Biology subjects

Singh, B.

Publications and source records attributed to Singh, B..

At least 19 recordsLinked to original sources

bioRxiv2026

Analysis of sperm processing and cryopreservation procedures in the common marmoset (Callithrix jacchus) to reduce fragmentation and maximize total and progressive motility

The marmoset has emerged as an ideal species for studying complex neurodevelopmental diseases, and IVF is required for gene-editing success. Reliable sperm processing is paramount to several IVF techniques, including traditional insemination. If not used immediately, thermal stress from cryopreservation diminishes sperm quality, requiring improved processing methods. Swim-up and gradient methods may limit adequate sperm quality, and the lack of a standardized freezing protocol often results in impaired post-thaw motility. Thus, reliable standards for sperm processing and cryopreservation in the marmoset are needed to support vital IVF processes. Collected semen underwent one of four pre-processing incubation steps before processing by swim-up, sucrose gradient, or a microfluidics assay. Sperm parameters were assessed using a Hamilton Thorne Computer Assisted Sperm Analysis (CASA) system. To evaluate cryopreservation, microfluidics-processed sperm were subjected to five protocols using different cryoprotectants and cooling methods. After thawing, sperm samples were analyzed with the CASA system and a DNA fragmentation assay. Incubation for 30 minutes at 38C in TYH media decreased sperm aggregation, and subsequent microfluidics resulted in a higher percentage of motile and progressively motile sperm than swim-up or gradient methods. Our optimized cryopreservation protocol consistently achieved at least 20% progressive motility, a key benchmark for usable marmoset sperm, while previously published or commercial methods were less consistent. The cryopreservation protocol outperformed other published methods, having the least significant change in post-thaw motility without causing DNA damage. These findings establish standardized methods for reliably procuring and storing sperm samples for IVF or husbandry in the common marmoset.

developmental biology↗

bioRxiv2026

Pathway-Based Analysis of Essential Metabolic Enzymes as Drug Targets

Tuberculosis (TB) , caused by Mycobacterium tuberculosis , remains a major global health crisis, aggravated by rapid emergence of multidrug-resistant (MDR) and extensively drug resistant (XDR) strains. Conventional drug discovery is time-consuming and expensive, making computational target identification and drug repurposing as crucial strategies to accelerate the development of novel antitubercular therapies. This study aimed to identify and prioritize the metabolic enzymes as potential drug targets through pathway based analysis and to screen the FDA-approved drug library for potential canidates for drug repurposing. Based on the pathway analysis, para-aminobenzoate synthase component I (PabB) was selected as a potential drug target owing to its role in folate biosynthesis. Subesquently, an FDA-approved drug library was screened based on ADMET properties and selected compounds were used for molecular docking agaist the protein. Molecular docking through DiffDock and validation using GNINA revealed that Ligand 5 and Ligand 27 exhibit favourable interaction profiles within the binding region of PabB, and emerged as potential candidates for further investigation in drug repurposing. The identification of PabB protein asan essential metabolic drug target, coupled with screening of FDA-approved drugs as inhibitors, provides a promising framework for anti tubercular drug discovery.

bioinformatics↗

bioRxiv2026

Enzyme Activation of Triggerable Polymeric Lysosome Targeting Chimeras

Targeted protein degradation (TPD) has been highly effective for intracellular targets, but extending this approach to extracellular and membrane-bound proteins remains difficult because most extracellular TPD (eTPD) strategies depend on ligand-targeting receptors (LTRs) whose expression and recycling vary across tissues. Existing LTR-independent, multivalent platforms expand the scope of eTPDs by eliminating this dependence on LTRs and enabling cancer-selective designs. Layering in an additional degree of selectivity through endogenously activatable triggers, such as overexpressed enzymes, can enhance the tissue tropism of the LTR-independent platforms and widen therapeutic window. Here we report triggerable polymeric lysosome targeting chimeras (tPolyTACs), which combine antibody-defined targeting with locally triggered covalent capture. tPolyTACs conjugate monoclonal antibodies to phosphatase-cleavable substrates that, upon engagement of endogenous cell-surface phosphatases, unmask a reactive quinone methide electrophile, covalently trapping the target complex and driving its clathrin-mediated internalization and autolysosomal degradation. We show tPolyTAC-mediated degradation of the membrane proteins EGFR, PD-L1, and cMET, and demonstrate that para-substituted electrophiles outperform ortho-substituted analogues likely due to more favorable active-site positioning. These results establish tPolyTACs as a modular, covalent, enzyme-responsive platform that resolves the efficiency-selectivity trade-off limitations in extracellular degradation.

cell biology↗

bioRxiv2026

Detection of Plasmodium infections in macaques from areas endemic for brugian filariasis in Belitung District, Indonesia

Background Malaria caused by Plasmodium knowlesi and lymphatic filariasis caused by Brugia malayi are mosquito-borne infections with non-human primates as reservoirs. P. knowlesi has emerged as a significant cause of human malaria in Southeast Asia over the past two decades. Belitung district, Indonesia, was until recently assumed to have eliminated B. malayi until infections were detected in humans and long-tailed macaques. To investigate whether the local reservoir of B. malayi is also a reservoir for malaria we screened macaques from 4 areas in Belitung for malaria parasites. Methods and findings Blood samples from 163 long-tailed macaques (Macaca fascicularis) that had been tested for B. malayi were examined by quantitative PCR assays specific for Plasmodium spp., P. knowlesi, P. inui, P. coatneyi and P. cynomolgi. A total of 130 macaques (79.8%) tested positive in the pan-Plasmodium qPCR assay. Plasmodium inui was most prevalent (41.7%), followed by P. knowlesi (38.7%), P. coatneyi (24.5%) and P. cynomolgi (13.5%). Multiple species infections, with 2-3 Plasmodium species were detected in 37% of macaques. Notably, 20 (91%) of 22 B. malayi-positive macaques were co-infected with at least one Plasmodium species. We sequenced the complete mitochondrion from 9 samples diagnosed by qPCR as mono-infections. Phylogenetic analysis confirmed 7 as P. knowlesi, and the other two as P. inui and P. coatneyi. Phylogenetic and pairwise analysis revealed that P. knowlesi isolates from Belitung were closely related to each other and to P. knowlesi from humans and monkeys from Thailand, Malaysia and Indonesia. Conclusions Molecular evidence shows high prevalence of zoonotic malaria parasites in macaques from Belitung, emphasizing the risk of human transmission. Increased surveillance, improved diagnostics, and targeted interventions are needed to prevent zoonotic spillover of P. knowlesi as it has been observed for B. malayi in Belitung.

microbiology↗

bioRxiv2026

Senescent cell networks link matrix remodeling and vascular dysfunction in human fibroids

Uterine fibroids (leiomyomas) are highly prevalent benign tumors defined by excessive extracellular matrix (ECM) deposition, altered vascular structure, and progressive tissue stiffening, yet the cellular programs that coordinate these features remain poorly understood. Cellular senescence has been implicated in fibroid biology, but whether senescence represents a uniform state or distinct, functionally specialized cell identities within fibroids is unknown. Here, we identify the distinct heterogeneous populations of senescent cells ("senotypes") present in human fibroids and characterize their role in shaping the fibroid microenvironment. Using single-cell RNA sequencing (scRNA-seq) integrated with a senescence gene signature and protein-level validation, we identify senescent cells (SnC) distributed across fibroblast, mural, and endothelial compartments, each exhibiting distinct transcriptional programs. SnC endothelial cells (ECs) are enriched in fibroids relative to matched myometrium and activate TEAD4-associated mechanosensing, angiogenic, and immune signaling pathways, despite being associated with impaired vessel maturation in situ. In parallel, SnC fibroblast and mural populations in fibroids upregulated SRF-associated cytoskeletal and ECM programs, accompanied by increased COL6A3 expression and collagen VI deposition, consistent with tissue stiffening. Ligand-receptor and spatial analyses reveal that these SnC populations function as interconnected signaling hubs, coordinating immune cell recruitment and stromal remodeling. Importantly, analysis of human fibroids treated with collagenase demonstrated a reduction in both ECM density and SnC burden, supporting a reinforcing relationship between matrix mechanics and senescence. Together, these findings establish senescence in fibroids as a heterogeneous, mechanically reinforced, and network-driven process that links vascular dysfunction, immune signaling, and fibrosis, highlighting distinct SnC states as potential translational targets for non-surgical therapies.

cell biology↗

bioRxiv2026

A human monoclonal antibody from hybrid immunity exhibits exceptional neutralization breadth against antigenically divergent contemporary Omicron JN.1 lineage variants

Hybrid immunity offers stronger and more durable antibody-mediated protection against symptomatic SARS-CoV-2 infection. In the present study, we report the development of a durable antibody response in an individual with hybrid immunity who also received three doses of the prototype COVID-19 vaccine. Polyclonal plasma antibody obtained from this donor also showed extraordinary neutralization breadth against contemporary Omicron variants. One of the functional monoclonal antibodies (ATHS-C30) isolated from this individual, representing the IGHV4-30 lineage-specific B cell with strong binding affinity to JN.1 spike protein, showed extraordinary neutralization breadth, including variants of Omicron lineages that emerged beyond JN.1, such as KP.2, KP.3.1.1, KP.3.2, KP.3.3, LB.1 and XEC. ATHS-C30 was found to bind RBD with high affinity and showed distinct epitope specificity to the other neutralizing mAbs isolated from the same donor through the epitope binning assay. Molecular modelling of the CDHR3 sequence using existing structures indicated that ATHSC-30 belongs to the class 4 antibody, a feature that contributes to breadth, while epitope conservation analysis indicated that the majority of RBD-interacting residues of ATHSC-30 are evolutionarily conserved. Taken together, our study indicate that ATHS-C30 forms the basis of development of a robust and broadly neutralizing antibody response in this individual with hybrid immunity, which overcomes the antigenic variation by targeting highly conserved and cryptic epitopes in destabilizing the spike structure. ImportanceSARS-CoV-2 continues to pose a significant public health threat, particularly to immunocompromised individuals and older adults with underlying comorbidities. Hybrid immunity to SARS-CoV-2 in vaccinated individuals leads to the development of B cells that are qualitatively superior to those that are expected to develop in only vaccinated individuals. In the present study, we found that among individuals with hybrid immunity who developed robust, durable antigen-specific antibody responses, one developed antibody response capable of broadly cross-neutralising contemporary Omicron variants. This was correlated with development of antigen-specific B cell lineage, such as IGHV4-30, that produced antibodies with potent and extraordinary neutralisation breadth against contemporary Omicron lineages, such as KP.2, KP.3.1.1, KP.3.2, KP.3.3, LB.1 and XEC. This is believed to be due to heterologous antigen exposures driving the development of an antigen-specific B cell repertoire that, in turn, facilitates immune imprinting capable of overcoming the ineffectiveness of antibodies to effectively neutralize newly emerging Omicron variants.

immunology↗

bioRxiv2026

Biomolecular Condensation and L-Cysteine Signaling Activates Dormant Protease Activity of Papain Droplets: Implication toward Meat Tenderization

Proteases are an important class of proteolytic enzymes having great importance in both basic science and industrial applications. While cells tightly regulate the spatio-temporal activity of different proteases for cellular homeostasis, mis-regulation often leads to adverse effects. In this context, the protease activity of papain and its activation by L-cysteine is poorly understood in the literature. Herein, we discover that the protease activity of papain can be effectively regulated via a spontaneous liquid-liquid phase separation (LLPS) pathway. We show that papain undergoes biomolecular condensation via spontaneous LLPS under macromolecular crowding through the involvement of intermolecular hydrophobic interactions. Secondary structure analyses revealed a compact conformation of phase-separated papain with increased -helix content. Although native free papain is found to be active towards synthetic and protein substrates, the proteolytic digestion produces heterogeneous peptide aggregates. In contrast, we found that papain droplets remain dormant toward protein digestion due to the disulfide linkage of the active cysteine residue (Cys-25) in its compact conformational state. More importantly, we show that the protease activity of phase-separated papain can be reactivated in the presence of L-cysteine to produce uniform soluble peptide fragments. Our findings indicate that although disulfide linkages are not necessary for the phase separation of papain, upon phase separation, intermolecular interactions between phase-separated papain result in the formation of disulfide linkages involving active Cys-25 residues. The present discovery has tremendous technological importance to boost the efficacy of meat tenderization in the food industry.

biophysics↗

bioRxiv2026

Efficient exploration of peptide libraries using active learning with AlphaFold-based screening

We previously showed that AlphaFold2 can be used to screen for peptide-binding epitopes targeting the extraterminal (ET) domain of Bromodomain and Extraterminal (BET) proteins from candidate protein partners identified in pull-down experiments. However, such approaches require large numbers of AlphaFold2 calculations, making exhaustive screening impractical for larger datasets, such as viral proteomes that may target the ET domain. In many cases, identifying a substantial fraction of binders--even without exhaustive coverage--would already provide valuable biological insight into these interaction networks. Here, we show that an active learning strategy based on Thompson sampling (TS) can efficiently explore peptide sequence space. Using a library derived from BRD3 pull-down experiments, TS recovers 50% of all binders using 15% of the queries required by exhaustive sampling (3.3 times improvement over random sampling). Moreover, TS consistently identifies experimentally known binding epitopes with substantially fewer queries. Because the approach relies only on binary labels, it is readily transferable to other protein-peptide systems where AF-based binding classification is applicable, as well as to peptide-property predictors for properties such as solubility or aggregation propensity.

bioinformatics↗

bioRxiv2026

Plasmodium falciparum invasion ligand gene transcript profiles in different populations

Plasmodium falciparum merozoites invade erythrocytes using various ligand-receptor interactions. Important ligands encoded by the eba and Rh gene families have varying expression levels in different parasite isolates, affecting their vaccine candidacy. Analyses of clinical isolates from endemic areas in Africa have indicated that most variation in these expression profiles exists within each local area, and only minor differences are seen between areas, although comparisons with non-African populations have not previously been performed. To enable this, relative transcript levels of three eba genes and five Rh genes have been analysed in new population samples, Malaysian isolates sampled from Sabah State in Borneo prior to endemic malaria elimination, and Gambian isolates, cultured under the same conditions to harvest schizonts for reverse transcription quantitative PCR assays. Significant differences between these populations were seen for three of the ligand genes, levels of eba175 being higher in Malaysia, while levels of eba181 and Rh2b were lower in Malaysia. The gene transcript profiles did not differ between single genotype and or multiple-genotype isolates. The distinctness of the Malaysian population expression profile was also supported by comparing previous data on clinical isolates from Ghana. In tests for correlation with previously determined parasite multiplication rates, eba181 transcript levels correlated positively among Malaysian isolates but not among Gambian isolates. These findings suggest that expression of three P. falciparum merozoite ligands involved in invasion may be regionally differentiated, and further analysis of Asian parasite populations would be important if vaccines based on these candidates are to be considered for future use.

microbiology↗

bioRxiv2026

KAMALA, a genome edited rice variety with improved yield by finetuning cytokinin oxidase activity released in India

Increasing yield is of major importance for Asian and African food security. Knock out mutants in the rice cytokinin oxidase gene CKX2 had shown potential for yield improvement. Here we explored whether subtle changes in CKX2 activity by editing FAD and cytokinin binding site sequences could improve the Indian mega-variety Samba Mahsuri. Knock out and single mutants in FAD and cytokinin binding sites induced by CRISPR/Cas12a caused moderate yield increases. Among 80 CKX2 alleles, five lines with in-frame mutations in both FAD and cytokinin binding domains produced even higher yield. One line, KAMALA, showed superior agronomic performance in 18 field locations (irrigated and rainfed ecologies) over three seasons in trials conducted by AICRPR (All India Coordinated Research Project on Rice), with an average 19% grain yield increase, early maturity, complete panicle emergence, and unaltered grain quality. KAMALA was registered as the first genome-edited variety ready for cultivation by Indian farmers.

plant biology↗

bioRxiv2025

A genome-wide association study to identify the genetic loci underlying carbapenem resistance in Acinetobacter baumannii

Carbapenem-resistant Acinetobacter baumannii (CRAB) is a major public health threat and a key contributor to the global antimicrobial resistance (AMR) crisis. This study applied a bacterial genome-wide association study (bGWAS) framework to identify genetic factors beyond the canonical carbapenemase OXA-23, that may contribute to carbapenem resistance. A. baumannii isolates with publicly available whole-genome sequencing (WGS) data and carbapenem-specific antimicrobial susceptibility testing (AST) results were compiled (n = 1,601). Unitigs were extracted from de novo assemblies, and single-nucleotide polymorphisms (SNPs) were called from raw sequence reads mapped to seven selected reference genomes. The population was highly clonal and comprised ten lineages, including three predominantly resistant ST2 lineages. The known CRAB-associated loci, including OXA-23, the RND efflux pump regulator AdeL, and an OXA-66 substitution (Leu167Val), were readily identified. Novel resistance-associated mutations were detected in outer-membrane proteins, including porins (OprD, DcaP) and proteins (PqiB, LptD) involved in lipopolysaccharide (LPS) biogenesis. Notably, the detection of OprD and DcaP was reference-dependent, indicating that a multi-reference bGWAS framework improves identification of resistance-associated variants that may be missed in single-reference analyses. Structural mapping of the identified mutations suggested plausible effects on protein function.

genomics↗

bioRxiv2025

A metagenomics-based tool for surveillance of bacterial pathogens in environmental samples

Bacterial pathogens are responsible for millions of human deaths and significant losses in food production annually. Soil acts as a natural reservoir for many critical bacterial pathogens, however, the lack of accurate, high-throughput methods to identify the distribution of bacterial pathogens in soil and other environments greatly limits our ability to develop effective surveillance and disease management strategies and policies. Here, we present MetaPatho, an easy-to-use, rapid, robust, and shotgun metagenomics-based tool for identifying human and plant bacterial pathogens in environmental metagenomes. We first constructed high-quality pathogenic databases for the identification of human and plant bacterial pathogens. In-silico tests and soil spike-in experiments, including pathogen DNA spike-in and cell spike-in tests, were then employed to examine the accuracy and robustness of our tool. The in-silico tests suggested that the tool accurately identified pathogenic sequences, achieving an average accuracy of 97.4%, with a specificity of 98.1% and a sensitivity of 97.2%. Further analyses from soil spike-in experiments showed that the tool accurately detected bacterial pathogens at different concentrations, achieving an average accuracy of 96.3%. Overall, our tools can provide a high-throughput and accurate surveillance of bacterial pathogens in environmental metagenomes, contributing to an effective risk management associated with human and plant diseases.

microbiology↗

bioRxiv2025

Therapeutic remodeling of the tuberculosis granuloma with 1-methyl-D-tryptophan enhances CD8+ T cell-macrophage interactions

Granulomas, the hallmark of tuberculosis (TB) disease, can both restrict Mycobacterium tuberculosis (Mtb) dissemination and impede its clearance. Recent studies indicate that indoleamine 2,3-dioxygenase (IDO1), an immunosuppressive metabolic enzyme, limits infiltration of activated T cells and can contribute to TB disease progression. Treatment with 1-methyl-D-tryptophan (D-1MT), a small molecule inhibitor that restores mTOR signaling, has been shown to improve immune responses Mtb-infected rhesus macaques. Here, we investigated the impact of D-1MT treatment on TB granuloma architecture using 30-plex high-dimensional issue imaging in rhesus macaques. By spatially mapping 13 distinct cell populations, we found D-1MT treatment corresponded with significantly increased infiltration CD8+ T cells into granulomas compared to untreated controls. Notably, these CD8+ T cells expressed markers of cell proliferation and cytotoxicity. D-1MT enhanced CD8+ T cell infiltration throughout the granuloma, with particularly pronounced effects in the myeloid core, where we observed significantly enhanced spatial interactions between macrophages and CD8+, but not CD4+ T cells. Our results demonstrate that: (i) effective intra-granulomatous Mtb control is associated with the close spatial proximity between CD8+ T cells and macrophages, a feature less abundant in uncontrolled pulmonary TB; (ii) IDO1 induction blocks CD8+ T cell infiltration and reduces T cell activation and proliferation; and (iii) therapeutic strategies, including D-1MT, that improve intra-granulomatous killing hold strong translational potential. Significance statementOur understanding of immune mechanisms within the TB granuloma has advanced greatly with the advent of high-resolution single cell multiplexed imaging. Using such imaging, we show that TB granulomas in rhesus macaques, a highly translational model of human TB pathology, are characterized by IDO1-mediated immunoregulation. Early pharmacologic restoration of mTOR signaling via D-1MT treatment can reduce IDO1 enzymatic activity and facilitate the recruitment and function of CD8+ T cells within the granulomas. These findings reveal specific mechanisms exploited by Mtb to maintain intra-granuloma persistence and underscore immune responses. Future vaccine and therapeutic design should consider these immunoregulatory features to achieve better control of Mtb infection.

immunology↗

bioRxiv2025

How Well Do Molecular Dynamics Force Fields Model Peptides? A Systematic Benchmark Across Diverse Folding Behaviors

Linear peptides play essential roles in biology and drug discovery, frequently mediating protein-protein interactions through short, flexible motifs. However, their structural plasticity--ranging from disordered to context-dependent folding--makes them challenging targets for molecular simulations. In this work, we benchmark the performance of eleven popular and emerging fixed-charge force fields across a curated set of twelve peptides spanning structured miniproteins, context-sensitive epitopes, and disordered sequences. Each peptide was simulated from both folded (200 ns) and extended (10 {micro}s) states to assess stability, folding behavior, and force field biases. Our analysis reveals consistent trends: some force fields exhibit strong structural bias, others allow reversible fluctuations, and no single model performs optimally across all systems. The study highlights limitations in current force fields ability to balance disorder and secondary structure, particularly when modeling conformational selection. These results offer practical guidance for peptide modeling and establish a benchmark framework for future force field development and validation in peptide-relevant regimes.

biophysics↗

bioRxiv2025

Plasminogen activator inhibitors orchestrate the immunosuppressive tumor microenvironment in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense extracellular matrix (ECM) that sustains an immunosuppressive tumor microenvironment (TME). While this protective niche has been described, the molecular determinants orchestrating its formation and dictating its immune interactions are not well defined. Using Perturb-map, we determine how dozens of different gene perturbations shape the growth and cellular environments of PDAC clones through space and time. Our study reveals dynamic, gene-specific adaptations of immune neighborhoods during clonal selection. We identified Serpinb2 (PAI2) and Serpine1 (PAI1) as key cancer-derived mediators of TME remodeling and immune evasion. These factors promote the deposition of a fibrin-rich ECM that shapes immune cell composition, locally retains and polarizes immunosuppressive macrophages and excludes cytotoxic T cells. Deletion of either Serpinb2 or Serpine1 greatly enhanced tumor response to anti-PD1 immunotherapy in an aggressive PDAC model. Transcriptomic analysis further linked their expression to distinct PDAC subtypes and poor patient survival. Our findings demonstrate that Serpinb2 and Serpine1 establish a permissive niche for tumor progression and show how PDAC cells exploit components of the fibrinolysis pathway to remodel the ECM, alter macrophage composition, and protect themselves from immune editing, ultimately reinforcing the role of extracellular factors in shaping an immune-privileged tumor niche.

cancer biology↗

bioRxiv2025

Multivalent Ligand-Protein Interactions Using Polymeric Lysosome-Targeting Chimeras (PolyTACs) Leads to Lysosome-Targeting Receptor-Independent Degradation of Transmembrane Proteins

Targeted protein degradation is growing rapidly as a therapeutic approach, with intracellular proteins degraded via the ubiquitin-proteasome or the autophagosome system and membrane proteins mainly through the lysosomal pathway. Current lysosomal degradation strategies rely on lysosome-targeting receptors (LTRs), limiting their applicability. We propose that multivalent non-covalent interactions on the cell membrane can drive lysosomal degradation of membrane proteins without the need of LTRs. To demonstrate this, we designed antibody-polymer conjugates, viz. Polymeric Lysosome-Targeting Chimeras (PolyTACs) functionalized with ligands that would non-covalently bind with transmembrane non-LTR proteins, viz., helper proteins on the cell surface in a polyvalent fashion. Cetuximab-based PolyTACs decorated with 4-(2-aminoethyl)benzenesulfonamide (ABS) ligands that cause multivalent interactions with membrane carbonic anhydrases induced degradation of EGFR, while atezolizumab- and trastuzumab-based PolyTACs effectively degraded PD-L1 and HER2, respectively. Additionally, PolyTACs using PD-L1 as the helper protein further improved degradation. Mechanistic studies confirmed clathrin- and caveolae-mediated endocytosis followed by lysosomal degradation of the target proteins. This LTR-independent nature of the approach offers opportunities for tissues targeting in membrane protein degradation that could open up new avenues in therapeutic strategies.

bioengineering↗

bioRxiv2025

Neural correlates of boundary extension during visual imagination

People typically remember seeing a greater expanse of a scene than was visible in a studied close-up (boundary extension, BE). Multivoxel pattern analysis was used to test the neural correlates of BE. Classifiers were trained using a whole-brain searchlight method to discriminate between close-up and wider-angle versions of 16 scenes during repeated perceptual exposures. Earlier, each subject studied either the close or wide version of each scene and then visually imagined it from memory. If a brain region reflects BE, then unlike classification during perception, visual images of close views should sometimes be misclassified as wide (capturing false memory beyond the view), whereas visual images of wide views should be correctly classified. BE-consistent patterns during imagery were found in high-level visual regions, including posterior superior parietal cortex. This pattern did not reflect a brain-wide bias toward better classification of wider-angle views: the pattern reversed (better classification of close views) in the early visual cortex, presenting a novel distinction between early and late visual representations in imagery. We propose that this method reflects active maintenance of boundary-extended scene representations in memory and that it holds promise as a general purpose tool for decoding false memory in the brain.

neuroscience↗

bioRxiv2025

Frontoparietal activity related to neuropsychological assessment of working memory

Executive functions, including working memory, are typically assessed clinically with neuropsychological instruments. In contrast, computerized tasks are used to test these cognitive functions in laboratory human and animal studies. Little is known of how neural activity captured by laboratory tasks relates to ability measured by clinical instruments and, by extension, clinical diagnoses of pathological conditions. We therefore sought to determine what aspects of neural activity elicited in laboratory tasks are predictive of performance in neuropsychological instruments. We recorded neural activity from intracranial electrodes implanted in human epilepsy patients as they performed laboratory working memory tasks. These patients had completed neuropsychological instruments preoperatively, including the Weschler Adult Intelligent Scale and the Wisconsin Card Sorting test. Our results revealed that increased high-gamma (70-150 Hz) power in the prefrontal and parietal cortex after presentation of visual stimuli to be remembered was indicative of lower performance in the neuropsychological tasks. On the other hand, we observed a positive correlation between high-frequency power amplitude in the delay period of the laboratory tasks and neuropsychological performance. Our results demonstrate how neural activity around task events relates to executive function and may be associated with clinical diagnosis of specific cognitive deficits.

neuroscience↗