Here, we propose that extra-synaptic diffusion of local neuromodulators such as neuropeptides may afford an effective mode of backpropagation lying within the bounds of biological plausibility.

Such models range broadly in both complexity and biological plausibility.

One frequently wishes to learn a range of similar tasks as efficiently as possible, re-using knowledge across tasks. In artificial neural networks, this is typically accomplished by conditioning a network upon task context by injecting context as input. Brains have a different strategy: the parameters themselves are modulated as a function of various neuromodulators such as serotonin. Here, we take inspiration from neuromodulation and propose to learn weights which are smoothly parameterized functions of task context variables. Rather than optimize a weight vector, i.e. a single point in weight space, we optimize a smooth manifold in weight space with a predefined topology. To accomplish this, we derive a formal treatment of optimization of manifolds as the minimization of a loss functional subject to a constraint on volumetric movement, analogous to gradient descent. During inference, conditioning selects a single point on this manifold which serves as the effective weight matrix for a particular sub-task. This strategy for conditioning has two main advantages. First, the topology of the manifold (whether a line, circle, or torus) is a convenient lever for inductive biases about the relationship between tasks. Second, learning in one state smoothly affects the entire manifold, encouraging generalization across states. To verify this, we train manifolds with several topologies, including straight lines in weight space (for conditioning on e.g. noise level in input data) and ellipses (for rotated images). Despite their simplicity, these parameterizations outperform conditioning identical networks by input concatenation and better generalize to out-of-distribution samples. These results suggest that modulating weights over low-dimensional manifolds offers a principled and effective alternative to traditional conditioning.

Deep brain stimulation (DBS) is an established intervention for Parkinson's disease (PD), but conventional open-loop systems lack adaptability, are energy-inefficient due to continuous stimulation, and provide limited personalization to individual neural dynamics. Adaptive DBS (aDBS) offers a closed-loop alternative, using biomarkers such as beta-band oscillations to dynamically modulate stimulation. While reinforcement learning (RL) holds promise for personalized aDBS control, existing methods suffer from high sample complexity, unstable exploration in binary action spaces, and limited deployability on resource-constrained hardware. We propose SEA-DBS, a sample-efficient actor-critic framework that addresses the core challenges of RL-based adaptive neurostimulation. SEA-DBS integrates a predictive reward model to reduce reliance on real-time feedback and employs Gumbel Softmax-based exploration for stable, differentiable policy updates in binary action spaces. Together, these components improve sample efficiency, exploration robustness, and compatibility with resource-constrained neuromodulatory hardware. We evaluate SEA-DBS on a biologically realistic simulation of Parkinsonian basal ganglia activity, demonstrating faster convergence, stronger suppression of pathological beta-band power, and resilience to post-training FP16 quantization. Our results show that SEA-DBS offers a practical and effective RL-based aDBS framework for real-time, resource-constrained neuromodulation.

A core aim in theoretical and systems neuroscience is to develop models which help us better understand biological intelligence. Such models range broadly in both complexity and biological plausibility. One widely-adopted example is task-optimized recurrent neural networks (RNNs), which have been used to generate hypotheses about how the brain's neural dynamics may organize to accomplish tasks. However, task-optimized RNNs typically have a fixed weight matrix representing the synaptic connectivity between neurons. From decades of neuroscience research, we know that synaptic weights are constantly changing, controlled in part by chemicals such as neuromodulators. In this work we explore the computational implications of synaptic gain scaling, a form of neuromodulation, using task-optimized low-rank RNNs.In our neuromodulated RNN (NM-RNN) model, a neuromodulatory subnetwork outputs a low-dimensional neuromodulatory signal that dynamically scales the low-rank recurrent weights of an output-generating RNN.

Three-factor learning rules in Spiking Neural Networks (SNNs) have emerged as a crucial extension to traditional Hebbian learning and Spike-Timing-Dependent Plasticity (STDP), incorporating neuromodulatory signals to improve adaptation and learning efficiency. These mechanisms enhance biological plausibility and facilitate improved credit assignment in artificial neural systems. This paper takes a view on this topic from a machine learning perspective, providing an overview of recent advances in three-factor learning, discusses theoretical foundations, algorithmic implementations, and their relevance to reinforcement learning and neuromorphic computing. In addition, we explore interdisciplinary approaches, scalability challenges, and potential applications in robotics, cognitive modeling, and AI systems. Finally, we highlight key research gaps and propose future directions for bridging the gap between neuroscience and artificial intelligence.

Continuous, adaptive learning--the ability to adapt to the environment and improve performance--is a hallmark of both natural and artificial intelligence. Biological organisms excel in acquiring, transferring, and retaining knowledge while adapting to dynamic environments, making them a rich source of inspiration for artificial neural networks (ANNs). This study explores how neuromodulation, a fundamental feature of biological learning systems, can help address challenges such as catastrophic forgetting and enhance the robustness of ANNs in continuous learning scenarios. Driven by neuromodulators including dopamine (DA), acetylcholine (ACh), serotonin (5-HT) and noradrenaline (NA), neuromodulatory processes in the brain operate at multiple scales, facilitating dynamic responses to environmental changes through mechanisms ranging from local synaptic plasticity to global network-wide adaptability. Importantly, the relationship between neuromodulators, and their interplay in the modulation of sensory and cognitive processes are more complex than expected, demonstrating a "many-to-one" neuromodulator-to-task mapping. To inspire the design of novel neuromodulation-aware learning rules, we highlight (i) how multineuromodulatory interactions enrich single-neuromodulator-driven learning, (ii) the impact of neuromodulators across multiple spatial and temporal scales, and correspondingly, (iii) strategies for approximating and integrating neuromodulated learning processes in ANNs. To illustrate these principles, we present a case study to demonstrate how neuromodulation-inspired mechanisms, such as DA-driven reward processing and NA-based cognitive flexibility, can enhance ANN performance in a Go/No-Go task. By integrating multi-scale neuromodulation, we aim to bridge the gap between biological learning and artificial systems, paving the way for ANNs with greater flexibility, robustness, and adaptability.

Navigating multiple tasks$\unicode{x2014}$for instance in succession as in continual or lifelong learning, or in distributions as in meta or multi-task learning$\unicode{x2014}$requires some notion of adaptation. Evolution over timescales of millennia has imbued humans and other animals with highly effective adaptive learning and decision-making strategies. Central to these functions are so-called neuromodulatory systems. In this work we introduce an abstract framework for integrating theories and evidence from neuroscience and the cognitive sciences into the design of adaptive artificial reinforcement learning algorithms. We give a concrete instance of this framework built on literature surrounding the neuromodulators Acetylcholine (ACh) and Noradrenaline (NA), and empirically validate the effectiveness of the resulting adaptive algorithm in a non-stationary multi-armed bandit problem. We conclude with a theory-based experiment proposal providing an avenue to link our framework back to efforts in experimental neuroscience.

Recent progress in artificial intelligence (AI) has been driven by insights from neuroscience, particularly with the development of artificial neural networks (ANNs). This has significantly enhanced the replication of complex cognitive tasks such as vision and natural language processing. Despite these advances, ANNs struggle with continual learning, adaptable knowledge transfer, robustness, and resource efficiency - capabilities that biological systems handle seamlessly. Specifically, ANNs often overlook the functional and morphological diversity of the brain, hindering their computational capabilities. Furthermore, incorporating cell-type specific neuromodulatory effects into ANNs with neuronal heterogeneity could enable learning at two spatial scales: spiking behavior at the neuronal level, and synaptic plasticity at the circuit level, thereby potentially enhancing their learning abilities. In this article, we summarize recent bio-inspired models, learning rules and architectures and propose a biologically-informed framework for enhancing ANNs. Our proposed dual-framework approach highlights the potential of spiking neural networks (SNNs) for emulating diverse spiking behaviors and dendritic compartments to simulate morphological and functional diversity of neuronal computations. Finally, we outline how the proposed approach integrates brain-inspired compartmental models and task-driven SNNs, balances bioinspiration and complexity, and provides scalable solutions for pressing AI challenges, such as continual learning, adaptability, robustness, and resource-efficiency.