Perspectives in 2021

The recollection of memories and voluntary actions are often perceived to be generated spontaneously. In this Perspective, Itzhak Fried examines evidence from human single-neuron studies indicating that brain systems involved in these acts can form a conceptual–volition interface, where representations of actions and stored memories interact, sometimes in the absence of sensory input and sometimes allowing such input to be overridden.

A prevailing theory of Parkinson disease pathogenesis revolves around the spread of α-synuclein toxicity from the periphery to the brain. In this Review, Blesa and colleagues discuss the idea that, although these bottom-up mechanisms are involved, early neuronal loss in the nigrostriatal system also plays a prominent role.

The amyloid hypothesis has been the dominant model for the pathogenesis of Alzheimer disease for several decades. In this Perspective, Giovanni Frisoni and colleagues examine evidence for and against this hypothesis before outlining an alternative model, the probabilistic model of Alzheimer disease.

Environmental stressors, including extreme ambient temperature, the presence of pathogens or predators, and a lack of food, can profoundly influence animal behaviour. In this Perspective, Nakamura, Nakamura and Kataoka present a hypothalamomedullary network model for physiological responses to various environmental stressors.

The encoding of itch by peripheral and central neural circuits is a topic of long-standing interest in the somatosensory field. Here, Zhou-Feng Chen outlines a model for itch coding that emphasizes the role of neuropeptides in conveying itch information from the periphery to the spinal cord.

Developing a better understanding of neural codes should enable the links between stimuli, brain activity and behaviour to become clearer. In this Perspective, Kriegeskorte and Wei examine neural tuning and representational geometry — complementary approaches used to understand neural codes — and the relationship between them.

Entorhinal cortical grid cells have been suggested to encode an internal map of the environment during spatial navigation. In this Perspective, Rueckemann, Sosa and colleagues propose that grid cells and hippocampal place cells cooperate to provide a topological representation of experience through temporal ordering of events, in both spatial and non-spatial contexts.

Homeobox genes were initially characterized on the basis of the homeotic transformations in segmental identity during development that resulted from mutation of the Hox cluster family of homeobox genes. In this Perspective article, Hobert proposes that homeobox genes specify neuronal identity in the nematode Caenorhabditis elegans and possibly in other animals too.

How category-specific regions of cortex, or ‘domains’, in the primate ventral stream arise is unclear. In this Perspective, Arcaro and Livingstone present a ‘bottom-up’ model for the generation of these domains, whereby experience refines a domain-general architecture based on topographic maps of the sensory environment.

Regions of the default mode network (DMN) are distributed across the brain and show patterns of activity that have linked them to various different functional domains. In this Perspective, Smallwood and colleagues consider how an examination of the topographic characteristics of the DMN can shed light on its contribution to cognition.

Neural network models have potential for improving our understanding of brain functions. In this Perspective, Pulvermüller and colleagues examine various aspects of such models that may need to be constrained to make them more neurobiologically realistic and therefore better tools for understanding brain function.

Evidence suggests that socio-economic status can affect not only the outcome of structural and functional development of the brain but also its rate. Tooley, Bassett and Mackey review this evidence and suggest that the valence and frequency of early experiences interact to influence brain development.

Neuroscience can explain cognition by considering single neurons and their connections (a ‘Sherringtonian’ view) or by considering neural spaces constructed by populations of neurons (a ‘Hopfieldian’ view). In this Perspective, Barack and Krakauer argue that the Hopfieldian view has the conceptual resources to explain cognition more fully the Sherringtonian view.

In this Perspective, Koban, Gianaros, Kober and Wager describe neural systems that construct models of the ‘self-in-context’. Such models endow events with personal meaning and enable predictive control over behaviour and peripheral physiology — with implications for health and disease.

The role of the default mode network (DMN) is unclear. In this Perspective, Yeshurun, Nguyen and Hasson review evidence that the DMN integrates extrinsic inputs with intrinsic information over long timescales, enabling it to represent meaning in a way that can be shared between individuals.