A framework to reconcile frequency scaling measurements, from intracellular recordings, local-field potentials, up to EEG and MEG signals

In this viewpoint article, we discuss the electric properties of the medium around neurons, which are important to correctly interpret extracellular potentials or electric field effects in neural tissue. We focus on how these electric properties shape the frequency scaling of brain signals at different scales, such as intracellular recordings, the local field potential (LFP), the electroencephalogram (EEG) or the magnetoencephalogram (MEG). These signals display frequency-scaling properties which are not consistent with resistive media. The medium appears to exert a frequency filtering scaling as $1/\sqrt{f}$, which is the typical frequency scaling of ionic diffusion. Such a scaling was also found recently by impedance measurements in physiological conditions. Ionic diffusion appears to be the only possible explanation to reconcile these measurements and the frequency-scaling properties found in different brain signals. However, other measurements suggest that the extracellular medium is essentially resistive. To resolve this discrepancy, we show new evidence that metal-electrode measurements can be perturbed by shunt currents going through the surface of the brain. Such a shunt may explain the contradictory measurements, and together with ionic diffusion, provides a framework where all observations can be reconciled. Finally, we propose a method to perform measurements avoiding shunting effects, thus enabling to test the predictions of this framework.Comment: (in press

Characterizing synaptic conductance fluctuations in cortical neurons and their influence on spike generation

Cortical neurons are subject to sustained and irregular synaptic activity which causes important fluctuations of the membrane potential (Vm). We review here different methods to characterize this activity and its impact on spike generation. The simplified, fluctuating point-conductance model of synaptic activity provides the starting point of a variety of methods for the analysis of intracellular Vm recordings. In this model, the synaptic excitatory and inhibitory conductances are described by Gaussian-distributed stochastic variables, or colored conductance noise. The matching of experimentally recorded Vm distributions to an invertible theoretical expression derived from the model allows the extraction of parameters characterizing the synaptic conductance distributions. This analysis can be complemented by the matching of experimental Vm power spectral densities (PSDs) to a theoretical template, even though the unexpected scaling properties of experimental PSDs limit the precision of this latter approach. Building on this stochastic characterization of synaptic activity, we also propose methods to qualitatively and quantitatively evaluate spike-triggered averages of synaptic time-courses preceding spikes. This analysis points to an essential role for synaptic conductance variance in determining spike times. The presented methods are evaluated using controlled conductance injection in cortical neurons in vitro with the dynamic-clamp technique. We review their applications to the analysis of in vivo intracellular recordings in cat association cortex, which suggest a predominant role for inhibition in determining both sub- and supra-threshold dynamics of cortical neurons embedded in active networks.Comment: 9 figures, Journal of Neuroscience Methods (in press, 2008

Investigating the frontoparietal network in mental calculation in primary school children - An fMRI study

The frontoparietal network activated during calculation processing is investigated in a pediatric population. Subjects assessed correctness of two and three operand equations. Besides traditional frontoparietal activation, clear activation of sites associated with error processing was observed

Morphomata. Kulturelle Figurationen: Genese, Dynamik und Medialität

Das griechische Wort mórphoma bezeichnet den Prozess der Gestaltwerdung und Gestaltgebung. Morphomata ist seit 2009 der Name eines Käthe Hamburger Kollegs in Köln, das als Internationales Kolleg für geisteswissenschaftliche Forschung mit Fellows aus aller Welt die Differenz von Kulturen in ihren künstlerischen Gestaltungen, in Artefakten, aufzuspüren versucht. »Freiraum für die Geisteswissenschaften« heißt die Initiative des Bundesministeriums für Bildung und Forschung, der sich die Entstehung des Kollegs Morphomata verdankt. Der Freiraum gebührt zuallererst den Fellows, die sich in ihren Forschungen im theoretischen Rahmen des Kollegs bewegen können. Das gilt im Besonderen für die erste Fellow-Generation, die an der allmählichen Verfertigung des Morphomkonzepts während der Aufbauphase beteiligt war und deren Ergebnis der erste Band der neuen Reihe Morphomata darstellt. Als wissenschaftlicher Terminus ist mórphoma neu. In drei Teilen gibt dieser Band eine Definition, eröffnet theoretische Perspektiven des Ansatzes und erschließt in Fallstudien die praktische Bedeutung für ein Verständnis konkreter Formen und der Nachhaltigkeit kultureller Figurationen

Eptifibatide provides additional platelet inhibition in Non–ST-Elevation myocardial infarction patients already treated with aspirin and clopidogrel Results of the platelet activity extinction in Non–Q-Wave myocardial infarction with aspirin, clopidogrel, and eptifibatide (PEACE) study

AbstractObjectivesThe present study hypothesis was that eptifibatide offered further antiplatelet efficacy above clopidogrel in non–ST-elevation myocardial infarction (NSTEMI) patients before an expeditive coronary intervention.BackgroundAlthough thienopyridines and glycoprotein (GP) IIb/IIIa antagonists are often co-prescribed in the context of NSTEMI, the antiplatelet interaction of these agents is poorly described and the superiority of GP IIb/IIIa antagonists above thienopyridine treatment alone is not clear.MethodsThirty-two NSTEMI patients treated with aspirin and enoxaparin were studied using flow cytometry to define parameters of platelet activation with a panel of agonists before clopidogrel, after clopidogrel, and during an eptifibatide infusion following the clopidogrel load.ResultsAfter platelet activation with adenosine diphosphate, thrombin receptor-activating peptide, or U46-619, relative reductions in conformationally activated GP IIb/IIIa receptor expression (evaluated with PAC-1) of 48%, 43%, and 33%, respectively (all p < 0.0001), were seen with clopidogrel, but further 80%, 78%, and 72% (all p < 0.0001) reductions were seen with eptifibatide. With the same agonists, fibrinogen binding was significantly reduced after clopidogrel by 70%, 64%, and 81% (all p < 0.0001) and again further reduced with eptifibatide by 90%, 95%, and 69% (all p < 0.0001). The total number of GP IIb/IIIa receptors (measured as P2 expression) and P-selectin expression fell after clopidogrel, after ex vivo stimulation with the same agonists; however, both parameters increased slightly during the eptifibatide infusion.ConclusionsThe activated GP IIb/IIIa expression and fibrinogen binding findings indicate that eptifibatide provides significant potent antiplatelet activity above aspirin and clopidogrel, suggesting additive immediate protection in the treatment of NSTEMI. The P2 and P-selectin findings suggest the possibility of a partial agonist and/or pro-inflammatory effect

Network-State Modulation of Power-Law Frequency-Scaling in Visual Cortical Neurons

Various types of neural-based signals, such as EEG, local field potentials and intracellular synaptic potentials, integrate multiple sources of activity distributed across large assemblies. They have in common a power-law frequency-scaling structure at high frequencies, but it is still unclear whether this scaling property is dominated by intrinsic neuronal properties or by network activity. The latter case is particularly interesting because if frequency-scaling reflects the network state it could be used to characterize the functional impact of the connectivity. In intracellularly recorded neurons of cat primary visual cortex in vivo, the power spectral density of Vm activity displays a power-law structure at high frequencies with a fractional scaling exponent. We show that this exponent is not constant, but depends on the visual statistics used to drive the network. To investigate the determinants of this frequency-scaling, we considered a generic recurrent model of cortex receiving a retinotopically organized external input. Similarly to the in vivo case, our in computo simulations show that the scaling exponent reflects the correlation level imposed in the input. This systematic dependence was also replicated at the single cell level, by controlling independently, in a parametric way, the strength and the temporal decay of the pairwise correlation between presynaptic inputs. This last model was implemented in vitro by imposing the correlation control in artificial presynaptic spike trains through dynamic-clamp techniques. These in vitro manipulations induced a modulation of the scaling exponent, similar to that observed in vivo and predicted in computo. We conclude that the frequency-scaling exponent of the Vm reflects stimulus-driven correlations in the cortical network activity. Therefore, we propose that the scaling exponent could be used to read-out the “effective” connectivity responsible for the dynamical signature of the population signals measured at different integration levels, from Vm to LFP, EEG and fMRI