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Biomedical subjects

Dorothee P Auer

Publications and source records attributed to Dorothee P Auer.

At least 19 recordsLinked to original sources
PubMed2006

Monthly intravenous methylprednisolone in relapsing-remitting multiple sclerosis - reduction of enhancing lesions, T2 lesion volume and plasma prolactin concentrations.

BACKGROUND: Intravenous methylprednisolone (IV-MP) is an established treatment for multiple sclerosis (MS) relapses, accompanied by rapid, though transient reduction of gadolinium enhancing (Gd+) lesions on brain MRI. Intermittent IV-MP, alone or with immunomodulators, has been suggested but insufficiently studied as a strategy to prevent relapses. METHODS: In an open, single-cross-over study, nine patients with relapsing-remitting MS (RR-MS) underwent cranial Gd-MRI once monthly for twelve months. From month six on, they received a single i.v.-infusion of 500 mg methylprednisolone (and oral tapering for three days) after the MRI. Primary outcome measure was the mean number of Gd+ lesions during treatment vs. baseline periods; T2 lesion volume and monthly plasma concentrations of cortisol, ACTH and prolactin were secondary outcome measures. Safety was assessed clinically, by routine laboratory and bone mineral density measurements. Soluble immune parameters (sTNF-RI, sTNF-RII, IL1-ra and sVCAM-1) and neuroendocrine tests (ACTH test, combined dexamethasone/CRH test) were additionally analyzed. RESULTS: Comparing treatment to baseline periods, the number of Gd+ lesions/scan was reduced in eight of the nine patients, by a median of 43.8% (p = 0.013, Wilcoxon). In comparison, a pooled dataset of 83 untreated RR-MS patients from several studies, selected by the same clinical and MRI criteria, showed a non-significant decrease by a median of 14% (p = 0.32). T2 lesion volume decreased by 21% during treatment (p = 0.001). Monthly plasma prolactin showed a parallel decline (p = 0.027), with significant cross-correlation with the number of Gd+ lesions. Other hormones and immune system variables were unchanged, as were ACTH test and dexamethasone-CRH test. Treatment was well tolerated; routine laboratory and bone mineral density were unchanged. CONCLUSION: Monthly IV-MP reduces inflammatory activity and T2 lesion volume in RR-MS.

Adult↗
PubMed2006

Neural networks of response shifting: influence of task speed and stimulus material.

Functional magnetic resonance imaging (fMRI) was used in 14 healthy subjects to measure brain activation, while response shifting was performed. In the activation phase, subjects were asked to shift their attention between two different types of visually presented stimuli. In the baseline phase, subjects were required to attend to one stimulus type only. Subjects responded by pressing a left or right key according to the side of presentation of the target stimuli. In a verbal task, subjects were required to switch between letters and numbers. In a figural task, subjects reacted to round and square shapes. Stimuli were presented for 750 or 1500 ms. Response shifting revealed significantly increased activation compared to non-switching in the bilateral superior parietal cortex, right occipital cortex, left inferior frontal cortex, left and right striatum, and bilateral dorsolateral prefrontal cortex (DLPFC). Superior parietal and occipital cortex activation may be due to spatial analysis during response shifting. Subvocal rehearsal of the task instructions may have led to activation in the left inferior frontal cortex. Activation in the striatum was related to prefrontal activation and may represent the association between basal ganglia and prefrontal activation during executive control. However, the most important brain region involved in the execution of response shifting was the bilateral DLPFC. Higher task speed increased executive top-down attentional control and, therefore, significantly increased activity in the bilateral DLPFC. Brain activation did not differ significantly between verbal and figural stimulus material. This result suggests that brain activation in the present study illustrates the brain regions involved in the basic cognitive mechanisms of response shifting.

Adult↗
PubMed2006

Anxiety and hippocampus volume in the rat.

In depressed patients as well as healthy controls, a positive relationship between hippocampal volume and trait anxiety has been reported. This study sought to explore the possible inter-relation between hippocampal volume and trait anxiety further. Magnetic resonance imaging at 7 T was used to measure hippocampal volumes in a rat model of extremes in trait anxiety (experiment 1) and in a Wistar population with normal anxiety-related behavior (experiment 2). In addition to anxiety-related behavior, potentially confounding factors (depression-like, exploratory, and locomotor behavior) were assessed. Experiment 1 globally supported the hypothesis of a positive relationship between hippocampus volume and trait anxiety but did not allow for ruling out possible confounds arising from cosegregation of other behavioral traits. Experiment 2 yielded strong evidence for a negative relationship which was specific for trait anxiety. Thus, the relationship between hippocampal volume and anxiety may be more complex than expected. Interestingly, anxiety-related behavior in experiment 2 had a stronger influence on hippocampal volume than depression-like behavior. In the light of hippocampal volume loss in anxiety disorder and frequent comorbidity of anxiety and depression, this finding suggests that further research into the relationship between anxiety and hippocampal volume may be critical for understanding hippocampal contributions to normal and pathological behavior.

Animals↗
PubMed2006

Chronic progressive external ophthalmoplegia: MR spectroscopy and MR diffusion studies in the brain.

OBJECTIVE: The purpose of our study was to show how, despite pathognomonic signs of cerebral involvement in chronic progressive external ophthalmoplegia (CPEO), mitochondrial respiratory chain insufficiency is associated with increased lactate and reduced N-acetylaspartate. CPEO and mitochondrial myopathy are caused by mitochondrial DNA mutations leading to impaired oxidative phosphorylation. Cortical and subcortical metabolites, cerebral diffusivity, and structural MRI were assessed to characterize possible subclinical cerebral pathology in CPEO. SUBJECTS AND METHODS: Ten patients with CPEO (n = 8), mitochondrial myopathy (n = 1), and Kearns-Sayre syndrome (n = 1) and 13 control group volunteers were studied by MRI, both long TE (144) proton MR spectroscopic imaging (1H MRSI), and diffusion-weighted imaging. Relative concentrations of N-acetylaspartate, choline, creatine, and lactate were estimated by Linear Combination of Model Spectra (LCModel) in healthy-appearing white matter, gray matter, and white matter hyperintensities. RESULTS: Of five patients with cortical atrophy, it was moderate in three and severe in two. One patient had severe and four had moderate cerebellar atrophy. Six of 10 patients showed unspecific white matter lesions, whereas the remainder had hyperintensities in the pyramidal tract (n =2) and middle cerebellar peduncle (n = 1) despite clinical signs. No basal ganglia lesions were found. Physiologic metabolite ratios were normal and lactate was absent in supratentorial healthy-appearing cortex and subcortical white matter. Global diffusion histogram metrics revealed no abnormalities. CONCLUSION: Normal spectroscopic imaging in radiologic unaffected brain and healthy global brain parenchymal diffusion findings do not support the hypothesis of a generalized cerebral energy loss in CPEO. Bilateral structural alteration of central motor pathways in two patients without clinical pyramidal signs may, however, reflect subclinical axonal injury in predilection sites in some patients.

Adult↗
PubMed2005

The phenylephrine blood pressure clamp in pharmacologic magnetic resonance imaging: reduction of systemic confounds and improved detectability of drug-induced BOLD signal changes.

RATIONALE: Peripheral physiologic changes accompany many central pharmacologic manipulations and can interact with brain activity and cerebral perfusion in complex ways. This considerably complicates the interpretation of drug-induced brain activity changes. OBJECTIVES: To evaluate a method whereby drug-induced blood pressure (BP) changes are prevented. METHODS: A continuously adjusted infusion of the peripheral vasoconstrictor phenylephrine (PEP) was used to counter-regulate BP changes elicited by application of the dopamine receptor agonist apomorphine (APO) in the rat. Central effects of APO were measured using pharmacologic magnetic resonance imaging (phMRI) with blood oxygenation level dependent (BOLD) contrast at a field strength of 7 T. RESULTS: Compared to a NOPEP control group, the PEP blood pressure clamp successfully prevented BP changes and improved the detectability of central APO effects. Moreover, APO-induced central changes no longer correlated with BP time courses. CONCLUSIONS: The method is suitable for isolating central drug effects from peripherally originating (BP) confounds in high-field functional magnetic resonance imaging (fMRI) studies. It may also be useful in fMRI studies of autonomic regulation, cognition, and emotion if the experimental manipulation entails BP changes.

Analysis of Variance↗
PubMed2005

Rapid eye movement-related brain activation in human sleep: a functional magnetic resonance imaging study.

In animal models, ponto-geniculo-occipital waves appear as an early sign of rapid eye movement sleep and may be functionally significant for brain plasticity processes. In this pilot study, we use a combined polysomnographic and functional magnetic resonance imaging approach, and show distinct magnetic resonance imaging signal increases in the posterior thalamus and occipital cortex in close temporal relationship to rapid eye movements during human rapid eye movement sleep. These findings are consistent with cell recordings in animal experiments and demonstrate that functional magnetic resonance imaging can be utilized to detect ponto-geniculo-occipital-like activity in humans. Studying intact neuronal networks underlying sleep regulation is no longer confined to animal models, but has been shown to be feasible in humans by a combined functional magnetic resonance imaging and electroencephalograph approach.

Adult↗
PubMed2005

Creatine supplementation lowers brain glutamate levels in Huntington's disease.

There is evidence from in vitro and animal experiments that oral creatine (Cr) supplementation might prevent or slow down neurodegeneration in Huntington's disease (HD). However, this neuroprotective effect could not be replicated in clinical trials, possibly owing to treatment periods being too short to impact on clinical endpoints. We used proton magnetic resonance spectroscopy ((1)H-MRS) as a surrogate marker to evaluate the effect of Cr supplementation on brain metabolite levels in HD.Twenty patients (age 46+/-7.3 years, mean duration of symptoms 4.0+/-2.1 years, number of CAG repeats 44.5+/-2.7) were included. The primary endpoint was metabolic alteration as measured by (1)H-MRS in the parieto-occipital cortex before (t1) and after 8-10 weeks (t2) of Cr administration. Secondary measures comprised the motor section of the Unified Huntington's Disease Rating Scale and the Mini Mental State Examination. (1)H-MRS showed a 15.6% decrease of unresolved glutamate (Glu)+glutamine (Gln; Glu+Gln=Glx; p<0.001) and a 7.8% decrease of Glu (p<0.027) after Cr treatment. N-acetylaspartate trended to fall (p=0.073) whereas total Cr, choline-containing compounds, glucose, and lactate remained unchanged. There was no effect on clinical rating scales. This cortical Glx and Glu decrease may be explained by Cr enhancing the energy-dependent conversion of Glu to Gln via the Glu-Gln cycle, a pathway known to be impaired in HD. Since Glu-mediated excitotoxicity is presumably pivotal in HD pathogenesis, these results indicate a therapeutic potential of Cr in HD. Thus, longterm clinical trials are warranted.

Administration, Oral↗
PubMed2005

Spinal cord imaging in multiple sclerosis.

Multiple sclerosis (MS) is a chronic neurological condition characterized pathologically by axonal loss, demyelination, inflammation, and gliosis. Magnetic resonance imaging (MRI) has had a major impact on diagnosing MS, understanding the condition, and monitoring the effects of treatments. Recently, spinal cord MRI has received increased attention. Advanced techniques have been used to image the spinal cord, particularly the cervical cord, and measure quantitative parameters such as T1 relaxation time, magnetization transfer ratio, and diffusivity. These metrics show central nervous system abnormalities in MS patients and various correlations with disability and might reflect specific pathological processes. Image analysis techniques have also been developed and combined with high-resolution MRI to measure the cord cross-sectional area (CSA), a metric that relates to cord atrophy. The cord CSA is reduced in MS patients compared to normal controls and correlates with disability. Furthermore, changes in CSA are detectable and correlate with changes in disability. Despite the technical difficulties of performing spinal cord MRI, imaging studies, particularly of the cervical cord, are becoming more common. Significant focus has been placed on measuring cord atrophy, and reproducible techniques have been developed to measure the cervical cord CSA. Spinal cord MRI may provide information about disease progression that is not readily available from brain MRI scans and could be useful in diagnosing MS in some cases, as well as for monitoring the effects of treatments.

Atrophy↗
PubMed2004

High trait anxiety and hyporeactivity to stress of the dorsomedial prefrontal cortex: a combined phMRI and Fos study in rats.

The neural basis of trait anxiety is poorly understood. In genetically selected hyperanxious (high anxiety-related behavior; HAB) rats, diazepam induces a stronger anxiolytic response than in hypoanxious (low anxiety-related behavior; LAB) rats. A screen for neuronal response differences to diazepam between HAB and LAB rats using pharmacologic fMRI (phMRI) at 7 T revealed a blunted diazepam-induced neuronal deactivation in the dorsomedial prefrontal cortex (dmPFC) of HABs. This was not due to reduced benzodiazepine (BDZ) receptor densities in this region. Instead, dmPFC tissue oxygenation at baseline was found to be significantly lower in HABs. This suggests a tonic relative hypoactivity under the highly stressful phMRI conditions, offering an explanation for the reduced responsivity to the neural depressant effect of diazepam in the sense of a floor effect. Subsequently, Fos immunoreactivity (Fos-IR) showed that ethologically relevant stressors also cause less dmPFC activation in HABs. In the context of an anxiety-inhibiting role of the dmPFC, we propose that failure to sufficiently activate this region in stressful situations may contribute to high trait anxiety.

Animals↗
PubMed2004

Functional MRI during sleep: BOLD signal decreases and their electrophysiological correlates.

Prominent local decreases in blood oxygenation level (BOLD) can be observed by functional magnetic resonance imaging (fMRI) upon acoustic stimulation during sleep. The goal of this study was to further characterize this BOLD signal decrease with respect to corresponding neurophysiological phenomena using a simultaneous electroencephalography (EEG)/fMRI approach in sleeping human subjects. Healthy volunteers were subjected to acoustic stimulation during non-rapid eye movement (NREM) sleep. On the basis of statistical parametric maps, the correlations between the fMRI response (both amplitude and extent of the BOLD response) and the concomittant changes in the EEG (delta power and K-complexes) were calculated. Amplitude and extent of the stimulus-induced negative BOLD effect correlated positively with measures of EEG synchronization, namely an increase in the number of K-complexes and EEG delta power. Stimulus-induced BOLD decreases were most prominent during light (stage 2) NREM sleep and disappeared during slow wave sleep, indicating an influence of the baseline degree of hyperpolarization. Our observations provide first evidence that 'negative' BOLD signal changes during human sleep are associated with electrophysiological indicators of altered neuronal activity. Increased number of K-complexes and delta power reflecting hyperpolarization suggests true cortical deactivation upon stimulus presentation. This sleep stage-dependent deactivation might serve to protect the brain from arousing stimuli, particularly during the light phases of sleep shortly after sleep onset.

Acoustic Stimulation↗
PubMed2003

Photoperiodic response may facilitate adaptation to climatic change in long-distance migratory birds.

Recent climatic change is causing spring events in northern temperate regions to occur earlier in the year. As a result, migratory birds returning from tropical wintering sites may arrive too late to take full advantage of the food resources on their breeding grounds. Under these conditions, selection will favour earlier spring arrival that could be achieved by overwintering closer to the breeding grounds. However, it is unknown how daylength conditions at higher latitudes will affect the timing of life cycle stages. Here, we show in three species of Palaearctic-African migratory songbirds that a shortening of migration distance induces an advancement of springtime activities. Birds exposed to daylengths simulating migration to and wintering in southern Europe considerably advanced their spring migratory activity and testicular development. This response to the novel photoperiodic environment will enable birds wintering further north to advance spring arrival and to start breeding earlier. Thus, phenotypic flexibility in response to the photoperiod may reinforce selection for shorter migration distance if spring temperatures continue to rise.

Acclimatization↗
PubMed2003

Human prefrontal and sensory cortical activity during divided attention tasks.

In our natural environment, the ability to divide attention is essential since we attend simultaneously to a number of sensory modalities, e.g., to visual and auditory stimuli. In this study, functional magnetic resonance imaging (fMRI) was used to study brain activation while a divided attention task was performed. Brain activation was also assessed under selective attention. Fourteen healthy male subjects aged between 19 and 28 years underwent fMRI studies using gradient EPI sequences. Cingulate activation was evident in all attention tasks. Focusing attention on one modality (visual or auditory) increased the activity in the corresponding primary and secondary sensory area. When attention is divided between both modalities, the activation in the sensory areas is decreased, possibly due to a limited capacity of the system for controlled processing. Left prefrontal activation, however, was evident selectively during the divided attention task. The present results suggest that this area may be important in the execution of controlled processing when attention is divided between two sources of information. These results support the view that the prefrontal cortex is involved in the central executive system and controls attention and information flow.

Acoustic Stimulation↗
PubMed2003

Is the brain cortex a fractal?

The notion of fractal has been largely used to describe geometrical properties of complex objects in biology and medicine. In the present study the question is addressed whether the human cerebral cortex is self-similar in a statistical sense, which is commonly referred to as being a fractal. A new calculational method is presented, which is volumetric and based on the fast Fourier transform (FFT) of segmented three-dimensional high-resolution magnetic resonance images. The analysis covers a wide range of spatial scales from the size of the whole cortex to the ultimate pixel size. Results obtained in six subjects confirm the fractal nature of the human cerebral cortex down to a spatial scale of 3 mm. The obtained fractal dimension is D = 2.80 +/- 0.05, which is in reasonable agreement with previously reported results. Deployment of FFT enables a simple interpretation of the results and yields a high performance, which is necessary to analyze the entire cortex. Thus the FFT-based analysis of segmented MR images offers a comprehensive approach to study neurodevelopmental and neurodegenerative changes in the fractal geometry of the cerebral cortex.

Algorithms↗
PubMed2002

T2*-weighted MRI differentiates multiple system atrophy from Parkinson's disease.

To compare the ability of T2*-weighted gradient echo (GE) and T2-weighted fast spin echo images to distinguish between patients with idiopathic PD and multiple system atrophy (MSA), the authors studied 15 patients with probable MSA, 40 patients with PD, and 17 healthy control subjects. Hypointense putaminal signal changes were more often observed in MSA than in PD using T2* but not T2-weighted images, indicating that T2*-weighted GE sequences are of diagnostic value for patients with parkinsonism.

Aged↗
PubMed2002

Reduced cortical gray matter in narcolepsy: preliminary findings with voxel-based morphometry.

There is a selective loss of hypocretin/orexin-containing hypothalamic neurons in patients with narcolepsy. The authors compared MRI-derived gray matter maps of 12 patients with narcolepsy with matched controls using voxel-based morphometry to ascertain whether there are other structural brain abnormalities. Patients with narcolepsy showed bilateral cortical gray matter reductions predominantly in inferior temporal and inferior frontal brain regions. Relative global gray matter loss was independent of disease duration or medication history. No significant subcortical gray matter alterations were noted.

Adult↗
PubMed2002

Activity of the hypothalamic-pituitary-adrenal axis in multiple sclerosis: correlations with gadolinium-enhancing lesions and ventricular volume.

The known interaction between the immune system and the hypothalamic-pituitary-adrenal axis led us to explore the interrelation between magnetic resonance imaging findings and the hypothalamic-pituitary-adrenal axis activity in 53 multiple sclerosis patients. The cortisol release induced by the dexamethasone-corticotropin-releasing hormone test was negatively associated with the presence and number of gadolinium-enhancing lesions and positively associated with ventricular size. This finding suggests a protective effect of the hypothalamic- pituitary-adrenal drive on acute lesional inflammation in multiple sclerosis, probably by limiting immune overshoot. In contrast, the nature of the correlation between hypothalamic-pituitary-adrenal hyperdrive and brain atrophy remains to be determined.

Adult↗
PubMed2002

Refractive anomalies and visual activation in functional magnetic resonance imaging (fMRI): a versatile and low-cost MR-compatible device to correct a potential confound.

PURPOSE: To develop a magnetic resonance (MR)-compatible, versatile, easy-to-use, and low-cost device for refractive correction. MATERIALS AND METHODS: We retrospectively evaluated the application and practicability of the refractive correction in 110 subjects who had participated in various functional MR imaging (fMRI) studies with complex visual stimulation paradigms since the introduction of the MR-compatible lens frame at our site. The subjects consisted of 31 patients with Parkinson's disease (age range, 40-85; mean age, 63.2 years) and 79 healthy volunteers (age range, 18-79; mean age, 46.7 years). RESULTS: In volunteers, experimentally induced myopia caused a substantial (>20%) reduction of the blood oxygenation level dependent (BOLD) response to a flickering dartboard. CONCLUSION: Refractive errors (and the resulting optical blur) may play a nonnegligible role as a possible interfering factor in fMRI experiments with visual stimuli. The MR-compatible frame (fitted with appropriate lenses) used in this study affords full refractive correction at reasonable cost and preparation time.

Adult↗