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Thomas Ernst

Publications and source records attributed to Thomas Ernst.

At least 19 recordsLinked to original sources
PubMed2007

Unified structural equation modeling approach for the analysis of multisubject, multivariate functional MRI data.

The ultimate goal of brain connectivity studies is to propose, test, modify, and compare certain directional brain pathways. Path analysis or structural equation modeling (SEM) is an ideal statistical method for such studies. In this work, we propose a two-stage unified SEM plus GLM (General Linear Model) approach for the analysis of multisubject, multivariate functional magnetic resonance imaging (fMRI) time series data with subject-level covariates. In Stage 1, we analyze the fMRI multivariate time series for each subject individually via a unified SEM model by combining longitudinal pathways represented by a multivariate autoregressive (MAR) model, and contemporaneous pathways represented by a conventional SEM. In Stage 2, the resulting subject-level path coefficients are merged with subject-level covariates such as gender, age, IQ, etc., to examine the impact of these covariates on effective connectivity via a GLM. Our approach is exemplified via the analysis of an fMRI visual attention experiment. Furthermore, the significant path network from the unified SEM analysis is compared to that from a conventional SEM analysis without incorporating the longitudinal information as well as that from a Dynamic Causal Modeling (DCM) approach.

Attention↗
PubMed2007

Is decreased prefrontal cortical sensitivity to monetary reward associated with impaired motivation and self-control in cocaine addiction?

OBJECTIVE: This study attempted to examine the brain's sensitivity to monetary rewards of different magnitudes in cocaine abusers and to study its association with motivation and self-control. METHOD: Sixteen cocaine abusers and 13 matched healthy comparison subjects performed a forced-choice task under three monetary value conditions while brain activation was measured with functional magnetic resonance imaging. Objective measures of state motivation were assessed by reaction time and accuracy, and subjective measures were assessed by self-reports of task engagement. Measures of trait motivation and self-control were assessed with the Multidimensional Personality Questionnaire. RESULTS: The cocaine abusers demonstrated an overall reduced regional brain responsivity to differences between the monetary value conditions. Also, in comparison subjects but not in cocaine abusers, reward-induced improvements in performance were associated with self-reports of task engagement, and money-induced activations in the lateral prefrontal cortex were associated with parallel activations in the orbitofrontal cortex. For cocaine abusers, prefrontal cortex sensitivity to money was instead associated with motivation and self-control. CONCLUSIONS: These findings suggest that in cocaine addiction 1) activation of the corticolimbic reward circuit to gradations of money is altered; 2) the lack of a correlation between objective and subjective measures of state motivation may be indicative of disrupted perception of motivational drive, which could contribute to impairments in self-control; and 3) the lateral prefrontal cortex modulates trait motivation and deficits in self-control, and a possible underlying mechanism may encompass a breakdown in prefrontal-orbitofrontal cortical communication.

Adult↗
PubMed2006

Removal selectivity of Prometheus: a new extracorporeal liver support device.

AIM: To evaluate whether treatment with the Prometheus reg system significantly affects cytokines, coagulation factors and other plasma proteins. METHODS: We studied nine patients with acute-on-chronic liver failure and accompanying renal failure. Prometheus reg therapy was performed on 2 consecutive days for up to 6 h in all patients. Several biochemical parameters and blood counts were assessed at regular time points during Prometheus reg treatment. RESULTS: We observed a significant decrease of both protein-bound (e.g. bile acids) and water-soluble (e.g. ammonia) substances after Prometheus reg therapy. Even though leukocytes increased during treatment (P<0.01), we found no significant changes of C-reactive protein, interleukin-6, and tumor necrosis factor-alpha plasma levels (all P>0.5). Further, antithrombin 3, factor II and factor V plasma levels did not decrease during Prometheus reg therapy (all P>0.5), and the INR remained unchanged (P=0.4). Plasma levels of total protein, albumin, and fibrinogen were also not altered during Prometheus reg treatment (all P>0.5). Finally, platelet count did not change significantly during therapy (P=0.6). CONCLUSION: Despite significant removal of protein-bound and water-soluble substances, Prometheus reg therapy did not affect the level of cytokines, coagulation factors or other plasma proteins. Thus, the filters and adsorbers used in the system are highly effective and specific for water-soluble substances and toxins bound to the albumin fraction.

Blood Coagulation Factors↗
PubMed2006

The human immunodeficiency virus reduces network capacity: acoustic noise effect.

OBJECTIVE: Increased acoustic noise (AN) during working memory leads to increased brain activation in healthy individuals and may have greater impact in human immunodeficiency virus (HIV) patients. RESULTS: Compared with control subjects, HIV patients showed reduced AN activation and lower neuronal marker N-acetylaspartate in prefrontal and parietal cortices. Competing use of the working memory network between AN and cognitive load showed lower dynamic range of the hemodynamic responses in prefrontal and parietal cortices in HIV patients. INTERPRETATION: These findings suggest that reduced reserve capacity of the working memory network in HIV patients and additional stress (eg, AN) might exhaust the impaired network for more demanding tasks.

Acoustic Stimulation↗
PubMed2006

Common deactivation patterns during working memory and visual attention tasks: an intra-subject fMRI study at 4 Tesla.

This parametric functional magnetic resonance imaging (fMRI) study investigates the balance of negative and positive fMRI signals in the brain. A set of visual attention (VA) and working memory (WM) tasks with graded levels of difficulty was used to deactivate separate but overlapping networks that include the frontal, temporal, occipital, and limbic lobes; regions commonly associated with auditory and emotional processing. Brain activation (% signal change and volume) was larger for VA tasks than for WM tasks, but deactivation was larger for WM tasks. Load-related increases of blood oxygenation level-dependent (BOLD) responses for different levels of task difficulty cross-correlated strongly in the deactivated network during VA but less so during WM. The variability of the deactivated network across different cognitive tasks supports the hypothesis that global cerebral blood flow vary across different tasks, but not between different levels of task difficulty of the same task. The task-dependent balance of activation and deactivation might allow maximization of resources for the activated network.

Adult↗
PubMed2005

The Prometheus device for extracorporeal support of combined liver and renal failure.

BACKGROUND/AIMS: Prometheus is a newly developed extracorporeal liver support system that combines removal of albumin-bound substances (adsorption on resin adsorbers) and water-soluble substances (diffusion during high-flux hemodialysis). Therefore, it is a promising treatment option for patients with hepatorenal syndrome (HRS). METHODS: We studied 10 patients with HRS in a prospective clinical study. All patients underwent 2 consecutive Prometheus treatments. A variety of clinical and biochemical parameters were assessed. RESULTS: Prometheus treatment was uncomplicated and safe. A statistically significant improvement of serum creatinine and urea concentrations as well as blood pH was observed after Prometheus treatment. Furthermore, liver detoxification was supported by a significant decrease of serum levels of conjugated bilirubin, bile acids and ammonia. CONCLUSIONS: Prometheus is a safe treatment for patients with HRS. Both, albumin-bound and water-soluble substances were effectively removed. Controlled studies will evaluate the effect of this new treatment option on survival in patients with HRS.

Blood Chemical Analysis↗
PubMed2005

Widespread occurrence of the JAK2 V617F mutation in chronic myeloproliferative disorders.

The analysis of rare chromosomal translocations in myeloproliferative disorders has highlighted the importance of aberrant tyrosine kinase signaling in the pathogenesis of these diseases. Here we have investigated samples from 679 patients and controls for the nonreceptor tyrosine kinase JAK2 V617F mutation. Of the 480 myeloproliferative disorder (MPD) samples, the proportion of positive cases per disease subtype was 30 (20%) of 152 for atypical or unclassified MPD, 2 of 134 (2%) for idiopathic hypereosinophilic syndrome, 58 of 72 (81%) for polycythemia vera, 24 of 59 (41%) essential thrombocythemia (ET), and 15 of 35 (43%) for idiopathic myelofibrosis. V617F was not identified in patients with systemic mastocytosis (n = 28), chronic or acute myeloid leukemia (n = 35), secondary erythrocytosis (n = 4), or healthy controls (n = 160). Homozygosity for V617F was seen in 43% of mutant samples and was closely correlated with chromosome 9p uniparental disomy. Homozygosity was significantly less common in ET compared with other MPD subtypes. In 53 cases analyzed, the median level of PRV1 expression was significantly higher in V617F-positive cases compared with cases without the mutation. We conclude that V617F is widespread in MPDs. Detection of this acquired mutation is likely to have a major impact on the way patients with MPD are diagnosed, as well as serving as an obvious target for signal transduction therapy.

Case-Control Studies↗
PubMed2005

Enlarged striatum in abstinent methamphetamine abusers: a possible compensatory response.

BACKGROUND: Little is known about structural brain abnormalities associated with methamphetamine (METH) abuse; therefore, we aimed: 1) to evaluate possible morphometric changes, especially in the striatum of recently abstinent METH-dependent subjects; 2) to evaluate whether morphometric changes are related to cognitive performance; and 3) to determine whether there are sex-by-METH interactions on morphometry. METHODS: Structural MRI was performed in 50 METH and 50 comparison subjects with the same age range and sex proportion; quantitative morphometric analyses were performed in the subcortical gray matter, cerebellum and corpus callosum. Neuropsychological tests were also performed in 44 METH and 28 comparison subjects. RESULTS: METH users showed enlarged putamen (left: + 10.3%, p = .0007; right: + 9.6%, p = .001) and globus pallidus (left: + 9.3%, p = .002; right: + 6.6%, p = .01). Female METH subjects additionally showed larger mid-posterior corpus callosum (+ 9.7%, p = .05). Although METH users had normal cognitive function, those with smaller striatal structures had poorer cognitive performance and greater cumulative METH usage. CONCLUSIONS: Since METH subjects with larger striatal structures had relatively normal cognitive performance and lesser cumulative METH usage, the enlarged putamen and globus pallidus might represent a compensatory response to maintain function. Possible mechanisms for the striatal enlargement include glial activation and inflammatory changes associated with METH-induced injury.

Adult↗
PubMed2005

The effect of small rotations on R2* measured with echo planar imaging.

Several modern MRI techniques, such as functional MRI (fMRI), rely on the detection of microscopic changes in magnetic susceptibility. However, differences in magnetic susceptibility between brain tissue, bone, and air also produce local magnetic field gradients that may interfere with the contrast of interest, particularly at high field strengths. Since the magnetic field distribution depends on the orientation of the human head in the MRI scanner, head rotations can change the effective transverse relaxation rate (R(2)*) and confound fMRI studies. The size of the R(2)* changes produced by small head rotations was estimated from a brain-shaped gel-phantom at 4 T, by measuring the signal decay at 96 different echo times. Similar measurements were carried out in a human study. Rotations larger than 2 degrees changed R(2)* more than 1.5 Hz in the phantom, and indicate that even small rotations may compromise fMRI results.

Adult↗
PubMed2005

A multicenter study of two magnetic resonance spectroscopy techniques in individuals with HIV dementia.

PURPOSE: To evaluate single-voxel proton magnetic resonance spectroscopy (SV-MRS) and magnetic resonance spectroscopic imaging (MRSI) metabolite results in individuals with HIV dementia. MATERIALS AND METHODS: Twenty HIV-positive (HIV+) individuals underwent SV-MRS (TE 35 msec) and MRSI (TE 280 msec). Results were stratified according to serostatus, dementia severity, psychomotor speed performance, and functional impairment. RESULTS: HIV+ individuals with psychomotor slowing had an increased myoinositol/creatine (mI/Cr) ratio (0.63 vs. 0.45) in the frontal white matter using SV-MRS and an increased choline (Cho)/Cr ratio (1.88 vs. 1.41) in the mesial frontal gray matter using MRSI compared to HIV+ individuals without psychomotor slowing. Using MRSI, subjects with HIV dementia also had a decreased N-acetyl aspartate (NAA)/Cho ratio (1.55 vs. 2.53) compared to HIV+ individuals without cognitive impairment in the mesial frontal gray matter. Both techniques detected metabolite ratio abnormalities associated with abnormal functional performance. CONCLUSION: SV-MRS and MRSI offer complementary roles in evaluating individuals with HIV dementia. Short TE SV-MRS measures mI, which may be elevated in early HIV dementia, whereas MRSI provides wider spatial coverage to examine specific regional changes.

AIDS Dementia Complex↗
PubMed2005

Additive effects of HIV and chronic methamphetamine use on brain metabolite abnormalities.

OBJECTIVE: Proton magnetic resonance spectroscopy (1H-MRS) showed decreased neuronal marker N-acetylaspartate and increased glial marker myo-inositol in subjects with chronic methamphetamine use and in subjects infected with HIV. The authors sought to determine whether HIV and a history of chronic methamphetamine use might have additive or interactive effects on brain metabolite abnormalities. METHOD: 1H-MRS was performed in 68 HIV-positive subjects (24 with a history of chronic methamphetamine use with a lifetime exposure of a mean of 2,167 g [SD=2,788] and last use a mean of 4.9 months earlier [SD=6.0]; 44 with no history of drug abuse) and 75 HIV-negative subjects (36 with a history of chronic methamphetamine use with a lifetime exposure of a mean of 8,241 g [SD=16,850] and last use a mean of 6.3 months earlier [SD=7.8]; 39 with no history of drug abuse). Concentrations of N-acetylaspartate, creatine, choline, and myo-inositol were measured in the frontal cortex, frontal white matter, and basal ganglia. RESULTS: HIV-negative subjects with a history of chronic methamphetamine use showed lower concentrations of the neuronal marker N-acetylaspartate in the frontal white matter and basal ganglia and higher concentrations of choline compounds and the glial marker myo-inositol in the frontal cortex, relative to subjects with no history of drug abuse. HIV-positive status was associated with lower concentrations of N-acetylaspartate and creatine in the frontal cortex and higher concentrations of myo-inositol in the white matter, compared with HIV-negative status. Compared to the mean concentrations of metabolites in HIV-negative subjects with no history of drug abuse, the mean concentrations in subjects with HIV and chronic methamphetamine use showed additive effects on N-acetylaspartate in all three regions (-9% in the basal ganglia, -7% in the frontal white matter, and -6% in the frontal gray matter), on creatine in the basal ganglia (-7%), and on myo-inositol in the frontal white matter (+11%). CONCLUSIONS: The combined effects of HIV and chronic methamphetamine use were consistent with an additive model, suggesting additional neuronal injury and glial activation due to the comorbid conditions.

Adult↗
PubMed2004

Smaller subcortical volumes and cognitive deficits in children with prenatal methamphetamine exposure.

The purpose of this pilot study was to examine possible neurotoxic effects of prenatal methamphetamine (Meth) exposure on the developing brain and on cognition. Meth-exposed children (n=13) and unexposed control subjects (n=15) were evaluated with MRI. Global brain volumes and regional brain structures were quantified. Ten Meth-exposed and nine unexposed children also completed neurocognitive assessments. Meth-exposed children scored lower on measures of visual motor integration, attention, verbal memory and long-term spatial memory. There were no differences among the groups in motor skills, short delay spatial memory or measures of non-verbal intelligence. Despite comparable whole brain volumes in each group, the Meth-exposed children had smaller putamen bilaterally (-17.7%), smaller globus pallidus (left: -27%, right: 30%), smaller hippocampus volumes (left: -19%, right: -20%) and a trend for a smaller caudate bilaterally (-13%). The reduction in these brain structures correlated with poorer performance on sustained attention and delayed verbal memory. No group differences in volumes were noted in the thalamus, midbrain or the cerebellum. In summary, compared with the control group, children exposed to Meth prenatally exhibit smaller subcortical volumes and associated neurocognitive deficits. These preliminary findings suggest prenatal Meth exposure may be neurotoxic to the developing brain.

Adolescent↗
PubMed2004

Decreased brain dopaminergic transporters in HIV-associated dementia patients.

HIV has a propensity to invade subcortical regions of the brain, which may lead to a subcortical dementia termed HIV-cognitive motor complex. Therefore, we aimed to assess whether dopamine (DA) D2 receptors and transporters (DAT) are affected in the basal ganglia of subjects with HIV, and how these changes relate to dementia status. Fifteen HIV subjects (age 44.5 +/- 11 years; CD4 185 +/- 130/mm3)) and 13 seronegative controls (42 +/- 12 years) were evaluated with PET to assess availability of DAT ([11C]cocaine) and DA D2 receptor ([11C]raclopride). HIV patients with associated dementia (HAD), but not those without dementia (ND) had significantly lower DAT availability in putamen (-19.3%, P = 0.009) and ventral striatum (-13.6%, P = 0.03) compared with seronegative controls. Higher plasma viral load in the HIV dementia patients correlated with lower DAT in the caudate (r = -0.7, P = 0.02) and putamen (r = -0.69, P = 0.03). DA D2 receptor availability, however, showed mild and non-significant decreases in HIV patients. These results provide the first evidence of DA terminal injury in HIV dementia patients, and suggest that decreased DAT may contribute to the pathogenesis of HIV dementia. The greater DAT decrease in the putamen than in the caudate parallels that observed in Parkinson's disease. The inverse relationship between viral burden and DAT availability further supports HIV-mediated neurotoxicity to dopaminergic terminals.

AIDS Dementia Complex↗
PubMed2004

Effect of aging on brain metabolism in antiretroviral-naive HIV patients.

OBJECTIVE: Normal aging as well as HIV infection may lead to inflammatory changes and injury to the brain; however, it is unclear if and how these processes interact. The goal of this pilot study was to evaluate the interaction between aging and HIV infection in the brain using proton magnetic resonance spectroscopy (H-MRS). DESIGN: Analyses of covariance (ANCOVA) were performed to determine the effects of HIV and age, and their interaction, on MRS variables. METHODS: Forty-six HIV patients naive to antiretroviral medications and 58 seronegative control subjects were examined using localized H-MRS in the frontal gray matter, frontal white matter and basal ganglia, and metabolite concentrations were determined. RESULTS: Compared with seronegative controls, HIV-positive subjects showed additional and marked increases in the concentration of glial markers, choline-containing compounds (seronegative controls +2%/decade; HIV-positive subjects +10%/decade) and myoinositol (seronegative controls +3%/decade; HIV-positive subjects +12%/decade), with aging in the frontal white matter. In the basal ganglia, N-acetyl compounds and total creatine decreased with age only in HIV patients (N-acetyl compounds -3.7%/decade; creatine -4%/decade). ANCOVA showed significant interaction effects between HIV and aging on the metabolites in the basal ganglia (N-acetyl peak P = 0.03; creatine P = 0.04) and in the frontal white matter (interaction: choline-containing compounds P = 0.002; myoinositol P = 0.007). CONCLUSION: In the basal ganglia, HIV infection appeared to induce neuronal damage or loss beyond that observed in normal aging. In the frontal white matter, HIV infection seemed to exacerbate glial activation beyond that observed in normal aging.

Adolescent↗
PubMed2004

Adaptation of the attention network in human immunodeficiency virus brain injury.

Human immunodeficiency virus (HIV)-positive patients commonly have attention and concentration problems. However, it remains unclear how HIV infection affects the attention network. Therefore, blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI) was performed in 36 subjects (18 HIV and 18 seronegative [SN] controls) during a set of visual attention tasks with increasing levels of attentional load. Compared with SN controls, HIV subjects showed similar task performance (accuracies and reaction times) but decreased activation in the normal visual attention network (dorsal parietal, bilateral prefrontal, and cerebellar regions) and increased activation in adjacent or contralateral brain regions. Cognitive performance (assessed with NPZ-8), CD4, and viral load all correlated with activated BOLD signals in brain regions that activated more in HIV subjects. Furthermore, HIV subjects activated more than SN controls in brain regions that showed load-dependent increase in activation (right prefrontal and right parietal regions) but less in regions that showed a saturation effect with increasing load. These findings suggest that HIV-associated brain injury leads to reduced efficiency in the normal attention network, thus requiring reorganization and increased usage of neural reserves to maintain performance during attention-requiring tasks. Exceeding the brain reserve capacity may lead to attention deficits and cognitive impairment in HIV patients.

Adult↗
PubMed2004

Localized in vivo human 1H MRS at very short echo times.

A new point-resolved spectroscopy (PRESS) sequence was developed that allows localized human proton MR spectra to be acquired at echo times (TEs) of 10 ms or less. The method was implemented on a 4 Tesla Varian research console and a clinical 3 Tesla Siemens Trio scanner. Human brain spectra acquired in vivo from the prefrontal cortex at TE=8 ms showed improved signals from coupled resonances (such as glutamate, glutamine, and myo-inositol) compared to spectra acquired at TE=30 ms. These improvements should result in more accurate quantitation of these metabolites.

Brain↗
PubMed2004

Regional patterns of brain metabolites in AIDS dementia complex.

The relationship of the cellular changes in the HIV-infected brain to the onset and progression of AIDS dementia complex (ADC) remains uncertain. We undertook an in vivo proton magnetic resonance spectroscopy (MRS) study and used factor analysis to identify specific cellular and regional brain changes that may serve as metabolic markers of ADC. The ratio of N-acetyl aspartate (NAA), choline (Cho), and myoinositol (MI) over creatine (Cr), markers of neuronal and glial cell metabolism, were measured in the basal ganglia, centrum semiovale, and parietal cortex from 100 subjects with and without ADC. Three metabolic patterns were identified, which we termed "inflammatory" (mainly MI/Cr elevations in all three regions plus Cho/Cr increases in the centrum semiovale and parietal cortex), "basal ganglia" (mostly NAA/Cr and Cho/Cr elevations in the basal ganglia), and "neuronal" (primarily NAA/Cr reductions in the centrum semiovale and the parietal cortex). Logistic regression analysis revealed that, adjusted for age, basal ganglia and neuronal pattern scores were strongly associated with ADC but inflammatory levels were not. We conclude that by using factor analysis, we are able to combine multiple metabolites across brain regions in a biologically plausible manner and construct a predictive model of ADC adjusting for relevant factors such as age.

AIDS Dementia Complex↗