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Biomedical subjects

Viktor Müller

Publications and source records attributed to Viktor Müller.

13 recordsLinked to original sources

Cortical EEG correlates of successful memory encoding: implications for lifespan comparisons.

In the course of their lives, individuals experience a myriad of events. Some of them leave stable traces, and others fade away quickly. Recent advances in functional imaging methods allow researchers to contrast neuronal patterns of remembered against not remembered events at initial encoding. Research on young adults using functional magnetic resonance imaging (fMRI), intracranial, and standard electroencephalographic (EEG) recordings has identified differences between remembered and not remembered items in patterns of medio-temporal and prefrontal brain activity. However, little is known about the ways in which such neuronal patterns of successful encoding evolve across the lifespan as a function of maturation, senescence, and the accumulation of experience. Here, we first review empirical evidence on neuronal correlates of successful memory from middle childhood to old age. Based on the observation that associative and strategic components of episodic memory seem to follow different age gradients, we propose a conceptual framework for predicting age changes in neuronal patterns of successful encoding.

Age Factors↗

Stable virulence levels in the HIV epidemic of Switzerland over two decades.

OBJECTIVE: To determine whether the virulence of HIV-1 has been changing since its introduction into Switzerland. DESIGN: A prospective cohort study of HIV-1 infected individuals with well-characterized pre-therapy disease history. METHODS: To minimize the effect of recently imported viruses and ethnicity-associated host factors, the analysis was restricted to the white, north-west-European majority population of the cohort. Virulence was characterized by the decline slope of the CD4 cell count (n = 817 patients), the decline slope of the CD4:CD8 ratio (n = 815 patients) and the viral setpoint (n = 549 patients) in untreated patients with sufficient data points. Linear regression models were used to detect correlations between the date of diagnosis (ranging between 1984 and 2003) and the virulence markers, controlling for gender, exposure category, age and CD4 cell count at entry. RESULTS: We found no correlation between any of the virulence markers and the date of diagnosis. Inspection of short-term trends confirmed that virulence has fluctuated around a stable level over time. CONCLUSIONS: The lack of long-term time trends in the virulence markers indicates that HIV-1 is not evolving towards increasing or decreasing virulence at a perceptible rate. Both highly virulent and attenuated strains have apparently been unable to spread at the population level. This result suggests that either the evolution of virulence may be slow or inhibited due to evolutionary constraints, or HIV-1 may have already evolved to optimal virulence in the human host.

Adult↗

Genetic influences on dynamic complexity of brain oscillations.

Human electroencephalogram (EEG) consists of complex aperiodic oscillations that are assumed to indicate underlying neural dynamics such as the number and degree of independence of oscillating neuronal networks. EEG complexity can be estimated using measures derived from nonlinear dynamic systems theory. Variations in such measures have been shown to be associated with normal individual differences in cognition and some neuropsychiatric disorders. Despite the increasing use of EEG complexity measures for the study of normal and abnormal brain functioning, little is known about genetic and environmental influences on these measures. Using the pointwise dimension (PD2) algorithm, this study assessed heritability of EEG complexity at rest in a sample of 214 young female twins consisting of 51 monozygotic (MZ) and 56 dizygotic (DZ) pairs. In MZ twins, intrapair correlations were high and statistically significant; in DZ twins, correlations were substantially smaller. Genetic analyses using linear structural equation modeling revealed high and significant heritability of EEG complexity: 62-68% in the eyes-closed condition, and 46-60% in the eyes-open condition. Results suggest that individual differences in the complexity of resting electrocortical dynamics are largely determined by genetic factors. Neurophysiological mechanisms mediating genetic variation in EEG complexity may include the degree of structural connectivity and functional differentiation among cortical neuronal assemblies.

Adolescent↗

Guanine-adenine bias: a general property of retroid viruses that is unrelated to host-induced hypermutation.

The recently discovered mammalian enzymes, APOBEC3G and 3F, induce guanine-to-adenine hypermutation in retroviruses. However, the preference of adenine over guanine in retroviral codon usage is not correlated with the presence or absence of APOBEC3G or its viral inhibitor (Vif), and its pattern does not reflect the biochemical properties of APOBEC3G action. The guanine-adenine bias of retroviruses is thus probably not a result of host-induced mutational pressure, but rather reflects a general predisposition associated with reverse transcription.

APOBEC-3G Deaminase↗

Recombination in HIV and the evolution of drug resistance: for better or for worse?

The rapid evolution of drug resistance remains a major obstacle for HIV therapy. The capacity of the virus for recombination is widely believed to facilitate the evolution of drug resistance. Here, we challenge this intuitive view. We develop a population genetic model of HIV replication that incorporates the processes of mutation, cellular superinfection, and recombination. We show that cellular superinfection increases the abundance of low fitness viruses at the expense of the fittest strains due to the mixing of viral proteins during virion assembly. Moreover, we argue that whether recombination facilitates the evolution of drug resistance depends critically on how resistance mutations interact to determine viral fitness. Contrary to the commonly held belief, we find that, under the most plausible biological assumptions, recombination is expected to slow down the rate of evolution of multi-drug-resistant virus during therapy.

Drug Resistance, Viral↗

Effects of hydration and hyperventilation on cortical complexity.

The effects of hydration and hyperventilation on cortical complexity were investigated in a sample of 19 healthy volunteers in a double-blind placebo design using magnetoencephalographic recordings. The subjects were asked to abstain from the intake of liquids 18 h before the study. Spontaneous magnetoencephalograms (MEG) were recorded before and after drinking 750 ml water (WAT group: nine subjects) or saline solution (SAL group: ten subjects) with eyes closed and open and during hyperventilation (HV) with eyes open. The MEG data were analysed using both linear (spectral power) and non-linear (pointwise dimension and largest Lyapunov exponent) algorithms. The prediction that intake of water, because of induced cell swelling, will lead to an increased synchronization and a decreased complexity of the spontaneous MEG during hyperventilation was confirmed. Hyperventilation following the drinking condition produced an increase in all power spectra with a stronger increase of delta and theta power after drinking of water. This synchronization of spontaneous MEG is accompanied by a general significant decrease of cortical complexity, especially after water drinking. Moreover, cortical complexity was inversely related to delta and theta power and partly also to alpha power. The SAL and WAT groups showed different relations between alpha power and dimensional complexity during HV: whereas in the SAL group the correlations between these measures became more negative during HV, they reversed in the WAT group to become positive. The synchronizing effect of hyperventilation, leading to a decrease of cortical complexity, is related in the SAL group to delta, theta and alpha power, whereas in the WAT group only delta and theta activity contribute to a reduction of cortical complexity.

Adult↗

Glancing behind virus load variation in HIV-1 infection.

Although the steady-state virus load during HIV-1 infection is remarkably stable within a patient, it displays variation over several orders of magnitude between patients. Despite intensive research, the host and virus factors that are responsible for the observed variation remain poorly understood. Comparison of model predictions with clinical data suggests that most of the variation in steady-state virus load between patients reflects variation of the net rate at which activated CD4 cells are produced.

Genetic Variation↗

Complexity of visual stimuli and non-linear EEG dynamics in humans.

The effects of stimulus complexity on the nonlinear electrical brain (EEG) dynamics were investigated in a sample of 24 healthy volunteers. Stimuli used were either a single mechanical low-friction pendulum with a periodic movement (temporal frequency about 1 Hz) or a double-pendulum with a chaotic movement, which were observed for 2-3 min in each case. The prediction that a more complex visual stimulus (double-pendulum) increases the dimensional complexity of brain activity as compared to a simple visual stimulus (single-pendulum), was confirmed by determination of pointwise correlation dimension. Further, there was a significant decrease of alpha power in the double-pendulum compared to a single-pendulum condition. Moreover, a correlation analysis showed a positive correlation between EEG complexity and beta power over the whole cortex in the single- and, above all, in the double-pendulum condition, and also a positive correlation between dimensional complexity and alpha power in the double-pendulum condition only, particularly in the brain regions responsible for the 'bottom-up' sustained attention processes.

Adult↗

Quantitative constraints on the scope of negative selection.

Maturing T cells with a high affinity for self-antigens presented in the thymus are deleted in the process of negative selection. Although the expression of various "tissue-specific" antigens has been described in the thymus, it is still controversial what fraction of all self-antigens induces tolerance by this mechanism. We demonstrate that the limited duration of the negative selection phase imposes a constraint on the number of self-peptides that can be reliably selected against. The analysis supports the theory that negative selection is confined to the subset of peptides produced by dendritic cells.

Animals↗

Effects of water on cortical excitability in humans.

The effects of water on cortical excitability, measured using magnetoencephalographic recordings, were investigated in a sample of 19 healthy volunteers in a double-blind, placebo experiment comparing water with saline solution. Spontaneous magnetoencephalogram as well as auditory-evoked magnetic fields were recorded before and after the drinking of 750 mL water (9 subjects) or saline solution (10 subjects) and during and after hyperventilation following the drinking conditions. Hyperventilation was used to enhance the hypothesized synchronizing effect of water on spontaneous magnetoencephalographic activity. In addition, the magnetic fields were measured during a dichotic listening task under attended and unattended conditions. The prediction, that intake of water, because of induced cell swelling, will increase neuronal excitability and lead to an increased synchronization of the spontaneous magnetoencephalogram during hyperventilation was confirmed. Hyperventilation induced an increase of spectral power in all frequency bands particularly theta and delta power after water drinking. Furthermore, there was an increase of magnetic mismatch negativity (MMNm) amplitude in attended conditions and a simultaneous decrease in unattended conditions after water drinking. N1m (magnetic N1 wave) revealed significant changes during experimental conditions: increase after drinking and decrease after hyperventilation in both groups. MMNm for attended conditions showed a high positive correlation with osmolality changes (difference in the mol solute per kg water before and after drinking); N1m and PNm (magnetic processing negativity) as well as MMNm for unattended conditions showed significant correlations with subjective ratings of thirst and mood state.

Acoustic Stimulation↗