Biomedical subjects

Gregor Wenning

Publications and source records attributed to Gregor Wenning.

8 recordsLinked to original sources

PubMed2006

The diagnosis of Parkinson's disease.

The correct diagnosis of Parkinson's disease is important for prognostic and therapeutic reasons and is essential for clinical research. Investigations of the diagnostic accuracy for the disease and other forms of parkinsonism in community-based samples of patients taking antiparkinsonian medication confirmed a diagnosis of parkinsonism in only 74% of patients and clinically probable Parkinson's disease in 53% of patients. Clinicopathological studies based on brain bank material from the UK and Canada have shown that clinicians diagnose the disease incorrectly in about 25% of patients. In these studies, the most common reasons for misdiagnosis were presence of essential tremor, vascular parkinsonism, and atypical parkinsonian syndromes. Infrequent diagnostic errors included Alzheimer's disease, dementia with Lewy bodies, and drug-induced parkinsonism. Increasing knowledge of the heterogeneous clinical presentation of the various parkinsonisms has resulted in improved diagnostic accuracy of the various parkinsonian syndromes in specialised movement-disorder units. Also genetic testing and various other ancillary tests, such as olfactory testing, MRI, and dopamine-transporter single-photon-emission computed-tomography imaging, help with clinical diagnostic decisions.

Diagnosis, Differential↗

PubMed2005

Detection of pulses in a colored noise setting.

Cortical neurons are exposed to a considerable amount of synaptic background activity, which increases the neurons' conductance and which leads to a fluctuating membrane potential. Here we investigate how the presence and the properties of this background noise influence the ability of a neuron to detect transient inputs, a task that is important for coincidence detection as well as for the detection of synchronous spiking events in a neural system. Using a leaky integrate-and-fire neuron as well as a biologically more realistic Hodgkin-Huxley type point neuron we find that noise enhances the detection of subthreshold input pulses and that the phenomenon of stochastic resonance occurs. When the noise is colored, pulse detection becomes more robust, because the number of false positive events decreases with increasing temporal correlation while the number of correctly detected events is almost unaffected. Therefore, the optimal variance of the noise also changes with the degree of temporal correlations of the background activity. For the integrate-and-fire model these effects can be described using an ansatz by Brunel and Sergi [J. Theor. Biol. 195, 87 (1998)]. Numerical simulations show that the leaky integrate-and-fire model and the Hodgkin-Huxley type point neuron behave qualitatively similarly.

Action Potentials↗

PubMed2004

Osteoprotegerin is a risk factor for progressive atherosclerosis and cardiovascular disease.

BACKGROUND: Osteoprotegerin is a novel member of the tumor necrosis factor receptor superfamily and a soluble decoy receptor of the receptor activator of nuclear factor-kappaB ligand. Recent experimental research has implicated osteoprotegerin in atherogenesis, but epidemiological confirmation of this concept is sparse. METHODS AND RESULTS: As part of the prospective, population-based Bruneck Study, severity, initiation, and progression of atherosclerosis were assessed in carotid arteries. Cases of incident cardiovascular disease and vascular mortality were carefully recorded over a 10-year period (1990 to 2000). Osteoprotegerin levels were measured in samples obtained at baseline and during follow-up. Serum osteoprotegerin showed a strong association with numerous vascular risk factors, including age, diabetes, markers of systemic inflammation, chronic infection, and smoking. In multivariate analyses, osteoprotegerin was significantly related to severity and 10-year progression of carotid atherosclerosis. Furthermore, a high level of osteoprotegerin was an independent risk factor for incident cardiovascular disease (adjusted relative risk for the top versus bottom tertile group for osteoprotegerin 2.2 [1.3 to 3.8]; P=0.001) and vascular mortality (adjusted relative risk for the top versus bottom tertile group for osteoprotegerin 3.1 [1.2 to 8.2]; P=0.010) but not for mortality due to nonvascular causes. CONCLUSIONS: Osteoprotegerin is an independent risk factor for the progression of atherosclerosis and onset of cardiovascular disease.

Aged↗

PubMed2004

Accuracy of clinical diagnosis of progressive supranuclear palsy.

We assessed the accuracy of clinical diagnosis of progressive supranuclear palsy (PSP, Steele-Richardson-Olszewski disease) and the validity of existing sets of clinical diagnostic criteria for PSP (see Appendix) using neuropathologically examined cases from the Queen Square Brain Bank for Neurological Disorders. Diagnosis of PSP was made by 40 different physicians, and 60 cases clinically diagnosed as PSP when last assessed in life were studied. In 47 cases (78%), the diagnosis of PSP was confirmed pathologically. False-positive diagnoses included Parkinson's disease with significant additional cortical Lewy body (n = 3) or Alzheimer (n = 1) pathology, multiple system atrophy (n = 4), and corticobasal degeneration, Pick's disease, motor neurone disease, cerebrovascular disease, and a sporadic case of frontotemporal dementia and parkinsonism linked to chromosome 17 (1 case each). Most cases of PSP were diagnosed accurately by neurologists at the final assessment. Although application of National Institute of Neurological Disorders and the Society for PSP possible category marginally improved the accuracy of initial clinical diagnosis, none of the existing operational criteria could significantly improve accuracy of the final clinical diagnosis.

Adult↗

PubMed2003

Optimal noise-aided signal transmission through populations of neurons.

Metabolic considerations and neurophysiological measurements indicate that biological neural systems prefer information transmission via many parallel low intensity channels, compared to few high intensity ones [S. B. Laughlin et al., Nature Neurosci. 1, 36 (1998)]. Furthermore, cortical neurons are exposed to a considerable amount of synaptic background activity, which increases the neurons' conductance and leads to a fluctuating membrane potential that, on average, is close to the threshold [A. Destexhe and D. Paré, J. Neurophysiol. 81, 1531 (1999)]. Recent studies have shown that noise can improve the transmission of subthreshold signals in populations of neurons, e.g., if their response is pooled. In general, the optimal noise level depends on the stimulus distribution and on the number of neurons in the population. In this contribution we show that for a large enough number of neurons the latter dependency becomes weak, such that the optimal noise level becomes almost independent of the number of neurons in the population. First we investigate a binary threshold model of neurons. We derive an analytic expression for the optimal noise level at each single neuron, which-for a large enough population size-depends only on quantities that are locally available to a single neuron. Using numerical simulations, we then verify the weak dependence of the optimal noise level on population size in a more realistic framework using leaky integrate-and-fire as well as Hodgkin-Huxley-type model neurons. Next we construct a cost function, where quality of information transmission is traded against its metabolic costs. Again we find that-for subthreshold signals-there is an optimal noise level which maximizes this cost. This noise level, however, is almost independent of the number of neurons, even for small population sizes, as numerical simulations using the Hodgkin-Huxley model show. Since the dependence of the optimal noise level on population size is weak for large enough populations, local neural adaptation is sufficient to adjust the level of noise to its optimal value.

Animals↗

PubMed2003

Increased daytime sleepiness in Parkinson's disease: a questionnaire survey.

We evaluated the frequency and severity of excessive daytime sleepiness in an outpatient population with Parkinson's disease in comparison to age-matched controls and examined its relationship with antiparkinsonian drug therapy and sleep history. Increased daytime sleepiness and involuntary sleep episodes have been described in Parkinson's disease, but the etiology is not completely understood. The Epworth Sleepiness Scale (ESS), a validated questionnaire for daytime sleepiness, was prospectively administered to 99 consecutive outpatients with Parkinson's disease and 44 age-matched controls. In addition, a short sleep-screening questionnaire was used. The ESS revealed significantly increased daytime sleepiness in PD patients compared to controls (7.5 +/- 4.6 vs. 5.8 +/- 3.0, P = 0.013). The ESS score was abnormally high (10 or more) in 33 % of PD patients and 11.4% of controls (P = 0.001). ESS was not different between PD patients on levodopa monotherapy and those on levodopa and dopamine agonists, or between patients taking ergoline or non-ergoline dopamine agonists. In PD patients and in controls, sleepiness was significantly associated with reported heavy snoring. Increased daytime sleepiness is more frequent in patients with PD than in elderly controls. Similar to controls, increased daytime sleepiness in PD patients is correlated with heavy snoring.

Aged↗

PubMed2002

Rapid adaptation to internal states as a coding strategy in visual cortex?

Adaptation is a prominent feature of biological neuronal systems. A common interpretation of adaptation in terms of function is that it provides flexibility for a neuronal system to perform well under varying external conditions, for example by adjusting the input/output relation of a sensory system with reference to the ensemble of stimuli the organism currently perceives. This interpretation, however, only applies if the time-scale of adaptation is slower than the time-scale at which the environment changes. Experimentally it is observed, however, that adaptation can be very rapid. Spike-frequency adaptation of cortical neurons, for example, occurs on a time-scale of approximately 100 ms. Here we show that those rapid adaptation processes can also be understood within the framework of information theory. We start with the hypothesis that neuronal codes are designed to optimize the information a neuronal representation conveys about an input stimulus for any increasing time window beginning with stimulus onset, and we show that this implies a rapid adaptation of the neuronal code on the time-scale of stimulus presentation. Adaptation, however, does not occur because the state of the environment changes. Rather it is a reaction to changes of the organisms own internal state, e.g. the level of noise in the neuronal representation. We apply this approach to a model of an orientation hypercolumn in the primary visual cortex, and predict that inter-columnar interactions should adapt on the time-scale of a typical fixation period ( approximately 300 ms).

Adaptation, Psychological↗

PubMed2002

Evaluation of striatal dopamine transporter function in rats by in vivo beta-[123I]CIT pinhole SPECT.

Striatal dopamine transporter (DAT) function was evaluated in rats by in vivo SPECT-MRI coregistration using the radioligand 2-beta-carbomethoxy-3-beta-(4-[123I]iodophenyl)tropane (beta-[123I]CIT). The reconstructed transaxial resolution of 3.5 mm full width at half-maximum and the system sensitivity of 0.081 c/s/kBq using a 2.0-mm pinhole collimator aperture provided adequate spatial detail and sufficient sensitivity for imaging striatal beta-[123I]CIT uptake. SPECT images, coregistered onto a MRI template, showed high accuracy in the coronal and transverse planes (maximum mismatch of 1.3 mm). Following estimation of the in vivo binding equilibrium of beta-[123I]CIT in the healthy rat striatum, we evaluated the 6-hydroxydopamine-induced loss of striatal DAT function using beta-[123I]CIT SPECT and MRI coregistration and correlated these findings with dopaminergic cell counts in the substantia nigra pars compacta using TH immunohistochemistry. A subtotal unilateral DAT deficit was detected by beta-[123I]CIT SPECT in all animals which correlated significantly with the cell counting of the remaining dopaminergic neurons. beta-[123I]CIT pinhole SPECT provides a powerful and widely available tool for in vivo investigations of rat striatal DAT function. In contrast to classical autoradiography, the present method will be helpful in imaging dynamic changes of neurotransmission in the CNS by virtue of serial study designs. Depending on SPECT ligand availability, a wide range of other CNS receptors may be imaged as well using the presented in vivo technique.

Animals↗