Prediction of neural activity in connectome-constrained recurrent networks.

We develop a theory of connectome-constrained neural networks in which a "student" network is trained to reproduce the activity of a ground-truth "teacher," representing a neural system for which a connectome is available. Unlike standard paradigms with unconstrained connectivity, here the two networks have the same connectivity but different biophysical parameters, reflecting uncertainty in neuronal and synaptic properties. We find that a connectome is often insufficient to constrain the dynamics of networks that perform a specific task, illustrating the difficulty of inferring function from connectivity alone. However, recordings from a small subset of neurons can remove this degeneracy, producing dynamics in the student that agree with the teacher. Our theory can also prioritize which neurons to record from to most efficiently predict unmeasured network activity. Our analysis shows that the solution spaces of connectome-constrained and unconstrained models are qualitatively different and provides a framework to determine when such models yield consistent dynamics.

Emergent neural dynamics and geometry for generalization in a transitive inference task.

Relational cognition-the ability to infer relationships that generalize to novel combinations of objects-is fundamental to human and animal intelligence. Despite this importance, it remains unclear how relational cognition is implemented in the brain due in part to a lack of hypotheses and predictions at the levels of collective neural activity and behavior. Here we discovered, analyzed, and experimentally tested neural networks (NNs) that perform transitive inference (TI), a classic relational task (if A > B and B > C, then A > C). We found NNs that (i) generalized perfectly, despite lacking overt transitive structure prior to training, (ii) generalized when the task required working memory (WM), a capacity thought to be essential to inference in the brain, (iii) emergently expressed behaviors long observed in living subjects, in addition to a novel order-dependent behavior, and (iv) expressed different task solutions yielding alternative behavioral and neural predictions. Further, in a large-scale experiment, we found that human subjects performing WM-based TI showed behavior inconsistent with a class of NNs that characteristically expressed an intuitive task solution. These findings provide neural insights into a classical relational ability, with wider implications for how the brain realizes relational cognition.

Structure of activity in multiregion recurrent neural networks.

Neural circuits are composed of multiple regions, each with rich dynamics and engaging in communication with other regions. The combination of local, within-region dynamics and global, network-level dynamics is thought to provide computational flexibility. However, the nature of such multiregion dynamics and the underlying synaptic connectivity patterns remain poorly understood. Here, we study the dynamics of recurrent neural networks with multiple interconnected regions. Within each region, neurons have a combination of random and structured recurrent connections. Motivated by experimental evidence of communication subspaces between cortical areas, these networks have low-rank connectivity between regions, enabling selective routing of activity. These networks exhibit two interacting forms of dynamics: high-dimensional fluctuations within regions and low-dimensional signal transmission between regions. To characterize this interaction, we develop a dynamical mean-field theory to analyze such networks in the limit where each region contains infinitely many neurons, with cross-region currents as key order parameters. Regions can act as both generators and transmitters of activity, roles that we show are in conflict. Specifically, taming the complexity of activity within a region is necessary for it to route signals to and from other regions. Unlike previous models of routing in neural circuits, which suppressed the activities of neuronal groups to control signal flow, routing in our model is achieved by exciting different high-dimensional activity patterns through a combination of connectivity structure and nonlinear recurrent dynamics. This theory provides insight into the interpretation of both multiregion neural data and trained neural networks.

Amplified cortical neural responses as animals learn to use novel activity patterns.

Cerebral cortex supports representations of the world in patterns of neural activity, used by the brain to make decisions and guide behavior. Past work has found diverse, or limited, changes in the primary sensory cortex in response to learning, suggesting that the key computations might occur in downstream regions. Alternatively, sensory cortical changes may be central to learning. We studied cortical learning by using controlled inputs we insert: we trained mice to recognize entirely novel, non-sensory patterns of cortical activity in the primary visual cortex (V1) created by optogenetic stimulation. As animals learned to use these novel patterns, we found that their detection abilities improved by an order of magnitude or more. The behavioral change was accompanied by large increases in V1 neural responses to fixed optogenetic input. Neural response amplification to novel optogenetic inputs had little effect on existing visual sensory responses. A recurrent cortical model shows that this amplification can be achieved by a small mean shift in recurrent network synaptic strength. Amplification would seem to be desirable to improve decision-making in a detection task; therefore, these results suggest that adult recurrent cortical plasticity plays a significant role in improving behavioral performance during learning.

Parametric control of flexible timing through low-dimensional neural manifolds.

Biological brains possess an unparalleled ability to adapt behavioral responses to changing stimuli and environments. How neural processes enable this capacity is a fundamental open question. Previous works have identified two candidate mechanisms: a low-dimensional organization of neural activity and a modulation by contextual inputs. We hypothesized that combining the two might facilitate generalization and adaptation in complex tasks. We tested this hypothesis in flexible timing tasks where dynamics play a key role. Examining trained recurrent neural networks, we found that confining the dynamics to a low-dimensional subspace allowed tonic inputs to parametrically control the overall input-output transform, enabling generalization to novel inputs and adaptation to changing conditions. Reverse-engineering and theoretical analyses demonstrated that this parametric control relies on a mechanism where tonic inputs modulate the dynamics along non-linear manifolds while preserving their geometry. Comparisons with data from behaving monkeys confirmed the behavioral and neural signatures of this mechanism.

The role of population structure in computations through neural dynamics.

Neural computations are currently investigated using two separate approaches: sorting neurons into functional subpopulations or examining the low-dimensional dynamics of collective activity. Whether and how these two aspects interact to shape computations is currently unclear. Using a novel approach to extract computational mechanisms from networks trained on neuroscience tasks, here we show that the dimensionality of the dynamics and subpopulation structure play fundamentally complementary roles. Although various tasks can be implemented by increasing the dimensionality in networks with fully random population structure, flexible input-output mappings instead require a non-random population structure that can be described in terms of multiple subpopulations. Our analyses revealed that such a subpopulation structure enables flexible computations through a mechanism based on gain-controlled modulations that flexibly shape the collective dynamics. Our results lead to task-specific predictions for the structure of neural selectivity, for inactivation experiments and for the implication of different neurons in multi-tasking.

Dopamine firing plays a dual role in coding reward prediction errors and signaling motivation in a working memory task.

Little is known about how dopamine (DA) neuron firing rates behave in cognitively demanding decision-making tasks. Here, we investigated midbrain DA activity in monkeys performing a discrimination task in which the animal had to use working memory (WM) to report which of two sequentially applied vibrotactile stimuli had the higher frequency. We found that perception was altered by an internal bias, likely generated by deterioration of the representation of the first frequency during the WM period. This bias greatly controlled the DA phasic response during the two stimulation periods, confirming that DA reward prediction errors reflected stimulus perception. In contrast, tonic dopamine activity during WM was not affected by the bias and did not encode the stored frequency. More interestingly, both delay-period activity and phasic responses before the second stimulus negatively correlated with reaction times of the animals after the trial start cue and thus represented motivated behavior on a trial-by-trial basis. During WM, this motivation signal underwent a ramp-like increase. At the same time, motivation positively correlated with accuracy, especially in difficult trials, probably by decreasing the effect of the bias. Overall, our results indicate that DA activity, in addition to encoding reward prediction errors, could at the same time be involved in motivation and WM. In particular, the ramping activity during the delay period suggests a possible DA role in stabilizing sustained cortical activity, hypothetically by increasing the gain communicated to prefrontal neurons in a motivation-dependent way.

Shaping Dynamics With Multiple Populations in Low-Rank Recurrent Networks.

An emerging paradigm proposes that neural computations can be understood at the level of dynamic systems that govern low-dimensional trajectories of collective neural activity. How the connectivity structure of a network determines the emergent dynamical system, however, remains to be clarified. Here we consider a novel class of models, gaussian-mixture, low-rank recurrent networks in which the rank of the connectivity matrix and the number of statistically defined populations are independent hyperparameters. We show that the resulting collective dynamics form a dynamical system, where the rank sets the dimensionality and the population structure shapes the dynamics. In particular, the collective dynamics can be described in terms of a simplified effective circuit of interacting latent variables. While having a single global population strongly restricts the possible dynamics, we demonstrate that if the number of populations is large enough, a rank R network can approximate any R-dimensional dynamical system.

Contrasting the effects of adaptation and synaptic filtering on the timescales of dynamics in recurrent networks.

Neural activity in awake behaving animals exhibits a vast range of timescales that can be several fold larger than the membrane time constant of individual neurons. Two types of mechanisms have been proposed to explain this conundrum. One possibility is that large timescales are generated by a network mechanism based on positive feedback, but this hypothesis requires fine-tuning of the strength or structure of the synaptic connections. A second possibility is that large timescales in the neural dynamics are inherited from large timescales of underlying biophysical processes, two prominent candidates being intrinsic adaptive ionic currents and synaptic transmission. How the timescales of adaptation or synaptic transmission influence the timescale of the network dynamics has however not been fully explored. To address this question, here we analyze large networks of randomly connected excitatory and inhibitory units with additional degrees of freedom that correspond to adaptation or synaptic filtering. We determine the fixed points of the systems, their stability to perturbations and the corresponding dynamical timescales. Furthermore, we apply dynamical mean field theory to study the temporal statistics of the activity in the fluctuating regime, and examine how the adaptation and synaptic timescales transfer from individual units to the whole population. Our overarching finding is that synaptic filtering and adaptation in single neurons have very different effects at the network level. Unexpectedly, the macroscopic network dynamics do not inherit the large timescale present in adaptive currents. In contrast, the timescales of network activity increase proportionally to the time constant of the synaptic filter. Altogether, our study demonstrates that the timescales of different biophysical processes have different effects on the network level, so that the slow processes within individual neurons do not necessarily induce slow activity in large recurrent neural networks.

Coding of time-dependent stimuli in homogeneous and heterogeneous neural populations.

We compare the information transmission of a time-dependent signal by two types of uncoupled neuron populations that differ in their sources of variability: i) a homogeneous population whose units receive independent noise and ii) a deterministic heterogeneous population, where each unit exhibits a different baseline firing rate ('disorder'). Our criterion for making both sources of variability quantitatively comparable is that the interspike-interval distributions are identical for both systems. Numerical simulations using leaky integrate-and-fire neurons unveil that a non-zero amount of both noise or disorder maximizes the encoding efficiency of the homogeneous and heterogeneous system, respectively, as a particular case of suprathreshold stochastic resonance. Our findings thus illustrate that heterogeneity can render similarly profitable effects for neuronal populations as dynamic noise. The optimal noise/disorder depends on the system size and the properties of the stimulus such as its intensity or cutoff frequency. We find that weak stimuli are better encoded by a noiseless heterogeneous population, whereas for strong stimuli a homogeneous population outperforms an equivalent heterogeneous system up to a moderate noise level. Furthermore, we derive analytical expressions of the coherence function for the cases of very strong noise and of vanishing intrinsic noise or heterogeneity, which predict the existence of an optimal noise intensity. Our results show that, depending on the type of signal, noise as well as heterogeneity can enhance the encoding performance of neuronal populations.