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Cantlon, J.

Publications and source records attributed to Cantlon, J..

6 recordsLinked to original sources

A number simplex in the human medial temporal lobe

Humans handle numbers nimbly, suggesting a richer neural manifold structure than the prevalent mental number line model. In populations of medial temporal lobe (MTL) neurons in humans performing two simple tasks (dot counting and arithmetic), we find robust neural coding of numerosity that results in high dimensional, simplex-shaped manifolds. This shape affords more flexibility than a linear manifold due to its high shattering dimensionality and expressibility. Dot arrays and Arabic numerals evoked distinct simplicial population codes, yet they were linked by a linearly transferable latent structure within the same task. We find similar simplicial geometry of number representations in large language models (LLMs). Moreover, subjects internally computed arithmetic results were decodable during the calculation period, with decoding accuracy correlating with individual mathematical capacity. Finally, linear transformations of simplicial operand representations modeled the brains conversion of operands into decodable results, suggesting that the brains arithmetic procedures have some resemblance to the attention architecture of LLMs. Together, these findings establish a high dimensional representational foundation for numerical cognition in the brain.

neuroscience↗

Mass Spectrometry-based Profiling of Single-cell Histone Post-translational Modifications to Dissect Chromatin Heterogeneity

Single-cell proteomics confidently quantifies cellular heterogeneity, yet precise quantification of post-translational modifications, such as those deposited on histone proteins, has remained elusive. Here, we developed a robust mass spectrometry-based method for the unbiased analysis of single-cell histone post-translational modifications (schPTM). schPTM identifies both single and combinatorial histone post-translational modifications (68 peptidoforms in total), which includes nearly all frequently studied histone post-translational modifications with comparable reproducibility to traditional bulk experiments. As a proof of concept, we treated cells with sodium butyrate, a histone deacetylase inhibitor, and demonstrated that our method can i) distinguish between treated and non-treated cells, ii) identify sub-populations of cells with heterogeneous response to the treatment, and iii) reveal differential co-regulation of histone post-translational modifications in the context of drug treatment. The schPTM method enables comprehensive investigation of chromatin heterogeneity at single-cell resolution and provides further understanding of the histone code.

molecular biology↗

Massively parallel sample preparation for multiplexed single-cell proteomics using nPOP

Single-cell proteomics by mass spectrometry (MS) allows quantifying proteins with high specificity and sensitivity. To increase its throughput, we developed nPOP, a method for parallel preparation of thousands of single cells in nanoliter volume droplets deposited on glass slides. Here, we describe its protocol with emphasis on its flexibility to prepare samples for different multiplexed MS methods. An implementation with plexDIA demonstrates accurate quantification of about 3,000 - 3,700 proteins per human cell. The protocol is implemented on the CellenONE instrument and uses readily available consumables, which should facilitate broad adoption. nPOP can be applied to all samples that can be processed to a single-cell suspension. It takes 1 or 2 days to prepare over 3,000 single cells. We provide metrics and software for quality control that can support the robust scaling of nPOP to higher plex reagents for achieving reliable high-throughput single-cell protein analysis. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=48 SRC="FIGDIR/small/568927v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@c82330org.highwire.dtl.DTLVardef@17e5f2forg.highwire.dtl.DTLVardef@19b200borg.highwire.dtl.DTLVardef@154e336_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

Common neural functions during children's naturalistic and controlled laboratory mathematics learning

A major goal of human neuroscience is to understand how the brain functions in the real world, and to measure neural processes under conditions that are ecologically valid. A critical step toward this goal is understanding how brain activity during naturalistic tasks that mimic the real world, relates to brain activity in more traditional laboratory tasks. In the present study, we used intersubject correlations to locate reliable stimulus-driven cerebral processes among children and adults in a naturalistic video lesson and a laboratory forced-choice task that shared the same arithmetic concept. We show that relative to a control condition with grammatical content, naturalistic and laboratory arithmetic tasks evoked overlapping activation within brain regions previously associated with math semantics. The regions of specific functional overlap between the naturalistic mathematics lesson and laboratory mathematics task included bilateral intraparietal cortex, which confirms that this region processes mathematical content independently of differences in task mode. These findings suggest that regions of the intraparietal cortex process mathematical content when children are learning about mathematics in the real world.

neuroscience↗

High-throughput and high-efficiency sample preparation for single-cell proteomics using a nested nanowell chip

Global quantification of protein abundances in single cells would provide more direct information on cellular function phenotypes and complement transcriptomics measurements. However, single-cell proteomics (scProteomics) is still immature and confronts technical challenges, including limited proteome coverage, poor reproducibility, as well as low throughput. Here we describe a nested nanoPOTS (N2) chip to dramatically improve protein recovery, operation robustness, and processing throughput for isobaric-labeling-based scProteomics workflow. The N2 chip allows reducing cell digestion volume to <30 nL and increasing processing capacity to > 240 single cells in one microchip. In the analysis of [~]100 individual cells from three different cell lines, we demonstrate the N2 chip-based scProteomics platform can robustly quantify [~]1500 proteins and reveal functional differences. Our analysis also reveals low protein abundance variations (median CVs < 16.3%), highlighting the utility of such measurements, and also suggesting the single-cell proteome is highly stable for the cells cultured under identical conditions.

systems biology↗

Entropy, complexity, and maturity in children's neural responses during naturalistic mathematics learning

AO_SCPLOWBSTRACTC_SCPLOWA major goal of human neuroscience is to understand how the brain functions in the real world, and to measure neural processes under naturalistic conditions that are more ecologically valid than traditional laboratory tasks. A critical step toward this goal is understanding how neural activity during real world naturalistic tasks relates to neural activity in more traditional laboratory tasks. In the present study, we used intersubject correlations to locate reliable stimulus-driven neural processes among children and adults in naturalistic and laboratory versions of a mathematics task that shared the same content. We show that relative to a control condition with grammatical content, naturalistic and simplified mathematics tasks evoked overlapping activation within brain regions previously associated with math semantics. We further examined the temporal properties of childrens neural responses during the naturalistic and laboratory tasks to determine whether temporal patterns of neural activity change over development, or dissociate based on semantic or task content. We introduce a rather novel measure, not yet used in fMRI studies of child learning: neural multiscale entropy. In addition to showing new evidence of naturalistic mathematics processing in the developing brain, we show that neural maturity and neural entropy are two independent but complementary markers of functional brain development. We discuss the implications of these results for the development of neural complexity in children.

neuroscience↗