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<title>bioRxiv Subject Collection: Neuroscience</title>
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This feed contains articles for bioRxiv Subject Collection "Neuroscience"
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<title>bioRxiv</title>
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<link>https://www.biorxiv.org</link>
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<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.08.07.743553v1?rss=1">
<title>
<![CDATA[
Multiple Nested Distributed Language Networks in the Human Brain 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.08.07.743553v1?rss=1
</link>
<description><![CDATA[
Brain regions specialized for language have been extensively described, yet their arrangement into one or multiple networks remains debated. Using precision functional mapping across three independent cohorts of intensively scanned individuals (22 individuals scanned over 216 separate MRI sessions), we dissociated two nested left-lateralized perisylvian networks: an intermediate language network (intLANG) and an anatomically distinct association language network (aLANG). intLANG is anchored to precentral speech areas and the Sylvian parietal-temporal area (Spt), whereas aLANG surrounds intLANG and extends into higher-order prefrontal and temporal association cortices. The two networks can be fully recapitulated by functional connectivity from adjacent cerebellar regions, indicating that they are segregated, brain-wide networks. Task-based analyses further reveal that intLANG and aLANG are functionally distinct: intLANG responds robustly during rhyme judgments and nonword reading that emphasize phonology, whereas aLANG is preferentially recruited during meaning-based sentence processing. These findings indicate that human language engages nested distributed networks each specialized for distinct components of language processing: a lower-order network biased toward phonology, and a surrounding association network that subserves higher-order syntax and semantics. This nested organization is similar to other brain systems suggesting a shared hierarchical motif that may give rise to specialized cognitive functions across the human brain.
]]></description>
<dc:creator><![CDATA[ Du, J., Billot, A., Sun, W., Hickok, G., Eldaief, M. C., Buckner, R. L. ]]></dc:creator>
<dc:date>2026-08-08</dc:date>
<dc:identifier>doi:10.64898/2026.08.07.743553</dc:identifier>
<dc:title><![CDATA[Multiple Nested Distributed Language Networks in the Human Brain]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-08-08</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.08.06.743388v1?rss=1">
<title>
<![CDATA[
Safety learning produces rapid fear suppression and distinct amygdala-prefrontal engagement 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.08.06.743388v1?rss=1
</link>
<description><![CDATA[
Animals detect and evaluate signs of danger and safety in their environment to ensure survival, yet the neural mechanisms that distinguish safety learning from other forms of conditioned inhibition, remain poorly understood. Here, we directly compared fear and safety learning in male rats. Fear conditioned rats showed high freezing to the tone and the conditioning context, whereas safety conditioned rats showed significant tone-specific reduction in freezing. This safety cue could also generalize to a novel, previously unassociated threat context leading to suppressed freezing when presented demonstrating that inhibitory actions of safety cues are not tied to its original training environment but can modify fear expression across settings. Fear and safety learning also produced unique patterns of neuronal activation and glutamatergic receptor expression in the medial prefrontal cortex (mPFC), basolateral amygdala (BLA), and central amygdala (CeA), as measured by c-Fos immunohistochemistry and Western blotting. Fear conditioning induced greater Fos expression in the BLA and CeA, as well as elevated amygdalar NMDA receptor (GluN1) levels, whereas safety learning increased amygdalar PSD-95 and AMPA receptor (GluA1) expression. Both safety and fear learning increased mPFC Fos expression without affecting glutamatergic receptors levels. Finally, safety conditioning was associated with lower tone-evoked freezing than fear conditioned rats across early extinction sessions and was accompanied by distinct patterns of prefrontal and amygdala activation across extinction. Together, these findings suggest that safety learning engages neural and behavioral mechanisms distinct from fear learning and extinction, while modifying amygdala-prefrontal circuits towards more rapid fear suppression.
]]></description>
<dc:creator><![CDATA[ Altaf, M., Cho, C., Maletta, T. A., Lim, S., Martin, L. J., Lehmann, H., Fournier, N. M. ]]></dc:creator>
<dc:date>2026-08-08</dc:date>
<dc:identifier>doi:10.64898/2026.08.06.743388</dc:identifier>
<dc:title><![CDATA[Safety learning produces rapid fear suppression and distinct amygdala-prefrontal engagement]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-08-08</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.08.07.742341v1?rss=1">
<title>
<![CDATA[
Geometric constraints and cognitive inputs jointly shape emergent brain dynamics and topology 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.08.07.742341v1?rss=1
</link>
<description><![CDATA[
How the brain's physical geometry gives rise to its flexible functional repertoire remains a central question in neuroscience. Here, we trained three classes of recurrent neural networks (RNNs) on a working-memory task, forming a graded hierarchy of spatial constraints: Vanilla RNNs (no spatial constraints), Masked RNNs (projection constraints limiting where information enters and leaves the network), and biophysical RNNs (bioRNNs; projection constraints and spatial embedding of the networks' connectivity using the brain's inter-regional Euclidean geometry). We assessed how well each RNN class predicted empirical fMRI activity without exposing them to it during training. Our results showed that bioRNNs were the only networks to successfully predict empirical brain activity and to organize their dynamics into a spatial pattern that recapitulated the brain's principal hierarchy (the sensorimotor-association axis). Additionally, bioRNNs' ability to predict empirical brain activity emerged along a trajectory in which geometry was laid down first, then partly traded back as the task was mastered. Importantly, brain-like topological features emerged in bioRNNs as they increased their task proficiency while maintaining their ability to predict brain activity. Taken together, our results indicate that physical geometry and cognitive inputs play distinct, complementary roles: while geometry constrains the space of possible brain dynamics, cognitive inputs determine which dynamics are expressed. They also situate topology as the scaffold through which the physically embedded brain reconciles wiring costs and computational demands.
]]></description>
<dc:creator><![CDATA[ Beyh, A., Kim, J. Z., Bajwa, W. U., Parkes, L. ]]></dc:creator>
<dc:date>2026-08-08</dc:date>
<dc:identifier>doi:10.64898/2026.08.07.742341</dc:identifier>
<dc:title><![CDATA[Geometric constraints and cognitive inputs jointly shape emergent brain dynamics and topology]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-08-08</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.08.06.742872v1?rss=1">
<title>
<![CDATA[
Exercise engages a mechanically activated astrocyte state linking muscle activity to hippocampal plasticity 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.08.06.742872v1?rss=1
</link>
<description><![CDATA[
Physical exercise promotes brain health in part through muscle-derived factors that enter the brain, but how peripheral signals are translated into neural responses remain unclear. Here, we identify astrocyte contraction as a previously unrecognized physiological response to exercise signals that may contribute to adult hippocampal neurogenesis. In vivo, voluntary running rapidly induced nuclear localization of the mechanically sensitive transcriptional regulator Yes-associated protein (YAP), and increased non-muscle myosin II phosphorylation in hilar astrocytes in mice, consistent with acute contraction. Using an in vitro platform with ultrasensitive force sensors, we found that factors released by contracting skeletal muscles activated astrocytes which in turn increased contraction that was necessary and sufficient for their proliferation and expansion. Activated astrocytes subsequently released soluble factors that modulated neuronal network tension and promoted immature neuron abundance. These findings identify astrocyte contractility as a physiological transducer of exercise-derived muscle signals and establish cellular force generation as a potential mechanism regulating neuroplasticity.
]]></description>
<dc:creator><![CDATA[ JOY, M. S. H., Manavbasi, I. E., Lee, K. Y., Connolly, M. G., Glueck, Q. V., Ahmed, M., Zayyad, M. A., Heidari, Y., Emon, B., Song, J., Deswal, Y., Lee, D., Ritchie, J. P., Sripraram, N., Rhodes, J. S., Saif, M. T. A. ]]></dc:creator>
<dc:date>2026-08-08</dc:date>
<dc:identifier>doi:10.64898/2026.08.06.742872</dc:identifier>
<dc:title><![CDATA[Exercise engages a mechanically activated astrocyte state linking muscle activity to hippocampal plasticity]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-08-08</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.08.07.743566v1?rss=1">
<title>
<![CDATA[
Two types of response inhibition failures in humans 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.08.07.743566v1?rss=1
</link>
<description><![CDATA[
Response inhibition is a key control function that allows humans to perform safe, goal-directed behaviors. The dominant behavioral-computational model holds that response inhibition fails when the inhibition process is too slow to intercept unwanted movements. However, many have hypothesized that some inhibitory failures instead result from a failure to launch the inhibition process altogether. Since no method exists to identify individual 'trigger failure' (TF) trials, they are hitherto a largely hypothetical phenomenon. We combined Bayesian process-mixture modeling with likelihood ratio testing and jackknife resampling to identify TF trials in 253 humans. We find that TF indeed represent a separate category from other inhibitory failures. Unlike other inhibitory failures, TF do not result from premature responses. Furthermore, TF lack a stop-signal P3 event-related potential, a neural index of response inhibition. Surprisingly, TF do not result from perceptual/attentional lapses. Thus, TF are a qualitatively distinct class of executive failure during response inhibition.
]]></description>
<dc:creator><![CDATA[ Acker, S. F., Wessel, J. R. ]]></dc:creator>
<dc:date>2026-08-08</dc:date>
<dc:identifier>doi:10.64898/2026.08.07.743566</dc:identifier>
<dc:title><![CDATA[Two types of response inhibition failures in humans]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-08-08</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.08.06.743398v1?rss=1">
<title>
<![CDATA[
Parabrachial oxytocin receptor-expressing neurons link social observation of distress to defensive behavior 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.08.06.743398v1?rss=1
</link>
<description><![CDATA[
The ability to detect and respond to threat signals in the environment, including those conveyed by the distress of a familiar social partner, is fundamental to survival and disrupted in a range of neuropsychiatric conditions. This study identifies oxytocin receptor (Oxtr)-expressing neurons within the lateral parabrachial nucleus (lPBN) of mice as a key node in the neural circuitry underlying threat-related and social behaviors. These Oxtr neurons are activated by aversive stimuli and by observing demonstrator mice in stressful situations, including foot shock or inflammatory pain. Chemogenetic inhibition of these neurons alters social proximity and pain contagion in observers without affecting general anxiety-like behavior. Inhibition also transiently suppresses non-social central sensitization. Direct activation of lPBNOxtr neurons with a selective Oxtr agonist is anxiogenic and results in increased tactile sensitivity. Together, these findings suggest that lPBNOxtr neurons are poised to integrate information about environmental threat, whether experienced directly or witnessed in a conspecific to coordinate appropriate defensive behavioral responses.
]]></description>
<dc:creator><![CDATA[ Judd, E. N., Pauli, J. L., Kenmochi, S. J., Bruchas, M. R., Palmiter, R. D. ]]></dc:creator>
<dc:date>2026-08-08</dc:date>
<dc:identifier>doi:10.64898/2026.08.06.743398</dc:identifier>
<dc:title><![CDATA[Parabrachial oxytocin receptor-expressing neurons link social observation of distress to defensive behavior]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-08-08</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.08.07.743556v1?rss=1">
<title>
<![CDATA[
Social Motivation and Hippocampal-Cortical Structural Development in Adolescent Girls 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.08.07.743556v1?rss=1
</link>
<description><![CDATA[
Adolescence is a fundamental developmental period marked by dramatic socio-affective and physiological changes, including shifts in social behavior and maturation of underlying brain architecture. In girls, this period coincides with the onset of the pubertal transition, which fundamentally influences motivated social behavior and neurodevelopment. The present study examines age- and pubertal maturation-related changes in social motivational goals and hippocampal and motivation-related cortical structural development in adolescent girls (n=154) across five timepoints. Social motivational goals showed substantial variability of each subdomain across age and pubertal development. Specifically, all social goals showed linear increases across age and pubertal stage, whereas goals centered around developing social competency increased non-linearly across age. Our neurodevelopmental findings align with established research, revealing volumetric increases of the hippocampus, and cortical thinning of the medial orbitofrontal cortex (mOFC) and rostral anterior cingulate cortex (rACC) across age and pubertal stages. Collectively, these results highlight simultaneous change in endorsement and prioritization of different social motivational goals across adolescence, and they underscore the simultaneous shifts in structural development in regions supporting social motivation and broader socio-affective development. This research highlights the importance of fostering positive social experiences during this critical developmental stage, with implications for adolescent well-being and social development.
]]></description>
<dc:creator><![CDATA[ Goldberg, M. N., Reck, A. J., Skyberg, A. M., Murty, V. P., Pfeifer, J. H. ]]></dc:creator>
<dc:date>2026-08-08</dc:date>
<dc:identifier>doi:10.64898/2026.08.07.743556</dc:identifier>
<dc:title><![CDATA[Social Motivation and Hippocampal-Cortical Structural Development in Adolescent Girls]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-08-08</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.08.07.743627v1?rss=1">
<title>
<![CDATA[
Distinct mitochondrial phenotypes align with visual and semantic representations across human cortex 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.08.07.743627v1?rss=1
</link>
<description><![CDATA[
How cellular energetics relates to the information represented by human cortex is unknown. Using 7T fMRI during natural-scene viewing, image-to-brain encoding frameworks, spatial-autocorrelation-preserving inference and postmortem molecular atlases, we separated cortical variance uniquely attributable to visual versus semantic features. Visual-specific variance aligned negatively with mitochondrial density and respiratory capacity, whereas semantic-specific variance aligned positively with mitochondrial density; convergent transcriptomic enrichment linked these representational axes to opposing mitochondrial and cellular programs.
]]></description>
<dc:creator><![CDATA[ Lu, Z., Wang, Y. ]]></dc:creator>
<dc:date>2026-08-08</dc:date>
<dc:identifier>doi:10.64898/2026.08.07.743627</dc:identifier>
<dc:title><![CDATA[Distinct mitochondrial phenotypes align with visual and semantic representations across human cortex]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-08-08</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.08.07.743469v1?rss=1">
<title>
<![CDATA[
Oligodendroglial deletion of the microcephaly gene Cit-k disrupts cortical connectivity and cognitive function 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.08.07.743469v1?rss=1
</link>
<description><![CDATA[
Neurodevelopmental disorders (NDDs) are increasingly recognized as disorders of brain connectivity and circuit dysfunction. Growing evidence suggests that glial cell and myelin abnormalities may actively contribute to these alterations. Yet, they have been often considered secondary consequences of impaired neuronal development rather than primary drivers of circuit dysfunction. Primary autosomal recessive microcephaly type 17 (MCPH17) is a severe NDD caused by mutations in the CIT gene, encoding Citron kinase (CIT-K). The disease is associated with cognitive and motor deficits, epilepsy susceptibility, and marked hypomyelination in both patients and mouse models, suggesting a contribution of oligodendroglial dysfunction to disease pathophysiology. Here, we investigated the specific role of oligodendroglial Cit-k loss using Sox10Cre;Cit-kfl/fl mice, in which Cit-k is selectively deleted in oligodendrocyte-lineage cells. Mutant mice displayed impaired forebrain myelination at juvenile stages and persistent cortical hypomyelination in adulthood. Despite preserved gross motor function, adult mutants showed deficits in fine motor control, working and recognition memory, and auditory fear memory. These impairments were associated with altered cortico-cortical and cortico-hippocampal functional connectivity. Moreover, consistent with the clinical MCPH17 phenotype, mutant mice exhibited increased susceptibility to kainate-induced seizures. Together, our findings show that oligodendroglial Cit-k loss and the resulting hypomyelination are sufficient to produce long-lasting neurological and behavioral impairments independently of primary neuronal defects. These results identify oligodendrocytes as active contributors to MCPH17 and support a broader role for myelin abnormalities in NDDs.
]]></description>
<dc:creator><![CDATA[ Bonato, M., Marchiotto, F., Khastkhodaei Ardakani, M., Ferrari, F. G. P., Di Cintio, N., Renna, A., Roggero, O. M., Montarolo, F., Cerrato, V., Frasca, A., Sacchetti, B., Buffo, A., Cambiaghi, M., Boda, E. ]]></dc:creator>
<dc:date>2026-08-08</dc:date>
<dc:identifier>doi:10.64898/2026.08.07.743469</dc:identifier>
<dc:title><![CDATA[Oligodendroglial deletion of the microcephaly gene Cit-k disrupts cortical connectivity and cognitive function]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-08-08</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.08.03.742447v1?rss=1">
<title>
<![CDATA[
Molecular Disease Stages of Oligodendrocytic and Neuronal Tau Burden in Progressive Supranuclear Palsy 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.08.03.742447v1?rss=1
</link>
<description><![CDATA[
Background. Progressive supranuclear palsy (PSP) is a primary tauopathy defined by the accumulation of 4R tau isoforms in neurons, oligodendrocytes and astrocytes. Despite evidence of genetic susceptibility operating through glial cell types, it remains poorly understood how cell type-specific epigenetic-transcriptional programs evolve with progression of tau pathology. Methods. We conducted single-nucleus chromatin accessibility (snATACseq) and RNA sequencing (snRNAseq) on postmortem frontal cortex samples from PSP patients (n = 8) and matched controls (n = 8), yielding over 144,000 nuclei passing quality control. Tau pathology burden, including neurofibrillary tangles, coiled bodies, and tufted astrocytes, was quantified on AT8-immunostained sections from the same individuals. We integrated differential gene expression analysis, transcription factor motif enrichment, weighted gene co-expression network analysis, and pseudotime modeling anchored to cell type-specific tau pathology burden to delineate molecular pseudo-progression trajectories. Results. In eight cell types, 20 subclasses, and 70 subclusters, PSP brains displayed a selective depletion of certain excitatory deep-layer neurons and oligodendrocyte subclusters, with relative preservation of inhibitory neurons and vascular cells. Genetic risk enrichment was localized to astrocytes and oligodendrocytes, whereas excitatory neurons exhibited the greatest transcriptional dysregulation. Oligodendrocyte pseudo-progression indicated a transition from homeostatic myelination programs (MBP, MOBP) through glucocorticoid-responsive stress (FKBP5, ZBTB16), to compensatory myelination (PLP1, CNP) and proteostasis stress (UCHL1, CYRAB, CLU). Neuronal pseudo-progression revealed early dysregulation of synaptic (RORB2, NRG3, NPTX1), microtubule dynamics (KIF2C, RAB27B, TUBA/B), and survival (MEG3, FTX) pathways, alongside a transient increase in neuron-glia interactions (GRIP, CNTNAP4, ERBB4), converging late on ribosomal translation and vesicular trafficking modules across all neuronal subtypes. Cross-modal integration with independent cerebrospinal fluid proteomics identified a concordant subset of glial reactivity, axonal injury, and synaptic markers jointly dysregulated in inhibitory neurons, oligodendrocytes, and excitatory deep-layer neurons. Conclusion. PSP pathogenesis reflects a combination of glial genetic susceptibility and staged, cell type-specific transcriptional dysfunction. Oligodendrocytes transition from myelination-competent states to FKBP5-mediated stress states, while neurons show variably timed loss of synaptic excitability and survival programs, preceded by neuron-glia interactions and followed by convergent ribosomal-proteostatic failure. These cytopathology-anchored trajectories outline a potential pathophysiological sequence and may inform candidate selection for stage-specific therapeutic interventions in PSP.
]]></description>
<dc:creator><![CDATA[ Briel, N., Ruf, V. C., Feyen, P. L. C., Roeber, S., Arzberger, T., Windl, O., Weiss, T., Arosio, P., Hoeglinger, G., Struebing, F. L., Herms, J. ]]></dc:creator>
<dc:date>2026-08-07</dc:date>
<dc:identifier>doi:10.64898/2026.08.03.742447</dc:identifier>
<dc:title><![CDATA[Molecular Disease Stages of Oligodendrocytic and Neuronal Tau Burden in Progressive Supranuclear Palsy]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-08-07</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.08.03.742511v1?rss=1">
<title>
<![CDATA[
Hypoglycosylation lowers the mechanical activation threshold of Piezo1 and enhances cortical neuronal mechanotransduction: implications for PMM2-CDG 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.08.03.742511v1?rss=1
</link>
<description><![CDATA[
Piezo1 is a mechanically activated cation channel whose N-linked glycans support protein maturation and plasma membrane trafficking, but their contribution to mechanical gating is unknown. We asked whether hypoglycosylation alters Piezo1 mechanosensitivity and cortical neuronal mechanotransduction, with potential relevance to neurological manifestations of congenital disorders of glycosylation (CDG). Human Piezo1 was studied in HEK293 cells after mutation of two conserved cap-domain N-glycosylation sites or inhibition of N-glycan maturation with swainsonine or kifunensine. Mechanically activated currents were recorded by cell-attached patch-clamp during incremental negative-pressure pulses, whereas Ca2+ responses were measured during uniaxial stretch. Piezo1 abundance, synaptic localisation and stretch-evoked Ca2+ signals were also examined in primary mouse cortical neurons. On poly-L-lysine, N2293Q or N2330Q shifted the pressure-response relationship towards lower activating pressures without changing maximal current or inactivation kinetics. This effect was absent on collagen. Swainsonine and kifunensine reduced mature Piezo1 glycosylation and lowered the mechanical activation threshold. Hypoglycosylation enhanced Ca2+ entry during submaximal stretch in HEK293 cells. In cortical neurons, inhibition of glycan maturation increased somatic Piezo1 immunoreactivity without changing its association with synaptic markers, and potentiated Ca2+ responses to both the Piezo1 activator Yoda1 and submaximal stretch. Thus, mature N-glycans and the extracellular adhesive environment jointly set Piezo1 mechanical activation threshold rather than merely regulating biosynthesis and trafficking. These findings establish glycosylation-mechanics coupling as a determinant of neuronal force sensing and suggest that, by facilitating Piezo1 recruitment, defective glycosylation may increase cortical vulnerability to mechanical stress, potentially contributing to head trauma-triggered neurological episodes in phosphomannomutase 2 deficiency (PMM2-CDG).
]]></description>
<dc:creator><![CDATA[ EDO-PEREZ, A., RODRIGUEZ-URQUIRIZAR, G., FERNANDEZ-ARROYO, A., CARRILLO-GARCIA, J., FERNANDEZ-FERNANDEZ, J. M. ]]></dc:creator>
<dc:date>2026-08-07</dc:date>
<dc:identifier>doi:10.64898/2026.08.03.742511</dc:identifier>
<dc:title><![CDATA[Hypoglycosylation lowers the mechanical activation threshold of Piezo1 and enhances cortical neuronal mechanotransduction: implications for PMM2-CDG]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-08-07</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.08.03.742517v1?rss=1">
<title>
<![CDATA[
Aperiodic neural activity links electromagnetic and hemodynamic representations of domain-general cognitive demand across the cortical hierarchy 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.08.03.742517v1?rss=1
</link>
<description><![CDATA[
The human brain demonstrates remarkable flexibility and capacity for domain-general cognitive control, allowing us to perform diverse and complex tasks. Central to this ability is the multiple-demand (MD) network, a domain-general system that is robustly engaged during demanding tasks in fMRI studies. However, the electrophysiological signatures underlying these domain-general responses remain elusive. While recent research has implicated aperiodic neural activity as a promising candidate, the limited spatial resolution of non-invasive electrophysiology has left it unresolved how this aperiodic signal relates to demand-related activity within the MD network and whether this relationship reflects a broader organizational principle across the cortex. To address these questions, we used a multimodal fusion framework to integrate fMRI and magnetoencephalography (MEG) data acquired while participants performed a diverse set of cognitive control tasks. We found that raw MEG-fMRI correspondence was strongest in unimodal sensorimotor cortices and progressively decreased toward transmodal association cortex during cognitive control tasks, revealing a hierarchical decline in correspondence between the electromagnetic and hemodynamic signals measured by these technologies. However, the proportion of this variance that was attributable to cognitive demand and carried by aperiodic signals showed the reverse gradient, systematically increasing along the sensorimotor-association axis. In particular, in the MD network, aperiodic broadband power showed the strongest demand-specific cross-modal commonality, outperforming canonical oscillatory components. These findings reveal two opposing hierarchical gradients: overall MEG-fMRI correspondence across all electrophysiological signals decreased toward association cortex, whereas the proportion attributable to aperiodic signals associated with cognitive demand increased. Our results identify aperiodic neural activity as a key electrophysiological substrate of cognitive control and a bridge linking electromagnetic and hemodynamic representations across the cortical hierarchy.
]]></description>
<dc:creator><![CDATA[ Lu, R., Assem, M., Liu, X., Duncan, J., Woolgar, A. ]]></dc:creator>
<dc:date>2026-08-07</dc:date>
<dc:identifier>doi:10.64898/2026.08.03.742517</dc:identifier>
<dc:title><![CDATA[Aperiodic neural activity links electromagnetic and hemodynamic representations of domain-general cognitive demand across the cortical hierarchy]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-08-07</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.08.03.742519v1?rss=1">
<title>
<![CDATA[
Differently sized soluble α-synuclein species from multiple system atrophy and Lewy body disease brains display different seeding propensities 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.08.03.742519v1?rss=1
</link>
<description><![CDATA[
Different conformations, or strains, of -synuclein (-syn) aggregates are believed to be responsible for the distinct seeding propensities, propagation profiles, and clinical presentations in Lewy body diseases (LBD) and multiple system atrophy (MSA). While biochemical properties and strain differences of insoluble deposits have been extensively characterized, the understanding of what influence soluble -syn species may have on these processes is limited to a small number of studies focusing on complex mixtures of soluble species or on a single -synucleinopathy. Given that soluble oligomers are considered highly pathologically relevant, we isolated and characterized the biochemical, seeding, and toxicity properties of size-fractionated soluble -syn species from MSA and LBD brains, comparing them to species from control brains without known neurological disease (Ctrl). We observed that levels of differently sized oligomers phosphorylated at Ser129, as well as soluble large oligomers (>450 kDa), were increased in LBD compared to both MSA and Ctrl brains. Nevertheless, species derived from MSA brain exhibited seeding activity across the spectrum of -syn species (oligomers, monomers, and truncated forms) in the seed amplification assay, whereas only oligomeric species (>150 kDa) from LBD cases were seeding-prone. In the HEK293 -syn (A53T)-YFP biosensor line, as well as in murine primary neurons, only large oligomers (>450 kDa) from MSA cases induced seeding and aggregation of -syn. Taken together, our study suggests that soluble -syn species derived from MSA and LBD brains show different biochemical, aggregation and seeding patterns, presumably due to strain variations of the respective oligomers. Our findings provide novel insight into the pathogenesis of different -synucleinopathies, which may guide us in the development of targeted therapeutics.
]]></description>
<dc:creator><![CDATA[ Zampar, S., Mei, Y., Samuel, F., Karadag, M., Martinez-Valbuena, I., Silver, N. R. G., Grimmer, G., Di Gregorio, S. E., Tandon, A., Kovacs, G. G., Watts, J. C., Ingelsson, M. ]]></dc:creator>
<dc:date>2026-08-07</dc:date>
<dc:identifier>doi:10.64898/2026.08.03.742519</dc:identifier>
<dc:title><![CDATA[Differently sized soluble α-synuclein species from multiple system atrophy and Lewy body disease brains display different seeding propensities]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-08-07</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.08.03.742546v1?rss=1">
<title>
<![CDATA[
Neuromuscular Architecture of the Siphonophore Colony 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.08.03.742546v1?rss=1
</link>
<description><![CDATA[
Siphonophores are colonial hydrozoans with unprecedented differentiation and specialization, in which individual zooids are transformed into functional organs rather than autonomous polyps capable of feeding. As a result, the entire colony acts as a single, modular individual with the highest level of coordination and integration, from development through behavior. Deciphering these integrative mechanisms requires understanding the microanatomical organization of the nervous and muscular systems in all elements of the colony. Here, using two immunohistochemical markers (anti-tubulin and anti-RFamide antibodies), we systematically characterize the neuromuscular organization across the entire Nanomia colony, encompassing pneumatophore, stem, and all zooid classes (nectophores, gastrozooids, palpons, male and female gonophores, and protective zooids). The use of two neural markers enables visualization of distinct neural subpopulations, some of which are not revealed by a single marker. We provide evidence of neuroanatomical interactions within all elements of the colony, including contributions of giant axons, stem polygonal nets, and RFamide-ir neural rings at the base of each zooid, as well as describe different subpopulations of neural nets and muscles elements in the body of various zooids. The presented mapping facilitates identification of novel conductive and signaling pathways for future analysis of the cellular basis of behavioral integration within decentralized, broadly distributed networks and non-neuronal elements of these unique superorganisms.
]]></description>
<dc:creator><![CDATA[ Moroz, L. L., Norekian, T. P. ]]></dc:creator>
<dc:date>2026-08-07</dc:date>
<dc:identifier>doi:10.64898/2026.08.03.742546</dc:identifier>
<dc:title><![CDATA[Neuromuscular Architecture of the Siphonophore Colony]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-08-07</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.08.03.742487v1?rss=1">
<title>
<![CDATA[
Distinct cognitive and structural correlates of pain extent and central sensitization symptoms in older women and men with chronic pain 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.08.03.742487v1?rss=1
</link>
<description><![CDATA[
Chronic pain in later life may be accompanied by alterations in brain structure and cognition, but whether pain extent and central sensitization symptoms identify distinct brain-behavior patterns remains unclear. We examined associations of pain extent and central sensitization symptoms, assessed using the 9-item Central Sensitization Inventory (CSI-9), with regional gray matter volume and cognitive function in community-dwelling older adults. This cross-sectional study included 272 participants with chronic pain from the Bunkyo Health Study. Participants were classified as having single-site or multisite pain and by CSI-9 score as having lower or higher scores, with 12 or higher defining the higher group. Regional gray matter volume was quantified using 0.3-Tesla magnetic resonance imaging, and cognition was assessed using the Trail Making Test Part B (TMT-B), processing speed, and global and domain-specific measures. Pain extent and CSI-9 group interacted for TMT-B performance, with the longest completion time in participants with single-site pain and a higher CSI-9 score. No other cognitive outcome remained significant after correction for multiple testing. In categorical analyses, the higher CSI-9 group had smaller volumes in the right middle frontal gyrus, bilateral anterior cingulate cortex, right insula, right hippocampus, and bilateral amygdala, whereas pain extent and the interaction were not associated with regional volume. In a contextual comparison, only the single-site/higher CSI-9 group showed slower TMT-B performance than participants with no current pain. Pain extent and central sensitization symptoms may represent partly distinct dimensions of chronic pain, although the small single-site/higher CSI-9 group and attenuation in several sensitivity analyses warrant caution.
]]></description>
<dc:creator><![CDATA[ Yamada, K., Tabata, H., Takabayashi, K., Hitoshi, N., Kaga, H., Kamagata, K., Tamura, Y. ]]></dc:creator>
<dc:date>2026-08-07</dc:date>
<dc:identifier>doi:10.64898/2026.08.03.742487</dc:identifier>
<dc:title><![CDATA[Distinct cognitive and structural correlates of pain extent and central sensitization symptoms in older women and men with chronic pain]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-08-07</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.08.03.742432v1?rss=1">
<title>
<![CDATA[
Cortical Thinning Predicts Resting Vagally Mediated Heart Rate Variability: A Longitudinal Study Across Adolescent Development 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.08.03.742432v1?rss=1
</link>
<description><![CDATA[
Introduction: Vagally mediated heart rate variability (vmHRV) reflects parasympathetic cardiac control and serves as a peripheral marker of brain-body interaction. While studies in adults link higher vmHRV to greater cortical thickness regions related autonomic regulatory, little is known about its association with longitudinal cortical maturation during puberty, a period of pronounced cortical thinning. Methods: This longitudinal study examined whether individual differences in cortical thinning trajectories are associated with vmHRV in two independent cohorts of children and adolescents. Structural MRI were acquired in an accelerated longitudinal design over three time points, each one year apart in two cohorts (n = 44; ages 9 and 12 at baseline). Cortical thickness was estimated using FreeSurfer, and annualized regional thinning slopes were derived for 62 cortical regions. vmHRV was measured one year later at follow-up. Elastic net regression with stability selection identified robust predictors, which were entered into linear models separately for each cohort. Results: Across both cohorts, vmHRV was associated with distributed patterns of cortical thinning. Consistent associations emerged in medial and posterior midline regions, including the precuneus, isthmus of the cingulate cortex, and medial prefrontal and orbitofrontal areas. Associations showed heterogeneous directions across regions, contrasting with uniform adult findings. Discussion: vmHRV may be linked to network-level cortical maturation during adolescence, particularly within default mode and fronto-limbic systems. Findings extend adult work by demonstrating that brain-autonomic coupling emerges during development and is characterized by regionally differentiated trajectories of cortical thinning.
]]></description>
<dc:creator><![CDATA[ Schmausser, M., Baumeister-Lingens, L., Schulte, S., Kaess, M., Brunner, R., Koenig, J. ]]></dc:creator>
<dc:date>2026-08-07</dc:date>
<dc:identifier>doi:10.64898/2026.08.03.742432</dc:identifier>
<dc:title><![CDATA[Cortical Thinning Predicts Resting Vagally Mediated Heart Rate Variability: A Longitudinal Study Across Adolescent Development]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-08-07</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.08.03.742404v1?rss=1">
<title>
<![CDATA[
Exploratory spatial peptidomic profiling during incubation of drug seeking following cocaine plus alcohol self-administration in young adult rats 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.08.03.742404v1?rss=1
</link>
<description><![CDATA[
Background: Concurrent cocaine and alcohol use is one of the most prevalent forms of polysubstance consumption and is associated with poorer clinical outcomes than cocaine use alone. However, the regional molecular adaptations induced by combined exposure remain poorly understood. Here, we used matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) to characterize peptide/protein alterations in addiction-related brain regions following cocaine and cocaine-alcohol self-administration. Methods: Young adult male and female Wistar rats underwent intravenous self-administration of saline, cocaine (1 mg/kg/infusion) or cocaine plus ethanol (1 mg/kg cocaine and 133 mg/kg ethanol per infusion), followed by extinction of drug-seeking behaviour. Coronal brain sections containing the anterior cingulate cortex (ACC) and ventral hippocampus (vHPC) were analysed by MALDI-IMS. Differential molecular features were identified using an exploratory statistical approach (FDR q < 0.20) and subsequently subjected to MS/MS analysis. Results: The ACC exhibited a substantially greater number of treatment-associated molecular alterations than the vHPC, suggesting a higher regional susceptibility to cocaine-induced molecular remodelling. Several molecular features were shared between the cocaine and cocaine-alcohol groups, indicating persistent cocaine-driven neuroadaptations. In contrast, additional signals were selectively associated with combined cocaine-alcohol exposure, while others present after cocaine alone were absent following alcohol co-exposure, supporting a modulatory effect of alcohol on specific cocaine-induced molecular responses. Overall, combined exposure generated a distinct regional molecular profile rather than simply reproducing the effects of cocaine alone. Conclusions: This exploratory study demonstrates that MALDI-IMS enables the identification of region-specific peptide/protein alterations associated with cocaine and cocaine-alcohol exposure while preserving their spatial distribution within the brain. These findings highlight the ACC as a particularly responsive region and provide a framework for future studies aimed at validating molecular pathways involved in cocaine-alcohol polysubstance use.
]]></description>
<dc:creator><![CDATA[ Puig, N., Castillo-Sarmiento, C. A., Garrido-Matilla, L., Marcos, A., Peinado, J. R., Rabanal-Ruiz, Y., Saiz-Sanchez, D., Spano, E., Vera Fernandez, C., Ballesteros-Yanez, I., Ambrosio, E. ]]></dc:creator>
<dc:date>2026-08-07</dc:date>
<dc:identifier>doi:10.64898/2026.08.03.742404</dc:identifier>
<dc:title><![CDATA[Exploratory spatial peptidomic profiling during incubation of drug seeking following cocaine plus alcohol self-administration in young adult rats]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-08-07</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.08.03.742281v1?rss=1">
<title>
<![CDATA[
Multimodal neuroimaging-microbiota integration identifies Akkermansia as a modulator of alcohol-induced gut-liver-brain pathology 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.08.03.742281v1?rss=1
</link>
<description><![CDATA[
Alcohol use disorder (AUD) disrupts the gut-liver-brain axis, yet mechanistically grounded and therapeutically actionable targets within this network remain poorly defined. To identify microbial modulators of alcohol-induced tissue pathology, longitudinal advanced diffusion MRI and fecal 16S rRNA profiling were integrated across Marchigian Sardinian alcohol-preferring rats evaluated at baseline, after four weeks of voluntary alcohol intake, and following six weeks of abstinence. Machine learning, specifically random forest models combining neuroimaging and microbiota data, improved phase classification and identified Akkermansia as the microbial feature most strongly associated with alcohol-related white matter microstructural abnormalities. Alcohol exposure induced widespread white matter alterations alongside gut dysbiosis characterized by reduced microbial diversity. To evaluate functional relevance, Akkermansia muciniphila was administered during the abstinence phase. Supplementation with A. muciniphila restored intestinal mucus, reduced liver injury markers, and elevated myelin basic protein levels within affected white matter regions. Collectively, these findings highlight Akkermansia as a critical modulator of alcohol-induced gut-liver-brain pathology and provide experimental support for a causal contribution of specific gut bacteria to persistent white matter damage in AUD. More broadly, this work establishes a robust multimodal framework for microbiome-based target discovery with clear translational relevance for disorders characterized by dysfunction along the gut-liver-brain axis.
]]></description>
<dc:creator><![CDATA[ Selim, M. K., Panadero Soler, D., De Santis, S., Bentez-Paez, A., Flor, A., Sanz, C., Mesquita, M., Cubero, F. J., Ciccociopo, R., Pertusa, A., Sanz, Y., Canals, S. ]]></dc:creator>
<dc:date>2026-08-07</dc:date>
<dc:identifier>doi:10.64898/2026.08.03.742281</dc:identifier>
<dc:title><![CDATA[Multimodal neuroimaging-microbiota integration identifies Akkermansia as a modulator of alcohol-induced gut-liver-brain pathology]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-08-07</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.08.03.742448v1?rss=1">
<title>
<![CDATA[
Age-dependent brain pigmentation drives early neuroinflammatory molecular signatures linked to neurodegeneration 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.08.03.742448v1?rss=1
</link>
<description><![CDATA[
Background: Neuromelanin (NM) is a pigment that progressively accumulates with age in catecholaminergic neurons, particularly in the substantia nigra, ventral tegmental area, and locus coeruleus. These neuronal populations are especially vulnerable to degeneration in Parkinson's disease (PD). Elevated intracellular NM levels have been linked to neurodegeneration and PD-like phenotypes in experimental models. However, the molecular mechanisms underlying NM-induced pathology remain poorly understood, as human studies cannot disentangle the specific effects of NM accumulation from those of normal aging. Methods: We performed transcriptomic microarray analysis on laser-captured catecholaminergic neurons and regions (substantia nigra, ventral tegmental area, locus coeruleus) from NM-producing transgenic mice (tgNM) and NM-free wild-type controls across different ages, and compared them to data from postmortem human brain tissue. One of the molecular targets identified, GPNMB, was validated in mouse and human tissue, and functionally tested in vivo. Results: We identified region- and age-dependent transcriptional changes associated with progressive NM accumulation. NM consistently upregulated neuroinflammatory pathways with enrichment of disease-associated microglial genes, while downregulating transcription, translation, and mitochondrial functions. Locus coeruleus exhibited the earliest and strongest transcriptional alterations, whereas substantia nigra and ventral tegmental area showed a later-onset, age-progressive transcriptional dysfunction. Neuron-specific analyses revealed that many changes originated within NM-containing neurons rather than being solely glial-driven. NM-driven transcriptional profiles in mice strongly correlated with postmortem data from PD patients, underscoring their translational relevance. Among molecular targets, the glycoprotein GPNMB was consistently upregulated in NM-containing neurons and validated at RNA and protein levels in both NM-producing transgenic mice and human PD brains. Functional experiments demonstrated that GPNMB overexpression attenuated NM-linked dopaminergic neurodegeneration and improved motor performance in mice. Conclusion: This study provides a comprehensive in vivo characterization of NM-specific transcriptomic changes in catecholaminergic neurons, showing that NM accumulation drives neuroinflammatory and neurodegenerative programs. Our results support that the neuroinflammatory changes observed in tgNM mice and in human PD represent early pathological events that precede overt neurodegeneration. The disease-associated gene GPNMB emerged as a conserved NM-induced factor with protective properties, highlighting its potential as a therapeutic target in PD and aging-related neurodegeneration.
]]></description>
<dc:creator><![CDATA[ Penuelas, N., Xicoy, H., Lorente-Picon, M., Nicolau-Vera, A., Parent, A., Gonzalez-Sepulveda, M., Laguna, A., Vila, M. ]]></dc:creator>
<dc:date>2026-08-07</dc:date>
<dc:identifier>doi:10.64898/2026.08.03.742448</dc:identifier>
<dc:title><![CDATA[Age-dependent brain pigmentation drives early neuroinflammatory molecular signatures linked to neurodegeneration]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-08-07</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.08.02.742348v1?rss=1">
<title>
<![CDATA[
A modular cranial window enabling maintainable widefield optical access in non-human primates 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.08.02.742348v1?rss=1
</link>
<description><![CDATA[
Longitudinal optical imaging of the primate cortex requires stable yet maintainable cortical access, but existing cranial window approaches remain limited by mechanical instability and tissue responses that progressively degrade optical clarity. These challenges are amplified in primates, where large craniotomies and physiological variability complicate chronic experiments. Moving beyond conventional fixed cranial windows, we present the PRIME cranial window (Primate Reconfigurable Interchangeable Modular Enclosure), a modular platform enabling maintainable, long-term, and widefield optical access in awake macaques. Built on a modular architecture, PRIME supports non-invasive adjustment, repeated cortical access, and on-demand maintenance, including tissue removal, without surgical re-entry, while a dual-ring sealing mechanism prevents cerebrospinal fluid leakage and contamination. Combined with optimized viral delivery, implantation, and maintenance strategies, PRIME preserves cortical integrity and optical clarity for long-term optical imaging. PRIME establishes a versatile, re-accessible experimental framework for chronic, large-area optical studies of the primate brain.
]]></description>
<dc:creator><![CDATA[ Jeong, W., Kim, D., Kim, J., Lee, Y., Yoo, R., Lee, J., Choi, M., Kim, H. F. ]]></dc:creator>
<dc:date>2026-08-07</dc:date>
<dc:identifier>doi:10.64898/2026.08.02.742348</dc:identifier>
<dc:title><![CDATA[A modular cranial window enabling maintainable widefield optical access in non-human primates]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-08-07</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.08.02.742221v1?rss=1">
<title>
<![CDATA[
Region-specific Bmal1 deletion in the dorsal striatum alters alcohol consumption in a sex-specific manner 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.08.02.742221v1?rss=1
</link>
<description><![CDATA[
Background: Circadian disruption is strongly associated with alcohol use disorder (AUD), but insight into the underlying brain-region and sex-specific mechanisms is limited. The function of the circadian clock gene Bmal1 within the striatum has been linked to alcohol drinking, yet its role within functionally distinct striatal subregions has not been systematically examined. Methods: We deleted Bmal1 in medium spiny neurons of the dorsomedial striatum (DMS) or dorsolateral striatum (DLS). Male and female mice were tested for anxiety-like behavior, depressive-like behavior, and motor coordination. Voluntary alcohol intake was measured with an intermittent two-bottle choice paradigm, followed by sucrose preference and quinine-adulterated alcohol tests. To assess hormonal contributions, a subset of female mice underwent ovariectomy before behavioral testing. Results: Deletion of Bmal1 in the DLS did not alter alcohol intake, alcohol preference, or quinine-adulterated alcohol intake in either sex. In contrast, DMS Bmal1 deletion significantly reduced alcohol consumption and alcohol preference in female mice, with no effect in males. These effects were not accompanied by changes in depressive-like behavior or motor coordination and were not explained by generalized reward changes, as sucrose preference was unaffected. Ovariectomy eliminated the effect of DMS Bmal1 deletion on alcohol intake, indicating dependence on ovarian hormones. Conclusions: The DMS is a critical site at which Bmal1 regulates alcohol consumption in a sex-specific manner. These findings support an interaction between local circadian mechanisms and ovarian hormones in controlling alcohol drinking and highlight a potential target for sex-specific therapeutics in AUD.
]]></description>
<dc:creator><![CDATA[ Darvish, M., Courtemanche, R., Amir, S. ]]></dc:creator>
<dc:date>2026-08-07</dc:date>
<dc:identifier>doi:10.64898/2026.08.02.742221</dc:identifier>
<dc:title><![CDATA[Region-specific Bmal1 deletion in the dorsal striatum alters alcohol consumption in a sex-specific manner]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-08-07</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.08.02.742327v1?rss=1">
<title>
<![CDATA[
A habenula-enriched GPCR, GPR151, regulates behavioral sensitivity to inflammation 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.08.02.742327v1?rss=1
</link>
<description><![CDATA[
Background: Inflammation-associated depression is a subtype of major depressive disorder that is often resistant to conventional pharmacotherapies, which act in a regionally non-specific manner and therefore also produce unwanted side effects. Here we test GPR151, an orphan GPCR associated with inflammation and highly expressed in the habenula--a region linked to negative valence and depression--as a therapeutic target for inflammation-associated depression. Methods: We integrated mouse and human habenular expression analyses with genetic loss-of-function and adult habenular re-expression approaches in mice. Gpr151 knockout mice and littermate controls were exposed to lipopolysaccharide (LPS) inflammatory challenge and assessed for stress coping and motivated behavior, body weight loss, and peripheral immune activation. To test whether adult habenular GPR151 expression is sufficient to restore inflammation-associated behavioral vulnerability, GPR151 was re-expressed in the habenula of knockout mice. Results: GPR151 was exceptionally enriched in the habenula and showed conserved topographic organization and similar expression relationships with habenular marker genes in mice and humans. Following LPS challenge, male Gpr151 knockout mice showed reduced passive coping despite body weight loss and immune activation comparable to littermate controls. Adult habenular GPR151 re-expression increased LPS-induced amotivation in male knockout mice without increasing LPS-induced weight loss or immune activation. Female Gpr151 knockout mice also showed reduced passive coping after LPS challenge; however, habenular GPR151 re-expression was insufficient to increase LPS-induced amotivation in females. Conclusions: These findings identify GPR151 as a conserved, regionally enriched regulator of behavioral sensitivity to inflammatory challenge and support GPR151 as a candidate therapeutic target for inflammation-associated depression.
]]></description>
<dc:creator><![CDATA[ Rios, L., Lin, Y.-H., Yuan, L., Sharma, Y., Arias, H., Jeddy, F., Thotakura, S., Geleta, A., Rajesh, R., Shabel, S. ]]></dc:creator>
<dc:date>2026-08-07</dc:date>
<dc:identifier>doi:10.64898/2026.08.02.742327</dc:identifier>
<dc:title><![CDATA[A habenula-enriched GPCR, GPR151, regulates behavioral sensitivity to inflammation]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-08-07</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.08.02.742256v1?rss=1">
<title>
<![CDATA[
BRAIN CAST: An MRIQC-guided pipeline for age- and sex-specific pediatric brain MRI template construction, validated by downstream structural fidelity 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.08.02.742256v1?rss=1
</link>
<description><![CDATA[
Pediatric neuroimaging needs age- and sex-appropriate references, yet existing atlases span broad age ranges that blur development or lack sex specificity. We present BRAIN CAST: 28 year-by-year, sex-specific brain MRI templates covering ages 5-18, built from 1,272 quality-screened children in the Healthy Brain Network by an MRIQC-guided pipeline combining reduced-strength denoising, cerebrospinal-fluid-anchored intensity normalization, deep-learning skull stripping and iterative groupwise diffeomorphic registration. We evaluate templates not by image sharpness, which is not comparable across intensity conventions, but by the structural bias they induce downstream. Held-out children align to their matched template with sub-voxel gray-white interface error (1.1 mm); on a direction-symmetric surface-distance metric BRAIN CAST matches the best single-template reference and outperforms an age-specific pediatric atlas in 189 of 189 subjects. Female cortex is fit measurably better by female than by male templates, an effect no sex-neutral reference can provide. Templates, tissue-probability maps and the containerized pipeline are released.
]]></description>
<dc:creator><![CDATA[ Hu, Y., Contreras-Vidal, J. L. ]]></dc:creator>
<dc:date>2026-08-07</dc:date>
<dc:identifier>doi:10.64898/2026.08.02.742256</dc:identifier>
<dc:title><![CDATA[BRAIN CAST: An MRIQC-guided pipeline for age- and sex-specific pediatric brain MRI template construction, validated by downstream structural fidelity]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-08-07</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.08.02.742381v1?rss=1">
<title>
<![CDATA[
Tracking emotional interference over time: Differential effects of dorsolateral and ventromedial prefrontal stimulation 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.08.02.742381v1?rss=1
</link>
<description><![CDATA[
Although a substantial body of evidence has demonstrated that emotional interference affects cognitive performance, relatively little is known about its temporal evolution and the respective brain regions underlying its regulation. The present study investigated the temporal dynamics of emotional interference and the contribution of prefrontal regions involved in its regulation. Forty-eight participants completed a 2-back task and a Set-switching task under neutral and negative emotional conditions while receiving sham, dorsolateral prefrontal cortex (dlPFC), or ventromedial prefrontal cortex (vmPFC) stimulation. Stimulation was administered either online during task performance or after a 5 min pre-task period. Consistent with previous findings, negative emotions impaired executive performance, particularly during high-demand updating conditions. Critically, time-resolved analyses revealed that emotional interference evolved dynamically throughout task performance and was differentially modulated by prefrontal stimulation. The most consistent stimulation effects emerged after approximately 10 minutes of cumulative stimulation exposure and varied as a function of the stimulation site, executive-control demands, and stimulation timing. Notably, online stimulation produced more consistent modulation than pre-task stimulation. Together, these findings indicate that both emotional interference and its neuromodulation are dynamic processes. More broadly, they suggest that the contribution of prefrontal control systems to emotion-cognition interactions may be better understood through their temporal evolution rather than through static measures of performance alone.
]]></description>
<dc:creator><![CDATA[ Feutren, T., Braud, V., Fabre, L. ]]></dc:creator>
<dc:date>2026-08-07</dc:date>
<dc:identifier>doi:10.64898/2026.08.02.742381</dc:identifier>
<dc:title><![CDATA[Tracking emotional interference over time: Differential effects of dorsolateral and ventromedial prefrontal stimulation]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-08-07</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.08.04.742773v1?rss=1">
<title>
<![CDATA[
Early AMPA receptor potentiation modifies synaptic maturation and disease progression in Rett models 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.08.04.742773v1?rss=1
</link>
<description><![CDATA[
Rett syndrome (RTT) is a severe neurodevelopmental disorder caused by mutations in MECP2 and characterized by impaired neuronal maturation and synaptic dysfunction. Positive allosteric modulators of AMPA receptors (AMPAR-PAMs) have shown therapeutic promise in RTT models, but the determinants of treatment responsiveness remain unclear. Here, we evaluated the clinically advanced AMPAR-PAM CX1632 in Mecp2-null male and Mecp2-heterozygous female mice across developmental stages and treatment regimens. Therapeutic efficacy was strongly influenced by developmental stage, disease severity, and treatment schedule. Brief neonatal treatment produced long-lasting improvements in survival, disease progression, motor function, and cognition, whereas later intervention was markedly less effective in symptomatic null mice but remained beneficial in less severely affected heterozygous females. Repeated intermittent administration further enhanced selected benefits. Mechanistically, early CX1632 treatment induced sustained activation of neuronal and synaptic gene programs, restored synaptic organization and neuronal activity, and rescued AMPA receptor-mediated transmission weeks after drug withdrawal. These findings identify disease stage as a key determinant of responsiveness to AMPA receptor potentiation and support developmentally informed therapeutic strategies for MECP2-related disorders.
]]></description>
<dc:creator><![CDATA[ De Rocco, G., de Donato, A., Indrigo, M., Varotto, V., Geusa, M., Taverna, S., Cifola, I., Pinatel, E. M., Frasca, A., Landsberger, N. ]]></dc:creator>
<dc:date>2026-08-07</dc:date>
<dc:identifier>doi:10.64898/2026.08.04.742773</dc:identifier>
<dc:title><![CDATA[Early AMPA receptor potentiation modifies synaptic maturation and disease progression in Rett models]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-08-07</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.08.06.743264v1?rss=1">
<title>
<![CDATA[
Thalamic and cortical signals synergistically represent auditory prediction errors 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.08.06.743264v1?rss=1
</link>
<description><![CDATA[
Prediction errors (PEs) are commonly described as cortical signals generated within sensory hierarchies, but whether the thalamus participates in their encoding and transmission remains unclear. We recorded Local Field Potentials (LFP) from the medial and lateral geniculate nuclei and electrocorticography (ECoG) from multiple cortical regions in three awake cats during two auditory prediction tasks. Mutual information (MI) analyses revealed PE encoding in both thalamic and cortical signals. Co-information (co-I) analyses showed off-diagonal temporal synergy between early and later thalamic response components, consistent with an early response inducing a neural state change that shaped the informational content of subsequent activity. Multivariate co-information (MVCo-I) further revealed that thalamic and cortical population activity carried complementary PE information unavailable from either thalamic or cortical areas alone. These synergistic interactions were reliable across animals for violations of structured auditory sequences and weaker for repetition-based deviants. These findings show that auditory PEs are not simply relayed or duplicated across the thalamocortical hierarchy. Instead, they emerge through state-dependent transformations within the thalamus and complementary interactions between thalamic and cortical populations, identifying the thalamus as an active node of context-dependent PE processing.
]]></description>
<dc:creator><![CDATA[ Pascovich, C., Aijala, J., Castro-Zaballa, S., Costa, A., Rodriguez-Cattaneo, A., Torterolo, P., Ince, R. A. A., Bekinschtein, T. A., Canales-Johnson, A. ]]></dc:creator>
<dc:date>2026-08-07</dc:date>
<dc:identifier>doi:10.64898/2026.08.06.743264</dc:identifier>
<dc:title><![CDATA[Thalamic and cortical signals synergistically represent auditory prediction errors]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-08-07</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.08.05.743008v1?rss=1">
<title>
<![CDATA[
A Polarized Histamine-GABA Core-Rim Architecture within Synaptic Vesicles 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.08.05.743008v1?rss=1
</link>
<description><![CDATA[
Abstract Neuroscience traditionally assumes that amino acid transmitters occupy clear synaptic vesicles, whereas monoamines reside in dense-core vesicles. Using a glutaraldehyde-NaBH4; epitope-engineering platform enabling ultrastructural detection of small amines, we identify a polarized histamine-GABA vesicular organization within conventional GABAergic vesicles. Quantitative electron microscopy demonstrates histamine condensed into a dense intraluminal core, while complementary GABA immunolabeling supports the localization of GABA toward the vesicle periphery, consistent with a membrane-proximal rim. This conserved architecture across central, autonomic, and endocrine GABAergic systems provides a structural framework for temporally differentiated inhibitory signaling, challenges the clear-versus-dense-core vesicle paradigm, and establishes a unified principle for dual-transmitter architecture.
]]></description>
<dc:creator><![CDATA[ Fujiwara, K. ]]></dc:creator>
<dc:date>2026-08-07</dc:date>
<dc:identifier>doi:10.64898/2026.08.05.743008</dc:identifier>
<dc:title><![CDATA[A Polarized Histamine-GABA Core-Rim Architecture within Synaptic Vesicles]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-08-07</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.08.03.742532v1?rss=1">
<title>
<![CDATA[
α-Synuclein aggregates in corticostriatal terminals impair glutamatergic transmission in the absence of neurodegeneration 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.08.03.742532v1?rss=1
</link>
<description><![CDATA[
Substantia nigra pars compacta dopamine neuron loss and Lewy pathology, aggregates of alpha-synuclein, characterize Parkinson disease and Dementia with Lewy Bodies. Lewy pathology localizes to cortical neurons, and is found as Lewy neurites in the striatum, but its effects on excitatory synaptic function are just beginning to be understood. Corticostriatal projections regulate motor and cognitive behaviors impaired in these disorders. Alpha-synuclein aggregation was induced in mouse M2 cortex, a vulnerable region in human disease. Early after initiation, aggregates localized to corticostriatal vesicular glutamate transporter 1 (vGLUT1)-positive terminals, with sparing of spiny projection neuron (SPN) soma, and dopamine terminals and neurons. Corticostriatal presynaptic aggregates significantly impaired glutamatergic transmission, without overt cortical neuron loss, and were associated with decreased synaptic density and volume. Thus, formation of presynaptic alpha-synuclein aggregates impairs corticostriatal function without degeneration of cortical neurons or striatal dopamine terminals, suggesting pathologic alpha-synuclein is sufficient for synaptic loss. Our findings also point to early synaptic dysfunction as a therapeutic target in Lewy body diseases.
]]></description>
<dc:creator><![CDATA[ Brzozowski, C. F., Fokakis, Z. N., Menard, M. A., Challa, H. V., Gallardo, I., Hall, J. D., Narbert, D., Millett, M. F., Hardaway, J. A., Moehle, M. S., Volpicelli-Daley, L. A. ]]></dc:creator>
<dc:date>2026-08-07</dc:date>
<dc:identifier>doi:10.64898/2026.08.03.742532</dc:identifier>
<dc:title><![CDATA[α-Synuclein aggregates in corticostriatal terminals impair glutamatergic transmission in the absence of neurodegeneration]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-08-07</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.08.06.743237v1?rss=1">
<title>
<![CDATA[
Cortico-hippocampal dynamics of hierarchical syntactic planning in natural speech production 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.08.06.743237v1?rss=1
</link>
<description><![CDATA[
The human brain must rapidly construct hierarchical structures to organize complex sequential behavior, yet the neural dynamics supporting this process during natural behavior remain poorly understood. Spoken language provides a powerful model system for investigating this computation, requiring rapid transformation of conceptual intent into structured sequential output. Using rare intracranial stereo-electroencephalography (SEEG) recordings from patients producing extended spontaneous speech, we examined how syntactic planning unfolds over time using measures of constituency, dependency structure, and probabilistic syntactic categories. We identified a hierarchical planning architecture in which global sentence structure and core syntactic categories (nouns and verbs) were specified before more local planning operations. Neural representations of these categories emerged up to 1 s before articulation and persisted throughout the planning period, whereas optional modifiers, including adjectives and adverbs, were recruited only closer to speech onset. These observations support a model of hierarchical incremental planning in which abstract sentence structure precedes the incremental specification of individual sentence elements. While core syntactic categories engaged a broader fronto-temporo-parietal network than other word classes, syntactic-depth-related activity emerged in parallel across cortical regions and the hippocampus, suggesting that hippocampal relational representations contribute to sentence structure building. Together, these findings support a cortico-hippocampal model of speech production in which hierarchical sentence structure and core syntactic categories are planned before secondary syntactic elements are incrementally incorporated into the evolving sentence plan. These results provide a neural account of how abstract linguistic structure is transformed into fluent speech.
]]></description>
<dc:creator><![CDATA[ Morucci, P., Nabe, M., Sauppe, S., Meyer, M., Megevand, P., Spinelli, L., Bickel, B., Proix, T., Giraud, A.-L. ]]></dc:creator>
<dc:date>2026-08-07</dc:date>
<dc:identifier>doi:10.64898/2026.08.06.743237</dc:identifier>
<dc:title><![CDATA[Cortico-hippocampal dynamics of hierarchical syntactic planning in natural speech production]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-08-07</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.07.25.740682v1?rss=1">
<title>
<![CDATA[
Effectiveness of the University Executive Network-Training Program (NExT-U) on executive functions in university students 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.07.25.740682v1?rss=1
</link>
<description><![CDATA[
Introduction: Executive functions (EF) are higher-order cognitive processes essential for academic performance in university settings. Although there is extensive research on EF training in children, studies in young adults are scarce, particularly those involving interventions tailored to specific needs. Objective: To evaluate the effect of the University Executive Network-Training Program (NExT-U), based on specific needs, on the executive functioning of Cuban university students. Methodology: A quasi-experimental study with a non-equivalent control group and pretest-posttest measurements. Participants were 27 second-year Psychology students (74% female; mean age = 19 years). The experimental group (n=7) received three training sessions focused on Conscious Regulation of Behavior, Decision-Making, Emotional Regulation, and Monitoring of Responsibilities, identified through an initial assessment using the UEF-1 Scale. The control group (n=20) continued with their usual academic activities. Non-parametric analyses 86 and the residual gain method were employed. Results: The experimental group showed significant improvements in Conscious Regulation of Behavior (p = .026; r = .51), Emotional Regulation (p = .030; r = .49), and the Supervisory Attention System (p = .046; r = .44), with large effect sizes. The control group experienced no significant changes in any of the functions evaluated. Conclusions: A brief, personalized program can enhance specific executive functions in university students, demonstrating cognitive plasticity in young adults. The findings support the design of contextually relevant interventions to strengthen transversal competencies in higher education.
]]></description>
<dc:creator><![CDATA[ Diaz-Guerra, D., Fernandez-Castillo, E., Ramos-Galarza, C., De la Torre Perez, M., Gonzalez Espinosa, Y., Hernandez-Lugo, M., Lugones Dapresa, V., Broche-Perez, Y. ]]></dc:creator>
<dc:date>2026-08-07</dc:date>
<dc:identifier>doi:10.64898/2026.07.25.740682</dc:identifier>
<dc:title><![CDATA[Effectiveness of the University Executive Network-Training Program (NExT-U) on executive functions in university students]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-08-07</prism:publicationDate>
<prism:section></prism:section>
</item>
</rdf:RDF>
