bioRxiv Subject Collection: Neuroscience's Journal

Somatosensory high frequency oscillations across the human central nervous system
Sensory information processing in the central nervous system (CNS) requires both post-synaptic responses and spiking activity, with human electroencephalography (EEG) research largely focused on the former. However, EEG data also contain high-frequency oscillations (HFOs), which have been linked to cortical spike bursts in animal models, thus providing a non-invasive macroscopic marker of population spiking in humans. Here, we go beyond cortical processing and demonstrate that it is possible to simultaneously record HFOs to somatosensory stimulation across the entire human CNS - from spinal cord over subcortical to cortical processing stages. Using multivariate spatial filtering approaches in two independent datasets, we identify replicable and generalizable HFOs across the CNS and obtain a detailed characterization of these signals at each processing level. Finally, we provide evidence at the between- and within-individual level that low and high frequency electrophysiological responses represent at least partly independent information across the CNS. Taken together, our approach offers the first evidence that it is possible to detect and characterise HFOs simultaneously across the CNS, providing a unique non-invasive and multi-level window into human neurophysiology in health and disease.

Rarely categorical, always high-dimensional: how the neural code changes along the cortical hierarchy
The brain is highly structured both at anatomical and functional levels. However, within individual brain areas, neurons often exhibit very diverse and seemingly disorganized responses. A more careful analysis shows that these neurons can sometimes be grouped together into specialized subpopulations (categorical representations). Organization can also be found at the level of the representational geometry in the activity space, typically in the form of low-dimensional structures. It is still unclear how the geometry in the activity space and the structure of the response profiles of individual neurons are related. Here, we systematically analyzed the geometric and selectivity structure of the neural population from 40+ cortical regions in mice performing a decision-making task (IBL public Brainwide Map data set). We used a reduced-rank regression approach to quantify the selectivity profiles of single neurons and multiple measures of dimensionality to characterize the representational geometry of task variables. We then related these measures within single areas to the position of each area in the sensory-cognitive cortical hierarchy. Our findings reveal that only a few regions (in primary sensory areas) are categorical. When multiple brain areas are considered, we observe clustering that reflects the brain's large-scale organization. The representational geometry of task variables also changed along the cortical hierarchy, with higher dimensionality in cognitive regions. These trends were explained by analytical computations linking the maximum dimensionality of representational geometry to the clustering of selectivity at the single neuron level. Finally, we computed the shattering dimensionality (SD), a measure of the linear separability of neural activity vectors; remarkably, the SD remained near maximal across all regions, suggesting that the observed variability in the selectivity profiles allows neural populations to maintain high computational flexibility. These results provide a new mathematical and empirical perspective on selectivity and representation geometry in the cortical neural code.

Postnatal maturation of serotonergic modulation of spinal RORβ interneurons in the medial deep dorsal horn
Proprioceptive input is essential for coordinated locomotion and this input must be properly gated to ensure smooth and effective movement. Presynaptic inhibition mediated by GABAergic interneurons provides regulation of sensory afferent feedback. Serotonin not only promotes locomotion, but also modulates feedback from sensory afferents, both directly and indirectly, potentially by acting on the GABAergic interneurons that mediate presynaptic inhibition. Developmental disruptions in presynaptic inhibition can produce deficits in sensorimotor processing. Importantly, both presynaptic inhibition of proprioceptive afferents and serotonergic innervation of the spinal cord become mature and functional after the first postnatal week. However, little is known about the serotonergic receptors involved in the modulation of interneurons mediating presynaptic inhibition and when developmentally their actions mature. Here, we used whole-cell patch clamp recordings in lumbar spinal slices from neonatal and juvenile mice to assess the intrinsic properties and serotonergic modulation of deep dorsal horn GABAergic ROR{beta} interneurons previously shown to mediate presynaptic inhibition of proprioceptive afferents. ROR{beta} interneurons from juvenile cords displayed more mature membrane properties. Further, serotonin increased the excitability of ROR{beta} interneurons via actions at 5-HT2A, 5-HT2B/2C, and 5-HT7 receptors in juvenile but not early neonatal spinal cords. Our findings indicate that deep dorsal horn ROR{beta} interneurons undergo postnatal maturation in both their intrinsic excitability and ability to respond to serotonin, concurrent with the maturation of serotonergic innervation of the dorsal horn. This information can prompt future targeted studies testing relationships between impairments of serotonergic development, proprioceptive processing disorders, and presynaptic inhibition mediated by ROR{beta} interneurons.

Uncovering dynamic human brain phase coherence networks
Complex behavioral and cognitive processes emerge from coordinated communication between sometimes disparate brain regions, implying a systems-level dynamic synchronization of underlying neural signals. This study presents approaches to multivariate mixture modeling of functional brain imaging data for analyzing phase coherence networks for human brain macroscale dynamic functional connectivity. We show that 1) the complex domain is required to analyze phase coherence in its entirety, 2) statistical models for complex-valued phase coherence, particularly the complex angular central gaussian (ACG) distribution, greatly exceeds performance over models for time-series data, rank-2 cosine phase coherence maps, or the leading eigenvector of cosine phase coherence maps (i.e., LEiDA), 3) methods should account for the inherent anisotropy of the brain's interconnections. We emphasize the need to utilize models that account for the manifold on which the data reside, and show that the proposed models provide valuable information about intrinsic functional connectivity networks and can easily distinguish task-related brain function. We provide an open-source, Python-based toolbox ("Phase Coherence Mixture Modeling" (PCMM): github.com/anders-s-olsen/PCMM) to facilitate and promote implementation of these models.

A novel rhodopsin-based voltage indicator for simultaneous two-photon optical recording with GCaMP in vivo
Genetically encoded voltage indicators (GEVIs) allow optical recording of membrane potential from targeted cells in vivo. However, red GEVIs that are compatible with two-photon microscopy and that can be multiplexed in vivo with green reporters like GCaMP, are currently lacking. To address this gap, we explored diverse rhodopsin proteins as GEVIs and engineered a novel GEVI, 2Photron, based on a rhodopsin from the green algae Klebsormidium nitens. 2Photron, combined with two photon ultrafast local volume excitation (ULoVE), enabled multiplexed readout of spiking and subthreshold voltage simultaneously with GCaMP calcium signals in visual cortical neurons of awake, behaving mice. These recordings revealed the cell-specific relationship of spiking and subthreshold voltage dynamics with GCaMP responses, highlighting the challenges of extracting underlying spike trains from calcium imaging.

Corticotropin-releasing factor neurons of the bed nucleus of the stria terminalis demonstrate sex- and estrous phase-dependent differences in synaptic activity and in their role in anxiety-potentiated startle
Background: The prevalence of post-traumatic stress disorder (PTSD) and anxiety disorders is higher in women than men. The severity of hallmark symptoms including hypervigilance and fear reactivity to unpredictable threats varies with sex and reproductive cycle, but the underlying mechanisms remain unclear. Here, we investigated corticotropin-releasing factor (CRF) neurons in the dorsolateral bed nucleus of the stria terminalis (BNSTDL) as a potential nexus for the influence of biological sex and reproductive cycle on fear- and anxiety-related behaviors. Methods: 103 male and 132 cycle-monitored female CRF-Cre rats were used. BNSTDL-CRF neuron excitability and synaptic activity was recorded with slice electrophysiology. Chemogenetic inhibition of BNSTDL-CRF neurons was performed before elevated-plus maze, predator odor exposure, shock-induced startle sensitization, and anxiety-potentiated startle (APS) following unpredictable fear conditioning. Results: BNSTDL-CRF neurons in females exhibit higher excitability (cycle-independent) and lower sensitivity to excitatory synaptic inputs (proestrus and diestrus) compared to males. BNSTDL-CRF neuron inhibition reduces open-arm time in estrous females but not males, suggesting that BNSTDL-CRF neurons reduce anxiety during sexual receptivity. In the APS, BNSTDL-CRF neuron inhibition attenuates short-term startle potentiation in males, whereas it causes persistent APS in diestrous females. Conclusions: Unpredictable fear conditioning elicits sex- and estrous phase-specific APS, differentially regulated by BNSTDL-CRF neurons. Persistent APS in females align with hormonal phases marked by low reproductive hormones, mirroring human PTSD findings. Our findings underscore the sex- and hormone-specific role of BNSTDL-CRF neurons in APS. Widely used in human studies, APS may bridge animal and human research, supporting biomarker development and more effective pharmacotherapies.

Brain-region-specific changes and dysregulation of activity regulated genes in Gria3 mutant mice, a genetic animal model of schizophrenia
Protein-truncating variants in GRIA3 (encoding the GluA3/GluR3 subunit of -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors) are associated with substantially increased risk of schizophrenia (SCZ). Here we characterized Gria3 mutant mice carrying a protein-truncating mutation that mimics a SCZ-associated variant. Transcriptomic analysis revealed that activity-regulated genes are downregulated in cortical regions, while immune and glia-related pathways exhibit brain-region-specific changes. The transcriptomic changes in Gria3 mutant mice are remarkably different from those in Grin2a mutant mice, particularly in the prefrontal cortex, even though both encode glutamate receptors and are associated with SCZ risk. Proteomic analysis further demonstrated that loss-of-function of Gria3 profoundly alters the protein composition of synapses. These findings in a genetic mouse model provide potential insights into the pathophysiological mechanisms underlying SCZ.

Social and Contextual Memory Impairments Induced by Amyloid-β Oligomers are Rescued by Sigma-1 Receptor Activation
Sigma-1 receptors (S1Rs) are widely expressed throughout the central nervous system and modulate neuron intracellular calcium levels, leading to changes in neurotransmitter release and neuronal activity. They also interact with various proteins and signaling pathways, playing a key role in regulating synaptic plasticity in brain areas such as the hippocampus, thereby influencing learning and memory processes. This opens a research avenue to explore S1R modulation as a potential therapeutic target in diseases involving hippocampal synaptic alterations and compromised cognitive processes, such as Alzheimer s disease (AD). Here, we hypothesize that pharmacological activation of S1R could counteract synaptic plasticity deficits and hippocampal-dependent cognitive alterations in an early-stage amyloidosis model of Alzheimer s disease, induced by intracerebroventricular (icv) administration of A{beta}1-42 oligomers (oA{beta}1-42). For that purpose, we investigate ex vivo CA3-CA1 synaptic plasticity, while in vivo, we performed open field habituation and social recognition tasks to assess contextual and social memory, respectively. Our data show that pharmacological activation of S1Rs with the selective agonist PRE-084 counteract oA{beta}1-42 deleterious effects on CA3-CA1 long-term synaptic plasticity (LTP), and hippocampal-dependent contextual and social memory, without alterations of spontaneous behaviors. Together, these results provide evidence for the role of S1Rs in ameliorating hippocampal synaptic and contextual memory dysfunctions and, for the first time, in early amyloid-induced social memory deficits, highlighting their potential in the development of comprehensive treatments for early AD. Also, the absence of adverse behavioral outcomes associated with PRE-084 treatment accentuates its safety profile, underscoring its potential as a therapeutic agent.

Modality-Specific and Amodal Language Processing by Single Neurons
According to psycholinguistic theories, during language processing, spoken and written words are first encoded along independent phonological and orthographic dimensions, then enter into modality-independent syntactic and semantic codes. Non-invasive brain imaging has isolated several cortical regions putatively associated with those processing stages, but lacks the resolution to identify the corresponding neural codes. Here, we describe the firing responses of over 1000 neurons, and mesoscale field potentials from over 1400 microwires and 1500 iEEG contacts in 21 awake neurosurgical patients with implanted electrodes during written and spoken sentence comprehension. Using forward modeling of temporal receptive fields, we determined which sensory or abstract dimensions are encoded. We observed a double dissociation between superior temporal neurons sensitive to phonemes and phonological features and previously unreported ventral occipito-temporal neurons sensitive to letters and orthographic features. We also discovered novel neurons, primarily located in middle temporal and inferior frontal areas, which are modality-independent and show responsiveness to higher linguistic features. Overall, these findings show how language processing can be linked to neural dynamics, across multiple brain regions at various resolutions and down to the level of single neurons.

Activation of hypothalamic-pontine-spinal pathway promotes locomotor initiation and functional recovery after spinal cord injury in mice
The hypothalamus is critical for regulating behaviors essential for survival and locomotion, but how it integrates internal needs and transmits locomotion commands to the spinal cord (SC) remains unclear. We found that glutamatergic neurons in lateral hypothalamic area (LHA) are essential for regulating motivated locomotor activity. Using single-neuron projectome analysis, trans-synaptic tracing, and optogenetic manipulation, we showed that LHA facilitates motivated locomotion during food seeking via pontine oral part (PnO) projection neurons, rather than direct SC projections or indirect stress signaling via medial septum and diagonal band. Activating PnO-SC projection neurons also initiated locomotion. Importantly, LHA-PnO projection neurons were crucial for regulating locomotor recovery following mouse spinal cord injury (SCI). Closed-loop deep brain stimulation (DBS) of LHA via gating by motor cortex signals markedly promoted long-term restoration of hindlimb motor functions after SCI. Thus, we have identified a hypothalamic-pontine-spinal pathway and the stimulation paradigm for potential therapeutic intervention after SCI.

Integration of cortical inputs in the lateral hypothalamus is dominated by the medial prefrontal cortex
The lateral hypothalamus (LH) is a critical brain region orchestrating survival behaviours including feeding. Its sparse intrinsic synaptic connectivity allows long-range projections to modulate its activity. Some of these projections arise from the cerebral cortex, which is known to influence feeding. However, the functional and anatomical organization of cortico-hypothalamic pathways have remained poorly studied. We used anatomical and optogenetic mapping to show that the medial prefrontal cortex (mPFC) is the strongest cortical input source to the LH, followed by a lateral associative region including the insular cortex (IC), and the ventral subiculum. Input from the mPFC and IC had markedly different synaptic dynamics and were integrated supralinearly. IC input surpassed that of the mPFC in a subpopulation of highly excitable dorsal LH neurons which had a strong h-current. Input from the mPFC showed selective targeting to LH neurons which project back to the mPFC, suggesting the existence of a direct feedback loop. Overall, these results identify a direct prefrontal hypothalamic pathway which is poised to dominate rapid cortical control of hypothalamic activity.

Clock genes period and timeless control synaptogenesis in Drosophila motor terminals
Some neurons undergo rhythmic morphological changes that persist in constant darkness and require the expression of clock genes. Flight motoneuron MN5, one of the best studied neurons of Drosophila melanogaster exhibits several examples of this type of circadian structural plasticity. During the morning, when the fly is active, synaptic boutons are larger than during the night when the fly is resting though more synaptic boutons and synapses are observed. Here, by comparing bouton numbers at different timepoints in normal flies and in flies carrying loss-of-function mutations in clock genes timeless (tim) or period (per), we investigate whether the rhythmic changes in numbers of boutons and synapses require the expression of these genes. Absence of tim expression abolished the rhythm in bouton number whereas absence of per expression appeared to increase the rhythm's amplitude. This indicates that in normal flies TIM protein is necessary to drive the normal rhythm of bouton number and PER probably has a damping effect on it. In addition, it appears that tim and per expression normally act as inhibitor of synaptogenesis because their loss-of-function mutations caused over-proliferation of synapses. Unexpectedly, TIM and PER were expressed in different cells. TIM was found in the glial sheath wrapping the motoneuron's axon and PER was predominantly found along the axon, suggesting that the control of the rhythmic change in bouton and synapse numbers requires interactions between different cell types.

Whole-brain causal connectivity during decoded neurofeedback: a meta study
Decoded Neurofeedback (DecNef) represents a pioneering approach in human neuroscience that enables modulation of brain activity patterns without subjective conscious awareness through the combination of real-time fMRI with multivariate pattern analysis. While this technique holds significant potential for clinical and cognitive applications, the causal mechanisms underlying successful DecNef regulation and the neural dynamics that distinguish successful learners from those who struggle remain poorly understood. To address this question, we conducted a meta-study across functional magnetic resonance imaging (fMRI) data from five DecNef experiments, each with multiple fMRI sessions, to reveal causal network dynamics associated with individual differences in neurofeedback performance. Using the newly proposed CaLLTiF causal discovery method, we computed causal maps to identify causal network patterns that distinguish DecNef regulation from baseline and account for variations in neurofeedback success. We found that enhanced connectivity within the bilateral control network--particularly stronger connections involving the posterior cingulate and precuneus cortex--predicted neurofeedback success across all five studies. Whole-brain causal connectivity during DecNef further exhibited distinct network reorganizations, characterized by reduced average path lengths and increased right-limbic nodal degrees. Further, comparisons across cognition- and perception-targeted DecNef revealed a remarkable separation in connections to and from the somatomotor network, where connections between somatomotor and control-default-attention networks are larger during cognitive neurofeedback while causal effects between somatomotor and subcortical-visual-limbic networks are larger during perceptive DecNef. This is despite the fact that none of the involved studies targeted or involved motor activity. Overall, our results demonstrated the key role of bilateral medial control network in successful DecNef regulation regardless of the DecNef targets, a clear separation in somatomotor involvement between cognitive and perceptive DecNef, and general promise of whole-brain causal discovery in understanding complex neural processes such as decoded neurofeedback.

ASAP: An automatic sustained attention prediction method for infants and toddlers using wearable device signals
Sustained attention (SA) is a critical cognitive ability that emerges in infancy. The recent development of wearable technology for infants enables the collection of large-scale multimodal data in the natural environment, including physiological signals. To capitalize on these new technologies, psychologists need methods to efficiently extract valid and robust SA measures from large datasets. In this study, we present an innovative automatic sustained attention prediction (ASAP) method that harnesses electrocardiogram (ECG) and accelerometer (Acc) signals recorded with wearable sensors from 75 infants (6-, 9-, 12-, 24- and 36-months). Infants undertook various naturalistic tasks similar to those encountered in their natural environment, including free play with their caregivers. Annotated SA was validated by fixation signals from eye-tracking. ASAP was trained on temporal and spectral features derived from the ECG and Acc signals to detect attention periods, and tested against human-coded SA. ASAP's performance is similar across all age groups, demonstrating its suitability for studying development. We also investigated the relationship between attention periods and low-level perceptual features (visual saliency, visual clutter) extracted from the egocentric videos recorded during caregiver-infant free play. Saliency increased during attention vs inattention periods and decreased with age for attention (but not inattention) periods. Crucially, there was no observable difference in results from ASAP attention detection relative to the human-coded attention. Our results demonstrate that ASAP is a powerful tool for detecting infant SA elicited in natural environments. Alongside the available wearable sensors, ASAP provides unprecedented opportunities for studying infant development in the "wild".

Combining NeuroPainting with transcriptomics reveals cell-type-specific morphological and molecular signatures of the 22q11.2 deletion
Neuropsychiatric conditions pose substantial challenges for therapeutic development due to their complex and poorly understood underlying mechanisms. High-throughput, unbiased phenotypic assays present a promising path for advancing therapeutic discovery, especially within disease-relevant neural tissues. Here, we introduce NeuroPainting, a novel adaptation of the Cell Painting assay, optimized for high-dimensional morphological phenotyping of neural cell types, including neurons, neuronal progenitor cells, and astrocytes derived from human stem cells. Using NeuroPainting, we quantified cell structure and organelle behavior across various brain cell types, creating a public dataset of over 4,000 cellular traits. This extensive dataset not only sets a new benchmark for phenotypic screening in neuropsychiatric research but also serves as a gold standard for the research community, enabling comparisons and validation of results. We then applied NeuroPainting to identify morphological signatures associated with the 22q11.2 deletion, a major genetic risk factor for schizophrenia. We observed profound cell-type-specific effects of the 22q11.2 deletion, with significant alterations in mitochondrial structure, endoplasmic reticulum organization, and cytoskeletal dynamics, particularly in astrocytes. Transcriptomic analysis revealed reduced expression of cell adhesion genes in 22q11.2 deletion astrocytes, consistent with recent post-mortem findings. Integrating the RNA sequencing data and morphological profiles uncovered a novel biological link between altered expression of specific cell adhesion molecules and observed changes in mitochondrial morphology in 22q11.2 deletion astrocytes. These findings underscore the power of combined phenomic and transcriptomic analyses to reveal mechanistic insights associated with human genetic variants of neuropsychiatric conditions.

Right posterior theta reflects human parahippocampal phase resetting by salient cues during goal-directed navigation
Animal and computational work indicate that phase resetting of theta oscillations (4-12 Hz) in the parahippocampal gyrus (PHG) by salient events (e.g., reward, landmarks) facilitates the encoding of goal-oriented information during navigation. Although well-studied in animals, this mechanism has not been empirically substantiated in humans. In the present article, we present data from two studies (Study 1: asynchronous EEG-MEG | Study 2: simultaneous EEG-fMRI) to investigate theta phase resetting and its relationship to PHG BOLD activation in healthy adults (aged 18-34 years old) navigating a virtual T-maze to find rewards. In the first experiment, both EEG and MEG data revealed a burst of theta power over right-posterior scalp locations following feedback onset (termed right-posterior theta, RPT), and RPT power and measures of phase resetting were sensitive to the subject's spatial trajectory. In Experiment 2, we used probabilistic tractography data from the human connectome project to segment the anterior and posterior PHG based on differential connectivity profiles to other brain regions. This analysis resulted in a PHG subdivision consisting of four distinct anterior and two posterior PHG clusters. Next, a series of linear mixed effects models based on simultaneous EEG-fMRI data revealed that single-trial RPT peak power significantly predicted single-trial hemodynamic responses in two clusters within the posterior PHG and one in the anterior PHG. This coupling between RPT power and PHG BOLD was exclusive to trials performed during maze navigation, and not during a similar task devoid of the spatial context of the maze. These findings highlight a role of PHG theta phase resetting for the purpose of encoding salient information during goal-directed spatial navigation. Taken together, RPT during virtual navigation integrates experimental, computational, and theoretical research of PHG function in animals with human cognitive electrophysiology studies and clinical research on memory-related disorders such as Alzheimer's disease.

Heat Shock Factor 1 Governs Sleep-Wake Cycles Across Species
Heat Shock Factor 1 (HSF1) is a critical transcription factor for cellular proteostasis, but its role in sleep regulation remains unexplored. We demonstrate that nuclear HSF1 levels in the mouse brain fluctuate with sleep-wake cycles, increasing during extended wakefulness and decreasing during sleep. Using CUT&RUN and RNA-seq, we identified HSF1-regulated transcriptional changes involved in synaptic organization, expanding its known functions beyond traditional heat shock responses. Both systemic and brain-specific Hsf1 knockout mice exhibit altered sleep homeostasis, including increased delta power after sleep deprivation and upregulation of sleep-related genes. However, these knockouts struggle to maintain sleep due to disrupted synaptic organization. In Drosophila, knockout of HSF1's ortholog results in fragmented sleep patterns, suggesting a conserved role for HSF1 in sleep regulation across species. Our findings reveal a novel molecular mechanism underlying sleep regulation and offer potential therapeutic targets for sleep disturbances.

Upregulating ANKHD1 in PS19 mice reduces Tau phosphorylation and mitigates Tau-toxicity-induced cognitive deficits
Abnormal accumulation of Tau protein in the brain disrupts normal cellular function and leads to neuronal death linked with many neurodegenerative disorders such as Alzheimer's disease. An attractive approach to mitigate Tau-induced neurodegeneration is to enhance the clearance of toxic Tau aggregates. We previously showed that upregulation of the fly gene mask protects against FUS- and Tau-induced photoreceptor degeneration in fly disease models. Here we have generated a transgenic mouse line carrying Cre-inducible ANKHD1, the mouse homolog of mask, to determine whether the protective role of mask is conserved from flies to mammals. Utilizing the TauP301S-PS19 mouse model for Tau-related dementia, we observed that ANKHD1 significantly reduced hyperphosphorylated human Tau in 6-month-old mice. Additionally, there was a notable trend towards reduced gliosis levels in these mice, suggesting a protective role of ANKHD1 against TauP301S-linked degeneration. Further analysis of 9-month-old mice revealed a similar trend of effects. Moreover, we found that ANKHD1 also suppresses the cognitive defect of 9-month-old PS19 female mice in novel object recognition (NOR) behavioral assay. Unlike previous therapeutic strategies that primarily focus on inhibiting Tau phosphorylation or directly clearing aggregates, this study highlights the novel role of ANKHD1 in promoting autophagy as a means to mitigate Tau pathology. This novel mechanism not only underscores ANKHD1's potential as a unique therapeutic target for tauopathies but also provides new insights into autophagy-based interventions for neurodegenerative diseases.

Neural correlates of unconscious and conscious visual processing
Postdictive effects, where later events influence the perception of earlier ones, suggest that conscious perception is not a continuous stream but occurs at discrete moments, preceded by extended periods of unconscious processing. This is evident in the Sequential Metacontrast Paradigm (SQM), where a stream of lines and vernier offsets is unconsciously integrated over several hundred milliseconds before conscious perception emerges: regardless of whether one or multiple verniers are shown, only a single offset is perceived from the first to the last line. Postdictive phenomena offer a unique opportunity to study the neural correlates of unconscious and conscious stages of perception because unconscious and conscious processing are well separated in time. Using EEG recordings during the SQM, we identified two distinct stages of neural activity. Early occipital EEG activity patterns (~200 ms after the initial vernier presentation) capture unconscious processing, while later centro-parietal EEG patterns (~400-600 ms after the onset of the stimulus stream) are associated with conscious perception, aligning closely with behavioral reports. We propose that the transition between these distinct neural topographies reflects the discrete moments when conscious perception emerges.

Cerebellar white matter development is regulated by fractalkine-dependent microglia phagocytosis of oligodendrocyte progenitor cells
Complex neurodevelopmental disorders involve motor as well as cognitive dysfunction and these impairments are associated with both cerebral and cerebellar maturity. A network of connections between these two brain regions is proposed to underlie neurodevelopmental impairments. The cerebellar gray matter has a protracted developmental timeline compared to the cerebral cortex, however, making the association of these relay pathways unclear for neurodevelopmental disabilities. We show that a population of amoeboid microglia infiltrate the cerebellar white matter through the fourth ventricular zone during early postnatal development. This infiltration is synchronized with the emergence of amoeboid microglia in the ventricular zone of the lateral ventricles and appearance in cerebral white matter. Amoeboid microglia phagocytosed oligodendrocyte progenitor cells (OPCs) in the cerebellar white matter during a restricted early postnatal time window before transitioning to a ramified morphology. Modulating fractalkine receptor signaling, shown to be involved in microglial pruning of synapses, significantly reduced microglial engulfment of OPCs resulting in increased numbers of OLs and altered myelin formation. Variants in the fractalkine receptor are associated with neurodevelopmental disorders including schizophrenia and autism where myelin perturbations have been documented. Overall, these data support that white matter refinement by amoeboid microglia is coordinated in both cerebral and cerebellar development with important implications for altered circuit function in neurodevelopmental disabilities.

Comparative fMRI reveals differences in the functional organization of the visual cortex for animacy perception in dogs and humans
The animate-inanimate category distinction is one of the general organizing principles in the primate high-level visual cortex. Much less is known about the visual cortical representations of animacy in non-primate mammals with a different evolutionary trajectory of visual capacities. To compare the functional organization underlying animacy perception of a non-primate to a primate species, here we performed an fMRI study in dogs and humans, investigating how animacy structures neural responses in the visual cortex of the two species. Univariate analyses identified animate-sensitive bilateral occipital and temporal regions, non-overlapping with early visual areas, in both species. Multivariate tests confirmed the categorical representations of animate stimuli in these regions. Regions sensitive to different animate stimulus classes (dog, human, cat) overlapped less in dog than in human brains. Together, these findings reveal that the importance of animate-inanimate distinction is reflected in the organization of higher-level visual cortex, also beyond primates. But a key species difference, that neural representations for animate stimuli are less concentrated in dogs than in humans suggests that certain underlying organizing principles that support the visual perception of animacy in primates may not play a similarly important role in other mammals.