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  • Perspective
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The generative grammar of the brain: a critique of internally generated representations

Nature Reviews Neuroscience volume 25, pages 60–75 (2024)Cite this article

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Abstract

The past decade of progress in neurobiology has uncovered important organizational principles for network preconfiguration and neuronal selection that suggest a generative grammar exists in the brain. In this Perspective, I discuss the competence of the hippocampal neural network to generically express temporally compressed sequences of neuronal firing that represent novel experiences, which is envisioned as a form of generative neural syntax supporting a neurobiological perspective on brain function. I compare this neural competence with the hippocampal network performance that represents specific experiences with higher fidelity after new learning during replay, which is envisioned as a form of neural semantic that supports a complementary neuropsychological perspective. I also demonstrate how the syntax of network competence emerges a priori during early postnatal life and is followed by the later development of network performance that enables rapid encoding and memory consolidation. Thus, I propose that this generative grammar of the brain is essential for internally generated representations, which are crucial for the cognitive processes underlying learning and memory, prospection, and inference, which ultimately underlie our reason and representation of the world.

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Fig. 1: Instructional-to-selectionist theoretical shift in immunology and neurobiology.
Fig. 2: Unified hierarchical generative grammar and coding across genetics, neurobiology and linguistics.
Fig. 3: Neural competence and neural performance in neuronal ensemble representations of the external world.
Fig. 4: Internally generated representation forms.

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Acknowledgements

The author thanks all the members of the Dragoi lab for their contribution to the primary research work that led to some of the findings included in this opinion. G.D. discloses support for the research of this work from the NIH grants R01NS104917, R01MH121372 and R35NS132342. The funding sources had no involvement in the content of this manuscript.

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  1. Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA

    George Dragoi

  2. Department of Neuroscience, Yale University School of Medicine, New Haven, CT, USA

    George Dragoi

  3. Wu Tsai Institute, Yale University, New Haven, CT, USA

    George Dragoi

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Glossary

Backbone

Robust pre-existing organization of neuronal (sequential) activity, on the framework of which new information is encoded.

Blank slate

An original state of neural networks (or the mind) believed to be devoid of any functional organization, which will be configured only because of direct experience. Also known as tabula rasa.

Cell assemblies

Groups of interconnected neurons repeatedly co-activated within short timeframes (of a few tens of milliseconds) thought to underlie an associative representational code.

Generative grammar

A set of organizational rules that can explain current patterns and predict the expression of future new patterns from (re)combination of existing elements.

Morpheme

The smallest unit of semantic meaning within a word.

Multi-neuronal primitive sequence

Overall probabilistic organization of neurons into one generic or backbone neuronal sequence characteristic to a network that is mostly preserved across experiences.

Network preconfiguration

A state of neural network functional organization often related to, constraining or predictive of future patterns of network activation; in contrast to a blank slate.

Neural code

Patterns of neuronal and neuronal ensemble activity believed to encode and represent specific stimuli or states, which could be decoded by a downstream entity.

Neural grammar

A set of hierarchical organization rules for the generation of current and future novel neural patterns from (re)combination of pre-existing cellular and circuit neural motifs.

Neural semantic

A representational feature gained by specific neural patterns for the depiction of specific objects or events from the external world, often interpreted as a neural code.

Neural syntax

A set of rules for the combinatorial hierarchical organization of the neuronal activity of individual neurons into cell assemblies and short circuit motifs towards extended neural sequences.

Neurobiological

A level of explanation of neuronal ensemble activity with a focus on the rules for the combinatorial organization of neural activity (neural syntax).

Neuro-codons

Recurring short sequence motifs of 3 ± 1 neurons, also called neuronal tuplets, that are further multiplexed into extended neuronal sequences; part of neural syntax.

Neuronal selection

A theory in neuroscience postulating that patterns of neural activity are selected from a larger pre-existing repertoire, rather than exclusively created de novo, during a novel experience.

Neuropsychological

A level of explanation of neuronal ensemble activity with a focus on the representational value of neuronal activity as a form of neural semantic or code.

Phoneme

The smallest perceptually distinct unit of sound that composes a word (and can separate it from another word), often represented by one letter or a small cluster of letters.

Place cells

A neuron type functionally tuned primarily to the position of an animal in external space; most abundant in the hippocampus.

Plasticity

The property of neural activity of being modified within normal ranges owing to a certain experience, lasting for a variable amount of time after the experience has ended.

Plasticity in replay

Recent experience-related changes in sequence replay that increase its fidelity, incidence or extent in depicting the experience compared with preplay (plasticity in replay over preplay). Considered a form of gain in network performance, not a new competence.

Preplay

Significant correlations between sequential patterns of neuronal ensemble activity during a novel (spatial) experience and those expressed during the preceding sleep or rest, prospective in nature. Demonstrates that preconfigured network patterns contribute to encoding of future novel experiences.

Pre-representations

Decoded neuronal ensemble activities during sleep and rest that resemble virtual trajectories through subsequently explored novel spaces.

Universal biological grammar

A set of rules for the hierarchical organization of elements into increasingly complex assemblies with added meaning, common across different aspects of biology.

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Dragoi, G. The generative grammar of the brain: a critique of internally generated representations. Nat. Rev. Neurosci. 25, 60–75 (2024). https://doi.org/10.1038/s41583-023-00763-0

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