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Widespread, perception-related information in the human brain scales with levels of consciousness How does the human brain generate coherent, subjective perceptions—transforming yellow and oblong visual sensory information into the perception of an edible banana? This is a hard problem. According to the standard viewpoint, processing in groups of dedicated regions—identified as active “blobs” when using functional magnetic resonance imaging (fMRI)—gives rise to perception. Here, our research reveals a new organizational concept by discovering stimulus-specific information distributed throughout the whole brain. Using fMRI, we found stimulus-specific information across the neocortex, even in voxels previously considered “noise,” challenging traditional analytical approaches. Surprisingly, these stimulus-specific signals were also present in the subcortex and cerebellum and could be detected from across-subject variances. Additionally, we observed that the widespread signal in brain regions beyond the primary and secondary sensory cortices is influenced by sedation levels, suggesting a connection to perception rather than sensory encoding. We hypothesize that these widespread, stimulus-specific, and consciousness level-dependent signals may underlie coherent and subjective perceptions.

Exploring complex and integrated information during sleep The Integrated Information Theory is a theoretical framework that aims to elucidate the nature of consciousness by postulating that it emerges from the integration of information within a system, and that the degree of consciousness depends on the extent of information integration within the system. When consciousness is lost, the core complex of consciousness proposed by the Integrated Information Theory disintegrates, and Φ measures, which reflect the level of integrated information, are expected to diminish. This study examined the predictions of the Integrated Information Theory using the global brain network acquired via functional magnetic resonance imaging during various tasks and sleep. We discovered that the complex located within the frontoparietal network remained constant regardless of task content, while the regional distribution of the complex collapsed in the initial stages of sleep. Furthermore, Φ measures decreased as sleep progressed under limited analysis conditions. These findings align with predictions made by the Integrated Information Theory and support its postulates.

Norepinephrine Drives Sleep Fragmentation Activation of Asparagine Endopeptidase, Locus Ceruleus Degeneration, and Hippocampal Amyloid-β42 Accumulation Chronic sleep disruption (CSD), from insufficient or fragmented sleep and is an important risk factor for Alzheimer’s disease (AD). Underlying mechanisms are not understood. CSD in mice results in degeneration of locus ceruleus neurons (LCn) and CA1 hippocampal neurons and increases hippocampal amyloid-β42 (Aβ42), entorhinal cortex (EC) tau phosphorylation (p-tau), and glial reactivity. LCn injury is increasingly implicated in AD pathogenesis. CSD increases NE turnover in LCn, and LCn norepinephrine (NE) metabolism activates asparagine endopeptidase (AEP), an enzyme known to cleave amyloid precursor protein (APP) and tau into neurotoxic fragments. We hypothesized that CSD would activate LCn AEP in an NE-dependent manner to induce LCn and hippocampal injury. Here, we studied LCn, hippocampal, and EC responses to CSD in mice deficient in NE [dopamine β-hydroxylase (Dbh)−/−] and control male and female mice, using a model of chronic fragmentation of sleep (CFS). Sleep was equally fragmented in Dbh−/− and control male and female mice, yet only Dbh−/− mice conferred resistance to CFS loss of LCn, LCn p-tau, and LCn AEP upregulation and activation as evidenced by an increase in AEP-cleaved APP and tau fragments. Absence of NE also prevented a CFS increase in hippocampal AEP-APP and Aβ42 but did not prevent CFS-increased AEP-tau and p-tau in the EC. Collectively, this work demonstrates AEP activation by CFS, establishes key roles for NE in both CFS degeneration of LCn neurons and CFS promotion of forebrain Aβ accumulation, and, thereby, identifies a key molecular link between CSD and specific AD neural injuries.

What is the Role of Spatial Attention in Statistical Learning During Visual Search? Our ability to learn the regularities embedded in our environment is a fundamental aspect of our cognitive system. Does such statistical learning depend on attention? Research on this topic is scarce and has yielded mixed findings. In this preregistered study, we examined the role of spatial attention in statistical learning, and specifically in learned distractor-location suppression. This phenomenon refers to the finding that during visual search, participants are better at ignoring a salient distractor at a high-probability location than at low-probability locations – a bias persisting long after the probability imbalance has ceased. Participants searched for a shape-singleton target and a color-singleton distractor was sometimes present. During the learning phase, the color-singleton distractor was more likely to appear in the high-probability location than in the low-probability locations. Crucially, we manipulated spatial attention by having the experimental group focus their attention on the target’s location in advance of the search display, using a 100%-informative spatial precue, while the control group was presented with a neutral, uninformative cue. During the subsequent test phase, the color-singleton distractor was equally likely to appear at any location and there were no cues. As expected, the results for the neutral-cue group replicated previous findings. Crucially, for the informative-cue group, interference from the distractor was minimal when attention was diverted from it (during learning) and no statistical learning was observed during test. Intertrial priming accounted for the small statistical-learning effect found during learning. These findings show that statistical learning in visual search requires attention.

Cortico-basal ganglia plasticity in motor learning One key function of the brain is to control our body’s movements, allowing us to interact with the world around us. Yet, many motor behaviors are not innate but require learning through repeated practice. Among the brain’s motor regions, the cortico-basal ganglia circuit is particularly crucial for acquiring and executing motor skills, and neuronal activity in these regions is directly linked to movement parameters. Cell-type-specific adaptations of activity patterns and synaptic connectivity support the learning of new motor skills. Functionally, neuronal activity sequences become structured and associated with learned movements. On the synaptic level, specific connections become potentiated during learning through mechanisms such as long-term synaptic plasticity and dendritic spine dynamics, which are thought to mediate functional circuit plasticity. These synaptic and circuit adaptations within the cortico-basal ganglia circuitry are thus critical for motor skill acquisition, and disruptions in this plasticity can contribute to movement disorders.

Cortico-striatal white-matter connectivity underlies the ability to exert goal-directed control The balance between goal-directed and habitual control has been proposed to determine the flexibility of instrumental behaviour, in both humans and animals. This view is supported by neuroscientific studies that have implicated dissociable neural pathways in the ability to flexibly adjust behaviour when outcome values change. A previous Diffusion Tensor Imaging study provided preliminary evidence that flexible instrumental performance depends on the strength of parallel cortico-striatal white-matter pathways previously implicated in goal-directed and habitual control. Specifically, estimated white-matter strength between caudate and ventromedial prefrontal cortex correlated positively with behavioural flexibility, and posterior putamen–premotor cortex connectivity correlated negatively, in line with the notion that these pathways compete for control. However, the sample size of the original study was limited, and so far, there have been no attempts to replicate these findings. In the present study, we aimed to conceptually replicate these findings by testing a large sample of 205 young adults to relate cortico-striatal connectivity to performance on the slips-of-action task. In short, we found only positive neural correlates of goal-directed performance, including striatal connectivity (caudate and anterior putamen) with the dorsolateral prefrontal cortex. However, we failed to provide converging evidence for the existence of a neural habit system that puts limits on the capacity for flexible, goal-directed action. We discuss the implications of our findings for dual-process theories of instrumental action.

The components of an electrical synapse as revealed by expansion microscopy of a single synaptic contact Most nervous systems combine both transmitter-mediated and direct cell-cell communication, known as ‘chemical’ and ‘electrical’ synapses, respectively. Chemical synapses can be identified by their multiple structural components. Electrical synapses are, on the other hand, generally defined by the presence of a ‘gap junction’ (a cluster of intercellular channels) between two neuronal processes. However, while gap junctions provide the communicating mechanism, it is unknown whether electrical transmission requires the contribution of additional cellular structures. We investigated this question at identifiable single synaptic contacts on the zebrafish Mauthner cells, at which gap junctions coexist with specializations for neurotransmitter release and where the contact unequivocally defines the anatomical limits of a synapse. Expansion microscopy of these single contacts revealed a detailed map of the incidence and spatial distribution of proteins pertaining to various synaptic structures. Multiple gap junctions of variable size were identified by the presence of their molecular components. Remarkably, most of the synaptic contact’s surface was occupied by interleaving gap junctions and components of adherens junctions, suggesting a close functional association between these two structures. In contrast, glutamate receptors were confined to small peripheral portions of the contact, indicating that most of the synaptic area functions as an electrical synapse. Thus, our results revealed the overarching organization of an electrical synapse that operates with not one, but multiple gap junctions, in close association with structural and signaling molecules known to be components of adherens junctions. The relationship between these intercellular structures will aid in establishing the boundaries of electrical synapses found throughout animal connectomes and provide insight into the structural organization and functional diversity of electrical synapses.

Glutamate acts on acid-sensing ion channels to worsen ischaemic brain injury Glutamate is traditionally viewed as the first messenger to activate NMDAR(N-methyl-d-aspartate receptor)-dependent cell death pathways in stroke1,2, butunsuccessful clinical trials with NMDAR antagonists implicate the engagement ofother mechanisms 3–7. Here we show that glutamate and its structural analogues,including NMDAR antagonist l-AP5 (also known as APV), robustly potentiate currentsmediated by acid-sensing ion channels (ASICs) associated with acidosis-inducedneurotoxicity in stroke 4. Glutamate increases the affinity of ASICs for protons andtheir open probability, aggravating ischaemic neurotoxicity in both in vitro andin vivo models. Site-directed mutagenesis, structure-based modelling and functionalassays reveal a bona fide glutamate-binding cavity in the extracellular domain ofASIC1a. Computational drug screening identified a small molecule, LK-2, that bindsto this cavity and abolishes glutamate-dependent potentiation of ASIC currents butspares NMDARs. LK-2 reduces the infarct volume and improves sensorimotor recoveryin a mouse model of ischaemic stroke, reminiscent of that seen in mice with Asic1aknockout or knockout of other cation channels 4–7. We conclude that glutamatefunctions as a positive allosteric modulator for ASICs to exacerbate neurotoxicity, andpreferential targeting of the glutamate-binding site on ASICs over that on NMDARs maybe strategized for developing stroke therapeutics lacking the psychotic side effects ofNMDAR antagonists.