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Biomedical subjects

G Fein

Publications and source records attributed to G Fein.

At least 37 records · Page 2Linked to original sources

Event-related potential evidence for frontal cortex effects of chronic cocaine dependence.

We examined the effects of cocaine dependence and cocaine and alcohol codependence on the P3A event-related potential component. Ten chronic cocaine-dependent subjects, 10 chronic cocaine and alcohol codependent subjects, and 20 controls were studied in an auditory paradigm that included target, nontarget, and novel rare nontarget conditions. Substance-dependent subjects were abstinent from cocaine and/or alcohol for 2-6 weeks. Eighteen of these subjects (4 chronic cocaine-dependent subjects, 4 chronic cocaine/alcohol codependent subjects, and 10 normal controls) were also studied in an analogous visual paradigm. In the auditory modality, the latency of the P3A response in the novel rare nontarget condition was delayed and its amplitude was reduced in both substance-dependent samples compared to controls. Comparable results were found for the smaller samples studied in the visual modality. These results suggest that chronic cocaine dependence produces deficits in frontal cortex functions.

Acoustic Stimulation↗

Human P50 suppression is not affected by variations in wakeful alertness.

The amplitude and suppression of the auditory P50 event-related potential may be useful for studying schizophrenia and drug abuse; however, the low reliability of the P50 suppression measure limits its value for correlation with clinical measures. Reliability can be increased either by improving measurement methods or by reducing or eliminating sources of variance in the recordings. In this paper, the effect on P50 amplitude and suppression of variation in wakeful alertness within an experimental session was examined in 20 normal subjects. The percentage of beta power in the interval immediately prior to the P50 stimuli was used as an index of alertness. P50 amplitudes or C-T ratios were estimated using peak-picking and using the singular value decomposition (SVD) method. No effects of variation of wakeful alertness were observed on any P50 amplitude or suppression measure. Comparing the peak-picking vs SVD estimates replicated our prior results showing markedly higher reliabilities with SVD. We conclude: 1) that variation within an experimental session in wakeful alertness level as indexed by the percentage of beta power does not affect P50 amplitude or suppression, and 2) the SVD method brings the reliability of the C-T ratio up to levels where its usefulness in clinical studies can be examined.

Acoustic Stimulation↗

Presurgical multimodality neuroimaging in electroencephalographic lateralized temporal lobe epilepsy.

The purpose of this study was to compare 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET), hippocampal volumetry (HV), T2 relaxometry, and proton magnetic resonance spectroscopic imaging (1H-MRSI) in the presurgical neuroimaging lateralization of patients with nonlesional, electroencephalogram (EEG)-defined unilateral temporal lobe epilepsy (TLE). Twenty-five patients were prospectively studied, along with age-matched controls. T2 relaxometry examinations were performed in 13 patients. Comparison of FDG-PET, HV, and 1H-MRSI was possible in 23 patients. FDG-PET lateralized 87% of patients, HV 65%, N-acetyl aspartate (NAA)/(choline [Cho] + creatine [Cr]) 61%, and [NAA] 57%. Combined HV and NAA/(Cho + Cr) results lateralized 83% of the patients, a value similar to PET. Of 10 patients with normal magnetic resonance imaging (MRI) scans, 2 were lateralized with HV, 6 with FDG-PET, 4 with NAA/(Cho + Cr), and 3 with [NAA]. T2 relaxometry lateralized no patients without hippocampal atrophy. Bilateral abnormality was present in 29 to 33% of patients with 1H-MRSI measures and 17% with HV. Only hippocampal atrophy correlated with postoperative seizure-free outcome. FDG-PET remains the most sensitive imaging method to correlate with EEG-lateralized TLE. Both FDG-PET and 1H-MRSI can lateralize patients with normal MRI, but only the presence of relative unilateral hippocampal atrophy is predictive of seizure-free outcome. Bilaterally abnormal MRI and 1H-MRSI measures do not preclude good surgical outcome.

Adult↗

Intra-hemispheric alpha coherence decreases with increasing cognitive impairment in HIV patients.

Inter-hemispheric and intra-hemispheric canonical coherences in the alpha range between EEG signals collected from frontal and posterior groups of electrodes were estimated for 38 HIV positive subjects and 23 uninfected controls. Neuropsychological testing was used to categorize the degree of cognitive impairment evident in each of the subjects. A linear regression analysis provided evidence that intra-hemispheric coherence decreased with increasing cognitive impairment in impaired HIV+ subjects, as measured by a Global Impairment Score (GIS). There was no evidence that cognitively unimpaired HIV+ subjects differed in coherence when compared to uninfected control subjects. Severely impaired HIV+ subjects showed significantly decreased coherence compared to uninfected controls. These data contradict previous work demonstrating increased intra-hemispheric and inter-hemispheric alpha coherence in impaired HIV subjects. In addition, they provide evidence that intra-hemispheric (and possibly inter-hemispheric) disconnection is associated with cognitive impairment in HIV.

Adult↗

A comparison of the repetitive click and conditioning-testing P50 paradigms.

The auditory P50 ERP component has previously been studied either in the repetitive click or the conditioning-testing (C-T) paradigm. For 20 subjects, we compared 4 repetitive click and 4 C-T protocols in a single experimental session with identical recording techniques and with interclick intervals comparable to the C-T intervals. In the C-T protocols, a long interval between click pairs ensured full recovery of P50 to the C click. The analysis of P50 topographies provided strong evidence that the same component was measured in the two paradigms. For both paradigms, P50 amplitude was progressively suppressed as the interclick or C-T interval decreased (P < 0.0001), with parallel interval vs. P50 amplitude regression lines for the two paradigms. There was a strong trend (P = 0.08) for the repetitive click amplitudes to be smaller than T amplitudes for comparable repetitive click and C-T intervals. Equivalently, this strong trend suggests that repetitive click intervals must be longer (by about 300 ms) than the C-T interval to generate equivalent amplitude P50 responses. We conclude that the same component is measured in both paradigms, that P50 amplitude decreases with decreasing interstimulus intervals in both paradigms, and that in normals, for comparable inter-click and C-T intervals, there is greater P50 suppression in the repetitive click paradigm. Finally, we note that the comparison of paradigms within normals does not necessarily apply to clinical samples.

Acoustic Stimulation↗

Temporal lobe epilepsy: bilateral hippocampal metabolite changes revealed at proton MR spectroscopic imaging.

PURPOSE: To determine which proton magnetic resonance (MR) spectroscopic imaging measures are best for lateralizing the seizure focus in patients who have temporal lobe epilepsy with and in those without hippocampal atrophy on MR images, the extent of contralateral abnormalities, and whether there is a correlation between MR spectroscopic imaging findings and surgical outcome. MATERIALS AND METHODS: MR spectroscopic imaging was performed in 16 adult patients with temporal lobe epilepsy and unilateral electroencephalographic findings and in 16 adult control subjects. Eleven patients underwent surgery; all patients underwent MR imaging. RESULTS: Nine patients had hippocampal atrophy on MR images. An ipsilateral decrease in the N-acetylaspartate concentration or the ratio of N-acetylaspartate to the sum of creatine and choline (N-acetylaspartate/ [creatine + choline]) was found in all patients. Decreased contralateral N-acetylaspartate concentration, N-acetylaspartate/(creatine + choline), or N-acetylaspartate concentration and N-acetylaspartate/(creatine + choline) were detected in eight patients (50%), which suggests bilateral abnormalities not detected with MR imaging. In the five patients who underwent surgery and did not show hippocampal atrophy on MR images, successful and unsuccessful outcomes were correctly predicted with N-acetylaspartate concentration. CONCLUSION: Decreased N-acetylaspartate concentration is not due solely to hippocampal atrophy. Contralateral abnormalities are much more frequent than expected. MR spectroscopic imaging is valuable in the presurgical evaluation of epilepsy.

Adult↗

Volumetric method for evaluating magnetization transfer ratio of tissue categories: application to areas of white matter signal hyperintensity in the elderly.

An objective technique for analyzing magnetization transfer ratio of segmented tissues was used to evaluate differences between normal-appearing white matter and areas of white matter signal hyperintensity on T2-weighted magnetic resonance images in 23 healthy elderly subjects (mean age, 75 years). Segmented brain images (cerebrospinal fluid, gray matter, white matter, areas of white matter signal hyperintensity) computed from T1- and T2-weighted images were combined with magnetization-transfer-ratio images to produce magnetization-transfer-ratio histograms for each tissue. There was a significant 8.1% reduction in mean magnetization transfer ratio for areas of white matter signal hyperintensity compared with normal-appearing white matter (P < .001). The magnetization transfer ratio for all tissue categories was significantly negatively correlated with age (all, P < .05). This method of measuring magnetization transfer ratio was objective, independent of regional variations, and as reproducible as the segmentation procedure.

Aged↗

Sensory gating deficit following cocaine exposure in the rat.

The purpose of this research was to examine changes in the ratio and amplitude of the N40 component of the auditory event-related potential (ERP) in the paired conditioning (C) test (T) stimulation paradigm following subchronic cocaine/vehicle administration. Free moving rats received cocaine (47.5 mg/kg) or saline for 7 consecutive days in a longitudinal crossover design. ERPs were recorded 4 and 7 days after each treatment and again 4 and 7 days following withdrawal of the drug/vehicle. Cocaine led to a progressive increase in the T/C ratio indicating impaired inhibition of the test response. This trend continued throughout the 7-day drug regimen. Following withdrawal of the drug the T/C ratio gradually normalized over the next 7 days but remained elevated at 4 days postdrug. A significant increase in the test response accompanied by a less pronounced decrease in the conditioning response accounted for the observed results. Behavioral state as measured on a rating scale during ERP sampling did not differ across experimental conditions.

Acoustic Stimulation↗

Changes of hippocampal N-acetyl aspartate and volume in Alzheimer's disease. A proton MR spectroscopic imaging and MRI study.

Hippocampal atrophy detected by MRI is a prominent feature of early Alzheimer's disease (AD), but it is likely that MRI underestimates the degree of hippocampal neuron loss, because reactive gliosis attenuates atrophy. We tested the hypothesis that hippocampal N-acetyl aspartate (NAA: a neuronal marker) and volume used together provide greater discrimination between AD and normal elderly than does either measure alone. We used proton MR spectroscopic imaging (1H MRSI) and tissue segmented and volumetric MR images to measure atrophy-corrected hippocampal NAA and volumes in 12 AD patients (mild to moderate severity) and 17 control subjects of comparable age. In AD, atrophy-corrected NAA from the hippocampal region was reduced by 15.5% on the right and 16.2% on the left (both p < 0.003), and hippocampal volumes were smaller by 20.1% (p < 0.003) on the right and 21.8% (p < 0.001) on the left when compared with control subjects. The NAA reductions and volume losses made independent contributions to the discrimination of AD patients from control subjects. When used separately, neither hippocampal NAA nor volume achieved to classify correctly AD patients better than 80%. When used together, however, the two measures correctly classified 90% of AD patients and 94% of control subjects. In conclusion, hippocampal NAA measured by 1H MRSI combined with quantitative measurements of hippocampal atrophy by MRI may improve diagnosis of AD.

Aged↗

Tissue segmentation of the brain in Alzheimer disease.

PURPOSE: To compare brain tissue in patients with Alzheimer disease with that in elderly control subjects by using high-resolution MR imaging and quantitative tissue-segmentation techniques. METHODS: MR imaging of the brain was performed in 21 patients with Alzheimer disease and 17 control subjects. A computerized segmentation program was used to quantify volumes of ventricular and sulcal cerebrospinal fluid (CSF), white matter, cortical gray matter, and white matter signal hyperintensity. Statistical analysis was performed using analysis of variance. RESULTS: We found a significant decrease in total brain tissue and cortical gray matter and an increase in the ventricular and sulcal CSF in Alzheimer patients compared with control subjects. There was no difference in the volume of white matter. More white matter signal hyperintensities were found in Alzheimer patients, and a significant interaction between age and group was noted. Neuropsychological test scores correlated significantly with sulcal CSF in patients with Alzheimer disease. CONCLUSION: Semiautomated segmentation of MR images of the brains of patients with Alzheimer disease reveals significant brain atrophy attributable to loss of cortical gray matter, which is compatible with the pathologic features of Alzheimer disease. There is also a significant increase in white matter signal hyperintensities. Tissue segmentation may increase our understanding of dementia but, as yet, when used alone, it does not play a role in the premorbid diagnosis of Alzheimer disease.

Aged↗

Brain atrophy in HIV infection is more strongly associated with CDC clinical stage than with cognitive impairment.

HIV infection often results in MRI-detectable brain atrophy and white matter signal hyperintensities (WMSHs). Magnetic resonance images were obtained from 31 HIV+ male patients and 10 high-risk controls. Variation within the HIV+ group on neuropsychological (NP) impairment and stage of systemic disease were relatively independent, allowing examination of the relative association of MRI measures with NP impairment versus with systemic stage of disease. HIV+ patients compared to high-risk controls evidenced global atrophy, reduced caudate nuclei volume, and a trend to gray matter volume loss but no difference in white matter volume or in WMSHs. These effects were progressive with CDC clinical stage such that patients at CDC stage A had values very close to those of controls, while patients at CDC stage C had the most abnormal values. In contrast, the relationship between these MRI variables and severity of NP impairment was much less dramatic, with the mildly to moderately impaired HIV+ subjects showing MRI volume effects greater than or equal to those of the severely impaired HIV+ subjects. These results suggest that MRI-detectable brain atrophy secondary to HIV infection is not the primary substrate underlying the progressive NP impairment in HIV disease.

AIDS Dementia Complex↗

Semantic priming impairment in HIV.

HIV+ subjects have shown impairment on tests of executive function including automatic attention and verbal tasks. Impairment of semantic priming in HIV patients would suggest a disruption of automatic semantic activation. We examined semantic priming in HIV+ individuals and HIV- control participants with no history of substance abuse, neurologic or psychiatric disorder unrelated to HIV. HIV+ participants were divided into cognitively normal and cognitively impaired subgroups on the basis of a neuropsychological battery of 15 tests. Participants were presented with English words and nonword letter strings and indicated if the stimulus was a word or nonword. The nonwords were orthographically and phonologically correct and were created by rearranging the letter sequence of words ("ulpit"). All words had an obvious antonym ("deep"); two-thirds were presented as sequential antonym pairs ("enter"-"exit"). There were no group differences in speed of response to nonwords, indicating no generalized reaction time deficit. While control and cognitively normal HIV+ participants showed an effect of priming on reaction time to correctly detected words, cognitively impaired HIV+ participants did not. The lack of semantic priming demonstrated by cognitively impaired HIV+ participants suggests that they have lessened activation of automatic semantic networks.

Adult↗

Cocaine abusers have reduced auditory P50 amplitude and suppression compared to both normal controls and alcoholics.

The auditory P50 evoked response to click stimuli was recorded from 10 2-week abstinent African-American chronic cocaine abusers and 10 African-American non-substance-abusing controls. Stimuli consisted of pairs of clicks with a 500-msec interval between clicks in a pair, and a 7-8 sec interval between pairs of clicks. After averaging responses to 100 pairs of clicks and digital bandpass filtering between 10 and 50 Hz, P50 amplitude to the first and the second click was measured. The conditioning/testing (C/T) ratio, an index of P50 suppression, was computed as the ratio of P50 amplitude to the second compared to the first click. Chronic cocaine abusers had markedly diminished P50 amplitudes and increased C/T ratios (indicating decreased P50 suppression) in comparison to the controls. These P50 abnormalities were not seen in additional Caucasian gay/bisexual comparison groups of active alcoholics (n = 15) and non-substance-abusing controls (n = 10). Thus, decrements in P50 amplitude and P50 suppression appear to be specific to cocaine abuse, and to differentiate cocaine abuse from alcohol abuse. A response analogous to P50 can be measured in animals, facilitating the development of animal models of this cocaine effect.

Adult↗

Regional gray and white matter metabolite differences in subjects with AD, with subcortical ischemic vascular dementia, and elderly controls with 1H magnetic resonance spectroscopic imaging.

OBJECTIVE: To use 1H magnetic resonance spectroscopic imaging to study differences in neuron density (N-acetylaspartate [NAA]), membrane phospholipid metabolites (choline [Cho]), and creatine-containing metabolites (creatine plus phosphocreatine [Cr]) in subjects with Alzheimer's disease (AD), with subcortical ischemic vascular dementia (SIVD), and elderly controls. DESIGN: Cross-sectional, between groups. SETTING: A Veterans Affairs medical center and university memory clinic. PARTICIPANTS: Forty elderly subjects with AD (n = 14), with SIVD (n = 8), and elderly controls (n = 18). MAIN OUTCOME MEASURES: We used 1H magnetic resonance spectroscopic imaging to acquire spectra from a 80 x 100 x 17-mm volume superior to the lateral ventricles. Spectra were analyzed from voxels in anterior, medial, and posterior gray and white matter using nuclear magnetic resonance-1 and the results were compared between groups using repeated measures analysis of variance (ANOVA), Tukey's test, and individual Student's t tests. RESULTS: Using ANOVA, significantly lower levels of NAA/Cho and NAA/Cr and significantly higher levels of Cho/Cr were observed across both gray and white matter voxels in subjects with AD. Using individual Student's t tests, a significantly lower level of NAA/Cho and a higher level of Cho/Cr were observed in the posterior gray matter in subjects with AD. Using ANOVA in subjects with SIVD, significantly lower gray and white matter NAA/Cr levels were observed. Using Tukey's test, the NAA/Cr level was significantly lower in frontal white matter voxels in subjects with SIVD compared with controls. CONCLUSIONS: Our findings in subjects with AD suggest neuron loss in gray matter, axon loss in white matter, and altered Cho metabolism in posterior brain regions. Our findings in subjects with SIVD are consistent with higher levels of creatine-containing metabolites and/or lower levels of NAA in frontal white matter.

Aged↗