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

Drawing on two decades of clinical experience with affective disorders, Jesús Ramírez-Bermúdez— runner up in the Brain Essay Competition 2024—explores the cultural significance of melancholy, with the aid of historical archives from the Inquisition and the introspections of a 17th century poet.

Matt Butler, runner up in the Brain Essay Competition 2024, considers what happens when memories fragment and certainties fade in this fictional tale of a professor of literature who loses her grasp on time.

The historical understanding of cerebrospinal fluid (CSF) production and flow comprises CSF production primarily in the choroid plexus of the 1st-3rd ventricles, flow through the aqueduct of Sylvius en route to the 4th ventricle, circulation around the subarachnoid space, and ultimately resorption into the blood circulation through arachnoid granulations. Since the discovery of a perivascular CSF clearance

Apathy is a common neuropsychiatric symptom (NPS) in Alzheimer’s disease (AD) but can emerge earlier in prodromal and even preclinical stages as part of mild behavioural impairment (MBI-apathy), a syndrome defined by emergent and persistent NPS. In dementia, apathy is associated with higher morbidity, mortality, and caregiver distress. However, the significance of MBI-apathy in dementia-free persons

Monoallelic pathogenic variants in LGI1 cause autosomal dominant epilepsy with auditory features with onset in childhood/adolescence. LGI1 is a secreted neuronal protein, functions as a ligand for ADAM22/23, and regulates excitatory synaptic transmission and neuronal excitability in the brain. While biallelic ADAM22 variants cause developmental and epileptic encephalopathy (DEE), the whole picture

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder caused by a preCGG repeat expansion in the FMR1 gene. Individuals with the FMR1 premutation often exhibit neuropsychiatric symptoms before FXTAS onset, leading to the identification of fragile X-associated neuropsychiatric disorders (FXAND). Rodent models of FXTAS show motor impairments, pathological intranuclear

Neuroinflammatory mechanisms drive cognitive impairments in mice treated with chimeric antigen receptor (CAR)-T cell therapy.

A number of neuropeptides including pituitary adenylate cyclase-activating polypeptide (PACAP) play an important role in the pathophysiology of migraine. Infusions of PACAP in patients with migraine can provoked migraine attacks. A placebo-controlled study with a monoclonal antibody directed against the PACAP-receptor failed to show efficacy. In a small, short, proof of concept study a monoclonal antibody

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)

Targeting of tau pathology has long been proposed as a potential therapeutic strategy for Alzheimer’s disease (AD). Semorinemab is a humanized IgG4 monoclonal antibody that binds to all known isoforms of full-length tau with high affinity and specificity. Semorinemab’s safety and efficacy have been studied in two Phase 2 randomized, double-blind, placebo-controlled, parallel-group clinical trials:

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

SLC35A2 encodes a UDP-galactose transporter essential for glycosylation of proteins and galactosylation of lipids and glycosaminoglycans. Germline genetic SLC35A2 variants have been identified in congenital disorders of glycosylation and somatic SLC35A2 variants have been linked to intractable epilepsy associated with malformations of cortical development. However, the functional consequences of these

Parkinson’s disease is most recognized for its impact on the CNS. However, recent breakthroughs underscore the crucial role of interactions between central and peripheral systems in Parkinson’s disease pathogenesis. The spotlight is now shifting as we explore beyond the CNS, discovering that peripheral changes such as inflammatory dysfunctions may predict the rate of disease progression and severity

Although growing evidence suggests that cholinergic basal forebrain degeneration is linked to cognitive impairment and axial motor symptoms in Lewy body disorders (LBDs), the cholinergic contribution to their prodromal phase remains largely unknown. Herein, we aimed to address three important yet unresolved questions focusing on prodromal LBDs: (1) to examine whether and where basal forebrain degeneration

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