The insula processes errors in the prediction of risky, motivationally relevant outcomes and thereby is thought to respond similarly to better-than-predicted and worse-than-predicted outcomes. However, the nature of the encoded risk prediction error signals remained unclear. Moreover, the insula was proposed to preferentially process events and stimuli in the aversive domain, rather than in a domain-general

Neural states shape perception at earliest cortical processing levels. Previous work in humans showed a relationship between initial cortical excitation, as indicated by the N20 component of the somatosensory evoked potential (SEP), prestimulus alpha oscillations, and the perceived intensity in a somatosensory discrimination paradigm. Here we address the follow-up question whether these excitability

Transcranial focused ultrasound stimulation (tFUS) is a promising neuromodulation technique capable of noninvasively modulating focal neuronal activities and neural circuits in both animals and humans. The cell-type selectivity of tFUS within targeted areas such as the somatosensory cortex (S1) during sonication has been shown to be parameter related. However, it remains unclear how tFUS affects neural

An age-dependent decline in the amyloid-β (Aβ)-degrading enzyme neprilysin (NEP) has been implicated in the pathogenesis of sporadic Alzheimer's disease (AD). Recently identified risk alleles in the NEP-coding gene further support its role in AD etiology. However, evidence for the impact of NEP on the pathophysiological progression of Aβ plaque formation, particularly in comparison with another Aβ-degrading

To navigate social life, humans make inferences about the intentions, beliefs, emotions, and personalities of other people, i.e., they mentalize. A network of brain regions consistently engages more during mentalizing than during carefully controlled comparison tasks, sometimes cited as evidence of domain-specific mentalizing processes. Here we investigated the possibility that engagement of these

Extracellular single-unit responses to tone-in-noise (TIN) stimuli were recorded in the inferior colliculus (IC) of awake female Dutch-belted rabbits. Stimuli consisted of wideband and narrowband TIN with on-and-off characteristic frequency tones. Neural responses to wideband TIN showed a pattern of rates that increased when the tone matched CF and decreased (with respect to noise-alone responses)

Repeated stimulus exposure alters the brain's response to the stimulus. Recording fMRI data from both men and women viewing 120 presentations of two Gabor patches (each Gabor repeating 60 times), we evaluated support for two prominent models of stimulus repetition, the fatigue model and the sharpening model. Our results uncovered a two-stage learning process in the primary visual cortex. In Stage 1

The cerebral cortex, cerebellum, and basal ganglia are essential for flexible learning in mammals. Although traditionally thought to operate under different learning rules, recent evidence suggests that both the basal ganglia and the cerebellum may employ reinforcement learning mechanisms. This raises the question of how these structures coordinate when a common reward prediction error mechanism is

Aligning one's decisions with the prevailing social norms and expectations of those around us constitutes a fundamental facet of moral decision-making. When faced with conflicting moral values, one adaptive approach is to rely on intuitive moral preference. Although theoretical accounts have proposed a link between moral preferences and interoceptive awareness—the capacity to sense internal bodily

Primates, including humans, use stimulus–reward associations to guide foraging. We previously showed that both the rhinal cortex (Rh) and rostromedial caudate (rmCD) of rhesus monkeys play causal roles in assigning value to visual stimuli. Layer 5 neurons in Rh project to rmCD. Here, we reversibly interrupted this Layer 5 connection in two male monkeys by combining a unilateral Rh lesion with contralateral

Damage to retinal cells from disease or injury causes vision loss and remodeling of downstream visual information processing circuits. As retinal cell replacement therapies and prosthetics become increasingly viable, we must understand the postretinal consequences of retinal cell loss to optimally recover visual perception. Here, we asked whether loss of retinal ganglion cells (RGCs) differentially

Voluntary movement control depends on plasticity in several interconnected brain regions, including the cerebellum (CB), primary motor cortex (M1), and posterior parietal cortex (PPC). It is thought that one role of the CB is to regulate communication between PPC and M1, but causal evidence for this regulatory role in humans remains lacking. Here, we evaluated how transiently altering activity in CB

Pyridoxine-dependent epilepsy (PDE), a rare autosomal recessively inherited metabolic disease, results from mutations in ALDH7A1, a gene crucial for lysine metabolism. Although early high-dose pyridoxine treatment can control seizures, ~75% of PDE patients still have intellectual disabilities. In this study, we test the hypothesis of substrate reduction therapy for PDE by genetically perturbing lysine

Adaptive behavior in complex environments requires integrating visual perception with memory of our spatial environment. Recent work has implicated three brain areas in posterior cerebral cortex—the place memory areas (PMAs) that are anterior to the three visual scene perception areas (SPAs)–in this function. However, PMAs' relationship to the broader cortical hierarchy remains unclear due to limited

Past cognitive neuroscience research has demonstrated that thinking about both the self and other activates the medial prefrontal cortex (mPFC), a central hub of the default mode network. The mPFC is also implicated in other cognitive processes, such as introspection and autobiographical memory, rendering elusive its exact role during thinking about the self. Specifically, it is unclear whether the

The transfer of retinal signals from the dorsal lateral geniculate nucleus (dLGN) to the primary visual cortex (V1) is modulated by a variety of extraretinal inputs, including extrinsic connections formed by GABAergic neurons in the pretectum (PT) and visual sector of the thalamic reticular nucleus (vTRN), as well as the intrinsic connections of GABAergic dLGN interneurons. In the current study, we

Movement-related dynamics in the beta and gamma bands have been studied in relation to motor execution and learning during unimanual movements, but their roles in complex bimanual tasks remain largely unexplored. This study aimed to investigate how beta and gamma activity differs between unimanual and bimanual movements and how these neural signatures evolve during the learning process. Our motor task

Facilitation of visual search by repeated distractor contexts is typically studied employing distractor configurations that are 100% predictive of the target location. Yet, real-world contexts vary in predictivity. We used electroencephalography (EEG) in human participants of either sex to explore how visual search facilitation arises from two distinct processing modes—contextual guidance and context

Neuropathic pain is one of the most intractable pain conditions associated with tumor growth compressing and damaging nerves. A troublesome hallmark symptom of neuropathic pain is hypersensitivity to innocuous stimuli, known as "tactile allodynia," which is often refractory to currently available analgesics. Diurnal variations in pain hypersensitivity are common in patients with cancer, but the underlying

To characterize the function of the Ca2+-activated Cl– current ICl(Ca) in mammalian rod photoreceptors, we made patch-clamp recordings from retinal slices of mice (Mus musculus) of both sexes that lack Ano2 (TMEM16B). Depolarizing voltage ramps in solutions blocking K+ currents elicited a large outward current inhibited by the Cl– channel blocker niflumic acid; this current was absent in Ano2–/– rods

Comprehension of spoken and written language involves a hierarchical sequence of modality-specific and heteromodal processes. While these have been localized to different regions, modality-selective responses extend beyond them, implicating large-scale network organization in language comprehension. Dimensions of whole-brain connectivity, derived from intrinsic activity, have been proposed as a general

Although several studies have demonstrated that perceptual discrimination of complex scenes relies on an extended hippocampal posteromedial system, we currently have limited insight into the specific functional and structural properties of this system in humans. Here, combining electrophysiological (magnetoencephalography) and advanced microstructural (multishell diffusion magnetic resonance imaging;

Recent research suggests that the detection of preserved cognitive function can assist in the diagnosis and prognosis of patients with disorders of consciousness (DoC). This study investigates EEG signals as indicators of neural activity associated with the processing of transitional probabilities during a learning paradigm in patients with DoC. By examining the sensitivity to transitional probabilities

The auditory brainstem response (ABR) is an acoustically evoked EEG potential that is an important diagnostic tool for hearing loss, especially in newborns. The ABR originates from the response sequence of auditory nerve and brainstem nuclei, and a click-evoked ABR typically shows three positive peaks ("waves") within the first six milliseconds. However, an assignment of the waves of the ABR to specific

Fear extinction is critical for decreasing fear responses to a stimulus that is no longer threatening. While it is known that the infralimbic (IL) region of the medial prefrontal cortex mediates retrieval of an extinction memory through projections to the basolateral amygdala (BLA), IL pathways contributing to extinction learning are not well understood. Given the dense projection from the IL to the

A prosocial response to others in distress is increasingly recognized as a natural behavior for many social species. While prosocial behavior is more frequently observed toward familiar conspecifics, even within the same social context, some individuals are more prone to help than others. In a rat helping behavior test where animals can release a distressed conspecific trapped inside a restrainer,

Direct projections from the ventral hippocampus (vHPC) to the medial frontal cortex (MFC) play crucial roles in memory and emotional regulation. Using anterograde transsynaptic tracing and ex vivo electrophysiology in male mice, we document a previously unexplored pathway that parallels the established vHPC-MFC connectivity. This pathway connects the dorsal–caudal hippocampus (dcHPC) to specific subregions

How does the brain process 3D motion? We focused on the human motion complex (hMT+), extending insights from monkey studies. Using 3D-motion stimuli containing perspective and/or stereoscopic cues, we investigated the hierarchy within the motion complex in humans of both sexes to understand the neural mechanisms underlying motion perception. On each trial we decoded 3D motion direction (toward/away)

N-methyl-D-aspartate receptors (NMDARs) play a crucial role in excitatory neurotransmission, with numerous pathogenic variants identified in the GluN subunits, including their ligand-binding domains (LBDs). The prevailing hypothesis postulates that the endoplasmic reticulum (ER) quality control machinery verifies the agonist occupancy of NMDARs, but this was tested in a limited number of studies. Using

Imitation plays a key role in the acquisition of speech and cultural behaviors. Studies suggest that social interaction facilitates imitative learning, indicating that neural circuits involved in social behaviors can also influence the process of imitation. Vocal imitation in juvenile songbirds serves as a valuable model to investigate this idea. Here, we explore the mechanisms of tutor-pupil social

The ventral striatum (VS) is a key brain region for reward processing and motivation, and its dysfunctions have been implicated in psychiatric disorders such as apathy and obsessive–compulsive disorder. Although functional heterogeneity within the VS has been well established in rodents, its relevance and mechanisms in primates remain unclear. To address this issue, we performed bilateral pharmacological

Optogenetic neuromodulation combined with functional MRI (opto-fMRI) enables noninvasive monitoring of brain-wide activity and probes causal connections. In this study, we focused on the secondary somatosensory (S2) cortex, a hub for integrating tactile and nociceptive information. By selectively stimulating excitatory neurons in the S2 cortex of monkeys using optogenetics, we observed widespread opto-fMRI

Real-world social cognition requires processing and adapting to multiple dynamic information streams. Interpreting neural activity in such ecological conditions remains a key challenge for neuroscience. This study leverages advancements in denoising techniques and multivariate modeling to extract interpretable EEG signals from pairs of (male and/or female) participants engaged in spontaneous dyadic

To learn complex motor skills, an organism must be able to assign sensory feedback events to the actions that caused them. This matching problem would be simple if motor neuron output led to sensory feedback with a fixed, predictable lag. However, nonlinear dynamics in the brain and the body's periphery can decouple the timing of critical events from that of the motor output which caused them. During

We investigate how respiration influences cognition by examining the interaction between respiratory phase and task-related brain activity during two visual categorization tasks. While prior research shows that cognitive performance varies along the respiratory cycle, the underlying neurophysiological mechanisms remain poorly understood. Though some studies have shown that large-scale neural activity

Through experience, humans can learn to suppress locations that frequently contain distracting stimuli. However, the neural mechanism underlying learned suppression remains largely unknown. In this study, we combined steady-state visually evoked potentials (SSVEPs) with event-related potentials (ERPs) to investigate the mechanism behind statistically learned spatial suppression. Twenty-four male and

"Are you talkin’ to me?!" If you ever watched the masterpiece "Taxi Driver" directed by Martin Scorsese, you certainly recall the monologue during which Travis Bickle rehearses an imaginary confrontation in front of a mirror. While remembering this scene, you recollect a myriad of speech features across visual and auditory senses with a smooth sensation of unified memory. The aim of this study was

Mesopic (dim light) conditions are prevalent in everyday environments, yet most human vision research is conducted under idealized, photopic (bright) conditions. Electrophysiological studies suggest that under mesopic conditions, contrast-encoding retinal ganglion cell receptive fields expand their center width while diminishing surround inhibition. These retinal modifications enhance light capture

Adipose-derived leptin contributes to energy homeostasis by balancing food intake and motor output, but how leptin acts in brain motor centers remains poorly understood. We investigated the influence of leptin on neuronal activity in two basal ganglia nuclei involved in motor control: the substantia nigra pars compacta (SNc) and pars reticulata (SNr). Using a mouse reporter line to identify cells expressing

Understanding the spatiotemporal dynamics of neural signal propagation is fundamental to unraveling the complexities of brain function. Emerging evidence suggests that corticocortical-evoked potentials (CCEPs) resulting from single-pulse electrical stimulation (SPES) may be used to characterize the patterns of information flow between and within brain networks. At present, the basic spatiotemporal

Serotonin critically modulates the activity of many brain networks, including circuits that control motivation and responses to rewarding and aversive stimuli. Furthermore, the serotonin system is targeted by first-line pharmacological treatments for several psychiatric disorders, including obsessive–compulsive disorder. However, understanding the behavioral function of serotonin is hampered by methodological

Sleep spindles, transient bursts of rhythmic activity during non-rapid eye movement sleep, are generated by the thalamocortical network through an intricate interplay between the thalamus and the cortex. Emerging research has shed light on the role of sleep spindles in cognitive function, memory consolidation, and overall brain health. Using a behavioral genetics approach in female and male adolescent

Patients with Parkinson's disease (PD) are impaired at incremental reward-based learning. It is typically assumed that this impairment reflects a loss of striatal dopamine. However, many open questions remain about the nature of reward-based learning deficits in PD. Recent studies have found that even simple reward-based learning tasks rely on a combination of cognitive and computational strategies

The cerebellar vermis plays an essential role in maintaining posture and balance by integrating sensory inputs from multiple modalities to effectively coordinate movement. By transforming convergent sensory information into precise motor commands, it ensures smooth, adaptive motor control, enabling the body to maintain stability in dynamic environments. This review examines recent findings that investigate

Intracortical circuits, including long-range callosal projections, are crucial for information processing. The development of neuronal connectivity in the cerebral cortex is contingent on ordered emergence of neuronal classes followed by the formation of class-specific axon projections. However, the genetic determinants of intracortical axon targeting are still unclear. We find that the transcription

All available antiseizure medications aim at symptomatic control of epilepsy, but there is no strategy to stop the development of the disease. The main reason is the lack of understanding of the epileptogenic mechanisms. Closing this knowledge gap is an essential prerequisite for developing disease-modifying therapies that can prevent the onset of epilepsy. Using primary cocultures of hippocampal neurons

Although domestic dogs were the first domesticated species, the nature of dog domestication remains a topic of ongoing debate. In particular, brain and behavior changes associated with different stages of the domestication process have been difficult to disambiguate. Most modern Western breed dogs possess highly derived physical and behavioral traits because of intense artificial selection for appearance

Friedreich ataxia (FA) is an autosomal recessive disease characterized by progressive damage to the nervous system and severe cardiac abnormalities. The disease is caused by a GAA•TTC triplet repeat expansion in the first intron of the FXN gene, which results in epigenetic repression of FXN transcription and reduction in FXN (frataxin) protein which results in mitochondrial dysfunction. Factors and

The human ability to track overlapping and asynchronous time intervals is crucial for a myriad of tasks, from engaging in conversation to driving a car. Additionally, unexpected events can trigger rapid, on-the-fly adjustments, necessitating quick updating of both timing intervals and action planning. Such events require immediate recalibration of decision variables to allow the system to promptly

We report here that microglia exert a surprisingly discrete but functionally critical influence on synaptic plasticity in mouse hippocampus. Treatment of adult male mice with colony stimulating factor 1 receptor antagonist PLX5622 (PLX), with resultant depletion of forebrain microglia, did not disturb basal synaptic transmission at four synaptic connections in hippocampus. Long-term potentiation (LTP)

The suprachiasmatic nucleus (SCN) serves as the central circadian clock in mammals, coordinating daily rhythms in both behavior and physiology. In the SCN, gastrin-releasing peptide (GRP)-producing neurons (GRPNs) are predominantly located in the core region, suggesting their possible involvement in photic entrainment. However, the specific contribution of GRPNs to the regulation of circadian rhythms

This study examined how amyloid burden affects structural and functional brain network topology in subjective cognitive decline (SCD), a risk condition for Alzheimer's disease (AD). Functional and structural brain networks were analyzed in 100 individuals with SCD and 86 normal controls (both sexes included) using resting-state functional MRI and diffusion tensor imaging. Topological properties of

Spatial frequency (SF) selectivity serves as a fundamental building block within the visual system, determining what we can and cannot see. Attention is theorized to augment the visibility of items in our environment by changing how we process SFs. However, the specific neural mechanisms underlying this effect remain unclear, particularly in humans. Here, we used functional magnetic resonance imaging

Previous studies have found that several neurochemicals are involved in formation of pair bonding. However, circuit mechanisms underlying pair bonding, especially how these chemicals interact in this circuit regulate pair bonding, remains unclear. Using male mandarin voles, the present study shows that cohabitation with a partner increased frequency of spontaneous excitatory postsynaptic current (sEPSC)

Sensorimotor integration processes are crucial for daily-life activities, such as grasping objects or driving a car. Theta band activity (TBA) in distributed brain networks is likely essential to perform sensorimotor integration successfully. Directed communication in these brain networks is shaped by brain maturation during adolescence. This study investigates how age-related effects attributable

Dynorphin (DYN)/kappa opioid receptor (KOR) activation contributes to aversion, dysphoria, sedation, depression, and enhanced psychostimulant-rewarding effects by inhibiting dopamine (DA) release. The precise neuronal mechanisms underlying these effects remain unclear, limiting the use of KOR agonists in treating mood and substance use disorders. DYN fibers form synapses with DA terminals that express

In humans, mutations or deletions of atypical FAT cadherin genes are linked to autism spectrum disorder and cerebellar ataxia. However, their large genomic size and the enormous size of their encoded proteins have hampered functional studies, leaving the roles of FAT cadherins poorly understood. To address this gap, we investigated FAT2-an atypical cadherin selectively expressed in cerebellar granule