Biomedical subjects

Nikolai Axmacher

Publications and source records attributed to Nikolai Axmacher.

9 recordsLinked to original sources

PubMed2006

Rhinal-hippocampal coupling during declarative memory formation: dependence on item characteristics.

Lesion and imaging studies have demonstrated that encoding and retrieval of declarative memories, i.e. consciously accessible events and facts, depend on operations within the rhinal cortex and the hippocampus, two substructures of the medial temporal lobe. Analysis of intracranially recorded EEG in presurgical epilepsy patients revealed that successful memory formation is accompanied within one second by a transient enhancement and later decrease of Rhinal-hippocampal phase synchronization in the gamma range, as well as enhanced connectivity in the low-frequency range. In these studies, words with a high frequency of occurrence were used as stimulus material. Here, we re-examined these effects in another group of 10 presurgical epilepsy patients, this time not only for high-frequency, but also for low-frequency words. For successfully memorized compared to later forgotten high-frequency words we again observed an early phase coupling and later decoupling within the gamma range, as well as enhanced coupling within the sub-gamma range. However, for remembered as compared to forgotten low-frequency words clear synchronization increases were only observed for the delta band, but not for the gamma band. Our data suggest, that broadband Rhinal-hippocampal coupling including the gamma range only occurs, when significant semantic associations are processed within rhinal cortex, as is the case for high-frequency words.

Adult↗

PubMed2006

Memory formation by neuronal synchronization.

Cognitive functions not only depend on the localization of neural activity, but also on the precise temporal pattern of activity in neural assemblies. Synchronization of action potential discharges provides a link between large-scale EEG recordings and cellular plasticity mechanisms. Here, we focus on the role of neuronal synchronization in different frequency domains for the subsequent stages of memory formation. Recent EEG studies suggest that synchronized neural activity in the gamma frequency range (around 30-100 Hz) plays a functional role for the formation of declarative long-term memories in humans. On the cellular level, gamma synchronization between hippocampal and parahippocampal regions may induce LTP in the CA3 region of the hippocampus. In order to encode spatial locations or sequences of multiple items and to guarantee a defined temporal order of memory processing, synchronization in the gamma frequency range has to be accompanied by a stimulus-locked phase reset of ongoing theta oscillations. Simultaneous gamma- and theta-dependent plasticity leads to complex learning rules required for realistic declarative memory formation. Subsequently, consolidation of declarative memories may occur via replay of newly acquired patterns in so-called sharp wave-ripple complexes, predominantly during slow-wave sleep. These irregular bursts induce longer lasting forms of synaptic plasticity in output regions of the hippocampus and in the neocortex. In summary, synchronization of neural assemblies in different frequency ranges induces specific forms of cellular plasticity during subsequent stages of memory formation.

Action Potentials↗

PubMed2006

Presurgical language fMRI in patients with drug-resistant epilepsy: effects of task performance.

PURPOSE: To determine whether language functional magnetic resonance imaging (fMRI) before epilepsy surgery can be similarly interpreted in patients with greatly different performance levels. METHODS: An fMRI paradigm using a semantic decision task with performance control and a perceptual control task was applied to 226 consecutive patients with drug-resistant localization-related epilepsy during their presurgical evaluations. The volume of activation and lateralization in an inferior frontal and a temporoparietal area was assessed in correlation with individual performance levels. RESULTS: We observed differential effects of task performance on the volume of activation in the inferior frontal and the temporoparietal region of interest, but performance measures did not correlate with the lateralization of activation. CONCLUSIONS: fMRI, as applied here, in patients with a wide range of cognitive abilities, can be interpreted regarding language lateralization in a similar way.

Adult↗

PubMed2005

Association between scalp hair-whorl direction and hemispheric language dominance.

Asymmetry is a common phenomenon in higher organisms. In humans, the cortical representation of language exhibits a high degree of asymmetry with a prevalence of about 90% of left hemispheric dominance, the underlying mechanisms of which are largely unknown. Another sign that exhibits a form of lateralization is the scalp hair-whorl direction, which is either clockwise or anti-clockwise. The scalp hair-whorl develops from the same germ layer as the nervous system, the ectoderm, between the 10th and 16th week in utero and has been shown to be associated with various neurodevelopmental disorders. Here, we use an established fMRI paradigm to examine the association of a solely biological marker of asymmetry, hair-whorl direction and language lateralization. We show that the mechanism that influences hair-whorl direction and handedness [Klar, A.J.S., 2003. Human handedness and scalp hair-whorl direction develop from a common genetic mechanism. Genetics 1651, 269-276.] also affects cerebral language dominance.

Adult↗

PubMed2005

Phase/amplitude reset and theta-gamma interaction in the human medial temporal lobe during a continuous word recognition memory task.

We analyzed intracranial electroencephalographic (EEG) recordings from the medial temporal lobes of 12 epilepsy patients during a continuous word recognition paradigm, contrasting trials of correctly recognized repeated words (hits) and correctly identified new words (correct rejections). Using a wavelet-based analysis, we investigated how power changes and phase clustering in different frequency bands contribute to the averaged event-related potentials (ERPs). In addition, we analyzed the actual mean phases of the different oscillations. Our analyses yielded the following results: (1) power changes contributed significantly only to the late components of the ERPs (>400 ms) (2) earlier ERP components were produced by a stimulus-related broad-band phase and amplitude reset of ongoing oscillatory activity about 190 ms after stimulus onset that involved not only the theta band, but also covered alpha and lower beta band frequencies (3) phase and amplitude reset occurred during an epoch of increased phase entrainment over time that lasted for about two oscillation periods for all involved frequencies and was more pronounced for correct rejections than for hits. The broad-band phase and amplitude reset was observed for both hits and correct rejections, and therefore, did not appear to support a specific cognitive function, but rather to act as a general facilitating factor for the processes involved in this memory task. Further analyses of synchronization between oscillations and power changes in different frequency bands revealed a task-dependent modulation of gamma activity by the entrained theta cycle, a mechanism potentially related to memory encoding and retrieval in the rhinal cortex and hippocampus, respectively.

Adult↗

PubMed2004

Inhibition of GABA release by presynaptic ionotropic GABA receptors in hippocampal CA3.

Vesicular transmitter release can be regulated by transmitter-gated ion channels at presynaptic axon terminals. The central inhibitory transmitter GABA acts on such presynaptic ionotropic receptors in various cells, including inhibitory interneurons. Here we report that GABA-mediated postsynaptic inhibitory currents in CA3 pyramidal cells of rat hippocampal slices are suppressed by agonists of GABAA receptors. The effect is present for both stimulus-induced and miniature IPSCs, indicating a reduction in the probability of vesicular release by presynaptic, action-potential-independent mechanisms. We conclude that the release of GABA from hippocampal CA3 interneurons is regulated by a negative feedback via presynaptic ionotropic GABA autoreceptors.

Animals↗

PubMed2004

Intrinsic cellular currents and the temporal precision of EPSP-action potential coupling in CA1 pyramidal cells.

We examined relations between cellular currents activated near firing threshold and the initiation of action potentials by excitatory postsynaptic potentials (EPSPs) in CA1 pyramidal cells in vitro. Small voltage steps elicited sequences of inward-outward currents at hyperpolarized potentials, but evoked largely inward currents at near threshold potentials. Similarly small EPSP-like waveforms initiated largely inward currents while larger stimuli evoked sequences of inward followed by outward currents. Shorter rise times of EPSP-like waveforms accentuated a transient component of inward currents. Voltage clamp data were consistent with the voltage dependence of current clamp responses to injection of EPSP shaped waveforms. Small events were prolonged at subthreshold potentials and could elicit action potentials at long latencies while responses to larger EPSP waveforms showed less voltage dependence and tended to induce spikes at shorter, less variable latencies. The precision of action potentials initiated by white noise depended also on stimulus amplitude. High variance stimuli induced firing with high precision, while the timing of spikes induced by lower variance signals was more variable between trials. In voltage clamp records, high variance noise commands induced sequences of inward followed by outward currents, while lower variance versions of the same commands elicited purely inward currents. These data suggest that larger synaptic stimuli recruit outward as well as inward currents. The resulting inward-outward current sequences enhance the temporal precision of EPSP-spike coupling. Thus, CA1 pyramidal cells initiate action potentials with different temporal precision, depending on stimulus properties.

Acoustic Stimulation↗

PubMed2004

Two-photon imaging of spontaneous vesicular release in acute brain slices and its modulation by presynaptic GABAA receptors.

Action potential-independent spontaneous vesicular release of gamma-aminobutyric acid (GABA) in the CNS mediates miniature inhibitory postsynaptic currents (mIPSCs) and exerts an important control on central excitability. Using dual-photon laser scan microscopy and hyperosmotic loading of the readily releasable vesicle pool with the fluorescent styryl dye FM1-43 in hippocampal slice, we demonstrate action potential-independent release of vesicles (fluorescence destaining) from proximal perisomatic, presumed GABAergic terminals and significant inhibition of this release by the specific GABA(A) receptor agonist muscimol in the presence of tetrodotoxin and glutamate receptor antagonists CNQX and AP5. These data agree with reduction of mIPSCs by muscimol in whole-cell recordings from CA3 pyramidal neurons. In contrast, rate of vesicle release from distal, presumably glutamatergic terminals, was significantly lower and not changed by muscimol. The effect of muscimol on mIPSCs was not blocked but rather enhanced in the absence of external calcium. Our data directly demonstrate a potent disinhibitory reduction of GABA release by GABA(A) receptor activation. Those novel methods should be well suited to study pathophysiological changes in inhibition in resections obtained from neurosurgical treatment of epilepsy patients.

Animals↗

PubMed2003

Transmitter metabolism as a mechanism of synaptic plasticity: a modeling study.

The nervous system adapts to experience by changes in synaptic strength. The mechanisms of synaptic plasticity include changes in the probability of transmitter release and in postsynaptic responsiveness. Experimental and neuropharmacological evidence points toward a third variable in synaptic efficacy: changes in presynaptic transmitter concentration. Several groups, including our own, have reported changes in the amplitude and frequency of postsynaptic (miniature) events indicating that alterations in transmitter content cause alterations in vesicular transmitter content and vesicle dynamics. It is, however, not a priori clear how transmitter metabolism will affect vesicular transmitter content and how this in turn will affect pre- and postsynaptic functions. We therefore have constructed a model of the presynaptic terminal incorporating vesicular transmitter loading and the presynaptic vesicle cycle. We hypothesize that the experimentally observed synaptic plasticity after changes in transmitter metabolism puts predictable restrictions on vesicle loading, cytoplasmic-vesicular transmitter concentration gradient, and on vesicular cycling or release. The results of our model depend on the specific mechanism linking presynaptic transmitter concentration to vesicular dynamics, that is, alteration of vesicle maturation or alteration of release. It also makes a difference whether differentially filled vesicles are detected and differentially processed within the terminal or whether vesicle filling acts back onto the terminal by presynaptic autoreceptors. Therefore, the model allows one to decide, at a given synapse, how transmitter metabolism is linked to presynaptic function and efficacy.

Animals↗