Synchrony in Networks of Type 2 Interneurons Is More Robust to Noise with Hyperpolarizing Inhibition Compared to Shunting Inhibition in Both the Stochastic Population Oscillator and the Coupled Oscillator Regimes.

Synchronization in the gamma band (25-150 Hz) is mediated by PV+ inhibitory interneurons, and evidence is accumulating for the essential role of gamma oscillations in cognition. Oscillations can arise in inhibitory networks via synaptic interactions between individual oscillatory neurons (mean-driven) or via strong recurrent inhibition that destabilizes the stationary background firing rate in the fluctuation-driven balanced state, causing an oscillation in the population firing rate. Previous theoretical work focused on model neurons with Hodgkin's Type 1 excitability (integrators) connected by current-based synapses. Here we show that networks comprised of simple Type 2 oscillators (resonators) exhibit a supercritical Hopf bifurcation between synchrony and asynchrony and a gradual transition via cycle skipping from coupled oscillators to stochastic population oscillator (SPO), as previously shown for Type 1. We extended our analysis to homogeneous networks with conductance rather than current based synapses and found that networks with hyperpolarizing inhibitory synapses were more robust to noise than those with shunting synapses, both in the coupled oscillator and SPO regime. Assuming that reversal potentials are uniformly distributed between shunting and hyperpolarized values, as observed in one experimental study, converting synapses to purely hyperpolarizing favored synchrony in all cases, whereas conversion to purely shunting synapses made synchrony less robust except at very high conductance strengths. In mature neurons the synaptic reversal potential is controlled by chloride cotransporters that control the intracellular concentrations of chloride and bicarbonate ions, suggesting these transporters as a potential therapeutic target to enhance gamma synchrony and cognition.

Synchrony in Networks of Type 2 Interneurons is More Robust to Noise with Hyperpolarizing Inhibition Compared to Shunting Inhibition in Both the Stochastic Population Oscillator and the Coupled Oscillator Regimes.

Synchronization in the gamma band (30-80 Hz) is mediated by PV+ inhibitory interneurons, and evidence is accumulating for the essential role of gamma oscillations in cognition. Oscillations can arise in inhibitory networks via synaptic interactions between individual oscillatory neurons (mean-driven) or via strong recurrent inhibition that destabilizes the stationary background firing rate in the fluctuation-driven balanced state, causing an oscillation in the population firing rate. Previous theoretical work focused on model neurons with Hodgkin's type 1 excitability (integrators) connected by current-based synapses. Here we show that networks comprised of simple type 2 oscillators (resonators) exhibit a supercritical Hopf bifurcation between synchrony and asynchrony and a gradual transition via cycle skipping from coupled oscillators to stochastic population oscillator, as previously shown for type 1. We extended our analysis to homogeneous networks with conductance rather than current based synapses and found that networks with hyperpolarizing inhibitory synapses were more robust to noise than those with shunting synapses, both in the coupled oscillator and stochastic population oscillator regime. Assuming that reversal potentials are uniformly distributed between shunting and hyperpolarized values, as observed in one experimental study, converting synapses to purely hyperpolarizing favored synchrony in all cases, whereas conversion to purely shunting synapses made synchrony less robust except at very high conductance strengths. In mature neurons the synaptic reversal potential is controlled by chloride cotransporters that control the intracellular concentrations of chloride and bicarbonate ions, suggesting these transporters as a potential therapeutic target to enhance gamma synchrony and cognition. Significance Statement: Brain rhythms in the gamma frequency band (30-80 Hz) depend on the activity of inhibitory interneurons and evidence for a causal role for gamma oscillations in cognitive functions is accumulating. Here we extend previous studies on synchronization mechanisms to interneurons that have an abrupt threshold frequency below which they cannot sustain firing. In addition to current based synapses, we examined inhibitory networks with conductance based synapses. We found that if the reversal potential for inhibition was below the average membrane potential (hyperpolarizing), synchrony was more robust to noise than if the reversal potential was very close to the average potential (shunting). These results have implications for therapies to ameliorate cognitive deficits.

Interneuronal network model of theta-nested fast oscillations predicts differential effects of heterogeneity, gap junctions and short term depression for hyperpolarizing versus shunting inhibition.

Theta and gamma oscillations in the hippocampus have been hypothesized to play a role in the encoding and retrieval of memories. Recently, it was shown that an intrinsic fast gamma mechanism in medial entorhinal cortex can be recruited by optogenetic stimulation at theta frequencies, which can persist with fast excitatory synaptic transmission blocked, suggesting a contribution of interneuronal network gamma (ING). We calibrated the passive and active properties of a 100-neuron model network to capture the range of passive properties and frequency/current relationships of experimentally recorded PV+ neurons in the medial entorhinal cortex (mEC). The strength and probabilities of chemical and electrical synapses were also calibrated using paired recordings, as were the kinetics and short-term depression (STD) of the chemical synapses. Gap junctions that contribute a noticeable fraction of the input resistance were required for synchrony with hyperpolarizing inhibition; these networks exhibited theta-nested high frequency oscillations similar to the putative ING observed experimentally in the optogenetically-driven PV-ChR2 mice. With STD included in the model, the network desynchronized at frequencies above ~200 Hz, so for sufficiently strong drive, fast oscillations were only observed before the peak of the theta. Because hyperpolarizing synapses provide a synchronizing drive that contributes to robustness in the presence of heterogeneity, synchronization decreases as the hyperpolarizing inhibition becomes weaker. In contrast, networks with shunting inhibition required non-physiological levels of gap junctions to synchronize using conduction delays within the measured range.

High-frequency oscillations in the ripple bands and amplitude information coding: Toward a biomarker of maximum entropy in the preictal signals.

Intracranial electroencephalography (iEEG) can directly record local field potentials (LFPs) from a large set of neurons in the vicinity of the electrode. To search for possible epileptic biomarkers and to determine the epileptogenic zone that gives rise to seizures, we investigated the dynamics of basal and preictal signals. For this purpose, we explored the dynamics of the recorded time series for different frequency bands considering high-frequency oscillations (HFO) up to 240 Hz. We apply a Hilbert transform to study the amplitude and phase of the signals. The dynamics of the different frequency bands in the time causal entropy-complexity plane, H × C, is characterized by comparing the dynamical evolution of the basal and preictal time series. As the preictal states evolve closer to the time in which the epileptic seizure starts, the, H × C, dynamics changes for the higher frequency bands. The complexity evolves to very low values and the entropy becomes nearer to its maximal value. These quasi-stable states converge to equiprobable states when the entropy is maximal, and the complexity is zero. We could, therefore, speculate that in this case, it corresponds to the minimization of Gibbs free energy. In this case, the maximum entropy is equivalent to the principle of minimum consumption of resources in the system. We can interpret this as the nature of the system evolving temporally in the preictal state in such a way that the consumption of resources by the system is minimal for the amplitude in frequencies between 220-230 and 230-240 Hz.

Abnormal EEG signal energy in the elderly: A wavelet analysis of event-related potentials during a stroop task.

BACKGROUND: Previous work showed that elderly with excess in theta activity in their resting state electroencephalogram (EEG) are at higher risk of cognitive decline than those with a normal EEG. By using event-related potentials (ERP) during a counting Stroop task, our prior work showed that elderly with theta excess have a large P300 component compared with normal EEG group. This increased activity could be related to a higher EEG signal energy used during this task. NEW METHOD: By wavelet analysis applied to ERP obtained during a counting Stroop task we quantified the energy in the different frequency bands of a group of elderly with altered EEG. RESULTS: In theta and alpha bands, the total energy was higher in elderly subjects with theta excess, specifically in the stimulus categorization window (258-516 ms). Both groups solved the task with similar efficiency. COMPARISON WITH EXISTING METHODS: The traditional ERP analysis in elderly compares voltage among conditions and groups for a given time window, while the frequency composition is not usually examined. We complemented our previous ERP analysis using a wavelet methodology. Furthermore, we showed the advantages of wavelet analysis over Short Time Fourier Transform when exploring EEG signal during this task. CONCLUSIONS: The higher EEG signal energy in ERP might reflect undergoing neurobiological mechanisms that allow the elderly with theta excess to cope with the cognitive task with similar behavioral results as the normal EEG group. This increased energy could promote a metabolic and cellular dysregulation causing a greater decline in cognitive function.

Heterogeneity across neural populations: Its significance for the dynamics and functions of neural circuits.

Neural populations show patterns of synchronous activity, as they share common correlated inputs. Neurons in the cortex that are connected by strong synapses cause rapid firing explosions. In addition, areas that are connected by weaker synapses have a slower dynamics and they can contribute to asymmetries in the input distributions. The aim of this work is to develop a neural model to investigate how the heterogeneities in the synaptic input distributions affect different levels of organizational activity in the brain dynamics. We analytically show how small changes in the correlation inputs can cause large changes in the interactions of the outputs that lead to a phase transition, demonstrating that a simple variation in the direction of a biased skewed distribution in the neuronal inputs can generate a transition of states in the firing rate, passing from spontaneous silence ("down state") to an absolute spiking activity ("up state"). We present an exact quantification of the dynamics of the output variables, showing that when considering a biased skewed distribution in the inputs of neuronal population, the critical point is not in an asynchronous or synchronous state but rather at an intermediate value.

Higher-Order Cumulants Drive Neuronal Activity Patterns, Inducing UP-DOWN States in Neural Populations.

A major challenge in neuroscience is to understand the role of the higher-order correlations structure of neuronal populations. The dichotomized Gaussian model (DG) generates spike trains by means of thresholding a multivariate Gaussian random variable. The DG inputs are Gaussian distributed, and thus have no interactions beyond the second order in their inputs; however, they can induce higher-order correlations in the outputs. We propose a combination of analytical and numerical techniques to estimate higher-order, above the second, cumulants of the firing probability distributions. Our findings show that a large amount of pairwise interactions in the inputs can induce the system into two possible regimes, one with low activity ("DOWN state") and another one with high activity ("UP state"), and the appearance of these states is due to a combination between the third- and fourth-order cumulant. This could be part of a mechanism that would help the neural code to upgrade specific information about the stimuli, motivating us to examine the behavior of the critical fluctuations through the Binder cumulant close to the critical point. We show, using the Binder cumulant, that higher-order correlations in the outputs generate a critical neural system that portrays a second-order phase transition.

Rhythmic activities of the brain: Quantifying the high complexity of beta and gamma oscillations during visuomotor tasks.

Electroencephalography (EEG) signals depict the electrical activity that takes place at the surface of the brain and provide an important tool for understanding a variety of cognitive processes. The EEG is the product of synchronized activity of the brain, and variations in EEG oscillations patterns reflect the underlying changes in neuronal synchrony. Our aim is to characterize the complexity of the EEG rhythmic oscillations bands when the subjects perform a visuomotor or imagined cognitive tasks (imagined movement), providing a causal mapping of the dynamical rhythmic activities of the brain as a measure of attentional investment. We estimate the intrinsic correlational structure of the signals within the causality entropy-complexity plane H×C, where the enhanced complexity in the gamma 1, gamma 2, and beta 1 bands allows us to distinguish motor-visual memory tasks from control conditions. We identify the dynamics of the gamma 1, gamma 2, and beta 1 rhythmic oscillations within the zone of a chaotic dissipative behavior, whereas in contrast the beta 2 band shows a much higher level of entropy and a significant low level of complexity that correspond to a non-invertible cubic map. Our findings enhance the importance of the gamma band during attention in perceptual feature binding during the visuomotor/imagery tasks.

Causal Shannon-Fisher Characterization of Motor/Imagery Movements in EEG.

The electroencephalogram (EEG) is an electrophysiological monitoring method that allows us to glimpse the electrical activity of the brain. Neural oscillations patterns are perhaps the best salient feature of EEG as they are rhythmic activities of the brain that can be generated by interactions across neurons. Large-scale oscillations can be measured by EEG as the different oscillation patterns reflected within the different frequency bands, and can provide us with new insights into brain functions. In order to understand how information about the rhythmic activity of the brain during visuomotor/imagined cognitive tasks is encoded in the brain we precisely quantify the different features of the oscillatory patterns considering the Shannon-Fisher plane H × F . This allows us to distinguish the dynamics of rhythmic activities of the brain showing that the Beta band facilitate information transmission during visuomotor/imagined tasks.

Causal information quantification of prominent dynamical features of biological neurons.

Neurons tend to fire a spike when they are near a bifurcation from the resting state to spiking activity. It is a delicate balance between noise, dynamic currents and initial condition that determines the phase diagram of neural activity. Many possible ionic mechanisms can be accounted for as the source of spike generation. Moreover, the biophysics and the dynamics behind it can usually be described through a phase diagram that involves membrane voltage versus the activation variable of the ionic channel. In this paper, we present a novel methodology to characterize the dynamics of this system, which takes into account the fine temporal 'structures' of the complex neuronal signals. This allows us to accurately distinguish the most fundamental properties of neurophysiological neurons that were previously described by Izhikevich considering the phase-space trajectory, using a time causal space: statistical complexity versus Fisher information versus Shannon entropy.