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Timescales of learning in prefrontal cortex

Abstract

The lateral prefrontal cortex (PFC) in humans and other primates is critical for immediate, goal-directed behaviour and working memory, which are classically considered distinct from the cognitive and neural circuits that support long-term learning and memory. Over the past few years, a reconsideration of this textbook perspective has emerged, in that different timescales of memory-guided behaviour are in constant interaction during the pursuit of immediate goals. Here, we will first detail how neural activity related to the shortest timescales of goal-directed behaviour (which requires maintenance of current states and goals in working memory) is sculpted by long-term knowledge and learning — that is, how the past informs present behaviour. Then, we will outline how learning across different timescales (from seconds to years) drives plasticity in the primate lateral PFC, from single neuron firing rates to mesoscale neuroimaging activity patterns. Finally, we will review how, over days and months of learning, dense local and long-range connectivity patterns in PFC facilitate longer-lasting changes in population activity by changing synaptic weights and recruiting additional neural resources to inform future behaviour. Our Review sheds light on how the machinery of plasticity in PFC circuits facilitates the integration of learned experiences across time to best guide adaptive behaviour.

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Fig. 1: Connections between short-term and long-term memory systems and timescales.
Fig. 2: Timescales of neural activity in lateral prefrontal cortex across multiple levels of organization.
Fig. 3: Physiological characteristics that make the lateral prefrontal cortex an ideal hub for learning processes.
Fig. 4: Synaptic and circuit mechanisms of long-term learning and working memory interactions.

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Acknowledgements

Research reported in this paper was supported by the National Institutes of Health under award numbers R01 EY017077 and R01 MH116675. The authors thank C. Suell for technical assistance.

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J.A.M. and C.C. conceived and wrote the manuscript.

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Glossary

Cognitive transfer

How well learning in a specific cognitive task or condition facilitates any potential benefit on a related cognitive task (‘near transfer’) or unrelated one (‘far transfer’).

Delayed saccade paradigm

A task (here, relating to working memory) requiring the subject to hold a spatial location in mind and make an eye movement to the same (saccade) or opposite (anti-saccade) location after a delay period.

Memory capacity

The number of specific items or associations that can be accurately maintained over a short (working memory) or long (long-term memory) delay. Stark differences are observed in the capacity limits of working memory (~4–7 items depending on the context) compared with long-term memory systems.

Recurrent networks

Circuits whose output is fed back into the network, thus allowing activity to be maintained even after the original stimulus is no longer present.

Representational dimensionality

For the population activity (or activity space) of a group of neurons, the number of axes that can capture most of the variance of the points, often indexed by the number of classifications that can be obtained between points via linear readouts (see ref. 129).

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Miller, J.A., Constantinidis, C. Timescales of learning in prefrontal cortex. Nat. Rev. Neurosci. 25, 597–610 (2024). https://doi.org/10.1038/s41583-024-00836-8

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