Biology subjects

Miller, J. A.

Publications and source records attributed to Miller, J. A..

At least 19 recordsLinked to original sources

bioRxiv2026

Single nucleus RNA sequencing and spatial transcriptomics reveal unique functionalities of gray matter versus white matter oligodendrocytes in aging and Alzheimer's Disease

Oligodendrocyte (OL) dysfunction and white-matter (WM) vulnerability are increasingly recognized as important aspects of aging and Alzheimer's Disease (AD), yet human WM-focused, cellular-resolution transcriptomic data remain limited. Here, we profiled prefrontal WM from 48 brain donors spanning young adulthood and late-life with low versus high AD Neuropathologic Change (ADNC) using single-nucleus RNA sequencing followed by spatial transcriptomics (CosMx) in a subset of matched donors. We integrated aged WM OLs with a reference dorsolateral prefrontal cortex grey-matter (GM) OL dataset (SEA-AD) to define region- and pathology-associated OL programs. Across modalities, GM OLs exhibited a robust synapse/neurotransmitter-associated transcriptional signature relative to WM OLs, whereas this program was reduced with aging and attenuated in high ADNC GM. In contrast, WM OLs showed stronger immune-associated programs with aging and further enhancement in high ADNC, including cytokine/chemokine signaling and antigen presentation-related pathways. High ADNC WM OLs also displayed amplified proteostasis and stress-adaptation signatures, including selective upregulation of chaperone/heat shock genes and ferritin subunits, consistent with increased protein-folding demand and altered iron handling. To resolve OL state organization beyond static differential expression, we annotated OL sub-states using marker panels and inferred pseudotime-guided directional state-to-state flows within each tissue/condition stratum. This analysis identified a conserved newly formed differentiating (NFOL)/differentiating [->] lipid remodeling (APOE/ABCA1/LPL+) [->] Stress/ISR-reactive architecture, with a pronounced expansion of the Stress/ISR-reactive compartment and altered transition-associated pathway enrichment in high ADNC WM. Together, these data define WM-specific OL programs linked to aging and ADNC and nominate a stress/immune-enriched OL state landscape consistent with a putative senescence-like phenotype in diseased WM.

neuroscience↗

bioRxiv2026

Patient-Specific Heart Rate Modulates Developmental Electrophysiology in Transcriptomic-Guided In Silico Models of Pediatric Human Atrial Cardiomyocytes

Cardiac electrophysiology adapts throughout pediatric development, driven by factors including age-associated ion channel expression changes and decreasing heart rate. Our prior transcriptomic-guided simulations of human atrial cardiomyocytes predicted developmental-associated changes in electrophysiology biomarkers at a fixed pacing rate, leaving the contribution of age- and patient-specific heart rate unresolved. In this study, we incorporated intrinsic heart rate into gene expression-guided computational models to predict the interaction between developmental maturation and pacing rate to shape atrial electrophysiology. Virtual patient-specific populations of atrial cardiomyocytes were generated from the right atrial cardiomyocyte gene expression data from 117 patients, spanning neonates to young adults. We simulated each population at pacing rates corresponding to each patients intrinsic ECG-based heart rate and at fixed rates corresponding to the patient cohort minimum, median, and maximum. Action potential and calcium transient biomarkers were quantified, and partial least squares regression assessed key biomarker dependencies. For intrinsic-rate pacing conditions, action potential duration at 50% and 90% repolarization increased with age, whereas early repolarization shortened; maximum upstroke velocity increased, resting membrane potential became more negative, and alternans prevalence decreased. Developmental differences persisted during fixed-rate pacing conditions, indicating that differences were not explained solely by the faster heart rates of younger patients. Notably, intrinsic-rate simulations exhibited stronger age associations for upstroke velocity and alternans than fixed-rate simulations. Sensitivity analyses indicated that electrophysiological phenotypes arose from interactions among ionic conductances, calcium handling, age, and heart rate. Collectively, we find that pediatric atrial electrophysiology reflects both intrinsic developmental remodeling and rate-dependent modulation.

biophysics↗

bioRxiv2026

A layered standards framework for integrating single-cell and spatial omics data into brain cell atlases

The BRAIN Initiative Cell Atlas Network (BICAN) is generating large-scale multimodal datasets to profile cell types in the human, non-human primate, and mouse brain. The diversity of single-cell and spatial transcriptomic and epigenomic assays, combined with varied experimental contexts, multiple data-generating laboratories and distributed infrastructure, poses substantial challenges for data integration and reuse in BICAN. To address this, we implemented a standards framework that enables layered integration of these data into knowledge-ready products for interoperable brain cell atlases. This framework organizes data based on three progressively structured layers. First, we introduced an assay-agnostic modeling layer that unifies the representation of single-cell and spatial omics data using a common set of biological entities and processes assessed by diverse experimental techniques. Second, we implemented harmonized metadata standards that capture key experimental features linked to biospecimen provenance across heterogeneous tissue sources, species, and preparations, supporting integration and validation while minimizing burden on data contributors. Third, we present an extensible representation for data-driven cell type taxonomies that integrates molecular data with annotations, ontology mappings, and evidence. Together, these contributions represent an end-to-end framework that transforms heterogeneous datasets into structured, interoperable resources that support broad community reuse via mapping algorithms, annotation systems, and visualization platforms. This approach links biospecimen provenance with cell-level outputs and embeds these in a standardized taxonomy format, enabling downstream applications such as cross-dataset integration, reference mapping, and knowledge-driven analysis. More broadly, our work demonstrates a generalizable strategy for enabling an efficient data-to-knowledge pipeline in a large-scale consortium setting.

genomics↗

bioRxiv2026

MapMyCells: High-performance mapping of unlabeled cell-by-gene data to reference brain taxonomies

Single-cell mapping methods convert raw, heterogeneous single-cell datasets into interpretable and comparable representations of biological identity. As reference cell-type taxonomies mature, mapping new datasets to shared references has become a central strategy for enabling cross-study integration, reproducible annotation, and cumulative biological knowledge. Here we present MapMyCells, an open-source framework designed to align diverse single-cell omics datasets to hierarchical reference taxonomies with minimal preprocessing. MapMyCells provides out-of-the-box support for an expanding set of high-quality brain cell-type references generated by the Allen Institute for Brain Science, the BRAIN Initiative, and the Seattle Alzheimers Disease Brain Cell Atlas, including whole-brain mouse and human atlases, aging and Alzheimers disease cohorts, and a cross-species consensus taxonomy initially focused on the basal ganglia. MapMyCells enables efficient mapping of hundreds of thousands of cells on standard workstations without specialized hardware, providing a deterministic, scalable, and modality-agnostic approach that is robust across species and molecular assays. The framework produces interpretable confidence metrics and quantitative summaries of mapping performance, allowing users to evaluate assignment precision and accuracy. We demonstrate the mapping of unlabeled transcriptomic, epigenomic, and spatial datasets to reference taxonomies and describe a general workflow for preparing arbitrary hierarchical taxonomies for reference-based mapping. As the ecosystem of single-cell reference atlases expands, MapMyCells offers a practical and reproducible solution for community-scale cell-type annotation and cross-dataset integration, supporting the development of unified and extensible brain cell atlases.

bioinformatics↗

bioRxiv2026

Morphoelectric Diversity and Specialization of Neuronal Cell Types in the Primate Striatum

The basal ganglia are evolutionary ancient subcortical nuclei that form interconnected loops with the neocortex and limbic system to regulate movement, learning, habit formation, emotion, and motivation. Their dysfunction contributes to major neurological and psychiatric disorders, yet most cellular-level insights derive from rodent studies, leaving knowledge gaps in humans and translationally relevant primate species. To address this, we generated multi-modal Patch-seq data linking transcriptomic identity with morphological and electrophysiological properties in macaque striatum, the input nucleus of the basal ganglia. We found underappreciated diversity among medium spiny neurons, including non-canonical types, and variation aligned with functional gradients. Interneurons also exhibited spatial variation and even greater morphoelectric diversity, highlighting their functional modularity. Despite broad evolutionary conservation, we identified primate-specific features and key differences from rodent striatal neurons. By integrating molecular classification with cellular properties that shape network function, our findings provide insights into the functional organization of the primate striatum.

neuroscience↗

bioRxiv2026

The Caudate Nucleus Exhibits Distinct Pathology and Cell Type-Specific Responses Across Alzheimer's Disease

A{beta} presence in the caudate nucleus (Ca) partially defines Thal stage III in Alzheimers disease (AD), but little is known about ADs cellular impact on the region. Leveraging a public basal ganglia taxonomy of cellular populations, we generated a cellular resolution atlas of AD-associated pathological changes in Ca. Unlike cortex, we found that Ca AD pathology is dominated by two key features: phosphorylated tau (pTau)-containing neuropil threads enriched near oligodendrocytes in white matter tracts and amyloid-{beta} diffuse plaques enriched in gray matter. Although AD pathology in affected cortical regions results in neuronal loss, we find no AD-driven reductions in neuron proportions in Ca. However, there were observable changes in multiple cellular populations. Protoplasmic astrocytes and FLT1+/IL1B+ microglia increased in abundance with global pTau levels. We also observe gene expression changes in fast-spiking PTHLH-PVALB interneurons indicative of disrupted signaling pathways and altered intrinsic physiological properties. This work provides a cellular-resolution framework for understanding AD pathology in Ca.

neuroscience↗

bioRxiv2026

Human Neocortical Glutamatergic Neurons Revealed Through Multimodal Profiling

The human neocortex underlies higher cognition and is the engine of complex thought. Yet our understanding of its neuronal diversity is limited by sparse access to tissue, inconsistent sampling across studies, and a lack of multiple modality data. Although single-cell transcriptomic taxonomies are an important framework for characterizing cell type diversity, transcriptomic information alone cannot reveal the cellular properties that define neuronal computations. To address this, we performed Patch-seq, a method for collecting Morphology, Electrophysiology, and Transcriptomic data from a single neuron. We focused on glutamatergic, neocortical, excitatory neurons, the principal long-range projecting neurons of the cortex, and systematically integrated their morphoelectric features with transcriptomic identity. In combination with spatial transcriptomic data, we interrogated 39 of 42 transcriptomically-defined neuron types with a layer-centric perspective. Morphoelectric properties, such as cortical depth, apical dendrite structure, and excitability clearly distinguish transcriptomic subclasses and support many finer transcriptomic types. Morphoelectric properties are influenced by spatial location in supragranular layers, while deeper layers exhibit greater heterogeneity. Cross-species comparisons reveal conserved subclass organization but pronounced differences in apical dendrite arborization between mouse and human, and surprising similarities between human and macaque. Together, these datasets provide a unified multimodal reference that advances our understanding of human cortical circuitry and establishes a foundation for experimental and computational studies of human brain function and disease.

neuroscience↗

bioRxiv2025

Genetic modulation of immune gene co-expression in the aged mouse hippocampus by the Apbb1ip locus

Ageing is a major risk factor for many neurodegenerative diseases, and the hippocampus is particularly vulnerable to the effects of ageing. To define the transcriptomic changes related to ageing and the impact of genetic variation, we analysed hippocampal gene expression data generated from a genetically diverse panel of inbred mouse strains belonging to the BXD Family. We applied a combination of differential expression, differential correlation, and weighted gene co-expression network analyses, followed by genetic mapping to delineate age-associated transcriptomic patterns and genetic modulators. This study revealed an upregulation in immune response and microglial genes. We identified a key age-associated co-expression module enriched in immune related genes, and quantitative trait locus mapping of this module uncovered a genetic regulatory locus in which Apbb1ip was the primary candidate gene. Additionally, gene level differential correlation analysis identified a substantial restructuring of the hippocampal transcriptome during ageing. Notably, Ywhab, an important signalling chaperone displayed altered gene expression correlations with >70 genes, between young and aged mice. These results provide novel insights into transcriptional dynamics of hippocampal ageing and identified the immune gene Apbb1ip as a potential modulator of immune response and microglial gene upregulation with implications for neurodegenerative disease pathogenesis. HighlightsO_LIComplementary gene expression analyses indicated an upregulation of immune responses in the ageing hippocampus of a genetically diverse mouse cohort, likely driven by microglia subtypes. C_LIO_LIA systems genetics approach revealed the Apbb1ip locus as a modulator of immune gene co-expression, highlighting a novel candidate regulator of age-associated neuroimmune dynamics. C_LIO_LISignalling chaperone Ywhab gene expression was highly differentially correlated with other transcripts during ageing which may underlie widespread age-associated molecular perturbations in the hippocampus. C_LI

bioinformatics↗

bioRxiv2025

Imbalance of Tregs/B cells and elevated complement signalling are hallmarks of Refractory Myasthenia Gravis

BackgroundA significant proportion of patients with myasthenia gravis (MG) remain refractory to standard immunosuppressive therapy, and biomarkers to help guide treatment decisions are lacking. MethodsWe examined the circulating immune profile of patients with acetylcholine receptor antibody positive MG with differing treatment requirements and compared them to controls. FindingsRefractory patients displayed the highest frequency of memory B cells, and increased production of interleukin (IL)-6 and tumour necrosis factor (TNF)- upon toll-like receptor/ CD40 activation in vitro, mirrored by a dramatic loss of regulatory T cells (Tregs) and dendritic cells. Refractory MG was further characterised by elevated circulating complement proteins (C3, C5 and clusterin) and increased expression of complement receptors on lymphocytes. Following anti-CD20 therapy, residual plasmablasts persisted in circulation. Notably, a low baseline B cell frequency (<3%) was associated with poor clinical response to rituximab in refractory disease, although the sample size was limited. ConclusionOur findings define a distinct immune signature in refractory MG, identify potential biomarkers of treatment resistance, and highlight plasma cell depletion, IL-6 or complement inhibition, and Treg expansion as promising therapeutic avenues. FundingFunding was received from the NorthCare Charity, Myaware, Academy of Medical Sciences and the Neuromuscular Study Group. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=156 SRC="FIGDIR/small/643341v3_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@13df9e2org.highwire.dtl.DTLVardef@1e086eborg.highwire.dtl.DTLVardef@1b9bb92org.highwire.dtl.DTLVardef@c9a164_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2025

Evidence for abstract codes in parietal cortex guiding prospective working memory

The recent past helps us predict and prepare for the near future. Such preparation relies on working memory (WM) which actively maintains and manipulates information providing a temporal bridge. Numerous studies have shown that recently presented visual stimuli can be decoded from fMRI signals in visual cortex (VC) and the intra-parietal sulcus (IPS) suggesting that these areas sustain the recent past. Yet, in many cases, concrete, sensory signals of past information must be transformed into the abstract codes to guide future cognition. However, this process remains poorly understood. Here, human participants used WM to maintain a separate spatial location in each hemifield wherein locations were embedded in a learned spatial sequence. On each trial, participants made a sequence-match decision to a probe and then updated their WM with the probe. The same abstract sequence guided judgments in each hemifield, allowing the separate detection of concrete spatial locations (hemifield-specific) and abstract sequence positions (hemifield-general), and also tracking of representations of the past (last location/position) and future (next location/position). Consistent with previous reports, concrete past locations held in WM could be decoded from VC and IPS. Moreover, in anticipation of the probe, representations shifted from past to future locations in both areas. Critically, we observed abstract coding of future sequence positions in the IPS whose magnitude related to speeded performance. These data suggest that the IPS sustains abstract codes to facilitate future preparation and reveal a transformation of the sensory past into abstract codes guiding future behavior. Significant StatementTo act efficiently, we must use the recent past to prepare for what comes next. For this purpose, working memory (WM) is critical. Although substantial research has shown that WM retains recently presented sensory information, preparation for the future involves abstraction wherein shared meaning is aggregated while superfluous sensory details are discarded. The mechanisms underlying this process remain unclear. Analyzing functional MRI signals in the intraparietal sulcus (IPS), we found that distinct sensory states with shared predictive meaning were initially maintained in a sensory-like fashion, but over time, became aggregated indicative of abstraction. Abstraction was associated with behavioral efficiency highlighting its role in preparation. These findings reveal neural mechanisms supporting the transformation from past to future in WM.

neuroscience↗

bioRxiv2025

Annotation Comparison Explorer (ACE): connecting brain cell types across studies of health and Alzheimer's Disease

BackgroundSingle-cell multiomic technologies have allowed unprecedented access to gene profiles of individual cells across species and organ systems, including the brain. The Allen Institute has created foundational atlases characterizing mammalian cell types in the adult mouse brain and the neocortex of humans with and without Alzheimers disease (AD). However, proliferation of public cell type classifications (or taxonomies) by us and others creates a challenge for knowledge integration. ResultsHere, we introduce Annotation Comparison Explorer (ACE), a web application for comparing cell type assignments and other cell-based annotations (e.g., donor demographics, anatomic locations, quality control metrics). ACE can filter cells and includes an interactive set of visualization tools, plot and data downloads, and statistics for comparing two or more taxonomy annotations alongside collected knowledge (e.g., cell type aliases, marker genes, abundance changes in disease). In this study we describe ACE functionality and present the following three ACE use cases. First, we demonstrate how a user can assign labels from the Seattle Alzheimers Disease Brain Cell Atlas (SEA-AD) taxonomy to their own cells and compare these mappings to user-defined cell type assignments and other cell metadata, using a previous cell type classification from the Allen Institute and two independent studies of different brain diseases as inputs. Second, we extend this approach for comparison of ten published human AD studies previously reprocessed through a common data analysis pipeline, and identify congruent cell type abundance changes in AD, including a decrease in certain somatostatin interneurons. Finally, ACE includes translation tables between different mouse and human brain cell type taxonomies on Allen Brain Map, from initial studies in neocortex to more recent studies spanning the whole brain, along with a human immune cell atlas focused on peripheral blood mononuclear cells. These use cases represent three of many possible applications for ACE. ConclusionsACE combines standard and custom visualizations into a user-friendly, open-source web tool for exploring categorical and numeric relationships and translating cell type classifications and knowledge across studies. ACE can be freely and publicly accessed at https://sea-ad.shinyapps.io/ACEapp/.

neuroscience↗

bioRxiv2024

Connecting Transcriptomics with Computational Modeling to Reveal Developmental Adaptations in the Human Pediatric Myocardium

BackgroundNearly 1% or 1.3 million babies are born with congenital heart disease (CHD) globally each year - many of whom will require palliative or corrective heart surgery within the first few years of life. A detailed understanding of cardiac maturation can help to expand our knowledge on cardiac diseases that develop during gestation, identify age-appropriate cardiovascular drug therapies, and inform clinical care decisions related to surgical repair, myocardial preservation, or postoperative management. Yet, to date, our knowledge of the temporal changes that cardiomyocytes undergo during postnatal development is largely limited to animal models. MethodsRight atrial tissue samples were collected from n=117 neonatal, infant, and pediatric patients undergoing correct surgery due to (acyanotic) CHD. Patients were stratified into five age groups: neonate (0-30 days), infant (31-364 days), toddler to preschool (1-5 years), school age (6-11 years), and adolescent to young adults (12-32 years). We measured age-dependent adaptations in cardiac gene expression, and used computational modeling to simulate action potential and calcium transients. ResultsEnrichment of differentially expressed genes (DEG) was explored, revealing age-dependent changes in several key biological processes (cell cycle, cell division, mitosis), cardiac ion channels, and calcium handling genes. Gene-associated changes in ionic currents exhibited both linear trends and sudden shifts across developmental stages, with changes in calcium handling (INCX) and repolarization (IK1) most strongly associated with an age-dependent decrease in the action potential plateau potential and increase in triangulation, respectively. We also note a shift in repolarization reserve, with lower IKr expression in younger patients, a finding likely tied to the increased amplitude of IKs triggered by elevated sympathetic activation in pediatric patients. ConclusionThis study provides valuable insights into age-dependent changes in human cardiac gene expression and electrophysiology among patients with CHD, shedding light on molecular mechanisms underlying cardiac development and function across different developmental stages.

cell biology↗

bioRxiv2023

Stochastic dispersal assembly dominates tropical invertebrate community assembly regardless of land use intensity.

Understanding how community assembly processes drive biodiversity patterns is a central goal of community ecology. While it is generally accepted that ecological communities are assembled by both stochastic and deterministic processes, quantifying their relative importance remains challenging. Few studies have investigated how the relative importance of stochastic and deterministic community assembly processes vary among taxa and along gradients of habitat degradation. Using data on 1,645 arthropod species across seven taxonomic groups in Malaysian Borneo, we quantified the importance of ecological stochasticity and of a suite of community assembly processes across a gradient of logging intensity. The relationship between logging and community assembly varied depending on the specific combination of taxa and stochasticity metric used, but, in general, the processes that govern invertebrate community assembly were remarkably robust to changes in land use intensity.

ecology↗

bioRxiv2022

Signature morpho-electric properties of diverse GABAergic interneurons in the human neocortex

Human cortical interneurons have been challenging to study due to high diversity and lack of mature brain tissue platforms and genetic targeting tools. We employed rapid GABAergic neuron viral labeling plus unbiased Patch-seq sampling in brain slices to define the signature morpho-electric properties of GABAergic neurons in the human neocortex. Viral targeting greatly facilitated sampling of the SST subclass, including primate specialized double bouquet cells which mapped to two SST transcriptomic types. Multimodal analysis uncovered an SST neuron type with properties inconsistent with original subclass assignment; we instead propose reclassification into PVALB subclass. Our findings provide novel insights about functional properties of human cortical GABAergic neuron subclasses and types and highlight the essential role of multimodal annotation for refinement of emerging transcriptomic cell type taxonomies. One Sentence SummaryViral genetic labeling of GABAergic neurons in human ex vivo brain slices paired with Patch-seq recording yields an in-depth functional annotation of human cortical interneuron subclasses and types and highlights the essential role of multimodal functional annotation for refinement of emerging transcriptomic cell type taxonomies.

neuroscience↗

bioRxiv2022

The BRAIN Initiative Cell Census Data Ecosystem: A User's Guide

Characterizing cellular diversity at different levels of biological organization across data modalities is a prerequisite to understanding the function of cell types in the brain. Classification of neurons is also required to manipulate cell types in controlled ways, and to understand their variation and vulnerability in brain disorders. The BRAIN Initiative Cell Census Network (BICCN) is an integrated network of data generating centers, data archives and data standards developers, with the goal of systematic multimodal brain cell type profiling and characterization. Emphasis of the BICCN is on the whole mouse brain and demonstration of prototypes for human and non-human primate (NHP) brains. Here, we provide a guide to the cellular and spatial approaches employed, and to accessing and using the BICCN data and its extensive resources, including the BRAIN Cell Data Center (BCDC) which serves to manage and integrate data across the ecosystem. We illustrate the power of the BICCN data ecosystem through vignettes highlighting several BICCN analysis and visualization tools. Finally, we present emerging standards that have been developed or adopted by the BICCN toward FAIR (Wilkinson et al. 2016a) neuroscience. The combined BICCN ecosystem provides a comprehensive resource for the exploration and analysis of cell types in the brain.

bioinformatics↗

bioRxiv2022

Morpho-electric and transcriptomic divergence of the layer 1 interneuron repertoire in human versus mouse neocortex

Neocortical layer 1 (L1) is a site of convergence between pyramidal neuron dendrites and feedback axons where local inhibitory signaling can profoundly shape cortical processing. Evolutionary expansion of human neocortex is marked by distinctive pyramidal neuron types with extensive branching in L1, but whether L1 interneurons are similarly diverse is underexplored. Using patch-seq recordings from human neurosurgically resected tissues, we identified four transcriptomically defined subclasses, unique subtypes within those subclasses and additional types with no mouse L1 homologue. Compared with mouse, human subclasses were more strongly distinct from each other across all modalities. Accompanied by higher neuron density and more variable cell sizes compared with mouse, these findings suggest L1 is an evolutionary hotspot, reflecting the increasing demands of regulating the expanding human neocortical circuit. One Sentence SummaryUsing transcriptomics and morpho-electric analyses, we describe innovations in human neocortical layer 1 interneurons.

neuroscience↗

bioRxiv2022

Inter-individual variation in human cortical cell type abundance and expression

Single cell transcriptomic studies have identified a conserved set of neocortical cell types from small post-mortem cohorts. We extend these efforts by assessing cell type variation across 75 adult individuals undergoing epilepsy and tumor surgeries. Nearly all nuclei map to one of 125 robust cell types identified in middle temporal gyrus, but with varied abundances and gene expression signatures across donors, particularly in deep layer glutamatergic neurons. A minority of variance is explainable by known factors including donor identity and small contributions from age, sex, ancestry, and disease state. Genomic variation was significantly associated with variable expression of 150-250 genes for most cell types. Thus, human individuals display a highly consistent cellular makeup, but with significant variation reflecting donor characteristics, disease condition, and genetic regulation. One-Sentence SummaryInter-individual variation in human cortex is greatest for deep layer excitatory neurons and largely unexplainable by known factors.

neuroscience↗

bioRxiv2022

Defining tertiary sulci in lateral prefrontal cortex in chimpanzees using human predictions

Similarities and differences in brain structure and function across species is of major interest in systems neuroscience, comparative biology, and brain mapping. Recently, increased emphasis has been placed on tertiary sulci, which are shallow indentations of the cerebral cortex that appear last in gestation, continue to develop after birth, and are largely either human- or hominoid-specific. While tertiary sulcal morphology in lateral prefrontal cortex (LPFC) has been linked to functional representations and cognition in humans, it is presently unknown if LPFC tertiary sulci also exist in non-human hominoids. To fill this gap in knowledge, we leveraged two freely available multimodal datasets to address the following main question: Can LPFC tertiary sulci be defined in chimpanzee cortical surfaces from human predictions? We found that 1-3 components of the posterior middle frontal sulcus (pmfs) in the posterior middle frontal gyrus are identifiable in nearly all chimpanzee hemispheres. In stark contrast to the consistency of the pmfs components, we could only identify components of the paraintermediate frontal sulcus (pimfs) in two chimpanzee hemispheres. LPFC tertiary sulci were relatively smaller and shallower in chimpanzees compared to humans. In both species, two of the pmfs components were deeper in the right compared to the left hemisphere. As these results have direct implications for future studies interested in the functional and cognitive role of LPFC tertiary sulci across species, we share probabilistic predictions of the three pmfs components to guide the definitions of these sulci in future studies.

neuroscience↗