Interactions between top-down and bottom-up processes in the cerebral cortex hold the key to understanding predictive coding, executive control and a gamut of other brain functions. The underlying circuit mechanism, however, remains poorly understood and represents a major challenge in neuroscience. In the present work we tackled this problem using a large-scale computational model of the primate cortex constrained by new directed and weighted connectivity data. In our model, the interplay between feedforward and feedback signaling depends on the cortical laminar structure and involves complex dynamics across multiple (intra-laminar, inter-laminar, inter-areal and whole cortex) scales. The model was tested by reproducing, and shedding insights into, a wide range of neurophysiological findings about frequency-dependent interactions between visual cortical areas: feedforward pathways are associated with enhanced gamma (30-70 Hz) oscillations, whereas feedback projections selectively modulate alpha/low beta (8-15 Hz) oscillations. We found that in order for the model to account for the experimental observations, the feedback projection needs to predominantly target infragranular layers in a target area, which leads to a proposed circuit substrate for predictive coding. The model reproduces a functional hierarchy based on frequency-dependent Granger causality analysis of inter-areal signaling, as reported in recent monkey and human experiments. Taken together, this work highlights the importance of multi-scale approaches and provides a modeling platform for studies of large-scale brain circuit dynamics and functions.

A large-scale laminar network model sheds light on frequency-dependent interactions in the primate cortex.

The effect of cellular heterogeneity on the coding properties of neural populations is studied analytically and numerically. We find that heterogeneity decreases the threshold for synchronization, and its strength is nonlinearly related to the network mean firing rate. In addition, conditions are shown under which heterogeneity optimizes network information transmission for either temporal or rate coding, with high input frequencies leading to different effects for each coding strategy. The results are shown to be robust for more realistic conditions.

Computational modeling of brain mechanisms of cognition has largely focused on the cortex, but recent experiments have shown that higher-order nuclei of the thalamus participate in major cognitive functions and are implicated in psychiatric disorders.Here, we show that a pulvino-cortical circuit model, composed of the pulvinar and two cortical areas, captures several physiological and behavioral observations related to the macaque pulvinar. Effective connections between the two cortical areas are gated by the pulvinar, allowing the pulvinar to shift the operation regime of these areas during attentional processing and working memory and resolve conflict in decision making. Furthermore, corticopulvinar projections that engage the thalamic reticular nucleus enable the pulvinar to estimate decision confidence. Finally, feedforward and feedback pulvino-cortical pathways participate in frequencydependent inter-areal interactions that modify the relative hierarchical positions of cortical areas. Overall, our model suggests that the pulvinar provides crucial contextual modulation to cortical computations associated with cognition.

Understanding reliable signal transmission represents a notable challenge for cortical systems, which display a wide range of weights of feedforward and feedback connections among heterogeneous areas. We re-examine the question of signal transmission across the cortex in a network model based on mesoscopic directed and weighted inter-areal connectivity data of the macaque cortex. Our findings reveal that, in contrast to purely feedforward propagation models, the presence of long-range excitatory feedback projections could compromise stable signal propagation. Using population rate models as well as a spiking network model, we find that effective signal propagation can be accomplished by balanced amplification across cortical areas while ensuring dynamical stability. Moreover, the activation of prefrontal cortex in our model requires the input strength to exceed a threshold, which is consistent with the ignition model of conscious processing. These findings demonstrate our model as an anatomically realistic platform for investigations of global primate cortex dynamics.

Neural activity underlying working memory is not a local phenomenon but distributed across multiple brain regions. To elucidate the circuit mechanism of such distributed activity, we developed an anatomically constrained computational model of large-scale macaque cortex. We found that mnemonic internal states may emerge from inter-areal reverberation, even in a regime where none of the isolated areas is capable of generating self-sustained activity. The mnemonic activity pattern along the cortical hierarchy indicates a transition in space, separating areas engaged in working memory and those which do not. A host of spatially distinct attractor states is found, potentially subserving various internal processes. The model yields testable predictions, including the idea of counterstream inhibitory bias, the role of prefrontal areas in controlling distributed attractors, and the resilience of distributed activity to lesions or inactivation. This work provides a theoretical framework for identifying large-scale brain mechanisms and computational principles of distributed cognitive processes.

Pyramidal cells and interneurons expressing parvalbumin (PV), somatostatin (SST), and vasoactive intestinal peptide (VIP) show cell-type-specific connectivity patterns leading to a canonical microcircuit across cortex. Experiments recording from this circuit often report counterintuitive and seemingly contradictory findings. For example, the response of SST cells in mouse V1 to top-down behavioral modulation can change its sign when the visual input changes, a phenomenon that we call response reversal. We developed a theoretical framework to explain these seemingly contradictory effects as emerging phenomena in circuits with two key features: interactions between multiple neural populations and a nonlinear neuronal input-output relationship. Furthermore, we built a cortical circuit model which reproduces counterintuitive dynamics observed in mouse V1. Our analytical calculations pinpoint connection properties critical to response reversal, and predict additional novel types of complex dynamics that could be tested in future experiments.

In this work, we study, analytically and employing Monte Carlo simulations, the influence of the competition between several activity-dependent synaptic processes, such as short-term synaptic facilitation and depression, on the maximum memory storage capacity in a neural network. In contrast to the case of synaptic depression, which drastically reduces the capacity of the network to store and retrieve "static" activity patterns, synaptic facilitation enhances the storage capacity in different contexts. In particular, we found optimal values of the relevant synaptic parameters (such as the neurotransmitter release probability or the characteristic facilitation time constant) for which the storage capacity can be maximal and similar to the one obtained with static synapses, that is, without activity-dependent processes. We conclude that depressing synapses with a certain level of facilitation allow recovering the good retrieval properties of networks with static synapses while maintaining the nonlinear characteristics of dynamic synapses, convenient for information processing and coding.