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Zhuang, K.

Publications and source records attributed to Zhuang, K..

11 recordsLinked to original sources

Hippocampal subfields support human novelty detection via distinct signals

Detecting novelty is fundamental to adaptive memory, yet the neural comparisons that allow new events to be distinguished from prior experience are not fully understood. Hippocampal novelty signals are often framed as associative comparator responses that register violations of learned relationships. However, recognition memory models also predict a broader form of comparison: a global, item-based mismatch between an incoming stimulus and aggregate memory traces. Whether such global matching is implemented within human hippocampal circuitry, and whether it contributes to memory decisions, remains unknown. Using ultra-high-field 7T fMRI during dense sampling of a continuous object recognition task (76,800 trials across five sessions), we estimated both univariate novelty responses and multivariate global mismatch signals across hippocampal subfields. CA1 carried the novelty response that most reliably predicted accurate novelty detection, whereas the subiculum expressed a global mismatch signal that predicted detection independently of CA1. This subicular signal also shaped subsequent recognition behaviour, in which low global mismatch was associated with false alarms to novel objects that propagated into later hits. Finally, subicular global mismatch scaled with the experienced similarity of past events, consistent with an item-based comparison against accumulated memory. These findings identify distinct hippocampal mismatch signals for novelty detection and extend the human hippocampal comparator role beyond local associative mismatch to include global, item-based matching.

neuroscience↗

Two dominant axes structure high-dimensional object representations in the human ventral temporal cortex

The ventral temporal cortex is critical for visual object recognition, yet the principles organising its representations remain unclear. Using ultra-high-field 7T fMRI and dense sampling of 1,854 object concepts, we applied exploratory factor analysis to multivoxel response patterns to estimate the main axes of representational variation. Despite high dimensionality, over half of the explainable variance concentrated along two dominant axes: a continuum spanning objects of high biological salience, and a second integrating spatial context, physical scale, and manipulability. Importantly, neither reduced to a single semantic label, instead reflecting mixtures of visual and conceptual properties. Together they defined a triangular geometry, anchored by animal-, furniture- and food-related objects, stable across participants and two independent datasets, that mapped onto a lateral-to-medial cortical gradient, with category-selective regions emerging as local peaks within a broader continuum. These findings reveal that high-dimensional object representations in the ventral temporal cortex are structured by a small number of interpretable axes.

neuroscience↗

Shaping a Collaborative, Sustainable, Accessible, and Reproducible Future for Computational Modeling

The o2S2PARC platform is an open-source, extensible, and scalable cloud-based platform developed in the context of the U.S. National Institutes of Health SPARC program to support collaborative, sustainable, FAIR (findable, accessible, interoperable, reusable) and reproducible computational modeling and analysis. This publication presents the main features of o2S2PARC, its underlying approaches and philosophy, innovative aspects of the developed technologies, while also drawing attention to its rapid adoption. The paper showcases a variety of applications and use cases enabled by the platform. These include hybrid electromagnetic-electrophysiology simulations of neural interfaces, personalized brain and spinal cord stimulation planning, in silico device safety assessments, the training and application of AI systems (e.g., for model-predictive control and medical image segmentation), hybridized surrogate modeling and multi-objective optimization in high-dimensional parameter spaces, sensitive and unbiased validation of measurement devices, and interactive data analysis as paper supplements.

neuroscience↗

Decoding the Molecular Language of Proteins with Evola

Proteins, natures intricate molecular machines, are the products of billions of years of evolution and play fundamental roles in sustaining life. Yet, deciphering their molecular language--understanding how sequences and structures encode biological functions--remains a cornerstone challenge. Here, we introduce Evolla, an interactive protein-language model designed to transcend static classification by interpreting protein function through natural language queries. Trained on 546 million protein-text pairs and refined via Direct Preference Optimization, Evolla couples high-dimensional molecular representations with generative semantic decoding. Benchmarking establishes Evollas superiority over general large language models in functional inference, demonstrates zero-shot performance parity with the state-of-the-art supervised model, and exposes remote functional relationships invisible to conventional alignment. We validate Evolla through two distinct applications: identifying candidate eukaryotic signature proteins in Asgard archaea, with functional Vps4 homologs validated via yeast complementation; and interactively discovering a novel deep-sea polyethylene terephthalate (PET) hydrolase, PsPETase, confirmed to degrade plastic films. These results position Evolla not merely as a predictor, but as a generative engine capable of complex hypothesis formulation, shifting the paradigm from static annotation to interactive, actionable discovery. The Evolla online service is available at http://www.chat-protein.com/.

bioinformatics↗

A cingulate-hippocampal circuit mediates early depressive symptoms in Alzheimer's disease

AbstractDepressive symptoms are prevalent and precedes cognitive decline in Alzheimers disease (AD), which worsen the clinical outcome and severely challenge the life quality of the patients. However, the neural circuitry mediating mood disturbance in AD remains elusive. Here we report that the glutamatergic projection from the anterior cingulate cortex (ACC) to the ventral hippocampal CA1 (vCA1) acts as the neural substrate of depressive symptoms in AD. We systemically mapped axonal projection in early stage of 5xFAD mice (3 months), which accompanies depressive- like behavior in these animals and identified reduced axonal projection from ACC to vCA1. This is in accordance with reduced axonal calcium signals detected with in vivo fiber photometry. Chemogenetic or optogenetic reversal of ACC-vCA1 circuitry activity efficiently ameliorated the depressive-like behaviors as well as cognitive impairment in 5xFAD mice. We further identified the synaptic molecules neuregulin-1 (Nrg1) as one vital signal regulating the synaptic glutamate transmission from the ACC to the vCA1. Collectively, these results indicated ACC-vCA1 as a critical pathway that regulates emotional states in Alzheimer disease. Targeting cingulate cortices with brain stimulation may treat depression in AD.

neuroscience↗

Safety Recommendations for Temporal Interference Stimulation in the Brain

Temporal interference stimulation (TIS) is a new form of transcranial electrical stimulation (tES) that has been proposed as a method for targeted, non-invasive stimulation of deep brain structures. While TIS holds promise for a variety of clinical and non-clinical applications, little data is yet available regarding its effects in humans. To inform the design and approval of experiments involving TIS, researchers require quantitative guidance regarding exposure limits and other safety concerns. To this end, we sought to delineate a safe range of exposure parameters (voltages and currents applied via external scalp electrodes) for TIS in humans through comparisons with well-established but related brain stimulation modalities. Specifically, we surveyed the literature for adverse events (AEs) associated with transcranial alternating/direct current stimulation (tACS/tDCS), deep brain stimulation (DBS), and TIS to establish known boundaries for safe operating conditions. Drawing on the biophysical mechanisms associated with the identified AEs, we determined appropriate exposure metrics for each stimulation modality. Using these metrics, we conducted an in silico comparison of various exposure scenarios for tACS, DBS, and TIS using multiphysics simulations in an anatomically detailed head model with realistic current strengths. By matching stimulation scenarios in terms of biophysical impact, we inferred the frequency-dependent TIS stimulation parameters that resulted in exposure magnitudes known to be safe for tACS and DBS. Based on the results of our simulations and existing knowledge regarding tES and DBS safety, we propose frequency-dependent thresholds below which TIS voltages and currents are unlikely to pose a risk to humans. Safety-related data from ongoing and future human studies are required to verify and refine the thresholds proposed here.

neuroscience↗

Reduced Hippocampal-Cortical Connectivity During Memory Suppression Predicts the Ability to Forget Unwanted Memories

The ability to suppress unwelcome memories is important for productivity and well-being. Successful memory suppression is associated with hippocampal deactivations and a concomitant disruption of this regions functionality. Much of the previous neuroimaging literature exploring such suppression-related hippocampal modulations has focused on the regions negative coupling with the prefrontal cortex. In contrast, task-based changes in functional connectivity between the hippocampus and other brain regions have remained relatively underexplored. Here, we utilize psychophysiological interactions and seed connectome-based predictive modeling (seed-CPM) to investigate the relationship between the hippocampus and the rest of the brain as 134 participants attempted to suppress unwanted memories during the Think/No-Think task. The results show that during retrieval suppression, the right hippocampus exhibited decreased functional connectivity with visual cortical areas (bilateral intracalcarine cortex, right cuneal cortex, left lingual gyrus, right supracalcarine cortex, right occipital pole), left nucleus accumbens and the brain-stem that predicted superior forgetting of unwanted memories on later memory tests. Validation tests verified that prediction performance was not an artifact of head motion or prediction method and that the negative features remained consistent across different brain parcellations. These findings suggest that systemic memory suppression involves more than the modulation of hippocampal activity--it alters functional connectivity patterns between the hippocampus and visual cortex, leading to successful forgetting.

neuroscience↗

Metacognition, cortical thickness, and tauopathy in aging

We investigated two aspects of metacognition and their relationship with cortical thickness and Alzheimers Disease (AD) biomarkers, amyloid and tau, in cognitively healthy older adults (N=151). The two metacognition measures were self-appraisal rating of task performance and the difference between self-appraisal rating and actual task performance (appraisal discrepancy). All participants underwent neuropsychological testing and 1.5T structural MRI. A subset (N=66) received amyloid-PET with [11C] PiB and tau-PET with [18F] Flortaucipir. We found that worse performers had lower self-appraisal ratings, but still overestimated their performance, consistent with the Dunning-Kruger effect. Self-appraisal rating and appraisal discrepancy revealed distinct relationships with cortical thickness and AD pathology. Greater appraisal discrepancy, indicating overestimation, was related to thinning of inferior-lateral temporal, fusiform, and rostral anterior cingulate cortices. Lower self-appraisal was associated with higher entorhinal and inferior temporal tau. These results suggest that overestimation could implicate structural atrophy beyond AD pathology, while lower self-appraisal could indicate early behavioral alteration due to AD pathology, supporting the notion of subjective cognitive decline prior to objective deficits.

neuroscience↗

The SPARC DRC: Building a resource for the autonomic nervous system community

The Data and Resource Center (DRC) of the NIH-funded SPARC program is developing databases, connectivity maps and simulation tools for the mammalian autonomic nervous system. The experimental data and mathematical models supplied to the DRC by the SPARC consortium are curated, annotated and semantically linked via a single knowledgebase. A data portal has been developed that allows discovery of data and models both via semantic search and via an interface that includes Google Map-like 2D flatmaps for displaying connectivity, and 3D anatomical organ scaffolds that provide a common coordinate framework for cross-species comparisons. We discuss examples that illustrate the data pipeline, which includes data upload, curation, segmentation (for image data), registration against the flatmaps and scaffolds, and finally display via the web portal, including the link to freely available online computational facilities that will enable neuromodulation hypotheses to be investigated by the autonomic neuroscience community and device manufacturers.

neuroscience↗

Electrical Stimulation Of The Cervical Dorsal Roots Enables Functional Arm And Hand Movements In Monkeys With Cervical Spinal Cord Injury

Recovering arm control is a top priority for people with paralysis. Unfortunately, the complexity of the neural mechanisms underlying arm control practically limited the effectiveness of neurotechnology approaches. Here, we exploited the neural function of surviving spinal circuits to restore voluntary arm and hand control in three monkeys with spinal cord injury using spinal cord stimulation. Our neural interface leverages the functional organization of the dorsal roots to convey artificial excitation via electrical stimulation to relevant spinal segments at appropriate movement phases. Stimulation bursts targeting specific spinal segments produced sustained arm movements enabling monkeys with arm paralysis to perform an unconstrained reach-and-grasp task. Stimulation specifically improved strength, task performances and movement quality. Electrophysiology suggested that residual descending inputs were necessary to produce coordinated movements. The efficacy and reliability of our approach hold realistic promises of clinical translation.

bioengineering↗

Structural and functional MRI from a cross-sectional Southwest University Adult lifespan Dataset (SALD)

Recently, the field of developmental neuroscience has aimed to uncover the developmental trajectory of the human brain and understand the changes that occur as a function of aging. Here we present an adult lifespan dataset of functional magnetic resonance imaging (fMRI) data including structural MRI and resting-state functional MRI. 494 healthy adults (age range: 19-80 years; Males=187) were recruited and completed two multi-modal MRI scan sessions in the Brain Imaging Central of Southwest University, Chongqing, China. The goals of the dataset are to give researchers the opportunity to map the developmental trajectory of structural and functional changes of human brain and to replicate previous findings.

neuroscience↗