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Biomedical subjects

G Fein

Publications and source records attributed to G Fein.

At least 19 recordsLinked to original sources

Alzheimer disease and subcortical ischemic vascular dementia: evaluation by combining MR imaging segmentation and H-1 MR spectroscopic imaging.

PURPOSE: To determine the association between H-1 magnetic resonance (MR) spectroscopic imaging and MR imaging differences in subjects with Alzheimer disease (AD) or subcortical ischemic vascular dementia (SIVD) versus control subjects and if both studies combined enable discrimination of AD from control subjects better than either study alone. MATERIALS AND METHODS: Measures were obtained in nine AD, eight SIVD, and 11 control subjects with MR imaging segmentation software. RESULTS: Statistically significantly lower N-acetylaspartate/choline-containing metabolites (Cho) and higher Cho/creatine-containing metabolites in posterior mesial gray matter in AD versus control subjects were independent of MR imagining differences. Combined measures allowed correct classification of AD and control subjects, but none of the MR measures allowed accurate discrimination between AD and SIVD subjects. CONCLUSION: Between-group differences in tissue-type contributions to H-1 MR spectroscopic imaging voxels must be accounted for when reporting H-1 MR spectroscopic imaging data in AD, SIVD, and control subjects. Combined studies allowed more accurate discrimination between AD and control subjects than either study alone.

Aged

Asymmetry of temporal lobe phosphorous metabolism in schizophrenia: a 31phosphorous magnetic resonance spectroscopic imaging study.

In vivo 31Phosphorous magnetic resonance spectroscopic imaging (31P MRSI) was performed on 18 chronic schizophrenic patients and 14 normal controls to determine if there was asymmetry of high-energy phosphorous metabolism in the temporal lobes of schizophrenic patients. Temporal lobe phosphorous metabolites were also correlated with severity of psychiatric symptomatology as assessed by the Brief Psychiatric Rating Scale (BPRS). Schizophrenics demonstrated significantly higher right relative to left temporal phosphocreatine/adenosine triphosphate (PCr/ATP), phosphocreatine/inorganic phosphate (PCr/Pi), and PCr as well as significantly lower right relative to left temporal ATP. There were no asymmetries of temporal lobe phosphorous metabolites in the control group. In addition, both left temporal PCr and the degree of asymmetry of temporal lobe PCr were highly correlated with the thinking disturbance subscale of the BPRS. This study provides further support for temporal lobe metabolic asymmetry in schizophrenia and its possible association with clinical symptoms.

Adult

Decreased temporal lobe phosphomonoesters in bipolar disorder.

In vivo [31P]magnetic resonance spectroscopic imaging ([31P]MRSI) was performed on 12 unmedicated, euthymic bipolar patients and 14 control subjects to determine if there were alterations in high-energy P metabolism in the temporal lobes of bipolar patients. Compared with the control group, the patients with bipolar disorder demonstrated significantly lower phosphomonoesters (PME) in both the left and right temporal lobes. No other group differences in P metabolites or lateralized asymmetries were noted. This preliminary study provides support for altered temporal lobe phospholipid metabolism in bipolar disorder.

Adenosine Triphosphate

Alcohol abuse and HIV infection have additive effects on frontal cortex function as measured by auditory evoked potential P3A latency.

Both alcohol and human immunodeficiency virus (HIV) infection have been shown to produce central nervous system (CNS) morbidity in frontal brain regions. The degree to which the CNS morbidity in HIV infection, as it affects frontal cortex function, may be preferentially increased by alcohol abuse was examined using the auditory P3A evoked potential. The P3A indexes an orienting response, maximal over frontal cortex that occurs when novel nontarget stimuli are presented in the midst of a target detection paradigm. Four groups of subjects were compared: HIV+ alcohol abusers, HIV+ light/nondrinkers, HIV- alcohol abusers, and HIV- light/nondrinkers. The alcohol abuser and light/nondrinker HIV+ groups were matched on percent CD4 lymphocytes, insuring that the results reflected specific CNS effects and were not a result of differences between the groups in the degree of systemic immune suppression. Alcohol abuse and HIV infection had at least additive effects on P3A latency, consistent with alcohol abuse worsening the effect of HIV disease on frontal cortex function. Post-hoc analyses suggested that concomitant alcohol abuse results in the effects of HIV infection on P3A latency becoming manifest earlier in the HIV disease process.

AIDS Dementia Complex

Delayed latency of the event-related brain potential P3A component in HIV disease. Progressive effects with increasing cognitive impairment.

OBJECTIVE: To examine the degree to which P3A latency was sensitive to the early and progressive effects of human immunodeficiency virus (HIV) disease on frontal cortex function by studying HIV-positive subjects who varied in degree of cognitive impairment. DESIGN: Event-related brain potential studies of four groups of subjects: cognitively nonimpaired high-risk HIV-negative subjects, cognitively nonimpaired HIV-positive subjects, cognitively mildly to moderately impaired HIV-positive subjects, and cognitively severely impaired HIV-positive subjects. SETTING: Voluntarily participating subjects on an outpatient basis at a medical center facility. PARTICIPANTS: Seventy-one community-residing gay or bisexual HIV-positive male volunteers were compared with 17 HIV-negative male gay or bisexual subjects used as a control sample. The HIV-positive subjects were stratified with regard to severity of cognitive impairment into the following three subsamples: subjects who were cognitively normal (n = 35), subjects with mild to moderate cognitive impairment (n = 20), and subjects with severe cognitive impairment (n = 16), with the samples closely matched in age. The HIV-positive subsamples were closely matched on percentage of CD4 lymphocytes. Subjects were excluded if they reported a history of drug or alcohol abuse, a major mental disorder, a head injury with loss of consciousness, or brain disease other than HIV related. MAIN OUTCOME MEASURE: P3A latency. RESULTS: P3A latency was significantly delayed in HIV-positive subjects compared with HIV-negative control subjects, with a delay of 12 milliseconds in the cognitively normal group (P < .02) and the magnitude of delay increasing with increasing severity of HIV-associated cognitive impairments (P < .001). Delayed P3A was primarily associated with the progression of HIV-associated cognitive impairment, with a secondary and additive association with severity of HIV-associated medical illness. CONCLUSION: This finding suggests that delayed P3A latency is sensitive to the relatively early central nervous system effects of HIV and progresses with worsening of the central nervous system effects of HIV.

Adult

Dreaming in the late morning: summation of REM and diurnal cortical activation.

Since the discovery that the characteristics of dreaming sleep are far stronger in Stage 1 rapid eye movement (REM) sleep than in any other biological state, investigators have attempted to determine the relative responsibility of the tonic versus the phasic properties of REM sleep for the different characteristics of dreaming--features such as the amount of information in the dream report, the brightness and clarity of the visual images, shifts in thematic continuity, and incongruities of image and meaning. The present experiment is designed to identify dream characteristics that are specifically associated with tonic changes in level of cortical activation within sleep. It samples reports of imagery and thought during spontaneous variations within one phase of the 24-h diurnal rhythm and across the REM-NREM (non-REM) sleep cycle in order to identify the independent and joint contributions of the two cycles to imagery and thought. The rising phase of the diurnal cycle in the late night and morning was estimated from clock time during the late night and early morning and was varied by delaying the sleep onset and waking time of the subjects. Considered together with other studies, the results suggest that the major determinant of vivid visual imagery and enhanced cognitive activity during sleep is a pattern of subcortical and cortical activation that is common to both the REM phase of the REM-NREM cycle and the activated phase of the 24-h diurnal wake-sleep cycle.

Adult

Improved method for computation of potentials in a realistic head shape model.

The Lead Field Analysis (LFA) algorithm, a new computational technique for the calculation of potentials on the surface of a realistic head shaped volume conductor model based on the Boundary Element Method and the Reciprocity Theorem, is presented. The new algorithm, in comparison to the Standard Boundary Element Method, offers improved computational efficiency and lower storage requirements. It also yields more accurate surface potential results in the face of varying dipole source locations for a head shape Boundary Element model with a given number of nodes. Additionally, the algorithm results in quasi-analytic expressions of the derivatives of the surface potential with respect to the location of the sources, allowing the use of optimization techniques with better convergence properties. A set of simulations demonstrating the increased robustness of the LFA Algorithm in the face of varying dipole source parameters is also described.

Algorithms

Delayed P3A in abstinent elderly male chronic alcoholics.

Significant central nervous system toxicity in frontal brain regions has been demonstrated with chronic alcohol consumption both on autopsy and using neuropsychological testing. This study examined the latency of an objective and reproducible brain event-related potential measure of frontal cortex function in chronic elderly male alcoholics who were abstinent 3 months-2 years, a patient group in whom the central nervous system effects of chronic alcohol abuse are thought to be largest and most persistent. We examined the latency of the P3A event-related potential component, which reflects a frontal maximum orienting response to novel stimuli. Twelve elderly abstinent chronic alcoholic males and 11 elderly male controls were studied in an auditory and a visual paradigm, each of which included target, nontarget, and novel rare nontarget conditions. In both modalities, the P3A response to the novel rare nontarget stimuli was significantly delayed in the chronic alcoholics. P3B delays to the target stimuli were also present in the alcoholics, with the P3A and P3B effects being independent of each other. For both P3A and P3B, the effects were larger and more consistent in the visual compared with the auditory modality. Our conclusions are as follows: (1) both P3A and P3B latency delays are evident in elderly abstinent chronic alcoholics; (2) separate mechanisms are responsible for these effects; (3) these effects are more sensitively detected in the visual versus the auditory modality; and (4) delayed P3A latency may be an objective and reproducible index of the frontal cortex effects of chronic alcohol abuse.

Aged

Effects of chronic alcohol abuse and HIV infection on brain phosphorus metabolites.

We examined the effects of human immunodeficiency virus (HIV) infection and chronic alcohol consumption on cerebral phosphorus metabolites to determine if chronic alcohol abuse is a risk factor for the progression of neurological effects of HIV infection. We studied 15 HIV- alcoholics, 8 HIV- light/nondrinkers, 32 HIV+ alcoholics, and 41 HIV+ light/nondrinking men, with both HIV+ groups having similar CD4 lymphocyte counts. We used localized 31-phosphorus magnetic resonance spectroscopy after magnetic resonance imaging to examine two brain volumes in superior white matter and subcortical gray matter. Chronic alcohol consumption was associated with reduced white matter concentrations of phosphodiester (PDE) and phosphocreatine (PCr). Also in the white matter, acquired immune deficiency syndrome (AIDS) and AIDS-related complex (ARC) were associated with reduced concentrations of PDE and PCr, compared with both HIV- and clinically asymptomatic HIV+ subjects. Because no alcohol-by-HIV interactions were detected, the effects of HIV infection and alcohol abuse were cumulative. This is reflected in a successive decrease of white matter PDE and PCr concentrations in the order HIV- light/nondrinkers/HIV- alcoholics/HIV+ light/nondrinkers/HIV+ alcoholics. Subcortical gray matter PDE concentrations were lower in ARC/AIDS alcoholics than in HIV- light/nondrinking individuals. These findings suggest altered brain phospholipid metabolites and energy metabolites with alcohol abuse and HIV infection. They demonstrate that the adverse metabolic effects of HIV on the brain are augmented by chronic alcohol abuse.

AIDS Dementia Complex

Brain atrophy and cognitive function in older abstinent alcoholic men.

We used computer-aided magnetic resonance image analysis and an age-normed battery of neuropsychological tests to measure brain atrophy and cognitive function in 14 older abstinent alcoholic men and 11 older controls in the expectation that these subject groups would show the greatest and most persistent cerebral effects consequent to chronic alcoholism. The abstinent alcoholics exhibited cognitive impairments (primarily in memory and visual-spatial-motor skills) compared with the controls. In contrast, we found no difference in global cerebral atrophy between the groups, although two alcoholics had extensive atrophy compared with all other subjects. However, there was a stronger association between age and ventricular dilation in the alcoholic sample compared with controls. We conclude that a substrate other than magnetic resonance imaging-detectable global atrophy must underlie the persistent cognitive impairments evident in the sampled alcoholics. Furthermore, if there are global atrophic changes in the brain associated with chronic alcoholism, these effects are not ubiquitous and/or may be reversible in most patients with sufficient abstinence.

Aged

H-1 MR spectroscopic imaging of white matter signal hyperintensities: Alzheimer disease and ischemic vascular dementia.

PURPOSE: To investigate the association of white matter signal hyperintensities (WMSHs) with changes in hydrogen-1 metabolites. MATERIALS AND METHODS: T2-weighted magnetic resonance (MR) imaging and H-1 MR spectroscopic imaging were performed in 21 elderly control subjects without or with minimal WMSHs, eight elderly subjects with substantial WMSHs, 11 probable Alzheimer disease patients with WMSHs, and eight ischemic vascular dementia (IVD) patients with WMSHs. N-acetylaspartate (NAA), choline-containing metabolites (Cho), and creatine-containing metabolites (Cr) were analyzed. RESULTS: Differences in regional metabolite levels were found within the supraventricular brain of elderly control subjects. In Alzheimer disease patients, extensive WMSHs showed a lower percentage of NAA and a higher percentage of Cho compared with contralateral normal-appearing white matter (NAWM); in IVD patients, extensive and large WMSHs were associated with a higher percentage of Cho and a lower percentage of Cr compared with contralateral NAWM. CONCLUSION: Regional metabolite variation and the presence of WMSHs are important covariants that must be accounted for in analysis of MR spectroscopic data.

Aged

Basal ganglia phosphorous metabolism in chronic schizophrenia.

OBJECTIVE: The authors examined whether there are abnormalities in high-energy phosphorous metabolism in the basal ganglia of schizophrenic patients. METHOD: In vivo 31P magnetic resonance spectroscopic imaging was performed on 18 chronic schizophrenic patients and 16 healthy comparison subjects. The percentages of total phosphorous signal for phosphomonoesters, inorganic phosphate, phosphodiesters, phosphocreatine, and beta-ATP were calculated. RESULTS: The mean percentages of beta-ATP signal in the right and left basal ganglia were significantly lower for the schizophrenic patients than for the comparison group. No other group differences in phosphorous metabolites and no lateral asymmetries in the schizophrenic group were noted. CONCLUSIONS: This preliminary study provides support for abnormal high-energy phosphorous metabolism in the basal ganglia of schizophrenic patients.

Adenosine Triphosphate

Abnormal frontal lobe phosphorous metabolism in bipolar disorder.

OBJECTIVE: Abnormalities in frontal lobe phosphorous metabolism in patients with bipolar disorder have been reported, but many of the patients studied were receiving lithium. In this study, medication-free bipolar patients were examined to determine abnormalities in frontal lobe high-energy phosphorous metabolism. METHOD: In vivo phosphorous-31 magnetic resonance spectroscopic imaging was performed on 12 unmedicated, euthymic bipolar patients and 16 healthy comparison subjects. The percentages of total phosphorous signal for phosphomonoesters, inorganic phosphate, phosphodiesters, phosphocreatine, and beta-ATP were calculated. RESULTS: In relation to the comparison group, the patients with bipolar disorder had significantly lower phosphomonoester values and higher phosphodiester values in both the left and right frontal lobes. The patients also had a significantly higher right-to-left ratio of frontal lobe phosphocreatine. No other differences in phosphorous metabolites or lateralized asymmetries were noted. CONCLUSIONS: This preliminary study provides support for abnormal frontal lobe phosphorous metabolism in bipolar disorder.

Adult

31phosphorus magnetic resonance spectroscopy of the frontal and parietal lobes in chronic schizophrenia.

In vivo 31Phosphorus magnetic resonance spectroscopic imaging (31P MRSI) was performed on 20 chronic schizophrenic patients and 16 normal controls to determine if there were specific changes in high energy phosphorus and phospholipid metabolism in the frontal lobes of schizophrenic patients. Phosphorous metabolites were assessed in each of the left and right frontal as well as the left and right parietal lobes. Frontal lobe phosphorous metabolites were also correlated with severity of psychiatric symptomatology as assessed by the Brief Psychiatric Rating Scale (BPRS). Schizophrenics demonstrated higher phosphodiesters (PDE) and lower phosphocreatine (PCr) in both the left and right frontal regions compared to controls. There was also lower left frontal inorganic phosphate (Pi) in the schizophrenic group. No group differences were noted in the left or right parietal regions. In addition, right frontal PDE and right frontal PCr were highly correlated with the hostility-suspiciousness and anxiety-depression subscales of the BPRS. This study provides further support for altered frontal lobe phosphorous metabolism in schizophrenia.

Adult

Axonal injury and membrane alterations in Alzheimer's disease suggested by in vivo proton magnetic resonance spectroscopic imaging.

We used spin-echo magnetic resonance imaging and proton magnetic resonance spectroscopic imaging in 8 patients with probable Alzheimer's disease and in 10 age-matched elderly control subjects to assess the effects of Alzheimer's disease on the brain. On magnetic resonance images the patients showed significant ventricular enlargements relative to the control subjects. We measured the distribution and relative signal intensities of N-acetylaspartate (a putative neuronal marker), of choline residues representing lipid metabolites, and of creatine-containing metabolites in a large section of the centrum semiovale containing white and mesial gray matter. Throughout the white matter of the patients with Alzheimer's disease compared to elderly control subjects, N-acetylaspartate was decreased relative to choline (N-acetylaspartate-choline ratio) and creatine-containing metabolites (N-acetylaspartate-creatine ratio) with no changes in the choline-creatine ratio. The N-acetylaspartate-choline ratio was lower and choline-creatine higher in the mesial gray matter of AD patients relative to elderly controls. The posterior section of the centrum semiovale in the patients showed increased choline-creatine and choline-N-acetylaspartate ratios with the N-acetylaspartate-creatine ratio unchanged between the patients and control subjects. These spectroscopic findings give suggestive evidence of diffuse axonal injury and membrane alterations in gray and white matter of the centrum semiovale in patients with Alzheimer's disease.

Aged

Biochemical alterations in multiple sclerosis lesions and normal-appearing white matter detected by in vivo 31P and 1H spectroscopic imaging.

The goals of the current study were threefold: first, to confirm previous single volume proton (1H) magnetic resonance spectroscopy results of reduced N-acetyl aspartate (NAA, a putative marker of neurons) in multiple sclerosis (MS) white matter lesions using multiple volume 1H magnetic resonance spectroscopic imaging (MRSI); second, to measure the phospholipid metabolites phosphomonoesters and phosphodiesters in such lesions using phosphorus (31P) MRSI; and third, to test the hypothesis that biochemical changes occur in the normal-appearing (on spin echo T2-weighted magnetic resonance images) white matter in patients with MS. Thirteen subjects with clinically definite MS were studied with both 1H and 31P MRSI, and 19 controls were studied with either 1H MRSI, 31P MRSI, or both. MS lesion, MS normal-appearing white matter, and region-matched control spectra from the centrum semiovale were analyzed. The major findings of this study were that in both white matter lesions and normal-appearing white matter in patients with MS, the metabolite ratio NAA/creatine and the total 31P peak integrals were significantly reduced compared with controls. In addition, in MS lesions NAA/choline and phosphodiesters/total 31P were significantly reduced compared with controls, and in MS normal-appearing white matter there was a trend for NAA/choline to be reduced compared with controls. In normal-appearing white matter in patients with MS, total creatine and phosphocreatine were significantly increased compared to controls, as detected with both 1H (total creatine peak integrals) and 31P (phosphocreatine/total 31P) MRSI techniques. These results suggest reduced neuronal density and altered phospholipid metabolites in white matter lesions in patients with MS.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Equivalent dipole parameter estimation using simulated annealing.

Equivalent-electrical dipole source modeling of evoked potential signals requires complicated non-linear multivariate optimization. Newton and non-linear simplex optimization methods often converge to a local minimum, and their results are affected by the procedure's starting parameter estimates. This paper describes simulated annealing, a more robust and resistant global optimization method. As an illustrative example, both the simplex and simulated annealing algorithms were used for parameter estimation in modeling wave V of the brain-stem auditory evoked potential (BAEP) using a single decaying sinusoid dipole source. Data for a single subject from 3000 responses to stimuli on each of 2 days were recorded, with modeling performed on 1000 response subaverages. Each estimation problem was run with 5 different sets of starting parameters. Simulated annealing always converged to the global minimum regardless of the starting parameter estimates while simplex often converged to markedly different solutions for different starting parameter estimates. No association was apparent between the simplex's converging to a local minimum and the closeness of the starting estimates to the true parameter values. Implementation of simulated annealing is discussed in terms of cooling schedules and other procedure parameters.

Acoustic Stimulation

The auditory P50 response is normal in Alzheimer's disease when measured via a paired click paradigm.

Recent findings of missing or markedly attenuated P50 (or P1) auditory ERPs in Alzheimer's disease (AD) patients suggest this may be a useful diagnostic and/or prognostic marker of AD cholinergic deficits. Those studies used repetitive 1/sec clicks. Given P50's long recovery time, all but the first click in that paradigm was presented during the recovery of the P50 generation system from the response to the prior click. We studied 8 AD patients and 17 elderly controls using a paradigm incorporating 7-8 sec intervals between clicks, which allows examination of P50 generation separate from P50 recovery. With the long inter-click interval, we identified P50 responses in most AD patients and controls, and found no difference in P50 amplitude between groups. These results suggest that if there is a P50 deficit in AD patients, it is the result of the accumulative effect of repetitive stimulation, rather than a primary deficit in P50 generation.

Acoustic Stimulation