Reviews & Analysis

Using long-term brain recordings in patients with chronic pain, we identified objective biomarkers of real-world subjective pain intensity over many months. Spontaneous chronic pain states were predicted most reliably by sustained changes in the activity of the orbitofrontal cortex, whereas acute pain was most associated with signals from the anterior cingulate cortex.

Two monkeys solved combinatorial optimization problems for rewards. They deliberated for extended durations, approximated efficient computational algorithms for managing complexity, and even selected algorithms according to the computational complexity of the trial. These findings reveal evidence for algorithm-based reasoning and establish a paradigm for studying the neurophysiological basis of deliberative thought.

In the brains of patients with epilepsy, apolipoprotein E-mediated lipid transfer from hyperactive neurons to astrocytes results in lipid metabolism reprogramming and formation of lipid-accumulated reactive astrocytes. These astrocytes exacerbate abnormal discharges of neighboring neurons and, in mice, aggravate seizure symptoms, leading to disease progression.

We developed a wearable platform (the Neuro-stack) for recording single-neuron and local field potentials in freely moving humans. The Neuro-stack enabled the recording of single-neuron activity during walking behavior in humans. The platform also enables personalized stimulation during real-time decoding of neural activity, which can potentially improve neurostimulation treatments.

Despite extensive studies on how social networks affect behavior at the population level, little is known about how the human brain makes decisions in networked environments. This study shows that the brain flexibly weighs information received from a social contact according to how well-connected that contact is on the network responsible for information transmission.

STARmap PLUS is a new spatial gene mapping method combined with histological staining. With STARmap PLUS, we created high-resolution, comprehensive maps of altered molecular pathways and reactive cells in a mouse model of Alzheimer’s disease. These maps enabled us to infer the trajectories of biological processes and cell states during disease progression.

The defense response to threat involves complex behavioral and autonomic adjustments. We identified integrated, short-lasting microstates and long-lasting macrostates evoked by threat, consisting of patterned behavioral and cardiac responses, which are dynamically interrelated, dependent on environmental threat levels, and controlled by neurons in the midbrain periaqueductal gray region.

Despite rich behavioral evidence, it is unclear how the brain expands its behavior repertoire. By building theoretical models with a deep reinforcement learning algorithm, I show that the brain composes a behavior to solve a novel task by combining previously acquired skills and augmenting their variability.

Although axonal GABA_A receptors are thought to cause presynaptic inhibition, we show that instead they often facilitate sodium channel activation at nodes of myelinated axons. This facilitation determines which branches of sensory axons conduct action potentials to motor neurons, enabling computation at the level of the node to regulate sensory feedback.

Frontal cortex activity contains a mixture of signals for different behavioral and cognitive processes. Analysis of 20,000 frontal cortical neurons during a tactile decision-making task revealed functional clusters encoding specific behavioral variables. By manipulating the inputs to frontal cortex, we attributed the origin of their activities to inputs from the thalamus.

We studied how the sex of human experimenters affected mouse behaviors and brain functions under normal conditions and in the context of ketamine administration. Identifying such unknown unknowns was critical to understanding how, specifically and quantitatively, they affected experimental outcomes, which led to fresh insight into ketamine’s mechanism as an antidepressant drug.

The language network in the brain shows similar properties across 45 languages spanning 12 language ‘families’. The language areas are lateralized to the left hemisphere, selective for language, and strongly functionally inter-connected. Variability among speakers of different languages is similar to the variability that has been reported among English speakers.

A new cell state of disease-associated oligodendrocytes (DOLs) has been identified, which presents a transcriptional program that is probably driven by neuroinflammation and is shared among different non-immune glial cells across multiple pathologies of the central nervous system.

We report light-gated channels in a fungus-like protist that are highly selective for K⁺ over Na⁺. These microbial rhodopsin channels, named kalium channelrhodopsins, enable robust inhibition of mouse cortical neurons with millisecond precision. In addition, kalium channelrhodopsins reveal a previously unknown potassium selectivity mechanism.

The extent to which neurogenesis occurs in adult primates is still controversial. Single-cell RNA sequencing, immunofluorescence staining, and ex vivo neurosphere culture experiments were performed using the adult macaque hippocampus. The results reveal robust adult neurogenesis in the dentate gyrus of the primate hippocampus.

Myelin, iron, and calcium are major constituents of brain tissue with magnetic properties that can be detected non-invasively using MRI. Using quantitative susceptibility mapping, we estimated the magnetic susceptibility of brain structures in 35,273 participants, creating a new resource to identify novel, non-invasive markers of brain health.

Dopamine (DA) neurons in the ventral tegmental area bidirectionally regulate the activity of serotonin neurons in the dorsal raphe nucleus. Low-strength activity causes inhibition via dopamine receptor D2, whereas high- strength activity causes activation via dopamine receptor D1, and this circuit contributes to anorexia nervosa-like behaviors in mice.

Activity-regulated myelination adaptively tunes neural circuit function in health. In rodent models of generalized epilepsy, recurrent seizures aberrantly increase myelination specifically within the seizure circuit. Blocking this seizure-induced myelination abrogates the progressive increase in seizure burden and ictal hypersynchrony that occurs in mice with intact activity-regulated myelination, indicating that maladaptive myelination can contribute to disease progression in epilepsy.

An efficient tool for neurite tracing has been developed that reconstructed the complete axons of 6,357 individual projection neurons in the mouse prefrontal cortex (PFC). The resulting single-neuron projectome analysis revealed comprehensive PFC neuron subtypes, topographic organization of PFC axon projections, modular structure within the PFC and correspondence with single-cell transcriptomes.