Perspectives

A revolution is underway in cognitive neuroscience, where tools and techniques from computer science and the tech industry are helping to extract more meaningful cognitive signals from noisy and increasingly large fMRI datasets. In this paper, the authors review the cutting edge of such computational analyses and discuss future opportunities and challenges.

The study of the mechanisms controlling RNA metabolism in neurons represents a new frontier in the understanding of gene–environment interactions and how they regulate brain function. In this Perspective, the authors describe the recent surge in newly identified epitranscriptomic processes and highlight their potential importance in coordinating the molecular underpinnings of cognition and memory.

A number of higher cognitive processes are linked to dorsal anterior cingulate cortex (dACC), yet its overall functions remain elusive. The authors discuss convergent findings suggesting it is part of a mechanism for tracking and evaluating reward environments in order to implement learning, search and goal-driven persistence.

The authors propose that dorsal anterior cingulate cortex (dACC) performs a cost/benefit analysis to specify how best to allocate cognitive control. They describe why this theory accounts well for dACC’s role in decision-making, motivation and cognitive control, including its observed role in foraging choice settings.

Given recent advances in genome engineering technology like CRISPR and the difficulty of modeling human diseases in rodents, transgenic nonhuman primates may be used to develop etiologically relevant models of disease. This perspective by Guoping Feng et al. highlights the technological advances, potential challenges and opportunities these models present to furthering our understanding of disease.

In the twenty-first century, microglia came of age. Their remarkable ontogeny, unique functions and gene expression profile, process motility, and disease relevance have all been highlighted. Neuroscientists interested in microglia encounter an obsolete concept, M1/M2 polarization, suggesting experimental strategies that produce neither conceptual nor technical advances. Ransohoff's Perspective argues against applying this flawed paradigm.

In this Perspective the authors provide a comparison of recent neurophysiological findings on the pathophysiology of three major movement disorders: Huntington's disease, l-DOPA-induced dyskinesia and dystonia. Both clinical and preclinical studies show that these hyperkinetic disorders share mechanisms underlying synaptic scaling and synaptic plasticity alterations in the basal ganglia–thalamo-cortical network.

In this Perspective, Murray Sherman discusses connectivity in the thalamocortical system, including the evidence that cortical areas are connected in parallel by direct and transthalamic pathways. Because thalamus receives inputs that form collaterals with subcortical motor regions, the author suggests that it may relay efference copy information.

The authors use recent probabilistic theories of neural computation to argue that confidence and certainty are not identical concepts. They propose precise mathematical definitions for both of these concepts and discuss putative neural representations.

Recent computational neuroscience developments have used deep neural networks to model neural responses in higher visual areas. This Perspective describes key algorithmic underpinnings in computer vision and artificial intelligence that have contributed to this progress and outlines how deep networks could drive future improvements in understanding sensory cortical processing.

The networks used by computer scientists and by modelers in neuroscience frequently consider unit activities as continuous. Neurons, however, com­municate primarily through discontinuous spiking. This Perspective offers a unifying view of the current methods for transferring our ability to construct functional networks from continuous to more realistic spiking network models.

The role of transient elevations of the intracellular concentration of calcium in astrocytes is controversial. Some neuroscientists believe that, by triggering the release of 'gliotransmitters', astrocyte calcium transients regulate synaptic strength and neuronal excitability, while others deny that gliotransmission exists. Bazargani and Attwell assess the status of this rapidly evolving field.

There is growing realization that glia actively signal with neurons and influence synaptic development, transmission and plasticity through an array of secreted and contact-dependent signals. We propose that disruptions in neuron-glia signaling contribute to synaptic and cognitive impairment in disease.

In their Perspective, Hariri & Holmes consider unique features of translational research on stress-related disorders that have helped fuel a productive dialogue from bench to bedside and back, as well as sparked important advances in identifying novel risk biomarkers and therapeutic strategies.

The amyloid cascade is perhaps the most dominant hypothesis in the field of Alzheimer's disease pathogenesis but it is also one of the most controversial. Here, we present two Perspective articles which argue both for and against the amyloid hypothesis. In this piece, Drs. Musiek and Holtzman argue that, despite sometimes conflicting data, there is ample evidence to suggest that Aβ accumulation is a key initiator of AD-related pathology and may act as a trigger of downstream effects such as tau aggregation.

The amyloid cascade is perhaps the most dominant hypothesis in the field of Alzheimer's disease pathogenesis, but it is also one of the most controversial. Here we present two Perspective articles that argue both for and against the amyloid hypothesis. In this opinionated piece, Dr. Herrup challenges the Alzheimer's field to re-examine the complex biochemical, clinical and epidemiological evidence and reassess its over-reliance on this proposed pathogenic mechanism.

In this Perspective article, Brian Grone and Scott Baraban examine some of the numerous nonhuman animal models of epilepsy. The authors outline how traditional animal models have advanced our understanding of seizure initiation and epileptogenesis and also describe how the use of more 'non-traditional' model systems may further improve insight into both disease mechanisms as well as potential therapeutic avenues.

Current treatment options are, for many patients with epilepsy, either insufficient or ineffective and, thus, new therapeutic methodologies are necessary. In this Perspective, Esther Krook-Magnuson and Ivan Soltesz look at recent advances in optogenetic-based modulation of circuit activity and seizures with an eye toward the prospect - and challenges - of utilizing these technologies for the treatment of epilepsy.

Temporally coordinated signals at gamma frequencies and higher are often used to study inter-regional communication in brain networks, but interpreting mechanisms from population measures can be troublesome. The authors discuss the physiological origins of gamma coherence and suggest ways to decipher its roles in neural function.

In this Perspective, the authors discuss the recent surge in the collection of "big behavioral data" and how it might contribute to the understanding of how the brain controls behavior. They also highlight the challenges of making sense of increasing amounts of behavioral data.