Biomedical subjects

G D Pearlson

Publications and source records attributed to G D Pearlson.

At least 91 records · Page 5Linked to original sources

PubMed1993

Reduced basal ganglia volume in HIV-1-associated dementia: results from quantitative neuroimaging.

Although brain atrophy is a common neuroradiologic and pathologic finding in patients with HIV-1 infection, especially those with HIV-1-associated dementia complex, it is not clear whether specific regions of the brain are differentially responsible for tissue loss. In this study, we measured volumes of basal ganglia structures on MRIs for three groups: HIV-1-infected homosexual men with HIV-1-associated dementia complex (HIV+ demented), HIV-1-infected homosexual men without HIV dementia (HIV+ nondemented), and noninfected homosexual men. All groups were comparable on age and years of education, and the HIV+ groups were comparable on level of immunosuppression. Total brain volume was smaller in the HIV+ nondemented patients in comparison with HIV- control subjects; the HIV+ demented patients demonstrated even smaller brain volumes than the HIV+ nondemented patients. Smaller basal ganglia volumes, after corrections for intracranial volume, distinguished HIV+ demented patients from the other two groups; there were no differences between the HIV+ nondemented and HIV- groups on basal ganglia volumes. This study suggests that HIV infection causes generalized brain atrophy, but that the clinical features of HIV dementia develop with selective basal ganglia atrophy, consistent with the characterization of HIV dementia as subcortical.

AIDS Dementia Complex↗

PubMed1992

Quantitative changes in mesial temporal volume, regional cerebral blood flow, and cognition in Alzheimer's disease.

Twenty-six patients with moderately severe Alzheimer's disease (AD) and 16 normal control subjects were studied using either quantitative magnetic resonance imaging (MRI) measures of mesial temporal atrophy (15 patients with AD and 16 normal control subjects) and/or quantitative radioactive iodine 123-N-isopropyl-iodoamphetamine single-photon emission computed tomography (SPECT) assessment of regional cerebral blood flow (20 patients with AD and eight normal control subjects). Nine individuals with AD and eight normal control subjects underwent both structural and functional imaging. On MRI, patients and controls were best discriminated using left amygdala and entorhinal cortex volumes, and on SPECT they were best discriminated by relative left temporoparietal cortex blood flow. Combining these MRI and SPECT measures yielded 100% discrimination. Relative left temporoparietal SPECT regional cerebral blood flow and left superior temporal gyral MRI volume correlated best with severity of cognitive deficit in patients with AD. Mesial temporal MRI atrophy exceeded generalized cerebral shrinkage. Both SPECT and MRI regional changes accorded with areas known to be affected by AD neuropathology.

Aged↗

PubMed1992

Putamen volume reduction on magnetic resonance imaging exceeds caudate changes in mild Huntington's disease.

The characteristic pathological features of Huntington's disease (HD) are neostriatal atrophy and neuronal loss. Although neuroradiological studies often show caudate atrophy in patients with moderate HD, frequently no caudate atrophy is found early in the illness. There have been no quantitative reports to date on in vivo putamen volume measures in mild HD, although the structure is known to be neuropathologically involved in the illness. We measured volumes of caudate nucleus and putamen and bicaudate ratios (BCR) from magnetic resonance images, blind to diagnosis, in 15 patients with mild HD and 19 age- and sex-matched control subjects using a computerized image analysis system. The region showing greatest atrophy was the putamen, which was reduced 50.1% in mean volume in HD patients compared with control subjects (p less than 0.000001). In contrast, caudate volume was reduced 27.7% (p = 0.004). BCR was increased 28.5% in HD patients (p = 0.0002). Discriminant function analysis was 94% effective in identifying the diagnostic group based on putamen volume alone, whereas caudate measures had considerable overlap. Correction of putamen volume for head size led to 100% separation by group. Putamen measures and BCR correlated with neurological examination scores but caudate volume did not. Volumetric measurement of putamen is a more sensitive indicator of brain abnormalities in mild HD than measures of caudate atrophy.

Adult↗

PubMed1992

Oculomotor performance in obsessive-compulsive disorder.

OBJECTIVE: Neuroimaging studies have shown abnormalities of the frontal cortex and basal ganglia in persons with obsessive-compulsive disorder. Since lesions in the frontal cortex and basal ganglia areas affect performance on goal-guided saccadic eye movements, this study investigated the relation between the diagnosis of obsessive-compulsive disorder and oculomotor performance. METHOD: Eleven patients with the clinical diagnosis of obsessive-compulsive disorder and 14 normal subjects were assessed with respect to their performance on both visual-guided and goal-guided oculomotor tasks. Fixation performance was also measured. RESULTS: The group with obsessive-compulsive disorder had a very significantly greater error rate and a significantly greater rate of inaccurate saccades on the goal-guided antisaccade task, whereas they were not different from the normal group in reaction time, saccadic velocity, and accuracy on the visual-guided saccade task. The distribution of error rates for the patients with obsessive-compulsive disorder was broad, with more than one-half outside the range of the normal group. Most of the abnormal findings were among male patients. CONCLUSIONS: The results support the hypothesis of a relationship between impaired performance on goal-guided saccadic eye movement tasks and the diagnosis of obsessive-compulsive disorder, but they also suggest a gender-related subgroup within the group with obsessive-compulsive disorder.

Basal Ganglia↗

PubMed1992

Sylvian fissure size in schizophrenia measured with the magnetic resonance imaging rating protocol of the Consortium to Establish a Registry for Alzheimer's Disease.

OBJECTIVE: Since previous work indicated smaller than normal temporal lobe structures in schizophrenic patients, the authors tested the hypothesis that this abnormality might be reflected in abnormally large sylvian fissures. METHOD: The subjects were 48 schizophrenic patients and 51 normal comparison subjects matched groupwise with regard to age and sex. CSF spaces (sylvian fissures, temporal lobe sulci, temporal horns, third ventricle, lateral ventricles, and superficial cerebral sulci) were visually assessed with the magnetic resonance imaging rating protocol of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD). RESULTS: The sylvian fissures of the schizophrenic patients were found to be bilaterally wider than those of the comparison subjects. There were no other significant differences. CONCLUSIONS: Schizophrenic patients appear to have larger than normal sylvian fissures, which may reflect smaller superior temporal gyri.

Adolescent↗

PubMed1991

Disengagement of attention in schizophrenia.

We compared covert shift of visual attention in patients with schizophrenia or bipolar disorder, both in states of remission, to normal controls to examine the persistence of lateralized attentional deficits into nonpsychotic states. Although patients were slower in all conditions than normals, there was no difference in pattern of attentional shift among the groups. This suggests that the left-hemisphere deficit in shift of covert attention in schizophrenia may be limited to periods of florid illness.

Attention↗

PubMed1991

Cortical circumferential profile of SPECT cerebral perfusion in Alzheimer's disease.

We developed a semiautomatic method termed "cortical circumferential profiling" for objective analysis of cerebral cortex function in emission tomographic neuroimaging studies. This method treats cortex as a continuous ring near the outer brain edge. A computer algorithm samples the cortex at 60 contiguous, equiangular locations, using 1-cm2 samples. These values are plotted as a function of cortical angle to produce the cortical circumferential profile. This method was used in a study of regional cerebral perfusion in 15 patients with Alzheimer's disease and 8 elderly control subjects using N-isopropyl[I-123]-iodoamphetamine. Cortical circumferential profiling decreases variability, examines the entire cortex within slices at preselected levels above the orbital-meatal line, and facilitates intrasubject and intersubject comparisons.

Aged↗

PubMed1991

User-friendly method for rapid brain and CSF volume calculation using transaxial MRI images.

A reliable computer method was developed for straightforward, rapid determination of whole brain and cerebrospinal fluid (CSF) volumes from a set of contiguous transaxial magnetic resonance images. The semiautomatic algorithm used a threshold-guided edge follower. Subtraction of proton-weighted from T2-weighted images was used to highlight CSF. Phantom studies were used for validity assessment. Interrater and intrarater reliability and correlation with manual measurement were excellent. Percent CSF and brain volumes were determined for small groups of Alzheimer's disease, HIV seropositive, obsessive-compulsive disorder, and schizophrenic patients as well as for young and elderly normal controls.

Algorithms↗

PubMed1991

Centrum semiovale white matter CT changes associated with normal ageing, Alzheimer's disease and late life depression with and without reversible dementia.

A standardized, reliable means of assessing CT attenuation numbers in the centrum semiovale and surrounding grey matter was developed. This was applied to cranial CT scans of 60 normal controls (36 aged greater than 60 years), 25 elderly patients with major depression (14 of whom had the dementia syndrome of depression), and 10 patients with Alzheimer's disease (AD). Subjects received neuropsychological evaluation. Centrum semiovale (CSO) CT attenuation numbers decreased with increasing age for both white and grey matter. White matter attenuation values best discriminated elderly controls from the three patient groups. Both white and grey matter CSO attenuation values correlated with performance on a number of cognitive tasks.

Adult↗

PubMed1991

Cortical magnetic resonance imaging changes in elderly inpatients with major depression.

OBJECTIVE: The purpose of the study was to determine if magnetic resonance imaging (MRI) scans of elderly depressed patients differ from MRI scans of age-matched control subjects and age-matched patients with Alzheimer's disease. METHOD: The authors studied 21 patients 60 years or older with major depression, 16 patients with Alzheimer's disease, and 14 age-matched control subjects. RESULTS: Compared to control subjects, depressed patients had greater cerebral sulcal and temporal sulcal atrophy; larger sylvian fissures, lateral ventricles, third ventricles, and temporal horns; and greater severity of subcortical white matter lesions. Depressed patients also had more basal ganglia lesions but similar levels of periventricular hyperintensity. There were no differences between depressed patients with and without delusions on any MRI measure. Depressed patients who received ECT had more temporal horn atrophy and greater subcortical abnormality summary scores than normal subjects. Cortical sulcal atrophy correlated with age at onset of depression. CONCLUSIONS: The findings suggest that elderly hospitalized depressed patients have greater cortical as well as subcortical atrophy and more basal ganglia lesions than age-matched normal control subjects. The correlation of these abnormalities with outcome remains unknown.

Aged↗

PubMed1991

Elevated medial-frontal cerebral blood flow in obsessive-compulsive patients: a SPECT study.

Regional cerebral blood flow was measured with single photon emission computed tomography in 10 obsessive-compulsive patients and eight comparison subjects. The patients had a significantly higher ratio of medial-frontal to whole cortex blood flow; this was unrelated to symptom severity but was correlated negatively with anxiety. No differences in orbital-frontal blood flow were found.

Adolescent↗

PubMed1991

Effects of fluoxetine on regional cerebral blood flow in obsessive-compulsive patients.

Six drug-free obsessive-compulsive patients were given single photon emission computerized tomography scans before and during treatment with fluoxetine. The treatment significantly reduced the patients' "hyperfrontality," as determined by the ratio between medial-frontal and whole cerebral cortex blood flow, and significantly lowered ratings of obsessive-compulsive and anxiety symptoms.

Adult↗

PubMed1991

A fluoxetine-induced frontal lobe syndrome in an obsessive compulsive patient.

The authors report the occurrence of apathy, indifference, inattention, and perseveration in an obsessive compulsive patient taking high doses of fluoxetine. These changes were associated with a decrease in cerebral blood flow in the frontal lobes and changes in neuropsychological tests generally associated with frontal lobe impairment. These clinical manifestations disappeared 4 weeks after discontinuation of fluoxetine.

Adult↗

PubMed1990

Demonstration of naturalistic methods for cocaine smoking by human volunteers.

Five, healthy, adult, male research volunteers participated in up to four daily laboratory sessions while residing on a Clinical Research Unit. Two subjects were tested twice. Fifty milligrams of cocaine base was smoked one, two or four times each session with a 14-min interval between doses. Two subjects smoked cocaine placed in 'smoke-free' cigarettes, while the remaining subjects smoked cocaine placed in a modified tobacco pipe. Significant and biologically relevant cocaine venous blood levels were engendered most consistently using the modified tobacco pipe. Large, transient increases in heart rate, blood pressure and self-reported 'stimulated' scores were observed during single dosing sessions. During multiple dose sessions, cardiovascular activity either increased, returning to near baseline levels between doses, or were sustained, while reported 'stimulated' scores peaked after the first dose and were lower following subsequent doses. Both cardiovascular and subjective effects were greater on the ascending limb than on the descending limb of the cocaine blood level curve suggesting acute tolerance. Although preliminary, these results demonstrate the usefulness of this relatively simple procedure requiring subjects to smoke in the manner they are accustomed, and suggest the importance of further research in this area.

Adult↗

PubMed1990

Auditory hallucinations and smaller superior temporal gyral volume in schizophrenia.

Recent neuropathologic investigations in schizophrenia report smaller volume of medial temporal lobe structures. These findings are confirmed by preliminary magnetic resonance imaging (MRI) studies. Direct stimulation of lateral temporal lobe structures in the region of the superior temporal gyrus provokes hallucinations. The authors' MRI study of young schizophrenic patients demonstrates smaller volume of the superior temporal gyrus (an auditory association area) and of the left amygdala. Smaller size of the left superior temporal gyrus and left amygdala is not accounted for by smaller size of the overall brain or temporal lobe. Shrinkage of the left superior temporal gyrus is strongly and selectively correlated with severity of auditory hallucinations.

Adult↗

PubMed1990

Association between family history of affective disorder and the depressive syndrome of Alzheimer's disease.

For each of 41 index patients with probable Alzheimer's disease and a first episode of major depression and 71 nondepressed Alzheimer's disease patients, two first-degree relatives were interviewed by a rater blind to presence or absence of depression in the proband. The depressed patients had significantly more first- and second-degree relatives with depression than did control subjects. The lifetime risk for major depression, adjusted for differences in age distribution, was significantly greater in first-degree relatives of index patients, suggesting that depression in Alzheimer's disease is genetically related to primary affective disorder. Alzheimer's disease may be useful for studying aspects of depressive pathophysiology.

Age Factors↗

PubMed1990

Effects of desipramine maintenance on cocaine self-administration by humans.

Six research volunteers with histories of cocaine use were tested in a cocaine choice paradigm to investigate the effects of desipramine maintenance on cocaine-taking behavior. Subjects were allowed to self-administer i.v. saline or cocaine (8, 16 or 32 mg) in daily 3-hr sessions to establish baseline levels of self-administration, self-reported effects of the drug and changes in heart rate and blood pressure. Each subject was then maintained on daily doses of desipramine for 3 to 4 weeks, after which a second cocaine self-administration dose-response curve was generated under desipramine maintenance. This maintenance had no effect on cocaine self-administration. There was, however, a significant increase in heart rate and blood pressure during desipramine maintenance. Desipramine maintenance also resulted in a change in the profile of cocaine's self-reported effects. In some cases (e.g., Arousal and Vigor on the Profile of Mood States, Benzedrine Group scale on the Addiction Research Center Inventory), reports of cocaine's effects were significantly reduced under conditions of desipramine maintenance, and in others (e.g., Anxiety, Anger and Confusion on the Profile of Mood States), those reports were significantly increased. Furthermore, there was a significant decrease in subjects response to an "I want cocaine" question while under desipramine maintenance. The data suggest that desipramine does not affect the reinforcing properties of cocaine, but may interfere with its other stimulus properties. Furthermore, the cardiovascular effects of desipramine appear to have the potential for toxicity when that drug is administered in combination with cocaine.

Adult↗

PubMed1989

Ventricle-brain ratio, computed tomographic density, and brain area in 50 schizophrenics.

A sample of 50 DSM-III-diagnosed schizophrenics (mean age, 34 years) intentionally biased to contain a relatively high proportion of persistently unemployed persons was compared with a sample of 87 normal volunteers on three computed tomographic measures. These were lateral ventricle-brain ratio, regional brain computed tomographic density values, and brain slice area. Images were made with the same computed tomographic scanner and identical scan parameters. Computed tomographic data were assessed blindly using a computer-linked image array processor and electronic planimeter. Ventricle-brain ratios were significantly higher in schizophrenics, with 28% of the patient sample exceeding 2 SDs of the control mean. Brain area measures were not associated with an enlarged ventricle-brain ratio. Contrary to our prediction, ventricular enlargement was unassociated with most negative symptom ratings, but was correlated with the absence of positive symptoms. A history of abnormal delivery and the presence of left-handedness were significant predictors of an enlarged ventricle-brain ratio on multiple regression analysis. Schizophrenics had a significantly smaller brain slice area compared with normal controls, a finding not attributable to height differences between groups. Brain slice area was inversely correlated with computed tomographic brain density across all subjects. After correction of computed tomographic density values for area using a linear regression model, no significant regional density differences were detectable between normal controls and schizophrenics. Within normal controls there was a significant relationship between social class and brain slice area, but not ventricle-brain ratio.

Adult↗