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Biomedical subjects

G Fein

Publications and source records attributed to G Fein.

At least 73 records · Page 4Linked to original sources

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↗

N-acetylaspartate reductions measured by 1H MRSI in cognitively impaired HIV-seropositive individuals.

We used magnetic resonance imaging (MRI) and water-suppressed proton MR spectroscopic imaging (1H MRSI) to study the effects of human immunodeficiency virus (HIV) infection on the brain. Our recent in vivo finding of lower N-acetylaspartate (NAA), a putative marker of neurons, in the supraventricular brain of cognitively impaired HIV-seropositive patients (CISP) compared to noninfected controls was replicated in a new cohort of 13 CISP patients and extended to include 10 high-risk homosexual HIV-seronegative controls. Throughout the supraventricular brain the ratio of NAA to choline-containing metabolites (NAA/Cho) was lower in CISP subjects than in high-risk controls (1.98 +/- 0.36 vs. 2.35 +/- 0.29, p = 0.016), and the ratio of NAA to creatine-containing metabolites (NAA/Cr) was also lower in CISP subjects than in high-risk controls (3.02 +/- 0.44 vs. 3.56 +/- 0.39, p = 0.007) with Cho/Cr unchanged in both groups. These findings indicate a NAA reduction which suggests neuron loss and/or dendritic and axonal damage. Homosexual high-risk HIV-seronegative controls had metabolite measures similar to previously studied heterosexual HIV-seronegative controls. NAA measures in six cognitively normal HIV-seropositive subjects (CNSP) (NAA/Cho = 2.34 +/- 0.39, NAA/Cr = 3.42 +/- 0.69) were similar to those of controls and tended to be increased relative to those in cognitively impaired HIV-seropositive subjects. This study demonstrates that reduced NAA in the supraventricular brain is associated with the development of severe cognitive impairments secondary to HIV infection and that 1H MRSI methodology reliably detects HIV effects on the brain.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The reliability of P50 suppression as measured by the conditioning/testing ratio is vastly improved by dipole modeling.

Suppression of auditory P50 evoked potential amplitude to the second of a pair of clicks is potentially important in psychiatric research because it has been shown to be abnormal in both schizophrenics and their relatives. However, its clinical utility using the standard single-channel electroencephalographic (EEG) peak picking methodology is under question because of low test-retest reliability. Dipole Components Modeling of the P50 component was attempted as a method for increasing the reliability of the P50 suppression measure. It was hypothesized that this procedure might work because of pooling of noise from the two responses and because of the use of topographic information. Six replications of a P50 suppression paradigm in 12 subjects were analyzed. Reliability using peak picking was 0.27, and was significantly increased to 0.63 using dipole modeling. Dipole modeling was helpful not only for better modeling the P50 when it was present, but also for deciding that there was no P50 response in one subject.

Acoustic Stimulation↗

Frequency domain dipole localization: extensions of the method and applications to auditory and visual evoked potentials.

We describe a statistical frequency domain approach to localizing equivalent dipole generators of human brain evoked potentials. The frequency domain representation allows considerable data reduction, constrains the magnitude function of the dipoles to be smooth, and accounts for the statistical properties of the background EEG. A previous paper described a restrictive model in which the dipole orientations were assumed to be fixed over time, and only one dipole was allowed. In this paper, we consider the more general model in which the orientation can vary over time, and which includes multiple dipole generators. The varying orientation model has the practical advantage of being more nearly linear and more flexible than the fixed orientation model, which facilitates convergence of the iterative fitting algorithm. We suggest a measure of goodness-of-fit that compares the likelihood of the dipole model with the likelihoods of saturated and null models. We report the results of fitting the model to recorded auditory and visual evoked potentials. A single dipole with fixed orientation seems to be an adequate model of the auditory midlatency response, while two dipoles with varying orientation are needed to fit the later P200 component. Analysis of the visual P100 response to unilateral stimulation localized a generator in the contralateral occipital cortex, as expected from anatomical considerations. A two-dipole model fit the visual P100 response of bilateral stimulations, and the locations of the two dipoles were similar to the locations obtained by single-dipole fits to the responses to left and right unilateral stimuli.

Computer Simulation↗

Reduced brain N-acetylaspartate suggests neuronal loss in cognitively impaired human immunodeficiency virus-seropositive individuals: in vivo 1H magnetic resonance spectroscopic imaging.

We used magnetic resonance imaging (MRI) and water-suppressed proton magnetic resonance spectroscopic imaging to study the effects of human immunodeficiency virus (HIV) infection on the brains of 10 individuals with cognitive impairment due to HIV and seven normal controls. 1H spectra from nine 2.5-ml volumes in the centrum semiovale and the mesial cortex showed significantly reduced N-acetylaspartate (NAA) relative to choline and creatine in the cognitively impaired HIV-infected subjects. This reduction was due to a nonlocalized decrease of NAA in these patients, only two of whom had moderate atrophy and white matter signal hyperintensities on MRI. Since NAA is a putative neuronal marker, the findings suggest neuronal damage in early stages of HIV infection that is not evident on standard MRI and are consistent with the neuropathologically known neuronal loss.

Adult↗

The Indented Paragraph Reading Test in the assessment of left hemi-neglect.

We investigated the validity of the Indented Paragraph Reading Test (IPRT), designed to assess left hemi-neglect (LHN) in reading behavior, with regard to education effects, scoring properties, and sensitivity to recovery of LHN. The IPRT was administered aspart of a larger battery to 50 right-hemisphere stroke patients approximately 1, 2, 3, and 7 months post-stroke if, and only if, the patient demonstrated LHN on the previous test battery. Contrary to expectations, performance on the IPRT was not correlated with education and even patients with minimal formal education were able to complete the test. We demonstrated that the author's suggested scoring criterion was valid and sensitive to the presence of LHN as well as to its recovery over time.

Journal Article↗

31Phosphorus magnetic resonance spectroscopy of the temporal lobes in schizophrenia.

Eleven schizophrenic patients and nine normal controls were studied using in vivo 31Phosphorous magnetic resonance spectroscopy (31P MRS) to test the hypothesis of metabolic asymmetry in the temporal lobes in schizophrenia. The controls did not demonstrate any asymmetry of phosphorous metabolite ratios, percentage of phosphorous metabolites, or pH. In the schizophrenics, however, phosphocreatine/beta-adenosine triphosphate (PCr/beta-ATP) and phosphocreatine/inorganic phosphate (PCr/Pi) effects appeared to primarily reflect higher ratios on the right side, while the percentage of beta-ATP appeared to primarily reflect higher relative concentrations in the left temporal lobe. Moreover, significant negative correlations were noted between total Brief Psychiatric Rating Scale scores and PCr/beta-ATP in both the right and left temporal lobes. These results support the hypothesis of an asymmetric distribution of 31P metabolites in the temporal lobe of schizophrenic patients, and also show an association between temporal lobe phosphorous metabolism and the severity of psychiatric symptomatology.

Adenosine Triphosphate↗

P50 suppression is not affected by attentional manipulations.

Auditory evoked potentials (EP) to high or moderate intensity, single or paired clicks were recorded from normal young adult subjects. A choice-reaction-time paradigm had two sets of instructions, for intensity discrimination and for number (single versus paired stimulus) discrimination. For intensity discrimination, the second click had no informative value and its N100 amplitude was markedly reduced relative to the first click. For number discrimination, the presence or absence of the second click provided the salient information, and N100 amplitude was actually slightly larger for the second compared to the first click. In contrast, the attentional manipulation had no effect on P50 amplitude, which showed over 50% suppression from the first to the second click for both tasks. Thus, suppression of P50 amplitude to the second of a pair of clicks is insensitive to attentional manipulations that have major effects on N100 amplitude. These findings suggest that abnormalities of schizophrenic P50 suppression reflect neuronal rather than psychological phenomena.

Adult↗

Proton magnetic resonance spectroscopy of human brain: applications to normal white matter, chronic infarction, and MRI white matter signal hyperintensities.

A modified ISIS method, for image-selected localized proton magnetic resonance spectroscopy (1H MRS), was used to determine the ratios and T2 relaxation times of proton metabolites in normal subjects and in patients with chronic infarction and MRI white matter signal hyperintensities (WMSH). First, in patients with cerebral infarctions, increased concentrations of lactate were found in the majority of patients, and N-acetyl aspartate (NAA) was reduced to a significantly greater extent than choline (Cho) or creatine (Cre). For TE = 270 ms, the raw ratios of Cho/NAA, Cre/NAA, and Lac/NAA were significantly (P less than 0.05) increased from 0.23 +/- 0.02 (mean +/- SE), 0.20 +/- 0.01, and 0.05 +/- 0.01, respectively in the normal group to 0.39 +/- 0.08, 0.37 +/- 0.05, and 0.48 +/- 0.15 in the stroke group. Also, the T2 relaxation time of creatine was significantly (P = 0.007) increased from 136 ms in normal white matter to 171 ms in cerebral infarcts. Second, in patients with WMSH, no significant change of the proton metabolite concentrations could be detected with the exception of the choline which was significantly (P = 0.003) altered. The Cho/NAA ratio, after T2 and excitation profile correction, increased from 0.47 +/- 0.02 in the normal group to 0.64 +/- 0.05 in the WMSH group. Third, in normal white matter, the concentration of N-acetyl aspartate, choline, and lactate was estimated to 11.5, 2.0, and 0.6 mM, respectively, by assuming a total creatine concentration of 10 mM.

Aged↗

EEG spectra in dyslexic and normal readers during oral and silent reading.

EEGs of extensively screened dyslexics and normal readers were recorded while they read easy and difficult texts silently and orally, and during two other verbal tasks which also differed in overt speaking but had no reading component: narrative speaking and listening to a story. Mid-temporal, central and parietal leads were referenced to linked ears and to Cz. Large differences between tasks and between groups were found. With the linked ears reference, power was higher in all bands in oral reading than in silent reading, with the largest change occurring in the temporal leads. In the theta and low beta bands the difference between oral and silent reading was greater for controls than for dyslexics. These effects were not accounted for by differences in reading speed or in difficulty. Similar results were found in two cohorts of subjects. The difference between groups in theta was found only in the reading tasks. In contrast, the group difference in low beta was also found in the change from listening to speaking. This implies that the oral-silent group difference in theta is related to some aspect of the reading tasks other than the presence or absence of overt speaking, and that the low beta group difference is related to some aspect of overt speaking rather than to reading per se. With the Cz reference no group differences were found. It is suggested that the groups differ in the reading strategies they use, and the degree to which they shift strategy between the silent and oral tasks. We hypothesize that these cognitive differences are reflected in the theta activity from the temporal lobe. While there were many differences between the tasks in alpha power and asymmetry, no group differences involving alpha were found.

Adolescent↗

Effect of photic stimulation on human visual cortex lactate and phosphates using 1H and 31P magnetic resonance spectroscopy.

Previous animal and human studies showed that photic stimulation (PS) increased cerebral blood flow and glucose uptake much more than oxygen consumption, suggesting selective activation of anaerobic glycolysis. In the present studies, image-guided 1H and 31P magnetic resonance spectroscopy (MRS) was used to monitor the changes in lactate and high-energy phosphate concentrations produced by PS of visual cortex in six normal volunteers. PS initially produced a significant rise (to 250% of control, p less than 0.01) in visual cortex lactate during the first 6.4 min of PS, followed by a significant decline (p = 0.01) as PS continued. The PCr/Pi ratios decreased significantly from control values during the first 12.8 min of PS (p less than 0.05), and the pH was slightly increased. The positive P100 deflection of the visual evoked potential recorded between 100 and 172 ms after the strobe was significantly decreased from control at 12.8 min of PS (p less than 0.05). The finding that PS caused decreased PCr/Pi is consistent with the view that increased brain activity stimulated ATPase, causing a rise in ADP that shifted the creatine kinase reaction in the direction of ATP synthesis. The rise in lactate together with an increase in pH suggest that intracellular alkalosis, caused by the shift of creatine kinase, selectively stimulated glycolysis.

Adenosine Diphosphate↗

Alterations in brain phosphorus metabolite concentrations associated with areas of high signal intensity in white matter at MR imaging.

Areas of high signal intensity in white matter are identified on brain magnetic resonance (MR) imaging studies in 25%-50% of elderly subjects. The authors used phosphorus-31 MR spectroscopy to characterize the metabolic status of hemispheric white matter brain volumes in 30 elderly subjects with white matter areas of high signal intensity at MR imaging. Compared with white matter volumes with no or minimal areas of high intensity, white matter volumes with extensive areas of high intensity evidenced a 26% decrease in the adenosine triphosphate (ATP)/inorganic phosphate (Pi) ratio (P = .03) and a 21% decrease in the ATP concentration (P = .05), with the Pi level unchanged. A pilot P-31 spectroscopic imaging study in a subject with a large, coalescing white matter area of high signal intensity demonstrated large reductions in metabolite concentrations in the high-signal-intensity area. These results suggest that extensive white matter areas of high signal intensity indicate a process that affects white matter cellular energy metabolism.

Adenosine Triphosphate↗

Alterations in brain phosphate metabolite concentrations in patients with human immunodeficiency virus infection.

Human immunodeficiency virus (HIV)-infected individuals often demonstrate neuropsychiatric impairment; however, it is unclear how brain metabolism may be altered in such patients. We used in vivo phosphorus 31 magnetic resonance spectroscopy to noninvasively assess brain energy and phospholipid metabolism by measuring brain concentrations of adenosine triphosphate (ATP), phosphocreatine (PCr), and inorganic phosphate (Pi), as well as phospholipid compounds and intracellular pH. In study 1, 17 HIV-seropositive men with varying degrees of neuropsychiatric impairment and six control subjects were studied. Localized spectra were obtained from a heterogeneous 5 x 5 x 5-cm volume of interest (VOI). Patients with HIV infection had a significantly lower ATP/Pi ratio and a trend for a lower PCr/Pi ratio than did the control group. In addition, the ATP/Pi and PCr/Pi ratios were both significantly negatively correlated with overall severity of neuropsychiatric impairment. In study 2, three HIV-seropositive men with neuropsychiatric impairment were compared with 11 HIV-seronegative men. Localized phosphorus 31 magnetic resonance spectra were obtained from two relatively homogeneous VOIs: (1) a predominantly white matter VOI, and (2) a predominantly subcortical gray matter VOI. The three HIV-infected patients demonstrated significantly decreased ATP and PCr concentrations in the white matter VOI. These results suggest that HIV infection of the brain may impair brain cellular oxidative metabolism and that the degree of metabolic compromise may be related to the severity of neuropsychiatric impairment.

AIDS Dementia Complex↗

Partitioning of deep versus superficial intracranial sources using current source densities is not valid.

An analytic method has recently been proposed for partitioning scalp-recorded EEG and evoked potential (EP) data into parts arising from deep (i.e., subcortical) vs. superficial (i.e., cortical) sources. The method is based on the observation that the current source density (CSD) is selectively sensitive to electrical activity arising from superficial sources, and the conjecture that the residual potential which remains after subtracting the CSD from the scalp potentials, represents activity from deep sources. We investigated the validity of this procedure by simulating scalp potential data for superficial and deep dipole sources with known locations and orientations. Our single-dipole simulations demonstrated that, when the actual location of the source was superficial, the partitioning procedure erroneously attributed a sizeable proportion of the total topographic variance to the activity of deeper sources. This produced a consistent bias in the simulations with two dipoles, when both superficial and deep sources were present. In such cases, the relative contribution of the deeper source was consistently overestimated, and the scalp topography of the deep source activity was profoundly misrepresented by the residual which results from subtracting the CSD from the scalp potential. We conclude that the proposed method for partitioning EEG and EP data into components arising from deep vs. superficial intracranial sources is not valid.

Electrodes↗

Artifactually high coherences result from using spherical spline computation of scalp current density.

Coherence computed from common reference montages inextricably confounds true coherence with power and phase at the recording and reference electrodes. Direct measurement of coherence requires reference-free EEG data, such as data from EEG scalp current densities (SCDs), which estimate the potential gradient perpendicular to the scalp. Perrin et al. (1989) presented a method for computing SCDs by taking the Laplacian of the scalp potential surface generated by spherical spline interpolation. When this method of computing SCDs was applied to EEG data gathered from young adults, very high values were observed for inter-electrode coherences computed from the spherical spline derived SCD data but not from coherences computed from the common reference data. These high coherences prompted further examination of the properties of the spherical spline function and of spherical spline derived SCDs. Simulated data were constructed, and coherence was computed on the simulated data and on the SCDs derived from the spherical spline procedure and from the Hjorth (1980) procedure. The results of those simulations are presented, which demonstrate that a major artifact is introduced by using the spherical spline procedure. This artifact results from the spline weighting matrix used to derive the SCDs and strongly inflates the inter-electrode coherences of the SCD transformed data.

Artifacts↗