1988) and to compare CT assessments of brain changes with magnetic resonance imaging (MRI) assessments made in the same alcoholic patients (Pfefferbaum et al., 1992). Regional brain changes associated with normal aging were derived by regression analysis, using CT data collected from the healthy control subjects. As in the earlier CT study and in the concurrent MRI study, ventricular and sulcal CSF volumes in alcoholic patients were greater than would be expected for their age. Furthermore, the present CT study replicated the previous CT and MRI findings of a positive relationship between age and CSF volume enlargement in alcoholic patients over and above the normal age-related increase in CSF volume, suggesting greater vulnerability of the aging brain to alcohol. Comparison of CT- and MRI-derived estimates of ventricular and cortical sulcal volume revealed high correlations (> 0.80). MRI and CT produced similar absolute ventricular volumes, while MRI produced larger sulcal volume estimates than did CT. The difference in sulcal volume estimate may be due to differences between CT and MRI in slice thickness and sensitivity to partial volume effects.

Adult

Widespread cerebral gray matter volume deficits in schizophrenia.

Magnetic resonance imaging was used to investigate whether the structural brain differences commonly observed in patients with schizophrenia as compared with normal control subjects are specific to gray or white matter, and furthermore whether such abnormalities are localizable to circumscribed cortical regions. Accordingly, 22 patients meeting DSM-III-R criteria for schizophrenia and 20 healthy community volunteers, all 23 to 45 years old, received magnetic resonance imaging scans. Seven axial magnetic resonance imaging sections of 5-mm thickness were segmented into cerebrospinal fluid, gray matter, and white matter compartments and used for volumetric quantification. For the healthy control subjects, age correlated significantly with the percentage of all magnetic resonance imaging sections taken up by gray matter but not white matter. After correcting for the normal effect of age, the schizophrenic group was found to have significantly less gray matter than the control group but no difference in white matter; ventricular volume was 34% greater in the schizophrenic group. The schizophrenic group had less gray matter in all six cortical subregions analyzed; these differences attained statistical significance for all but the parietal measure. These findings have implications for studies of localized gray matter abnormalities and suggest that regional brain volume measurements need to be expressed in the context of possible widespread gray matter volume deficits in schizophrenia.

Adult

Decreased gray matter in normal aging: an in vivo magnetic resonance study.

Using in vivo magnetic resonance (MR) images, the percentages of gray matter, white matter, and cerebrospinal fluid (CSF) in the brains of 8 young and 6 elderly normal male community volunteers were quantified. Compared with the young men, the elderly men had a significantly lower percentage of gray matter (p less than .01) and higher percentage of CSF (p less than .01). The percentage of white matter was not significantly different between the two groups. This finding suggests that the age-related decrease in brain tissue is chiefly due to loss of gray matter.

Adult

Brain gray and white matter volume loss accelerates with aging in chronic alcoholics: a quantitative MRI study.

Magnetic resonance imaging (MRI) was used to study in vivo the brains of 49 patients with chronic alcoholism, 3 to 4 weeks post-withdrawal, and 43 normal healthy controls, all right-handed male veterans between the ages of 23 and 70 years. MRI scans were analyzed using a semi-automated procedure, which allowed the subcortical regions to be segmented into cerebrospinal fluid (CSF) and brain tissue and the cortical regions to be segmented into CSF, gray matter, and white matter. An age regression model was used to examine the effects of alcohol on brain structure, over and above that expected from the normal aging process. The alcoholics exhibited decreased tissue and increased CSF after correcting for aging. In the cortex, there was significant loss of both gray matter and white matter volume. In this sample of alcoholics, no particular cortical region was preferentially affected or spared. Furthermore, brain tissue volume loss increased with advanced age in the alcoholics. In this group of alcoholics there was no relationship between length of illness and age, i.e., the younger alcoholics had as heavy alcohol use histories as did the older alcoholics. Thus, the increased brain tissue loss with advanced age is interpreted as evidence for age-related increase in brain vulnerability to chronic alcohol abuse.

Adult

Hepatobiliary MR imaging: first human experience with MnDPDP.

The first human MR imaging results for the hepatobiliary contrast agent manganese(II)N,N'-dipyridoxylethylenediamine-N,N'-diacetate 5,5'-bis(phosphate) (MnDPDP) are reported. MnDPDP is a paramagnetic contrast agent specific for hepatobiliary imaging. An imaging study was performed to investigate the presence of contrast enhancement or facilitated visualization of normal structures. Twelve healthy subjects receiving MnDPDP at doses of 3, 10, or 15 mumol/kg were imaged after injection for approximately 30 minutes at 1-5-minute intervals. Transaxial abdominal images were obtained at 1.5 T in a single breath-hold interval of 21 seconds with use of a spin-echo pulse sequence (repetition time = 150 msec, echo time = 20 msec). Liver parenchyma enhancement was observed 1 minute after injection and persisted for at least 30 minutes. Clearance into the gallbladder was visualized within 15 minutes. Enhancement was dose-dependent; a dose of 10 mumol/kg produced a 75%-100% signal enhancement of the liver at 10 minutes after injection.

Adult