Artificial intelligence has created tremendous advances for many scientific and engineering applications. In this Review, we synthesize recent advances in joint brain-behaviour modelling of neural and behavioural data, with a focus on methodological innovations, scientific and technical motivations, and key areas for future innovation. We discuss how these tools reveal the shared structure between the brain and behaviour and how they can be used for both science and engineering aims. We highlight how three broad classes with differing aims - discriminative, generative and contrastive - are shaping joint modelling approaches. We also discuss recent advances in behavioural analysis approaches, including pose estimation, hierarchical behaviour analysis and multimodal-language models, which could influence the next generation of joint models. Finally, we argue that considering not only the performance of models but also their trustworthiness and interpretability metrics can help to advance the development of joint modelling approaches.

The increasing prevalence of opioid use disorder (OUD) represents an important global public health crisis, often referred to as the 'opioid epidemic'. Opioids are known for their potent pain-relieving effects, but also have serious side effects, including OUD and respiratory depression, which can lead to fatal overdoses. To address this growing concern, we require a better understanding of the mechanisms underlying OUD, which typically begins with either medical or recreational opioid use and evolves into a complex and chronic brain disorder. In this Review, we highlight recent advances in our understanding of opioid receptors and the neural circuits in which they operate (including the broad network of circuits involved in reward and relief processing), focusing on the changes that follow long-term opioid exposure, abstinence and withdrawal. Additionally, we discuss recent findings that highlight the importance of the local cellular environment in shaping responses to these drugs. Overall, we aim to provide an updated overview of the field that may give us new insights into the multifaceted landscape of OUD.

Half a century of neurophysiological recordings from single electrodes established a 'localized' viewpoint on function in the brain - that complex behaviour results from computations that are carried out and representations that occur across distinct brain areas, each of which has a specialized role. Data generated from new techniques for specific, high-throughput measurement of neuronal activity and behaviour in rodents have prompted an alternative viewpoint, which posits that neural encoding of behavioural variables is distributed across a wide range of areas: 'everything, everywhere, all at once'. After briefly introducing these paradigms, we evaluate which of them better describes cognition - the manipulation of internal variables that enables flexible behaviour. Measurements of neuronal activity in both rodents and primates suggest that cognitive variables are reflected broadly but not ubiquitously across the brain, including, to a surprising degree, in regions engaged in controlling movement. We close by discussing why cognitive signals may appear in such areas, as well as the factors that affect the breadth of the brain-wide network that is recruited for cognition.

Time and space are crucial concepts in neuroscience, because our personal memories are tied to specific events that occur 'in' a particular space and on a 'timeline'. Thus, we seek to understand how the brain constructs time and space and how these are related to episodic memory. Place cells and time cells have been identified in the brain and have been proposed to 'represent' space and time via single-neuron or population coding, thus acting as hypothetical coordinates within a Newtonian framework of space and time. However, there is a fundamental tension between the linear and unidirectional flow of physical time and the variable nature of experienced time. Moreover, modern physics no longer views space as a fixed container and time as something in which events occur. Here, I articulate an alternative view: that time (physical and experienced) is an abstracted relational measure of change. Physical time is measured using arbitrary units and artificial clocks, whereas experienced time is linked to a hierarchy of brain-body rhythms that provide a range of reference scales that reflect the full span of experienced time. Changes in body and brain circuits, tied to these rhythms, may be the source of our subjective feeling of time.

Programmed axon degeneration (PAxD) is an evolutionarily conserved mechanism in the nervous system that is activated by axonal injury (axotomy) to execute the self-destruction of a severed distal axon. It can also be triggered by non-axotomy insults, resulting in the loss of axons connected to their cell bodies. PAxD is therefore a promising target for therapeutic intervention and drugs that inhibit it are currently being tested in clinical trials. In this Review, we summarize the molecular mechanism of PAxD, focusing on its regulation by nicotinamide adenine dinucleotide (NAD) metabolism and how it dictates Ca-mediated axonal demise. We examine its involvement in human disease and its potential as a therapeutic target by dissecting its role in various non-axotomy disease models. Finally, we address key challenges for its clinical translation, including the need for relevant biomarkers and safety considerations. Further advancements in understanding PAxD will pave the way for new therapeutic strategies targeting human axonopathies.

Stroke remains a leading cause of disability owing to the irreversible neuronal loss that it causes and the limited regenerative capacity of the CNS. Although reperfusion therapies such as thrombolysis and mechanical thrombectomy can restore blood flow after stroke, their stringent eligibility criteria leave many patients without treatment options. The immune response, involving complex interactions between brain-resident and peripheral immune cells, has a critical role in stroke recovery. Stem cell-based therapies, particularly those involving neural stem cells and mesenchymal stem cells, may be able to reshape the inflammatory microenvironment after stroke, mitigating secondary injury and promoting tissue repair. However, the precise mechanisms driving their effects remain incompletely understood, hindering clinical translation. In this Review, we highlight the bidirectional crosstalk between stem cells and immune cells (including microglia, T cells and peripheral immune cells) and discuss how these interactions influence neuroinflammation, neural plasticity and circuit remodelling in stroke recovery. We examine key determinants of stem cell therapy efficacy, emphasizing the role of stem cell-immune cell interactions, and discuss targeted strategies to enhance immune modulation and neuroprotection.

Human sociality is grounded in the dynamic coordination of individuals as they interact with one another. Indeed, various levels of interpersonal coordination - neural, behavioural, physiological, affective, linguistic - are hallmarks of successful social communication and cooperation. However, describing these complex, interdependent dynamics has been limited by current methodological approaches, owing to a restrictive repertoire of tools and the absence of a unified, standardized methodological framework. Here, we identify information theory - the mathematical theory of communication - as a particularly well-suited conceptual framework to address this shortfall, given its appropriate sensitivity to complex dynamics, including potential nonlinearity and higher-order interactions, and its data-driven, model-agnostic foundations. With deep roots in computational, cognitive and systems neuroscience, the formal introduction of information-theoretic quantities and methods into the study of interpersonal coordination is perhaps overdue. In this Perspective, we advance the case for a unified information-theoretic framework for the field while paving the way for a new generation of empirically testable, theoretically grounded research questions.

Emerging evidence highlights the crucial role of peripheral immune cells in maintaining brain homeostasis and their influence on the pathology of Alzheimer disease (AD). Genome-wide association studies have identified numerous AD risk variants in genes expressed by immune cells, implicating innate and adaptive immune pathways in disease progression. Advances in neuroimmunology have revealed that immune cell crosstalk involving T cells, B cells, monocytes and/or macrophages and neutrophils can modulate the hallmark features of AD, including amyloid plaque accumulation, tau pathology and chronic neuroinflammation. Mechanistic insights suggest that chronic peripheral inflammation, immune exhaustion, metabolic dysfunction and epigenetic reprogramming exacerbate neurodegeneration in AD by promoting toxic inflammation and impairing protein clearance in the brain. These findings may catalyse the development of novel immunomodulatory strategies, such as immune checkpoint inhibition and cytokine targeting, among others, for AD. This Review examines peripheral immune alterations in AD, evaluates related therapeutic opportunities and highlights key knowledge gaps, particularly the need for human-derived data to advance translational progress. Future research should prioritize personalized approaches that integrate genetic risk, immune profiling and ageing to inform next-generation therapies for AD.

The question of how the first synapses and neurons evolved remains unanswered. Chemical synapses are highly organized functional assemblies, linking two cells between presynaptic and postsynaptic structures. The core set of proteins making these two structures are well conserved in animals, and many of them predate animal evolution. In order to reconstruct the history of how these components came together into a functional unit, it is important to study the conserved and unique functions of synaptic proteins across modern lineages. Here, we provide an overview of the current state of knowledge on the distribution and function of synaptic proteins in early branching animals and their closest protistan relatives. We propose a model in which the evolution of chemical synapses from specialized secretory cells was tightly linked to lifestyle and behaviour in early animals.