Adaptive erasure of spurious sequences in sensory cortical circuits.

Sequential activity reflecting previously experienced temporal sequences is considered a hallmark of learning across cortical areas. However, it is unknown how cortical circuits avoid the converse problem: producing spurious sequences that are not reflecting sequences in their inputs. We develop methods to quantify and study sequentiality in neural responses. We show that recurrent circuit responses generally include spurious sequences, which are specifically prevented in circuits that obey two widely known features of cortical microcircuit organization: Dale's law and Hebbian connectivity. In particular, spike-timing-dependent plasticity in excitation-inhibition networks leads to an adaptive erasure of spurious sequences. We tested our theory in multielectrode recordings from the visual cortex of awake ferrets. Although responses to natural stimuli were largely non-sequential, responses to artificial stimuli initially included spurious sequences, which diminished over extended exposure. These results reveal an unexpected role for Hebbian experience-dependent plasticity and Dale's law in sensory cortical circuits.

Characterizing the Short-Term Habituation of Event-Related Evoked Potentials.

Fast-rising sensory events evoke a series of functionally heterogeneous event-related potentials (ERPs). Stimulus repetition at 1 Hz induces a strong habituation of the largest ERP responses, the vertex waves (VWs). VWs are elicited by stimuli regardless of their modality, provided that they are salient and behaviorally relevant. In contrast, the effect of stimulus repetition on the earlier sensory components of ERPs has been less explored, and the few existing results are inconsistent. To characterize how the different ERP waves habituate over time, we recorded the responses elicited by 60 identical somatosensory stimuli (activating either non-nociceptive Aß or nociceptive Aδ afferents), delivered at 1 Hz to healthy human participants. We show that the well-described spatiotemporal sequence of lateralized and vertex ERP components elicited by the first stimulus of the series is largely preserved in the smaller-amplitude, habituated response elicited by the last stimuli of the series. We also found that the earlier lateralized sensory wave habituates across the 60 trials following the same decay function of the VWs: this decay function is characterized by a large drop at the first stimulus repetition followed by smaller decreases at subsequent repetitions. Interestingly, the same decay functions described the habituation of ERPs elicited by repeated non-nociceptive and nociceptive stimuli. This study provides a neurophysiological characterization of the effect of prolonged and repeated stimulation on the main components of somatosensory ERPs. It also demonstrates that both lateralized waves and VWs are obligatory components of ERPs elicited by non-nociceptive and nociceptive stimuli.

Hierarchy of transcriptomic specialization across human cortex captured by structural neuroimaging topography.

Hierarchy provides a unifying principle for the macroscale organization of anatomical and functional properties across primate cortex, yet microscale bases of specialization across human cortex are poorly understood. Anatomical hierarchy is conventionally informed by invasive tract-tracing measurements, creating a need for a principled proxy measure in humans. Moreover, cortex exhibits marked interareal variation in gene expression, yet organizing principles of cortical transcription remain unclear. We hypothesized that specialization of cortical microcircuitry involves hierarchical gradients of gene expression. We found that a noninvasive neuroimaging measure-MRI-derived T1-weighted/T2-weighted (T1w/T2w) mapping-reliably indexes anatomical hierarchy, and it captures the dominant pattern of transcriptional variation across human cortex. We found hierarchical gradients in expression profiles of genes related to microcircuit function, consistent with monkey microanatomy, and implicated in neuropsychiatric disorders. Our findings identify a hierarchical axis linking cortical transcription and anatomy, along which gradients of microscale properties may contribute to the macroscale specialization of cortical function.

Stable population coding for working memory coexists with heterogeneous neural dynamics in prefrontal cortex.

Working memory (WM) is a cognitive function for temporary maintenance and manipulation of information, which requires conversion of stimulus-driven signals into internal representations that are maintained across seconds-long mnemonic delays. Within primate prefrontal cortex (PFC), a critical node of the brain's WM network, neurons show stimulus-selective persistent activity during WM, but many of them exhibit strong temporal dynamics and heterogeneity, raising the questions of whether, and how, neuronal populations in PFC maintain stable mnemonic representations of stimuli during WM. Here we show that despite complex and heterogeneous temporal dynamics in single-neuron activity, PFC activity is endowed with a population-level coding of the mnemonic stimulus that is stable and robust throughout WM maintenance. We applied population-level analyses to hundreds of recorded single neurons from lateral PFC of monkeys performing two seminal tasks that demand parametric WM: oculomotor delayed response and vibrotactile delayed discrimination. We found that the high-dimensional state space of PFC population activity contains a low-dimensional subspace in which stimulus representations are stable across time during the cue and delay epochs, enabling robust and generalizable decoding compared with time-optimized subspaces. To explore potential mechanisms, we applied these same population-level analyses to theoretical neural circuit models of WM activity. Three previously proposed models failed to capture the key population-level features observed empirically. We propose network connectivity properties, implemented in a linear network model, which can underlie these features. This work uncovers stable population-level WM representations in PFC, despite strong temporal neural dynamics, thereby providing insights into neural circuit mechanisms supporting WM.

A hierarchy of intrinsic timescales across primate cortex.

Specialization and hierarchy are organizing principles for primate cortex, yet there is little direct evidence for how cortical areas are specialized in the temporal domain. We measured timescales of intrinsic fluctuations in spiking activity across areas and found a hierarchical ordering, with sensory and prefrontal areas exhibiting shorter and longer timescales, respectively. On the basis of our findings, we suggest that intrinsic timescales reflect areal specialization for task-relevant computations over multiple temporal ranges.

The interplay of plasticity and adaptation in neural circuits: a generative model.

Multiple neural and synaptic phenomena take place in the brain. They operate over a broad range of timescales, and the consequences of their interplay are still unclear. In this work, I study a computational model of a recurrent neural network in which two dynamic processes take place: sensory adaptation and synaptic plasticity. Both phenomena are ubiquitous in the brain, but their dynamic interplay has not been investigated. I show that when both processes are included, the neural circuit is able to perform a specific computation: it becomes a generative model for certain distributions of input stimuli. The neural circuit is able to generate spontaneous patterns of activity that reproduce exactly the probability distribution of experienced stimuli. In particular, the landscape of the phase space includes a large number of stable states (attractors) that sample precisely this prior distribution. This work demonstrates that the interplay between distinct dynamical processes gives rise to useful computation, and proposes a framework in which neural circuit models for Bayesian inference may be developed in the future.

A diversity of localized timescales in network activity.

Neurons show diverse timescales, so that different parts of a network respond with disparate temporal dynamics. Such diversity is observed both when comparing timescales across brain areas and among cells within local populations; the underlying circuit mechanism remains unknown. We examine conditions under which spatially local connectivity can produce such diverse temporal behavior. In a linear network, timescales are segregated if the eigenvectors of the connectivity matrix are localized to different parts of the network. We develop a framework to predict the shapes of localized eigenvectors. Notably, local connectivity alone is insufficient for separate timescales. However, localization of timescales can be realized by heterogeneity in the connectivity profile, and we demonstrate two classes of network architecture that allow such localization. Our results suggest a framework to relate structural heterogeneity to functional diversity and, beyond neural dynamics, are generally applicable to the relationship between structure and dynamics in biological networks. DOI: http://dx.doi.org/10.7554/eLife.01239.001.

Decorrelation by recurrent inhibition in heterogeneous neural circuits.

The activity of neurons is correlated, and this correlation affects how the brain processes information. We study the neural circuit mechanisms of correlations by analyzing a network model characterized by strong and heterogeneous interactions: excitatory input drives the fluctuations of neural activity, which are counterbalanced by inhibitory feedback. In particular, excitatory input tends to correlate neurons, while inhibitory feedback reduces correlations. We demonstrate that heterogeneity of synaptic connections is necessary for this inhibition of correlations. We calculate statistical averages over the disordered synaptic interactions and apply our findings to both a simple linear model and a more realistic spiking network model. We find that correlations at zero time lag are positive and of magnitude K(-1/2) where K is the number of connections to a neuron. Correlations at longer timescales are of smaller magnitude, of order K(-1), implying that inhibition of correlations occurs quickly, on a timescale of K(-1/2). The small magnitude of correlations agrees qualitatively with physiological measurements in the cerebral cortex and basal ganglia. The model could be used to study correlations in brain regions dominated by recurrent inhibition, such as the striatum and globus pallidus.

On the equivalence of Hopfield networks and Boltzmann Machines.

A specific type of neural networks, the Restricted Boltzmann Machines (RBM), are implemented for classification and feature detection in machine learning. They are characterized by separate layers of visible and hidden units, which are able to learn efficiently a generative model of the observed data. We study a "hybrid" version of RBMs, in which hidden units are analog and visible units are binary, and we show that thermodynamics of visible units are equivalent to those of a Hopfield network, in which the N visible units are the neurons and the P hidden units are the learned patterns. We apply the method of stochastic stability to derive the thermodynamics of the model, by considering a formal extension of this technique to the case of multiple sets of stored patterns, which may act as a benchmark for the study of correlated sets. Our results imply that simulating the dynamics of a Hopfield network, requiring the update of N neurons and the storage of N(N-1)/2 synapses, can be accomplished by a hybrid Boltzmann Machine, requiring the update of N+P neurons but the storage of only NP synapses. In addition, the well known glass transition of the Hopfield network has a counterpart in the Boltzmann Machine: it corresponds to an optimum criterion for selecting the relative sizes of the hidden and visible layers, resolving the trade-off between flexibility and generality of the model. The low storage phase of the Hopfield model corresponds to few hidden units and hence a overly constrained RBM, while the spin-glass phase (too many hidden units) corresponds to unconstrained RBM prone to overfitting of the observed data.

A reservoir of time constants for memory traces in cortical neurons.

According to reinforcement learning theory of decision making, reward expectation is computed by integrating past rewards with a fixed timescale. In contrast, we found that a wide range of time constants is available across cortical neurons recorded from monkeys performing a competitive game task. By recognizing that reward modulates neural activity multiplicatively, we found that one or two time constants of reward memory can be extracted for each neuron in prefrontal, cingulate and parietal cortex. These timescales ranged from hundreds of milliseconds to tens of seconds, according to a power law distribution, which is consistent across areas and reproduced by a 'reservoir' neural network model. These neuronal memory timescales were weakly, but significantly, correlated with those of monkey's decisions. Our findings suggest a flexible memory system in which neural subpopulations with distinct sets of long or short memory timescales may be selectively deployed according to the task demands.

Impact of spatiotemporally correlated images on the structure of memory.

How does experience modify what we store in long-term memory? Is it an effect of unattended experience or does it require supervision? What role is played by temporal correlations in the input stream? We present a plastic recurrent network in which memory of faces is initially embedded and then, in the absence of supervision, the presentation of temporally correlated faces drastically changes long-term memory. We model and interpret the results of recent experiments and provide predictions for future testing. The stimuli are frames of a morphing film, interpolating between two memorized faces: If the temporal order of presentation of the frame stimuli is random, then the structure of memory is basically unaffected by synaptic plasticity (memory preservation). If the temporal order is sequential, then all image frames are classified as the same memory (memory collapse). The empirical findings are reproduced in the simulated dynamics of the network, in which the evolution of neural activity is conditioned by the associated synaptic plasticity (learning). The results are captured by theoretical analysis, which leads to predictions concerning the critical parameters of the stimuli; a third phase is identified in which memory is erased (forgetting).

Multi-item working memory--a behavioral study.

Macaque monkeys were trained to recognize the repetition of one of the images already seen in a sequence of random length. On average, performance decreased with sequence length. However, this was due to a complex combination of factors, as follows: performance was found to decrease with the separation in the sequence of the test (repetition image) from the cue (its first appearance in the sequence), for trials with sequences of fixed length. In contrast, performance improved as a function of sequence length, for equal cue-test separations. Reaction times followed a complementary trend: they increased with cue-test separation and decreased with sequence length. The frequency of false positives (FPs) indicates that images are not always removed from working memory between successive trials, and that the monkeys rarely confuse different images. The probability of miss errors depends on number of intervening stimulus presentations, while FPs depend on elapsed time. A simple two-state stochastic model of multi-item working memory is proposed that guides the account for the main effects of performance and false positives, as well as their interaction. In the model, images enter WM when they are presented, or by spontaneous jump-in. Misses are due to spontaneous jump-out of images previously seen.