Biology subjects

Lewis, J. D.

Publications and source records attributed to Lewis, J. D..

At least 19 recordsLinked to original sources

bioRxiv2026

Mechanochemical cues control the coupling of metabolic and migratory patterns in cancer

Confined migration is essential for metastasis, yet how cells adapt their migratory and metabolic programs across stiffness-varying microenvironments remains unclear. We uncover a stiffness-dependent mechano-metabolic switch governing migration. In stiff microchannels, cells utilize the osmotic engine model (OEM), relying on NHE1 activity, front-polarization, and glycolysis. In soft microchannels, migration is OEM-independent and requires pyruvate-fueled oxidative phosphorylation (OxPHOS). This OxPHOS-driven motility depends on Arp3, {beta}1-integrin and integrin-linked kinase, which increase membrane tension in confinement that in turn triggers TRPM7-mediated calcium influx and RhoA-/myosin-II contractility. Activating and polarizing NHE1, via overexpression, hypoxia or elevated viscosity, restore OEM- and glycolysis-dependent migration in soft microchannels, bypassing the need for actin polymerization in vitro and in chick embryos. Mitochondria addition reinstates Arp3 polarization and enhances migration in NHE1-overexpressing cells, enabling engagement of both mechanisms in vitro and in zebrafish. These findings uncover a previously unrecognized mechano-metabolic link, revealing that intracellular rewiring overrides stiffness-dependent metabolic demands.

cell biology↗

bioRxiv2026

Human Gut Bacteria Convert Endogenous Steroids into Host Cortisol Shuttle Inhibitors

11{beta}-hydroxysteroid dehydrogenase 2 (HSD11B2) protects the mineralocorticoid receptor from glucocorticoid overstimulation by inactivating cortisol. HSD11B2 inhibition can drive receptor overactivation and contribute to hypertension; however, endogenous inhibitors remain poorly defined. Glycyrrhetinic acid-like factors (GALFs) are steroid-like metabolites that inhibit HSD11B2. Given the capacity of gut bacteria to metabolize host steroids, we hypothesized that the gut microbiome could generate GALF-like inhibitors. Here, we identify two 11-oxygenated steroid metabolites that potently inhibit human HSD11B2 in colonic cells and organoids, enabling cortisol-dependent mineralocorticoid receptor activation. We identify gut bacteria and enzymes that produce these compounds and show that their levels are markedly reduced in antibiotic-treated humans. One metabolite is elevated during pregnancy, and both are higher in individuals with stage 2 hypertension-range blood pressure. These findings reveal a bacterial route to altered host cortisol signaling and suggest a potential link between microbiome-derived GALFs and blood pressure regulation.

microbiology↗

bioRxiv2026

The Unified Human Virome Database: A toolkit for expanded human virome analysis

Current computational methods for analyzing viruses in human metagenomes rely on static databases composed largely of fragmented virus genomes mostly derived from gastrointestinal samples. This limits the identification of viruses exclusively found outside the gastrointestinal tract and impairs analyses requiring high-quality genomes. To address these issues, we created the Updateable Human Virome Database (UHVDB), an expandable database of high-quality, clustered, and annotated virus genomes integrated from pre-existing human virome databases and diverse human sample metagenome assemblies. We developed an associated toolkit that enables users to 1) update by UHVDB mining, clustering, and annotating virus sequences, 2) taxonomically profile viruses in metagenomes and metatranscriptomes, 3) estimate phage replication activity using phage-to-host ratios, and 4) identify putatively uninducible prophages from bulk metagenomes. To illustrate the utility of UHVDB and its associated toolkit, we analyzed 1,983 oral/airway samples from people with Cystic Fibrosis, finding that over 25% of viruses present were likely uninducible prophages and that many others had low replication activity, suggesting far less viral activity than estimated from previous studies. UHVDB is a novel framework for virome analysis that expands the capacity to define virus contributions to health and disease.

microbiology↗

bioRxiv2025

Neonatal White Matter Microstructure Predicts Infant Attention Disengagement from Fearful Faces

Infants develop an attentional bias towards faces already at birth, with further specification towards fearful faces emerging at 6 months and diminishing around 11 months of age. However, the neurobiological origins of attentional bias to fear are still poorly understood. To understand the neural structures underlying perception of facial expressions, the current study utilized newborn diffusion magnetic resonance images (N = 86; 41 females; = 27.15 days) and eye tracking from the same infants at 8-months ( = 8.75 months) as a behavioural measure. An overlap paradigm was used to measure attention disengagement from fearful, happy, and neutral faces. Tract-based spatial statistics revealed that higher white matter (WM) mean diffusivity in widespread regions across the brain was associated with lower attention disengagement from fearful faces. The same association was found with happy faces but was limited to only the splenium of the corpus callosum and sensorimotor pathways. Variance in neonatal WM microstructure may reflect individual differences in growth that is related to attentional bias development later in infancy.

neuroscience↗

bioRxiv2024

Neonatal Amygdala Mean Diffusivity: A Potential Predictor of Emotional Face Perception

The ability to differentiate between different facial expressions is an important part of human social and emotional development that begins in infancy. Studies have shown that within the first year of life, infants develop a distinctive attentional bias towards fearful facial expressions. Investigations into the neural basis for this bias have highlighted the significance of the amygdala. The amygdalas role in directing attention towards fearful facial expressions underscores its importance in early emotional development, significantly influencing how infants interpret and react to facial expressions. To date, no studies have been conducted to investigate the associations between the amygdala microstructure and infants perception of emotional faces. This study aimed to elucidate this relationship while also investigating whether this association is sex specific. We measured the amygdala microstructural properties using diffusion tensor imaging mean diffusivity (MD) measurements in 40 healthy infants aged 2 to 5 weeks. Eye tracking was used to assess attention disengagement from fearful vs. non-fearful (happy and neutral) facial expressions as well as scrambled non-face control picture at 8 months. Generally, infants were age-typically less likely to disengage from fearful faces than from non-fearful faces towards salient distractors. A significant negative association was observed between the right amygdala MD measures and disengagement probability from fearful faces in the overall sample. Moreover, there was a positive association between the bilateral amygdala MD measures and the disengagement probability from scrambled non-face control picture in girls. These results indicate that the amygdala MD is associated with attention disengagement processes already in infancy, both in fear processing and in non-emotional conditions. Specifically, these findings highlight the role of the amygdala microstructure in modulating attentional processes, which may have implications for emotional regulation and susceptibility to emotional dysregulation later in life.

neuroscience↗

bioRxiv2024

The FinnBrain Multimodal Neonatal Template and Atlas Collection: T1, T2, and DTI brain templates, and accompanying cortical and subcortical atlases

The accurate processing of neonatal and infant brain MRI data is crucially important for developmental neuroscience, but presents challenges that child and adult data do not. Tissue segmentation and image coregistration accuracy can be improved by optimizing template images and / or related segmentation procedures. Here, we describe the construction of the FinnBrain Neonate (FBN-125) template; a multi-contrast template with T1- and T2-weighted as well as diffusion tensor imaging derived fractional anisotropy and mean diffusivity images. The template is symmetric and aligned to the Talairach-like MNI 152 template and has high spatial resolution (0.5 mm3). In addition, we provide atlas labels, constructed from manual segmentations, for cortical grey matter, white matter, cerebrospinal fluid, brainstem, and cerebellum as well as the bilateral hippocampi, amygdalae, caudate nuclei, putamina, globi pallidi, and thalami. We provide this multi-contrast template along with the labelled atlases for the use of the neuroscience community in the hope that it will prove useful in advancing developmental neuroscience, for example, by helping to achieve reliable means for spatial normalization and measures of neonate brain structure via automated computational methods. Additionally, we provide standard co-registration files that will enable investigators to reliably transform their statistical maps to the adult MNI space, which has the potential to improve the consistency and comparability of neonatal studies or the use of adult MNI space atlases in neonatal neuroimaging.

neuroscience↗

bioRxiv2023

The leucine-rich repeat receptor kinase QSK1 is a novel regulator of PRR-RBOHD complex and is employed by the bacterial effector HopF2Pto to modulate plant immunity

Plants detect pathogens using cell-surface pattern recognition receptors (PRRs) like EFR and FLS2, which recognize bacterial EF-Tu and flagellin, respectively. These PRRs, belonging to the leucine-rich repeat receptor kinase (LRR-RK) family, activate the production of reactive oxygen species via the NADPH oxidase RBOHD. The PRR-RBOHD complex is tightly regulated to prevent unwarranted or exaggerated immune responses. However, certain pathogenic effectors can subvert these regulatory mechanisms, thereby suppressing plant immunity. To elucidate the intricate dynamics of the PRR-RBOHD complex, we conducted a comparative co-immunoprecipitation analysis using EFR, FLS2, and RBOHD. We identified QSK1, an LRR-RK, as a novel component of the PRR-RBOHD complex. QSK1 functions as a negative regulator of PRR-triggered immunity (PTI) by downregulating the abundance of FLS2 and EFR. QSK1 is targeted by the bacterial effector HopF2Pto, a mono-ADP ribosyltransferase, resulting in the reduction of FLS2 and EFR levels through both transcriptional and transcription-independent pathways, thereby inhibiting PTI. Furthermore, HopF2Pto reduces transcript levels of PROSCOOP genes encoding important stress-regulated phytocytokines and their receptor MIK2. Importantly, HopF2Pto requires QSK1 for its accumulation and virulence functions within plants. In summary, our results provide novel insights into the mechanism by which HopF2Pto employs QSK1 to desensitize plants to pathogen attack. One Sentence SummaryQSK1, a novel component in the plant immune receptor complex, downregulates these receptors and phytocytokines, and is exploited by bacterial effector HopF2Pto to desensitize plants to pathogen attack.

plant biology↗

bioRxiv2023

Associations between maternal pre-pregnancy BMI and infant striatal mean diffusivity

Background/ObjectivesIt is well-established that parental obesity is a strong risk factor for associates with offspring obesity. Further, a converging body of evidence now suggests that maternal weight profiles may affect the developing offspring brain in a manner that confers future obesity risk. Here, we investigated how pre-pregnancy maternal weight status influences the reward-related striatal areas of the offspring brain during in utero development. MethodsWe used diffusion tensor imaging to quantify the microstructure of the striatal brain regions of interest in neonates (N = 116 mean gestational weeks at birth 39.88, SD = 1.14; and at scan 43.56, SD = 1.05). Linear regression was used to test the associations between maternal pre-pregnancy body mass index and infant striatal mean diffusivity. ResultsA strong positive association was found between the maternal pre-pregnancy body mass index and newborn left caudate nucleus mean diffusivity. Results remained unchanged after the adjustment for covariates. ConclusionsIn utero exposure to maternal adiposity might have a growth impairing impact on the mean diffusivity of infant left caudate nucleus. Considering the involvement of caudate nucleus in regulating eating behaviour and food-related reward processing later in life, this finding calls for further investigations to define the prognostic relevance of early life caudate development and weight trajectories of the offspring.

neuroscience↗

bioRxiv2023

Infant Left Amygdala Volume Is Negatively Associated with Fecal Microbiota Diversity

IntroductionRodent studies have addressed the importance of early life gut microbiota in the development of emotional and social functioning. Studies in human infants are still scarce, but associations with cognition and temperament have been reported. Neuroimaging studies have linked the amygdala with fecal microbiota diversity in infants, but crucially these studies have not covered the neonatal period, and the current study addressed this gap. MethodsThe study population included 65 infants drawn from the ongoing, general population based FinnBrain Birth Cohort Study. Brain MRI was performed around the age of one month (mean age 25 days). Fecal microbiota profiles (mean 68 days) were assessed by 16s rRNA amplicon sequencing at the age of 2.5 months. ResultsWe found a negative association between infant left amygdala volume and alpha diversity (n=52, beta =-0.0043, p=0.034, adjusted for infant sex, breastfeeding, delivery mode, age during fecal sampling, age from conception during scan, and intracranial volume, Fig.1). Amygdala volumes were not associated with beta diversity (p=0.21), nor with the abundances of individual genera when adjusted for the same covariates and multiple testing. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=112 SRC="FIGDIR/small/537273v1_fig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@bf1304org.highwire.dtl.DTLVardef@798edeorg.highwire.dtl.DTLVardef@92c040org.highwire.dtl.DTLVardef@8bc2a9_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure. 1.C_FLOATNO Gut microbiota alpha diversity associates negatively with left (A), but not with right (B) amygdala volume. The grey areas depict 95% confidence intervals. C_FIG ConclusionOur results provide first evidence for associations between the brain and fecal microbiota in human neonates. Although the reported data do not allow investigation of underlying mechanisms, i.e. about the directionality of the hypothesized gut-brain connection, the reported connection encourages for future investigations of manifestations of gut-brain axis in early life.

neuroscience↗

bioRxiv2023

Effect of number of diffusion encoding directions in Neonatal Diffusion Tensor Imaging using Tract-Based Spatial Statistical analysis

Diffusion Tensor Imaging (DTI) has been used to study the developing brain in early childhood, infants and in utero studies. In infants, number of used diffusion encoding directions has traditionally been smaller in earlier studies down to the minimum of 6 orthogonal directions. While the more recent studies often involve more directions, number of used directions remains an issue when acquisition time is optimized without compromising on data quality and in retrospective studies. Variability in the number of used directions may introduce bias and uncertainties to the DTI scalar estimates that affect cross-sectional and longitudinal study of the brain. We analyzed DTI images of 133 neonates, each data having 54 directions after quality control, to evaluate the effect of number of diffusion weighting directions from 6 to 54 with interval of 6 to the DTI scalars with Tract-based spatial statistics (TBSS) analysis. The TBSS analysis was applied to DTI scalar maps, and the mean Region of Interest (ROI) values were extracted using JHU atlas. We found significant bias in ROI mean values when only 6 directions were used (positive in FA, negative in MD, AD, RD), while when using 24 directions and above, the difference to scalar values calculated from 54 direction DTI was negligible. Using DTI measurements from data with at least 24 directions may be used in comparisons with DTI measurements from data with higher numbers of directions.

neuroscience↗

bioRxiv2023

Parental childhood maltreatment associates with offspring left amygdala volume at early infancy

BackgroundChildhood maltreatment exposure (CME) and related trauma could be considered some of psychiatrys greatest public health challenges. CME and early adversity have been associated with increased amygdala volume in exposed individuals. Emerging evidence implies that CME could also affect prenatal development of the offspring. MethodsAs part of the FinnBrain Birth Cohort Study, we measured bilateral amygdala volumes from MR images in 76 healthy infants at 2-5 weeks of gestation corrected age and obtained the Trauma and Distress Scale (TADS) questionnaire from both parents. The associations between neonatal amygdala volumes and TADS scores were examined in stepwise regression models. ResultsWe found that maternal CME associated positively with infant left amygdala volume (p = .045) while the positive association for the paternal trauma score was only marginally significant (p = .099). Similar associations were not observed for the right amygdala. In the exploratory analyses, we used age ranges (0-6, 7-12, and 13-18 years) as estimate of the timing of the CME and included all three time points from both parents using left amygdala volume into the stepwise regression models. We found that maternal TADS scores from 13-18 years of age associated positively with infant left amygdala volumes (p = .008). Correspondingly, paternal TADS scores from 0-6 years of age associated positively with the infant left amygdala volumes (p = .014). ConclusionsOur link the infant offspring amygdala volume with parental CME with some agreement with prior findings, and they also imply links paternal CME to infant amygdala volumes. Amygdala is one of the key brain structures associated with both early life exposures and later psychiatric health, which makes it crucially important to elucidate both the underlying mechanisms and the later relevance of these associations in future studies.

neuroscience↗

bioRxiv2023

Sex differences, asymmetry and age-related white matter development in infants and 5-year-olds as assessed with Tract-Based Spatial Statistics

The rapid white matter (WM) maturation of first years of life is followed by slower yet long-lasting development, accompanied by learning of more elaborate skills. By the age of five years, behavioural and cognitive differences between females and males, and functions associated with brain lateralization such as language skills are appearing. Diffusion tensor imaging (DTI) can be used to quantify fractional anisotropy (FA) within the WM and increasing values correspond to advancing brain development. To investigate the normal features of WM development during early childhood, we gathered a DTI data set of 166 healthy infants (mean 3.8 wk, range 2-5wk; 89 males; born on gestational week 36 or later) and 144 healthy children (mean 5.4 years, range 5.1-5.8 years; 76 males). The sex differences, lateralization patterns and age-dependent changes were examined using tractbased spatial statistics (TBSS). In 5-year-olds, females showed higher FA in wide-spread regions in the posterior and the temporal WM and more so in the right hemisphere, while sex differences were not detected in infants. Gestational age showed stronger association with FA values compared to age after birth in infants. Additionally, child age at scan associated positively with FA around the age of 5 years in the body of corpus callosum, the connections of which are important especially for sensory and motor functions. Lastly, asymmetry of WM microstructure was detected already in infants, yet significant changes in lateralization pattern seems to occur during early childhood, and in 5-year-olds the pattern already resembles adult-like WM asymmetry. HighlightsO_LIWhite matter tract integrity shows widespread sex differences at the age of 5 years. C_LIO_LIWhite matter structure is highly lateralized during early childhood, and changes in asymmetry occur between the birth and 5 years of age. C_LIO_LIThe white matter lateralization pattern of 5-year-olds, unlike of infants, resembles asymmetry observed in adults. C_LI

neuroscience↗

bioRxiv2022

Targeted Proteomics and Support Vector Classification Reveal Potential Biomarkers for the Early Detection of High-grade Serous Ovarian Cancer

PurposeThe five-year prognosis for patients with late-stage high-grade serous carcinoma (HGSC) remains dismal, underscoring the critical need for identifying early-stage biomarkers. This study explores the potential of extracellular vesicles (EVs) circulating in blood, which are believed to harbor proteomic cargo reflective of the HGSC microenvironment, as a source for biomarker discovery. Experimental DesignWe conducted a comprehensive proteomic profiling of EVs isolated from blood plasma, ascites, and cell lines of patients, employing both data-dependent (DDA) and data-independent acquisition (DIA) methods to construct a spectral library tailored for targeted proteomics. Our investigation aimed at uncovering novel biomarkers for the early detection of HGSC by comparing the proteomic signatures of EVs from women with HGSC to those with benign gynecological conditions. The initial cohort, comprising 9-10 donors, utilized DDA proteomics for spectral library development. The subsequent cohort, involving 30 HGSC patients and 30 control subjects, employed DIA proteomics for a similar purpose. Support vector machine (SVM) classification was applied in both cohorts to identify combinatorial biomarkers with high specificity and sensitivity (ROC-AUC > 0.90). ResultsNotably, MUC1 emerged as a significant biomarker in both cohorts when used in combination with additional biomarkers. Validation through an ELISA assay on a subset of benign (n=18), Stage I (n=9), and stage II (n=9) plasma samples corroborated the diagnostic utility of MUC1 in the early-stage detection of HGSC. ConclusionsThis study highlights the value of EV-based proteomic analysis in the discovery of combinatorial biomarkers for early ovarian cancer detection.

cancer biology↗

bioRxiv2022

Genome-wide identification of fitness determinants in the Xanthomonas campestris bacterial pathogen during early stages of plant infection

Plant diseases are an important threat to food production. While major pathogenicity determinants required for disease have been extensively studied, less is known on how pathogens thrive during host colonization especially at early infection stages. Here, we used randomly barcoded-transposon insertion site sequencing (RB-TnSeq) to perform a genome-wide screen and identify key bacterial fitness determinants of the vascular pathogen Xanthomonas campestris pv. campestris (Xcc) during infection of the cauliflower host plant (Brassica oleracea). This high-throughput analysis was conducted in hydathodes, the natural entry site of Xcc, in xylem sap and in synthetic media. Xcc did not face a strong bottleneck during hydathode infection. 183 genes important for fitness were identified in plant-associated environments with functional enrichment in genes involved in metabolism when only few genes known to be involved in virulence were found to be affected. The biological relevance of 13 genes was independently confirmed by phenotyping single mutants. Notably, we show that the XC_3388, a protein with no known function (DUF1631), plays a key role in the adaptation and virulence of Xcc possibly through c-di-GMP-mediated regulation. This study thus revealed yet unsuspected social behaviors adopted by Xcc individuals when confined inside hydathodes at early infection stages.

microbiology↗

bioRxiv2021

In-phase and in-antiphase connectivity in EEG

Zero-lag synchrony is generally discarded from functional connectivity studies to eliminate the confounding effect of volume conduction. Demonstrating genuine and significant unlagged synchronization between distant brain regions would indicate that most electroencephalography (EEG) connectivity studies neglect an important mechanism for neuronal communication. We previously demonstrated that local field potentials recorded intracranially tend to synchronize with no lag between homotopic brain regions. This synchrony occurs most frequently in antiphase, potentially supporting corpus callosal inhibition and interhemispheric rivalry. We are now extending our investigation to EEG. By comparing the coherency in a recorded and a surrogate dataset, we confirm the presence of a significant proportion of genuine zero-lag synchrony unlikely to be due to volume conduction or to recording reference artifacts. These results stress the necessity for integrating zero-lag synchrony in our understanding of neural communication and for disentangling volume conduction and zero-lag synchrony when estimating EEG sources and their functional connectivity.

neuroscience↗

bioRxiv2020

Assembly of the amphibian microbiome is influenced by the effects of land-use change on environmental reservoirs

0A growing focus in microbial ecology is understanding of how beneficial microbiome function is created and maintained through both stochastic and deterministic assembly mechanisms. This study explores the role of both the environment and disease in regulating the composition of microbial species pools in the soil and local communities of an amphibian host. To address this, we compared the microbiomes of over 200 Plethodon cinereus salamanders along a 65km land-use gradient in the greater New York metropolitan area and paired these with associated soil cores. Additionally, we characterized the diversity of bacterial and fungal symbionts that putatively inhibit the pathogenic fungus Batrachochytrium dendrobatidis. We predicted that if soil functions as the main regional species pool to amphibian skin, variation in skin microbial community composition would correlate with changes seen in soil. We found that salamanders share many microbial taxa with their soil environment but that these two microbiomes exhibit key differences, especially in the relative abundances of the bacteria phyla Acidobacteria, Actinobacteria, and Proteobacteria and the fungal phyla Ascomycota and genus Basidiobolus. Microbial community composition varied with changes in land-use associated factors such as canopy cover, impervious surface, and concentrations of the soil elements Al, Ni, and Hg, creating site-specific compositions. In addition, high dissimilarity among individual amphibian microbiomes across and within sites suggest that both stochastic and deterministic mechanisms guide assembly of microbes onto amphibian skin, with likely consequences in disease preventative function.

ecology↗

bioRxiv2020

Nuclear IQGAP1 promotes gastric cancer cell growth by altering the splicing of a cell-cycle regulon in co-operation with hnRNPM

In response to oncogenic signals, Alternative Splicing (AS) regulators such as SR and hnRNP proteins show altered expression levels, subnuclear distribution and/or post-translational modification status, but the link between signals and these changes remains unknown. Here, we report that a cytosolic scaffold protein, IQGAP1, performs this task in response to heat-induced signals. We show that in gastric cancer cells, a nuclear pool of IQGAP1 acts as a tethering module for a group of spliceosome components, including hnRNPM, a splicing factor critical for the response of the spliceosome to heat-shock. IQGAP1 controls hnRNPMs sumoylation, subnuclear localization and the relevant response of the AS machinery to heat-induced stress. Genome-wide analyses reveal that IQGAP1 and hnRNPM co-regulate the AS of a cell cycle-related RNA regulon in gastric cancer cells, thus favouring the accelerated proliferation phenotype of gastric cancer cells. Overall, we reveal a missing link between stress signals and AS regulation.

molecular biology↗

bioRxiv2019

A sub+ cortical fMRI-based surface parcellation

Both the cortex and the subcortical structures are organized into a large number of distinct areas reflecting functional and cytoarchitectonic differences. Mapping these areas is of fundamental importance to neuroscience. A central obstacle to this task is the inaccuracy associated with mapping results from individuals into a common space. The vast individual differences in morphology pose a serious problem for volumetric registration. Surface-based approaches fare substantially better, but have thus far been used only for cortical parcellation. We extend this surface-based approach to include also the subcortical deep gray-matter structures. Using the life-span data from the Enhanced Nathan Klein Institute - Rockland Sample, comprised of data from 590 individuals from 6 to 85 years of age, we generate a functional parcellation of both the cortical and subcortical surfaces. To assess this extended parcellation, we show that our extended functional parcellation provides greater homogeneity of functional connectivity patterns than do arbitrary parcellations matching in the number and size of parcels. We also show that our subcortical parcels align with known subnuclei. Further, we show that this parcellation is appropriate for use with data from other modalities; we generate cortical and subcortical white/gray contrast measures for this same dataset, and draw on the fact that areal differences are evident in the relation of white/gray contrast to age, to sex, to brain volume, and to interactions of these terms; we show that our extended functional parcellation provides an improved fit to the complexity of the life-span changes in the white/gray contrast data compared to arbitrary parcellations matching in the number and size of parcels. We provide our extended functional parcellation for the use of the neuroimaging community.

neuroscience↗