The goal of the Human Brain Project is to develop, during the next decade, an infrastructure capa... more The goal of the Human Brain Project is to develop, during the next decade, an infrastructure capable of simulating a draft human brain model based on available experimental data. One of the key issues is therefore to integrate and make accessible the experimental data necessary to constrain and fully specify this model. The required data covers many different spatial scales, ranging from the molecular scale to the whole brain and these data are obtained using a variety of techniques whose measurements may not be directly comparable. Furthermore, these data are incomplete, and will remain so at least for the coming decade. Here we review new neuroinformatics techniques that need to be developed and applied to address these issues.
Pyramidal cells and interneurons in rat prefrontal cortical slices exhibit subthreshold oscillati... more Pyramidal cells and interneurons in rat prefrontal cortical slices exhibit subthreshold oscillations when depolarized by constant current injection. For both types of neurons, the frequencies of these oscillations for current injection just below spike threshold were 2--10 Hz. Above spike threshold, however, the subthreshold oscillations in pyramidal cells remained low, but the frequency of oscillations in interneurons increased up to 50 Hz. To explore the interaction between these intrinsic oscillations and external inputs, the reliability of spiking in these cortical neurons was studied with sinusoidal current injection over a range of frequencies above and below the intrinsic frequency. Cortical neurons produced 1:1 phase locking for a limited range of driving frequencies for fixed amplitude. For low-input amplitude, 1:1 phase locking was obtained in the 5- to 10-Hz range. For higher-input amplitudes, pyramidal cells phase-locked in the 5- to 20-Hz range, whereas interneurons pha...
In the primate visual cortex, the phase of spikes relative to oscillations in the local field pot... more In the primate visual cortex, the phase of spikes relative to oscillations in the local field potential (LFP) in the gamma frequency range (30-80 Hz) can be shifted by stimulus features such as orientation and thus the phase may carry information about stimulus identity. According to the principle of communication through coherence (CTC), the relative LFP phase between the LFPs in the sending and receiving circuits affects the effectiveness of the transmission. CTC predicts that phase shifting can be used for stimulus selection. We review and investigate phase shifting in models of periodically driven single neurons and compare it with phase shifting in models of cortical networks. In a single neuron, as the driving current is increased, the spike phase varies systematically while the firing rate remains constant. In a network model of reciprocally connected excitatory (E) and inhibitory (I) cells phase shifting occurs in response to both injection of constant depolarizing currents ...
Two recent monkey studies demonstrate that feedforward processing in the visual system is reflect... more Two recent monkey studies demonstrate that feedforward processing in the visual system is reflected by activity in the 40-90 Hz gamma band, whereas feedback is reflected by activity in the 5-18 Hz alpha and beta band. These findings can be applied to interpret human electrophysiological activity in complex visual tasks.
Major depressive disorder (MDD) is a serious condition with a lifetime prevalence exceeding 16% w... more Major depressive disorder (MDD) is a serious condition with a lifetime prevalence exceeding 16% worldwide. MDD is a heterogeneous disorder that involves multiple behavioral symptoms on the one hand and multiple neuronal circuits on the other hand. In this review, we integrate the literature on cognitive and physiological biomarkers of MDD with the insights derived from mathematical models of brain networks, especially models that can be used for fMRI datasets. We refer to the recent NIH research domain criteria initiative, in which a concept of "constructs" as functional units of mental disorders is introduced. Constructs are biomarkers present at multiple levels of brain functioning - cognition, genetics, brain anatomy, and neurophysiology. In this review, we propose a new approach which we called circuit to construct mapping (CCM), which aims to characterize causal relations between the underlying network dynamics (as the cause) and the constructs referring to the clinical symptoms of MDD (as the effect). CCM involves extracting diagnostic categories from behavioral data, linking circuits that are causal to these categories with use of clinical neuroimaging data, and modeling the dynamics of the emerging circuits with attractor dynamics in order to provide new, neuroimaging-related biomarkers for MDD. The CCM approach optimizes the clinical diagnosis and patient stratification. It also addresses the recent demand for linking circuits to behavior, and provides a new insight into clinical treatment by investigating the dynamics of neuronal circuits underneath cognitive dimensions of MDD. CCM can serve as a new regime toward personalized medicine, assisting the diagnosis and treatment of MDD.
Recent studies have emphasized an important role for long non-coding RNAs (lncRNA) in epigenetic ... more Recent studies have emphasized an important role for long non-coding RNAs (lncRNA) in epigenetic regulation, development, and disease. Despite growing interest in lncRNAs, the mechanisms by which lncRNAs control cellular processes are still elusive. Improved understanding of these mechanisms is critical, because the majority of the mammalian genome is transcribed, in most cases resulting in non-coding RNA products. Recent studies have suggested the involvement of lncRNA in neurobehavioral and neurodevelopmental disorders, highlighting the functional importance of this subclass of brain-enriched RNAs. Impaired expression of lnRNAs has been implicated in several forms of intellectual disability disorders. However, the role of this family of RNAs in cognitive function is largely unknown. Here we provide an overview of recently identified mechanisms of neuronal development involving lncRNAs, and the consequences of lncRNA deregulation for neurodevelopmental disorders.
We propose a preprocessing method to separate coherent neuronal network activity, referred to as ... more We propose a preprocessing method to separate coherent neuronal network activity, referred to as "bursts", from background spikes. High background activity in neuronal recordings reduces the effectiveness of currently available burst detection methods. For long-term, stationary recordings, burst and background spikes have a bimodal ISI distribution which makes it easy to select the threshold to separate burst and background spikes. Finite, nonstationary recordings lead to noisy ISIs for which the bimodality is not that clear. We introduce a preprocessing method to separate burst from background spikes to improve burst detection reliability because it efficiently uses both single and multichannel activity. The method is tested using a stochastic model constrained by data available in the literature and recordings from primary cortical neurons cultured on multielectrode arrays. The separation between burst and background spikes is obtained using the interspike interval return map. The cutoff threshold is the key parameter to separate the burst and background spikes. We compare two methods for selecting the threshold. (1) The 2-step method, in which threshold selection is based on fixed heuristics. (2) The iterative method, in which the optimal cutoff threshold is directly estimated from the data. The proposed preprocessing method significantly increases the reliability of several established burst detection algorithms, both for simulated and real recordings. The preprocessing method makes it possible to study the effects of diseases or pharmacological manipulations, because it can deal efficiently with nonstationarity in the data.
Many neurons in the visual cortex are orientation-selective, increase their firing rate with cont... more Many neurons in the visual cortex are orientation-selective, increase their firing rate with contrast and are modulated by attention. What is the cortical circuit that underlies these computations? We examine how synchrony can be modulated by the excitability of interneurons, in a model layer 4 network displaying contrast-invariant orientation-tuning. We did not find parameter settings for which the standard ring
Brain circuitry processes information by rapidly and selectively engaging functional neuronal net... more Brain circuitry processes information by rapidly and selectively engaging functional neuronal networks. The dynamic formation of networks is often evident in rhythmically synchronized neuronal activity and tightly correlates with perceptual, cognitive and motor performances. But how synchronized neuronal activity contributes to network formation and how it relates to the computation of behaviorally relevant information has remained difficult to discern. Here we structure recent empirical advances that link synchronized activity to the activation of so-called dynamic circuit motifs. These motifs explicitly relate (1) synaptic and cellular properties of circuits to (2) identified timescales of rhythmic activation and to (3) canonical circuit computations implemented by rhythmically synchronized circuits. We survey the ubiquitous evidence of specific cell and circuit properties underlying synchronized activity across theta, alpha, beta and gamma frequency bands and show that their activation likely implements gain control, context-dependent gating and state-specific integration of synaptic inputs. This evidence gives rise to the dynamic circuit motifs hypothesis of synchronized activation states, with its core assertion that activation states are linked to uniquely identifiable local circuit structures that are recruited during the formation of functional networks to perform specific computational operations. npg
Traditionally, most basal forebrain (BF) functions have been attributed to its cholinergic neuron... more Traditionally, most basal forebrain (BF) functions have been attributed to its cholinergic neurons. However, the majority of corticalprojecting BF neurons are noncholinergic and their in vivo functions remain unclear. We investigated how BF modulates cortical dynamics by simultaneously recording Յ50 BF single neurons along with local field potentials (LFPs) from the prefrontal cortex (PFCx) in different wake-sleep states of adult rats. Using stereotypical spike time correlations, we identified a large (roughly 70%) subset of BF neurons, which we named BF tonic neurons (BFTNs). BFTNs fired tonically at 2-8 Hz without significantly changing their average firing rate across wake-sleep states. As such, these cannot be classified as cholinergic neurons. BFTNs substantially increased the spiking variability during waking and rapid-eye-movement sleep, by exhibiting frequent spike bursts with Ͻ50-ms interspike interval. Spike bursts among BFTNs were highly correlated, leading to transient population synchronization events of BFTN ensembles that lasted on average 160 ms. Most importantly, BFTN synchronization occurred preferentially just before the troughs of PFCx LFP oscillations, which reflect increased cortical activity. Furthermore, BFTN synchronization was accompanied by transient increases in prefrontal cortex gamma oscillations. These results suggest that synchronization of BFTN ensembles, which are likely to be formed by cortical-projecting GABAergic neurons from the BF, could be primarily responsible for fast cortical modulations to provide transient amplification of cortical activity.
Responses of neurons in monkey visual cortex are modulated when attention is directed into the re... more Responses of neurons in monkey visual cortex are modulated when attention is directed into the receptive field of the neuron: the gain or sensitivity of the response is increased or the synchronization of the spikes to the local field potential (LFP) is increased. We investigated, using model simulations, whether the synchrony of inhibitory networks could link these observations. We found that, indeed, an increase in inhibitory synchrony could enhance the coherence of the model neurons with the simulated LFP, and could have different effects on the firing rate. When the firing rate vs. current (f-I) response curves saturated at high I, attention yielded a shift in sensitivity; alternatively, when the f-I curves were non-saturating, the most significant effect was on the gain of the response. This suggests that attention may act through changes in the synchrony of inhibitory networks.
Cells in primary auditory cortex respond preferably to frequency sweeps of a certain rate and dir... more Cells in primary auditory cortex respond preferably to frequency sweeps of a certain rate and direction. In a model by Fishbach et al. [J. Neurophysiol. 90 (2003) 3663-3678], direction selective cells emerged through patterned thalamocortical projections. The thalamic inputs to the auditory cortex were modeled as time-varying firing rates without explicit spikes. We investigate the biophysical constraints for the emergence of direction selectivity using a model that includes spiking thalamic neurons. We find that directional selectivity can still be achieved for a broad range of parameter values using an architecture similar to that proposed previously for visual cortex models. Furthermore, recurrent connections could improve the directional selectivity of the neurons. r
We introduce a new correlation-based measure of spike timing reliability. Unlike other measures, ... more We introduce a new correlation-based measure of spike timing reliability. Unlike other measures, it does not require the deÿnition of a posteriori "events". It relies on only one parameter, which relates to the timescale of spike timing precision. We test the measure on surrogate data sets with varying amounts of spike time jitter, and missing or additional spikes, and compare it with a widely used histogram-based measure. The measure is e cient and faithful in characterizing spike timing reliability and produces smaller errors in the reliability estimate than the histogram-based measure based on the same number of trials.
Granger-causality metrics have become increasingly popular tools to identify directed interaction... more Granger-causality metrics have become increasingly popular tools to identify directed interactions between brain areas. However, it is known that additive noise can strongly affect Granger-causality metrics, which can lead to spurious conclusions about neuronal interactions. To solve this problem, previous studies have proposed the detection of Granger-causal directionality, i.e. the dominant Granger-causal flow, using either the slope of the coherency (Phase Slope Index; PSI), or by comparing Granger-causality values between original and time-reversed signals (reversed Granger testing). We show that for ensembles of vector autoregressive (VAR) models encompassing bidirectionally coupled sources, these alternative methods do not correctly measure Granger-causal directionality for a substantial fraction of VAR models, even in the absence of noise. We then demonstrate that uncorrelated noise has fundamentally different effects on directed connectivity metrics than linearly mixed noise...
The visual system is thought to represent the direction of moving objects in the relative activit... more The visual system is thought to represent the direction of moving objects in the relative activity of large populations of cortical neurons that are broadly tuned to the direction of stimulus motion; but how changes in the direction of a moving stimulus are represented in the population response remains poorly understood. Here we take advantage of the orderly mapping of direction selectivity in ferret primary visual cortex (V1) to explore how abrupt changes in the direction of a moving stimulus are encoded in population activity using voltage-sensitive dye (VSD) imaging. For stimuli moving in a constant direction, the peak of the V1 population response accurately represented the direction of stimulus motion; but following abrupt changes in motion direction, the peak transiently departed from the direction of stimulus motion in a fashion that varied with the direction offset angle and was well predicted from the response to the component directions. We conclude that cortical dynamics and population coding mechanisms combine to place constraints on the accuracy with which abrupt changes in direction of motion can be represented by cortical circuits.
When a cortical neuron is repeatedly injected with the same fluctuating current stimulus (frozen ... more When a cortical neuron is repeatedly injected with the same fluctuating current stimulus (frozen noise) the timing of the spikes is highly precise from trial to trial and the spike pattern appears to be unique. We show here that the same repeated stimulus can produce more than one reliable temporal pattern of spikes. A new method is introduced to find these patterns in raw multitrial data and is tested on surrogate data sets. Using it, multiple coexisting spike patterns were discovered in pyramidal cells recorded from rat prefrontal cortex in vitro, in data obtained in vivo from the middle temporal area of the monkey and from the cat lateral geniculate nucleus . The spike patterns lasted from a few tens of milliseconds in vitro to several seconds in vivo. We conclude that the prestimulus history of a neuron may influence the precise timing of the spikes in response to a stimulus over a wide range of time scales.
Field potential recordings from the rat hippocampus in vivo contain distinct frequency bands of a... more Field potential recordings from the rat hippocampus in vivo contain distinct frequency bands of activity, including ␦ (0.5-2 Hz), (4 -12 Hz), and ␥ (30 -80 Hz), that are correlated with the behavioral state of the animal. The cholinergic agonist carbachol (CCH) induces oscillations in the ␦ (CCH-␦), (CCH-), and ␥ (CCH-␥) frequency ranges in the hippocampal slice preparation, eliciting asynchronous CCH-, synchronous CCH-␦, and synchronous CCH-with increasing CCH concentration (Fellous and Sejnowski, Hippocampus 2000;10:187-197).
Event-related potential studies in schizophrenia have demonstrated amplitude reduction of the P3 ... more Event-related potential studies in schizophrenia have demonstrated amplitude reduction of the P3 in oddball tasks. The P3 has been linked to attention and memory brain functions. In 24 schizophrenia patients and 28 control subjects, wavelet transform was used to reveal event-related modulations of the EEG signal during target trials in delta, theta, alpha, beta, and gamma frequency bands. Patients showed reductions in P3 amplitude accompanied by reduced low frequency delta-theta and increased beta-gamma band EEG activity. These results indicate abnormalities in the synchronization and/or efficiency of neural processes involved in memory and attention networks in schizophrenia.
The response of a neuron to sensory stimuli can only give correlational support for functional hy... more The response of a neuron to sensory stimuli can only give correlational support for functional hypotheses. To experimentally test causal function, the neural activity needs to be manipulated in a cell-type specific, as well as spatially and temporally precise way. We review recent optogenetic experiments on parvalbumin-positive cortical interneurons that link modeling studies of synchronization to experimental studies on attentional modulation of gamma oscillations in primates.
The synchrony of neurons in the extrastriate visual cortex is modulated by selective attention ev... more The synchrony of neurons in the extrastriate visual cortex is modulated by selective attention even when there are only small changes in firing rate (Fries et al., Science 291 (2001) 1560). We used Hodgkin–Huxley type models of cortical neurons to investigate the mechanism by which the degree of synchrony can be modulated independently of changes in firing rate. The synchrony of local networks of model cortical interneurons interacting through inhibitory synapses with short-term synaptic plasticity was modulated on a fast timescale by selectively activating a fraction of the interneurons. We found that facilitation enhanced the synchrony of the system whereas depression reduced it. In systems with synaptic plasticity, the synchrony modulation was accompanied by larger changes in the firing rate.
The goal of the Human Brain Project is to develop, during the next decade, an infrastructure capa... more The goal of the Human Brain Project is to develop, during the next decade, an infrastructure capable of simulating a draft human brain model based on available experimental data. One of the key issues is therefore to integrate and make accessible the experimental data necessary to constrain and fully specify this model. The required data covers many different spatial scales, ranging from the molecular scale to the whole brain and these data are obtained using a variety of techniques whose measurements may not be directly comparable. Furthermore, these data are incomplete, and will remain so at least for the coming decade. Here we review new neuroinformatics techniques that need to be developed and applied to address these issues.
Pyramidal cells and interneurons in rat prefrontal cortical slices exhibit subthreshold oscillati... more Pyramidal cells and interneurons in rat prefrontal cortical slices exhibit subthreshold oscillations when depolarized by constant current injection. For both types of neurons, the frequencies of these oscillations for current injection just below spike threshold were 2--10 Hz. Above spike threshold, however, the subthreshold oscillations in pyramidal cells remained low, but the frequency of oscillations in interneurons increased up to 50 Hz. To explore the interaction between these intrinsic oscillations and external inputs, the reliability of spiking in these cortical neurons was studied with sinusoidal current injection over a range of frequencies above and below the intrinsic frequency. Cortical neurons produced 1:1 phase locking for a limited range of driving frequencies for fixed amplitude. For low-input amplitude, 1:1 phase locking was obtained in the 5- to 10-Hz range. For higher-input amplitudes, pyramidal cells phase-locked in the 5- to 20-Hz range, whereas interneurons pha...
In the primate visual cortex, the phase of spikes relative to oscillations in the local field pot... more In the primate visual cortex, the phase of spikes relative to oscillations in the local field potential (LFP) in the gamma frequency range (30-80 Hz) can be shifted by stimulus features such as orientation and thus the phase may carry information about stimulus identity. According to the principle of communication through coherence (CTC), the relative LFP phase between the LFPs in the sending and receiving circuits affects the effectiveness of the transmission. CTC predicts that phase shifting can be used for stimulus selection. We review and investigate phase shifting in models of periodically driven single neurons and compare it with phase shifting in models of cortical networks. In a single neuron, as the driving current is increased, the spike phase varies systematically while the firing rate remains constant. In a network model of reciprocally connected excitatory (E) and inhibitory (I) cells phase shifting occurs in response to both injection of constant depolarizing currents ...
Two recent monkey studies demonstrate that feedforward processing in the visual system is reflect... more Two recent monkey studies demonstrate that feedforward processing in the visual system is reflected by activity in the 40-90 Hz gamma band, whereas feedback is reflected by activity in the 5-18 Hz alpha and beta band. These findings can be applied to interpret human electrophysiological activity in complex visual tasks.
Major depressive disorder (MDD) is a serious condition with a lifetime prevalence exceeding 16% w... more Major depressive disorder (MDD) is a serious condition with a lifetime prevalence exceeding 16% worldwide. MDD is a heterogeneous disorder that involves multiple behavioral symptoms on the one hand and multiple neuronal circuits on the other hand. In this review, we integrate the literature on cognitive and physiological biomarkers of MDD with the insights derived from mathematical models of brain networks, especially models that can be used for fMRI datasets. We refer to the recent NIH research domain criteria initiative, in which a concept of "constructs" as functional units of mental disorders is introduced. Constructs are biomarkers present at multiple levels of brain functioning - cognition, genetics, brain anatomy, and neurophysiology. In this review, we propose a new approach which we called circuit to construct mapping (CCM), which aims to characterize causal relations between the underlying network dynamics (as the cause) and the constructs referring to the clinical symptoms of MDD (as the effect). CCM involves extracting diagnostic categories from behavioral data, linking circuits that are causal to these categories with use of clinical neuroimaging data, and modeling the dynamics of the emerging circuits with attractor dynamics in order to provide new, neuroimaging-related biomarkers for MDD. The CCM approach optimizes the clinical diagnosis and patient stratification. It also addresses the recent demand for linking circuits to behavior, and provides a new insight into clinical treatment by investigating the dynamics of neuronal circuits underneath cognitive dimensions of MDD. CCM can serve as a new regime toward personalized medicine, assisting the diagnosis and treatment of MDD.
Recent studies have emphasized an important role for long non-coding RNAs (lncRNA) in epigenetic ... more Recent studies have emphasized an important role for long non-coding RNAs (lncRNA) in epigenetic regulation, development, and disease. Despite growing interest in lncRNAs, the mechanisms by which lncRNAs control cellular processes are still elusive. Improved understanding of these mechanisms is critical, because the majority of the mammalian genome is transcribed, in most cases resulting in non-coding RNA products. Recent studies have suggested the involvement of lncRNA in neurobehavioral and neurodevelopmental disorders, highlighting the functional importance of this subclass of brain-enriched RNAs. Impaired expression of lnRNAs has been implicated in several forms of intellectual disability disorders. However, the role of this family of RNAs in cognitive function is largely unknown. Here we provide an overview of recently identified mechanisms of neuronal development involving lncRNAs, and the consequences of lncRNA deregulation for neurodevelopmental disorders.
We propose a preprocessing method to separate coherent neuronal network activity, referred to as ... more We propose a preprocessing method to separate coherent neuronal network activity, referred to as "bursts", from background spikes. High background activity in neuronal recordings reduces the effectiveness of currently available burst detection methods. For long-term, stationary recordings, burst and background spikes have a bimodal ISI distribution which makes it easy to select the threshold to separate burst and background spikes. Finite, nonstationary recordings lead to noisy ISIs for which the bimodality is not that clear. We introduce a preprocessing method to separate burst from background spikes to improve burst detection reliability because it efficiently uses both single and multichannel activity. The method is tested using a stochastic model constrained by data available in the literature and recordings from primary cortical neurons cultured on multielectrode arrays. The separation between burst and background spikes is obtained using the interspike interval return map. The cutoff threshold is the key parameter to separate the burst and background spikes. We compare two methods for selecting the threshold. (1) The 2-step method, in which threshold selection is based on fixed heuristics. (2) The iterative method, in which the optimal cutoff threshold is directly estimated from the data. The proposed preprocessing method significantly increases the reliability of several established burst detection algorithms, both for simulated and real recordings. The preprocessing method makes it possible to study the effects of diseases or pharmacological manipulations, because it can deal efficiently with nonstationarity in the data.
Many neurons in the visual cortex are orientation-selective, increase their firing rate with cont... more Many neurons in the visual cortex are orientation-selective, increase their firing rate with contrast and are modulated by attention. What is the cortical circuit that underlies these computations? We examine how synchrony can be modulated by the excitability of interneurons, in a model layer 4 network displaying contrast-invariant orientation-tuning. We did not find parameter settings for which the standard ring
Brain circuitry processes information by rapidly and selectively engaging functional neuronal net... more Brain circuitry processes information by rapidly and selectively engaging functional neuronal networks. The dynamic formation of networks is often evident in rhythmically synchronized neuronal activity and tightly correlates with perceptual, cognitive and motor performances. But how synchronized neuronal activity contributes to network formation and how it relates to the computation of behaviorally relevant information has remained difficult to discern. Here we structure recent empirical advances that link synchronized activity to the activation of so-called dynamic circuit motifs. These motifs explicitly relate (1) synaptic and cellular properties of circuits to (2) identified timescales of rhythmic activation and to (3) canonical circuit computations implemented by rhythmically synchronized circuits. We survey the ubiquitous evidence of specific cell and circuit properties underlying synchronized activity across theta, alpha, beta and gamma frequency bands and show that their activation likely implements gain control, context-dependent gating and state-specific integration of synaptic inputs. This evidence gives rise to the dynamic circuit motifs hypothesis of synchronized activation states, with its core assertion that activation states are linked to uniquely identifiable local circuit structures that are recruited during the formation of functional networks to perform specific computational operations. npg
Traditionally, most basal forebrain (BF) functions have been attributed to its cholinergic neuron... more Traditionally, most basal forebrain (BF) functions have been attributed to its cholinergic neurons. However, the majority of corticalprojecting BF neurons are noncholinergic and their in vivo functions remain unclear. We investigated how BF modulates cortical dynamics by simultaneously recording Յ50 BF single neurons along with local field potentials (LFPs) from the prefrontal cortex (PFCx) in different wake-sleep states of adult rats. Using stereotypical spike time correlations, we identified a large (roughly 70%) subset of BF neurons, which we named BF tonic neurons (BFTNs). BFTNs fired tonically at 2-8 Hz without significantly changing their average firing rate across wake-sleep states. As such, these cannot be classified as cholinergic neurons. BFTNs substantially increased the spiking variability during waking and rapid-eye-movement sleep, by exhibiting frequent spike bursts with Ͻ50-ms interspike interval. Spike bursts among BFTNs were highly correlated, leading to transient population synchronization events of BFTN ensembles that lasted on average 160 ms. Most importantly, BFTN synchronization occurred preferentially just before the troughs of PFCx LFP oscillations, which reflect increased cortical activity. Furthermore, BFTN synchronization was accompanied by transient increases in prefrontal cortex gamma oscillations. These results suggest that synchronization of BFTN ensembles, which are likely to be formed by cortical-projecting GABAergic neurons from the BF, could be primarily responsible for fast cortical modulations to provide transient amplification of cortical activity.
Responses of neurons in monkey visual cortex are modulated when attention is directed into the re... more Responses of neurons in monkey visual cortex are modulated when attention is directed into the receptive field of the neuron: the gain or sensitivity of the response is increased or the synchronization of the spikes to the local field potential (LFP) is increased. We investigated, using model simulations, whether the synchrony of inhibitory networks could link these observations. We found that, indeed, an increase in inhibitory synchrony could enhance the coherence of the model neurons with the simulated LFP, and could have different effects on the firing rate. When the firing rate vs. current (f-I) response curves saturated at high I, attention yielded a shift in sensitivity; alternatively, when the f-I curves were non-saturating, the most significant effect was on the gain of the response. This suggests that attention may act through changes in the synchrony of inhibitory networks.
Cells in primary auditory cortex respond preferably to frequency sweeps of a certain rate and dir... more Cells in primary auditory cortex respond preferably to frequency sweeps of a certain rate and direction. In a model by Fishbach et al. [J. Neurophysiol. 90 (2003) 3663-3678], direction selective cells emerged through patterned thalamocortical projections. The thalamic inputs to the auditory cortex were modeled as time-varying firing rates without explicit spikes. We investigate the biophysical constraints for the emergence of direction selectivity using a model that includes spiking thalamic neurons. We find that directional selectivity can still be achieved for a broad range of parameter values using an architecture similar to that proposed previously for visual cortex models. Furthermore, recurrent connections could improve the directional selectivity of the neurons. r
We introduce a new correlation-based measure of spike timing reliability. Unlike other measures, ... more We introduce a new correlation-based measure of spike timing reliability. Unlike other measures, it does not require the deÿnition of a posteriori "events". It relies on only one parameter, which relates to the timescale of spike timing precision. We test the measure on surrogate data sets with varying amounts of spike time jitter, and missing or additional spikes, and compare it with a widely used histogram-based measure. The measure is e cient and faithful in characterizing spike timing reliability and produces smaller errors in the reliability estimate than the histogram-based measure based on the same number of trials.
Granger-causality metrics have become increasingly popular tools to identify directed interaction... more Granger-causality metrics have become increasingly popular tools to identify directed interactions between brain areas. However, it is known that additive noise can strongly affect Granger-causality metrics, which can lead to spurious conclusions about neuronal interactions. To solve this problem, previous studies have proposed the detection of Granger-causal directionality, i.e. the dominant Granger-causal flow, using either the slope of the coherency (Phase Slope Index; PSI), or by comparing Granger-causality values between original and time-reversed signals (reversed Granger testing). We show that for ensembles of vector autoregressive (VAR) models encompassing bidirectionally coupled sources, these alternative methods do not correctly measure Granger-causal directionality for a substantial fraction of VAR models, even in the absence of noise. We then demonstrate that uncorrelated noise has fundamentally different effects on directed connectivity metrics than linearly mixed noise...
The visual system is thought to represent the direction of moving objects in the relative activit... more The visual system is thought to represent the direction of moving objects in the relative activity of large populations of cortical neurons that are broadly tuned to the direction of stimulus motion; but how changes in the direction of a moving stimulus are represented in the population response remains poorly understood. Here we take advantage of the orderly mapping of direction selectivity in ferret primary visual cortex (V1) to explore how abrupt changes in the direction of a moving stimulus are encoded in population activity using voltage-sensitive dye (VSD) imaging. For stimuli moving in a constant direction, the peak of the V1 population response accurately represented the direction of stimulus motion; but following abrupt changes in motion direction, the peak transiently departed from the direction of stimulus motion in a fashion that varied with the direction offset angle and was well predicted from the response to the component directions. We conclude that cortical dynamics and population coding mechanisms combine to place constraints on the accuracy with which abrupt changes in direction of motion can be represented by cortical circuits.
When a cortical neuron is repeatedly injected with the same fluctuating current stimulus (frozen ... more When a cortical neuron is repeatedly injected with the same fluctuating current stimulus (frozen noise) the timing of the spikes is highly precise from trial to trial and the spike pattern appears to be unique. We show here that the same repeated stimulus can produce more than one reliable temporal pattern of spikes. A new method is introduced to find these patterns in raw multitrial data and is tested on surrogate data sets. Using it, multiple coexisting spike patterns were discovered in pyramidal cells recorded from rat prefrontal cortex in vitro, in data obtained in vivo from the middle temporal area of the monkey and from the cat lateral geniculate nucleus . The spike patterns lasted from a few tens of milliseconds in vitro to several seconds in vivo. We conclude that the prestimulus history of a neuron may influence the precise timing of the spikes in response to a stimulus over a wide range of time scales.
Field potential recordings from the rat hippocampus in vivo contain distinct frequency bands of a... more Field potential recordings from the rat hippocampus in vivo contain distinct frequency bands of activity, including ␦ (0.5-2 Hz), (4 -12 Hz), and ␥ (30 -80 Hz), that are correlated with the behavioral state of the animal. The cholinergic agonist carbachol (CCH) induces oscillations in the ␦ (CCH-␦), (CCH-), and ␥ (CCH-␥) frequency ranges in the hippocampal slice preparation, eliciting asynchronous CCH-, synchronous CCH-␦, and synchronous CCH-with increasing CCH concentration (Fellous and Sejnowski, Hippocampus 2000;10:187-197).
Event-related potential studies in schizophrenia have demonstrated amplitude reduction of the P3 ... more Event-related potential studies in schizophrenia have demonstrated amplitude reduction of the P3 in oddball tasks. The P3 has been linked to attention and memory brain functions. In 24 schizophrenia patients and 28 control subjects, wavelet transform was used to reveal event-related modulations of the EEG signal during target trials in delta, theta, alpha, beta, and gamma frequency bands. Patients showed reductions in P3 amplitude accompanied by reduced low frequency delta-theta and increased beta-gamma band EEG activity. These results indicate abnormalities in the synchronization and/or efficiency of neural processes involved in memory and attention networks in schizophrenia.
The response of a neuron to sensory stimuli can only give correlational support for functional hy... more The response of a neuron to sensory stimuli can only give correlational support for functional hypotheses. To experimentally test causal function, the neural activity needs to be manipulated in a cell-type specific, as well as spatially and temporally precise way. We review recent optogenetic experiments on parvalbumin-positive cortical interneurons that link modeling studies of synchronization to experimental studies on attentional modulation of gamma oscillations in primates.
The synchrony of neurons in the extrastriate visual cortex is modulated by selective attention ev... more The synchrony of neurons in the extrastriate visual cortex is modulated by selective attention even when there are only small changes in firing rate (Fries et al., Science 291 (2001) 1560). We used Hodgkin–Huxley type models of cortical neurons to investigate the mechanism by which the degree of synchrony can be modulated independently of changes in firing rate. The synchrony of local networks of model cortical interneurons interacting through inhibitory synapses with short-term synaptic plasticity was modulated on a fast timescale by selectively activating a fraction of the interneurons. We found that facilitation enhanced the synchrony of the system whereas depression reduced it. In systems with synaptic plasticity, the synchrony modulation was accompanied by larger changes in the firing rate.
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Papers by Paul Tiesinga