Biology subjects

Jazayeri, M.

Publications and source records attributed to Jazayeri, M..

32 records · Page 2Linked to original sources

bioRxiv2019

Engineering recurrent neural networks from task-relevant manifolds and dynamics

Many cognitive processes involve transformations of distributed representations in neural populations, creating a need for population-level models. Recurrent neural network models fulfill this need, but there are many open questions about how their connectivity gives rise to dynamics that solve a task. Here, we present a method for finding the connectivity of networks for which the dynamics are specified to solve a task in an interpretable way. We apply our method to a working memory task by synthesizing a network that implements a drift-diffusion process over a ring-shaped manifold. We also use our method to demonstrate how inputs can be used to control network dynamics for cognitive flexibility and explore the relationship between representation geometry and network capacity. Our work fits within the broader context of understanding neural computations as dynamics over relatively low-dimensional manifolds formed by correlated patterns of neurons. Author SummaryNeurons in the brain form intricate networks that can produce a vast array of activity patterns. To support goal-directed behavior, the brain must adjust the connections between neurons so that network dynamics can perform desirable computations on behaviorally relevant variables. A fundamental goal in computational neuroscience is to provide an understanding of how network connectivity aligns the dynamics in the brain to the dynamics needed to track those variables. Here, we develop a mathematical framework for creating recurrent neural network models that can address this problem. Specifically, we derive a set of linear equations that constrain the connectivity to afford a direct mapping of task-relevant dynamics onto network activity. We demonstrate the utility of this technique by creating and analyzing a set of network models that can perform a simple working memory task. We then extend the approach to show how additional constraints can furnish networks whose dynamics are controlled flexibly by external inputs. Finally, we exploit the flexibility of this technique to explore the robustness and capacity limitations of recurrent networks. This network synthesis method provides a powerful means for generating and validating hypotheses about how task-relevant computations can emerge from network dynamics.

neuroscience↗

bioRxiv2019

Distinct spatiotemporal mechanisms underlie extra-classical receptive field modulation in macaque V1 microcircuits

Complex scene perception depends upon the interaction between signals from the classical receptive field (CRF) and the extra-classical receptive field (eCRF) in primary visual cortex (V1) neurons. While much is known about V1 eCRF properties, it remains unknown how the underlying mechanisms map onto the cortical microcircuit. We probed the spatio-temporal dynamics of eCRF modulation using a reverse correlation paradigm, and found three principal eCRF mechanisms: tuned-facilitation, untuned-suppression, and tuned-suppression. Each mechanism had a distinct timing and spatial profile. Laminar analysis showed that the timing, orientation-tuning, and strength of eCRF mechanisms had distinct signatures within magnocellular and parvocellular processing streams in the V1 microcircuit. The existence of multiple eCRF mechanisms provides new insights into how V1 responds to spatial context. Modeling revealed that the differences in timing and scale of these mechanisms predicted distinct patterns of net modulation, reconciling many previous disparate physiological and psychophysical findings.

neuroscience↗

bioRxiv2019

PGRMC1 phosphorylation status and cell plasticity 1: glucose metabolism, mitochondria, and mouse xenograft tumorigenesis

Progesterone Receptor Membrane Component 1 (PGRMC1) is expressed in many cancer cells, where it is associated with detrimental patient outcomes. It contains phosphorylated tyrosines which evolutionarily preceded deuterostome gastrulation and tissue differentiation mechanisms. Here, we demonstrate that manipulating PGRMC1 phosphorylation status in MIA PaCa-2 (MP) cells imposes broad pleiotropic effects. Relative to parental cells over-expressing hemagglutinin-tagged wild-type (WT) PGRMC1-HA, cells expressing a PGRMC1-HA-S57A/S181A double mutant (DM) exhibited reduced levels of proteins involved in energy metabolism and mitochondrial function, and altered glucose metabolism suggesting modulation of the Warburg effect. This was associated with increased PI3K/Akt activity, altered cell shape, actin cytoskeleton, motility, and mitochondrial properties. An S57A/Y180F/S181A triple mutant (TM) indicated the involvement of Y180 in PI3K/Akt activation. Mutation of Y180F strongly attenuated mouse xenograft tumor growth. An accompanying paper demonstrates altered metabolism, mutation incidence, and epigenetic status in these cells, indicating that PGRMC1 phosphorylation strongly influences cancer biology.

cancer biology↗

bioRxiv2019

A neural circuit model for human sensorimotor timing

Humans can rapidly and flexibly coordinate their movements with external stimuli. Theoretical considerations suggest that this flexibility can be understood in terms of how sensory responses reconfigure the neural circuits that control movements. However, because external stimuli can occur at unexpected times, it is unclear how the corresponding sensory inputs can be used to exert flexible control over the ongoing activity of recurrent neural circuits. Here, we tackle this problem in the domain of sensorimotor timing and develop a circuit-level model that provides insight into how the brain coordinates movement times with expected and unexpected temporal events. The model consists of two interacting modules, a motor planning module that controls movement times and a sensory anticipation module that anticipates external events. Both modules harbor a reservoir of latent dynamics and their interaction forms a control system whose output is adjusted adaptively to minimize timing errors. We show that the models output matches human behavior in a range of tasks including time interval production, periodic production, synchronization/continuation, and Bayesian time interval reproduction. These results demonstrate how recurrent interactions in a simple and modular neural circuit could create the dynamics needed to control temporal aspects of behavior.

neuroscience↗

bioRxiv2019

Reinforcement regulates timing variability in thalamus

Learning reduces variability but variability can facilitate learning. This paradoxical relationship has made it challenging to tease apart sources of variability that degrade performance from those that improve it. We tackled this question in a context-dependent timing task requiring humans and monkeys to flexibly produce different time intervals with different effectors. Subjects timing variability featured two novel and context-specific sources of variability: (1) slow memory-contingent fluctuations of the mean that degraded performance, and (2) fast reinforcement-dependent regulation of variance that improved performance. Signatures of these processes were evident across populations of neurons in multiple nodes of the cortico-basal ganglia circuits. However, only in a region of the thalamus involved in flexible control of timing were the slow performance-degrading fluctuations aligned to performance-optimizing regulation of variance. These findings provide direct evidence that the nervous system makes strategic use of exploratory variance to guard against other undesirable sources of variability.

neuroscience↗

bioRxiv2018

Delay activity dynamics: task dependent time encoding and low dimensional trajectories

Our decisions often depend on multiple sensory experiences separated by time delays. The brain can remember these experiences and, simultaneously, estimate the timing between events. To understand the mechanisms underlying working memory and time encoding we analyze neural activity recorded during delays in four experiments on non-human primates. To disambiguate potential mechanisms, we propose two analyses, namely, decoding the passage of time from neural data, and computing the cumulative dimensionality of the neural trajectory over time. Time can be decoded with high precision in tasks where timing information is relevant and with lower precision when irrelevant for performing the task. Neural trajectories are always observed to be low dimensional. These constraints rule out working memory models that rely on constant, sustained activity, and neural networks with high dimensional trajectories, like reservoir networks. Instead, recurrent networks trained with backpropagation capture the time encoding properties and the dimensionality observed in the data.

neuroscience↗

bioRxiv2018

Bayesian computation through cortical latent dynamics

Statistical regularities in the environment create prior beliefs that we rely on to optimize our behavior when sensory information is uncertain. Bayesian theory formalizes how prior beliefs can be leveraged, and has had a major impact on models of perception 1, sensorimotor function 2,3, and cognition 4. However, it is not known how recurrent interactions among neurons mediate Bayesian integration. Using a time interval reproduction task in monkeys, we found that prior statistics warp the underlying structure of population activity in the frontal cortex allowing the mapping of sensory inputs to motor outputs to be biased in accordance with Bayesian inference. Analysis of neural network models performing the task revealed that this warping was mediated by a low-dimensional curved manifold, and allowed us to further probe the potential causal underpinnings of this computational strategy. These results uncover a simple and general principle whereby prior beliefs exert their influence on behavior by sculpting cortical latent dynamics.

neuroscience↗

bioRxiv2018

Entrainment and maintenance of an internal metronome in premotor cortex

To prepare timely motor actions we constantly predict future events. Regularly repeating events are often perceived as a rhythm to which we can readily synchronize our movements, just as in dancing to music. However, the neuronal mechanisms underlying the capacity to encode and maintain rhythms are not understood. We trained nonhuman primates to maintain the rhythm of a visual metronome of different tempos and then we recorded neural activity in the supplementary motor area (SMA). SMA exhibited rhythmic bursts of gamma band (30-40 Hz) reflecting an internal tempo that matched the extinguished visual metronome. Moreover, gamma amplitude increased throughout the trial and provided an estimate of total elapsed time. Notably, the timing and amplitude of gamma bursts reflected systematic timing biases and errors in the behavioral responses. Our results indicate that premotor areas use dynamic motor plans to encode a metronome for rhythms and a stopwatch for total elapsed time.

neuroscience↗

bioRxiv2018

A nonlinear updating algorithm captures suboptimal inference in the presence of signal-dependent noise

Bayesian models of behavior have advanced the idea that humans combine prior beliefs and sensory observations to minimize uncertainty. How the brain implements Bayes-optimal inference, however, remains poorly understood. Simple behavioral tasks suggest that the brain can flexibly represent and manipulate probability distributions. An alternative view is that brain relies on simple algorithms that can implement Bayes-optimal behavior only when the computational demands are low. To distinguish between these alternatives, we devised a task in which Bayes-optimal performance could not be matched by simple algorithms. We asked subjects to estimate and reproduce a time interval by combining prior information with one or two sequential measurements. In the domain of time, measurement noise increases with duration. This property makes the integration of multiple measurements beyond the reach of simple algorithms. We found that subjects were able to update their estimates using the second measurement but their performance was suboptimal, suggesting that they were unable to update full probability distributions. Instead, subjects behavior was consistent with an algorithm that predicts upcoming sensory signals, and applies a nonlinear function to errors in prediction to update estimates. These results indicate that inference strategies humans deploy may deviate from Bayes-optimal integration when the computational demands are high.

neuroscience↗

bioRxiv2018

Flexible sensorimotor computations through rapid reconfiguration of cortical dynamics

Sensorimotor computations can be flexibly adjusted according to internal states and contextual inputs. The mechanisms supporting this flexibility are not understood. Here, we tested the utility of a dynamical system perspective to approach this problem. In a dynamical system whose state is determined by interactions among neurons, computations can be rapidly and flexibly reconfigured by controlling the system s inputs and initial conditions. To investigate whether the brain employs such control strategies, we recorded from the dorsomedial frontal cortex (DMFC) of monkeys trained to measure time intervals and subsequently produce timed motor responses according to multiple context-specific stimulus-response rules. Analysis of the geometry of neural states revealed a control mechanism that relied on the system s inputs and initial conditions. A tonic input specified by the behavioral context adjusted firing rates throughout each trial, while the dynamics in the measurement epoch allowed the system to establish initial conditions for the ensuing production epoch. This initial condition in turn set the speed of neural dynamics in the production epoch allowing the animal to aim for the target interval. These results provide evidence that the language of dynamical systems can be used to parsimoniously link brain activity to sensorimotor computations.

neuroscience↗

bioRxiv2017

An integral role for timing in interception

Timing is critical for myriad behaviors in dynamic environments. For example, to intercept an object, the brain must compute a reliable estimate of time-to-contact (TTC). Prior work suggests that humans compute TTC using kinematic information such as distance and speed without explicitly relying on temporal cues, just as one would do in a physics classroom using kinematic equations. Considering the inherent uncertainty associated with estimates of speed and distance and the ability of human brain to combine different sources of information, we asked whether humans additionally rely on temporal cues. We found that humans actively integrate speed information with both explicit and implicit timing cues. Analysis of behavior in relation to a Bayesian model revealed that the additional temporal information helps subjects optimize their performance in the presence of measurement uncertainty. These findings suggest that brains timing mechanisms are actively engaged while interacting with dynamic stimuli.

animal behavior and cognition↗

bioRxiv2017

Flexible control of speed of cortical dynamics

Musicians can perform at different tempos, speakers can control the cadence of their speech, and children can flexibly vary their temporal expectations of events. To understand the neural basis of such flexible timing, we recorded from the medial frontal cortex of primates trained to produce different time intervals with different effectors. The activity of neurons was heterogeneous, nonlinear and complex. However, responses were unified under a remarkable form of invariance: firing rate profiles were temporally stretched for longer intervals and compressed for short ones. At the network level, this phenomenon was evident by flexible changes in the speed with which the population activity traced an invariant trajectory. To identify the origin of speed control, we recorded from both downstream caudate neurons and thalamic neurons projecting to the medial frontal cortex. Speed adjustments were a prominent feature in the caudate but not in the thalamus suggesting that this phenomenon originates within cortical networks. To understand the underlying mechanisms, we created recurrent neural network models at different levels of complexity that could explain flexible timing with speed control. Analysis of the models revealed that the key to flexible speed control was the action of an external input upon the nonlinearities of individual neurons whose recurrent interactions set the networks relaxation dynamics. These findings demonstrate a simple and general mechanism for conferring temporal flexibility upon sensorimotor and cognitive functions.

neuroscience↗

bioRxiv2017

A cerebellar mechanism for learning prior distributions of time intervals

Knowledge about the statistical regularities of the world is essential for cognitive and sensorimotor function. In the domain of timing, prior statistics are crucial for optimal prediction, adaptation and planning. Where and how the nervous system encodes temporal statistics, however, is not known. Deriving from physiological and anatomical evidence for cerebellar learning, we develop a computational model that demonstrates how the cerebellum could learn prior distributions of time intervals and support Bayesian temporal estimation. The model shows that salient features observed in human Bayesian time interval estimates can be readily captured by learning in the cerebellar cortex and circuit level computations in the cerebellar deep nuclei.

neuroscience↗

bioRxiv2017

Late Bayesian inference in sensorimotor behavior

Sensorimotor skills rely on performing noisy sensorimotor computations on noisy sensory measurements. Bayesian models suggest that humans compensate for measurement noise and reduce behavioral variability by biasing perception toward prior expectations. Whether the same holds for noise in sensorimotor computations is not known. Testing human subjects in tasks with different levels of sensorimotor complexity, we found a similar bias-variance tradeoff associated with increased sensorimotor noise. This result was accurately captured by a model which implements Bayesian inference after - not before - sensorimotor transformation. These results indicate that humans perform \"late inference\" downstream of sensorimotor computations rather than, or in addition to, \"early inference\" in the perceptual domain. The brain thus possesses internal models of noise in both sensory measurements and sensorimotor computations.

animal behavior and cognition↗