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Li et al. develop neural fragility, a networked dynamic system biomarker, for localizing seizures in patients with epilepsy and find that it is more robust compared to traditional features that clinicians and researchers look at in a 91-patient study.

Schaeffer and Iadecola review the anatomical, molecular and functional heterogeneity of the neurovasculature and highlight the coordinated interaction of factors intrinsic and extrinsic to the brain in its dynamic regulation and role in disease.

The authors utilize information theory to show that four of the output pathways in the primate retina encode predictive information about visual motion. They further show the nonlinear circuit mechanisms that contribute to this computation.

The conventional view is that the cortex generates brain oscillations, while subcortical structures control global sleep–wake switching. This study shows that the cortex plays an important role in both global state control and sleep homeostasis.

Rupprecht et al. compiled a large database of simultaneous electrophysiological and calcium recordings from the same neurons. An algorithm (termed CASCADE) trained with this ground truth enables reliable spike inference without the need to tune parameters.

Shamash et al. probe the navigational strategies mice use as they escape from a threat. By systematically placing and removing obstacles blocking their initial path, the authors find evidence that mice memorize intermediate ‘subgoal’ locations to find their way home.

Shamash et al. examine how mice learn to get past an obstacle blocking their path to a goal. They found that mice instinctively adopt a subgoal memory strategy, which combines elements from both habitual learning and the cognitive map theory.

The authors construct brain-wide coexpression networks to characterize regional versus global features, determine if disease susceptibility maps onto regional or brain-wide processes and assess how these networks capture genetic models of disease risk.

Mallard et al. study the often overlooked X-chromosome’s influences on the human brain. They find that X-chromosome influences on cortical surface area are sex biased and concentrated in specific cortical systems.

By recording and manipulating neural activity in rats performing a skilled behavior, the authors show that the basal ganglia control the detailed kinematics of learned skills and can do so independently of the motor cortex.

Peter Lakatos passed away on Sunday, 30 May 2021. He was 49 years old. Peter was a Research Scientist at the Nathan S. Kline Institute for Psychiatric Research in New York State and a Research Assistant Professor in the Department of Psychiatry at NYU Grossman School of Medicine. With Peter’s sudden death, neuroscience has lost a gentle giant.

The skull dura contains B cells and B lineage precursors under homeostatic conditions. These cells are long-term tissue resident and mature upon neuroinflammation. This identifies the dura as a site of B cell residence and potentially development.

Lee et al. show that in male Shank3-mutant mice, mPFC neurons are impaired in encoding of social agency. Shank3 reexpression in mPFC restored this ability in real time, and this was accompanied by rescue of normal social behavior.

In the nucleus, specific stretches of DNA are ‘anchored’ to distinct membrane-less compartments that harbor gene regulatory function. Using GO-CaRT, the authors discovered unique aspects of genome architecture in neural precursors in vivo, providing new insights into brain development and disease.

Yang et al. generated a genomic atlas of protein levels in brain, cerebrospinal fluid and plasma and used human genetics approaches to identify proteins implicated in neurological diseases as well as druggable targets.

Understanding how the brain makes decisions is a major area of focus in both animal and human cognitive neuroscience. Much of this work, especially in primates, has explicated the role of various cortical areas in forming decisions. In new research, perturbations of the superior colliculus by Jun et al. reveal a large and causal role in accumulating evidence for this midbrain structure classically thought of as being involved in simpler functions related to eye movement control.

Ketamine has transformed the treatment of depression by providing rapid relief from depressive symptoms, but the mechanisms mediating its long-term effects are unclear. Kim et al. show that MeCP2 signaling in the hippocampus is critical for supporting sustained antidepressant effects.

How ketamine and scopolamine produce sustained antidepressant effects remains unknown. Kim et al. show that BDNF-dependent MeCP2 phosphorylation drives sustained antidepressant effects of ketamine and scopolamine with distinct synaptic plasticity changes.

Unilateral inactivation of the superior colliculus in monkeys reveals that a brainstem structure plays a causal role in how evidence is computed for decisions, a process usually attributed to the forebrain.