Biology subjects

Dickinson, A.

Publications and source records attributed to Dickinson, A..

13 recordsLinked to original sources

bioRxiv2026

System-Specific Epigenetic Aging Signatures in Autistic Adults

Background: Autism is a lifelong neurodevelopmental condition, but the biological processes shaping aging are poorly understood. DNA methylation-based measures index physiological decline and mortality risk independently of chronological age. We tested whether biological aging differs in autistic adults, whether differences are system-specific, and which factors predict within-autism variation. Methods: Saliva DNA methylation (Illumina EPIC) was assayed in 37 autistic adults (31 male, 6 female; mean age 29.8 years), followed from early childhood, spanning a broad ability range including intellectual disability, and 188 non-autistic adults from four public datasets, processed jointly. Fifteen measures were calculated: four global (Horvath, GrimAge, DunedinPACE, SystemsAge) and 11 system-specific SystemsAge subscores. Models adjusted for age, sex, and epithelial-cell proportion. Results: Global aging measures did not differ between groups (all q > .34). However, autistic adults had higher Brain ({beta} = 0.81), Blood ({beta} = 0.65), and Liver SystemsAge ({beta} = 0.58; all q < .01), with Brain and Blood robust across sensitivity analyses. Within autism, aging measures were unrelated to symptom severity, IQ, co-occurring diagnoses, or medication use. Instead, elevations were associated with psychosocial circumstances, including a lack of structured daytime activity, greater loneliness, and lower quality of life. Conclusions: Differences in aging biology in autism appeared system-specific rather than global, with no evidence of generalized epigenetic age acceleration. This vulnerability appeared more closely tied to psychosocial factors than core clinical features. System-specific DNAm measures may therefore provide a more sensitive framework for identifying biological heterogeneity and potentially modifiable contributors to healthy aging in autistic adulthood.

genomics↗

bioRxiv2026

Antagonistic action of a nuclear hormone receptor pair coordinates a switch from lytic to biotrophic effector production in a plant-parasitic nematode

Pathogens secrete overlapping and sequential waves of effectors to manipulate their host, and yet the regulators that conduct the ensemble are poorly understood. Here, we identify the Dorsal Gland Regulator DGR-1 in the beet cyst nematode Heterodera schachtii. DGR-1 controls the expression of 131 putative effectors, acting as a dual-functional switch that "switches off" early stage effectors involved in plant invasion, and "switches on" later stage effectors associated with biotrophic establishment in the host. Interestingly, DGR-1 works antagonistically with the only other known transcriptional regulator of effectors in plant-parasitic nematodes, the Subventral Gland Regulator-1 (SUGR-1), to coordinate this apparent switch from lytic to biotrophic effector production. Together, DGR-1 and SUGR-1 control the expression of nearly one half of all H. schachtii early-stage effectors, and over one fifth of effectors of any kind. The requirement to activate lytic effector functions in the cortex, and biotrophic effector functions in the vascular cylinder, suggests that this transcription factor pair must differentially respond to signals from the host. Consistent with this, we find that diffusates from the roots of A. thaliana Casparian strip mutant myb36/sgn3, which are enriched in molecules ordinarily restricted to the vascular cylinder, upregulate dgr-1, but not sugr-1, compared to Col-0. Taken together, these data indicate that H. schachtii responds to compartmentalised host-derived signals to appropriately regulate spatiotemporal effector expression during infection. Given that misregulating DGR-1 results in delayed development of parasitic nematodes in Arabidopsis and Mustard, strategies which impair effector regulation as a whole may hold promise for crop protection against these agriculturally important pathogens.

pathology↗

bioRxiv2026

Visual Cortical Response Variability in Infants at High Familial Likelihood for Autism

Visual processing undergoes rapid development in the first year of life, supporting the emergence of higher-order cognitive, language, and motor functions. Visual evoked potentials (VEPs) provide a non-invasive measure of visual system maturation that may shed light on heterogeneous developmental trajectories among infants at high familial likelihood for autism. Infants with an older sibling with autism spectrum disorder (N = 177 at 6 months; N = 132 at 12 months) participated in the Infant Brain Imaging Study-Early Prediction (IBIS-EP) study. Pattern-reversal VEPs were recorded at 6 and 12 months, and developmental skills were assessed at 24 months using the Bayley Scales of Infant and Toddler Development (Bayley-4). VEP components (P1 and N1) were characterized by their amplitude and latency, as well as trial-to-trial variability in these measures. Associations with 24-month cognitive, language, and motor scores were examined using general linear models controlling for age, site, sex, and trial count. Robust VEPs were observed at both time points, with age-appropriate morphology and expected developmental changes, including decreases in P1 latency and amplitude from 6 to 12 months. Greater trial-to-trial variability in P1 latency at both time points was associated with higher cognitive and language scores at 24 months. In contrast, conventional measures of mean P1 latency and amplitude were not associated with developmental outcomes. These findings suggest that temporal variability in early visual responses may index adaptive sensory-circuit flexibility during a period of rapid experience-dependent development. VEP response-timing variability may therefore provide an early mechanistic marker of sensory-circuit organization relevant to later developmental trajectories. Research HighlightsO_LIGreater trial-to-trial variability in visual cortical response timing was associated with higher cognitive and language scores in infants at high familial likelihood for autism. C_LIO_LIConventional average VEP measures were unrelated to outcomes, suggesting temporal variability may more sensitively capture relevant neural-circuit differences in this population. C_LIO_LIGreater variability in early visual responses may reflect adaptive sensory-circuit flexibility during a critical period of neurodevelopment. C_LIO_LIVEP response-timing measures provide an early mechanistic window into sensory-circuit organization and its relation to later developmental trajectories. C_LI

neuroscience↗

bioRxiv2026

Intentional control of instrumental punishment

Punishment raises a basic question for human cognition: do agents suppress actions because they represent the negative consequences those actions produce? Everyday deterrence, from parental reprimands to legal sanctions, assumes that people regulate behavior by learning what their actions cause and by evaluating those consequences negatively. However, in spite of this widely-held assumption, experimental evidence that punished instrumental behavior is controlled by the current value of the punisher is currently lacking. To test this idea, we applied an outcome revaluation procedure to instrumental punishment in rats. Rats first learned to press two levers for food. One lever was then additionally punished by response-contingent footshock, whereas the other remained unpunished. The aversiveness of the shock was subsequently reduced by pairing it with food in the absence of the levers. To test if the punishers value was part of the animals representation of the consequences of their actions, responding was tested in extinction, with no shock delivered. We found that revaluation of the shock selectively abolished the suppression of the punished response. Thus, punishment was not a fixed behavior controlled by the prior occurrence of shock, but depended on the shocks current value. Our results show that instrumental punishment can be controlled by a value-sensitive representation of the aversive consequence produced by the action and is, in this sense, structured in the same manner as canonical goal-directed reward seeking.

animal behavior and cognition↗

bioRxiv2025

Transcriptomic stress responses in Vaccinium spp. F1 hybrids: Implications for temperature-resilient cranberry breeding using a crop wild relative

O_LICranberry (Vaccinium macrocarpon) is an important North American fruit crop with vulnerability to temperature extremes and a relatively recent domestication history. Hybridization with a cold-adapted crop wild relative (CWR), V. oxycoccos, offers a strategy for improving temperature stress tolerance. C_LIO_LIWe conducted RNA sequencing (RNA-seq) on V. macrocarpon and F1 hybrids between V. macrocarpon and V. oxycoccos subjected to acute heat and cold stress, capturing early transcriptional responses up to 30 minutes (heat) and 95 minutes (cold) after treatment onset. We then evaluated differences in responses across genotypes and stress conditions. C_LIO_LIDifferential expression analysis and functional profiling revealed cold-induced differences in pathways related to photosynthesis, ribosomes, defense, and hormone signaling. No subgenome-specific functional specialization was observed. Two F1 hybrids exhibited suggestive cold resilience, with expression changes elevated at 60 minutes but declining by 95 minutes. Hybrids also displayed substantial regulatory variation under stress and transgressive downregulation of photosynthesis genes under ambient conditions. C_LIO_LIThese findings suggest that V. oxycoccos introgression could be utilized in breeding cold-tolerant cranberry cultivars. Variation observed between F1 hybrids reflects the diversity introduced through CWR germplasm and provides opportunities for selection. Conservation of V. oxycoccos and other CWRs remains critical for future crop improvement. C_LI Plain Language SummaryCranberries face increasing threats from temperature extremes. We explored crossbreeding cultivated cranberry (Vaccinium macrocarpon) and a cold-adapted wild relative (V. oxycoccos) to improve resilience to temperature stress. Hybrids showed different gene expression patterns from their parents, especially under cold stress. Our findings support the value of wild relatives in crop improvement and emphasize the importance of protecting wild plant diversity.

plant biology↗

bioRxiv2025

The status of human goal-directed actions after manipulations of the action-outcome contingency

Goal-directed actions are those performed with the expectation of producing a specific outcome and are therefore sensitive to changes in the outcomes current value without re-experiencing the action-outcome contingency. Disrupting the action-outcome association by a number of interventions can reduce responding, but whether such interventions also affect the goal-directedness of human responses remains unknown. We trained participants to perform different actions for two distinct outcomes in two groups. One group experienced extinction (i.e., complete suspension of outcome delivery for a specific previously rewarded action) whereas the other was given non-contingent training (i.e., outcomes were presented independently of responding). Goal-directed control was tested by outcome devaluation, making one of the two outcomes less desirable, and responding was then tested in the absence of outcome presentations. Despite having been significantly reduced in both groups by extinction and non-contingent training, responding remained sensitive to outcome value, suggesting that human goal-directed behavior is resistant to action-outcome contingency interventions. We discuss these results in light of recent theories of goal-directed behavior.

animal behavior and cognition↗

bioRxiv2023

Dual-system avoidance: extension of a theory

Our theory of positively reinforced free-operant behavior (Perez & Dickinson, 2020) assumes that responding is controlled by 2 systems. One system is sensitive to the correlation between response and reinforcement rates and controls goal-directed behavior, whereas a habitual system learns by reward prediction error. We present an extension of this theory to the aversive domain that explains why free-operant avoidance responding increases with both the experienced rate of negative reinforcement and the difference between this rate and that programmed by the avoidance schedule. The theory also assumes that the habitual component is reinforced by the acquisition of aversive inhibitory properties by the feedback stimuli generated by responding, which then act as safety signals that reinforce habit performance. Our analysis suggests that the distinction between habitual and goal-directed control of rewarded behavior can also be applied to the aversive domain.

animal behavior and cognition↗

bioRxiv2021

Electrophysiological signatures of brain aging in autism spectrum disorder.

Emerging evidence suggests that aging processes may be altered in adults with autism spectrum disorder (ASD). However, it remains unclear if oscillatory slowing, a key neurophysiological change in the aging brain, manifests atypically in this population. This study sought to examine patterns of age-related oscillatory slowing in adults with ASD, captured by reductions in the brains peak alpha frequency. Resting-state EEG data from adults (18-70 years) with ASD (N=93) and age-matched neurotypical (NT) controls (N=87) were pooled from three independent datasets. A robust curve-fitting procedure quantified the peak frequency of alpha oscillations (7-13Hz) across all brain regions. Associations between peak alpha frequency and age were assessed and compared between groups. Consistent with characteristic patterns of oscillatory slowing, peak alpha frequency was negatively associated with age across the entire sample (p<.0001). A significant group by age interaction revealed that this relationship was more pronounced in adults with ASD (p<.01), suggesting that that age-related oscillatory slowing may be accelerated in this population. Scalable EEG measures such as peak alpha frequency could provide insights into neural aging that are crucially needed to inform care plans and preventive interventions that can promote successful aging in ASD.

neuroscience↗

bioRxiv2019

Functional connectivity differences in early infancy precede autism symptoms: a multivariate pattern analysis

Functional brain connectivity is altered in children and adults with autism spectrum disorder (ASD). Mapping pre-symptomatic functional disruptions in ASD could identify infants based on neural risk, providing a crucial opportunity to mediate outcomes before behavioral symptoms emerge. Here we quantify functional connectivity using scalable EEG measures of oscillatory phase coherence (6-12Hz). Infants at high and low familial risk for ASD (N=65) underwent an EEG recording at 3 months of age and were assessed for ASD symptoms at 18 months using the Autism Diagnostic Observation Schedule-Toddler Module. Multivariate pattern analysis was used to examine early functional patterns that are associated with later ASD symptoms. Support vector regression (SVR) algorithms accurately predicted observed ASD symptoms at 18 months from EEG data at 3 months (r=0.76, p=0.02). Specifically, lower frontal connectivity and higher right temporo-parietal connectivity predicted higher ASD symptoms. The SVR model did not predict non-verbal cognitive abilities at 18 months (r=0.15, p=0.36), suggesting specificity of these brain alterations to ASD. These data suggest that frontal and temporo-parietal dysconnectivity play important roles in the early pathophysiology of ASD. Early functional differences in ASD can be captured using EEG during infancy and may inform much-needed advancements in the early detection of ASD.

neuroscience↗

bioRxiv2019

A theory of actions and habits in free-operant behavior: The interaction of rate correlation and contiguity systems.

Contemporary theories of instrumental performance assume that responding can be controlled by two behavioral systems, one goal-directed that encodes the outcome of an action, and one habitual that reinforces the response strength of the same action. Here we present a model of free-operant behavior in which goal-directed control is determined by the correlation between the rates of the action and the outcome whereas the total prediction error generated by contiguous reinforcement by the outcome controls habitual response strength. The outputs of these two systems summate to generate a total response strength. This cooperative model addresses the difference in the behavioral impact of ratio and interval schedules, the transition from goal-directed to habitual control with extended training, the persistence of goal-directed control under choice procedures and following extinction, among other phenomena. In these respects, this dual-system model is unique in its account of free-operant behavior.

animal behavior and cognition↗

bioRxiv2019

Serum Flt3 ligand is a biomarker of progenitor cell mass and prognosis in acute myeloid leukemia

Fms-like tyrosine kinase 3 (Flt3) is a hematopoietic growth factor receptor expressed on lymphomyeloid progenitors and frequently, by AML blasts. Its ligand, Flt3L, has non-hematopoietic and lymphoid origins, is detectable during homeostasis and increases to high levels in states of hypoplasia due to genetic defects or treatment with cytoreductive agents. Measurement of Flt3L by ELISA reveals that Flt3+AML, is associated with depletion of Flt3L to undetectable levels. After induction chemotherapy, Flt3L is restored in patients entering CR, but remains depressed in those with refractory disease. Weekly sampling reveals marked differences in the kinetics of Flt3L response during the first 6 weeks of treatment, proportionate to the clearance of blasts and cellularity of the BM. In the UK NCRI AML17 trial, Flt3L was measured at day 26 in a subgroup of 135 patients with Flt3 mutation randomized to the tyrosine kinase inhibitor lestaurtinib. In these patients, attainment of CR was associated with higher Flt3L at day 26 (Mann-Whitney p < 0.0001). Day 26 Flt3L was also associated with survival: Flt3L [≤] 291pg/ml was associated with inferior event-free survival; and, Flt3L >1185pg/ml was associated with higher overall survival (p = 0.0119). Serial measurement of Flt3L in patients who had received a hematopoietic stem cell transplant for AML further illustrated the potential value of declining Flt3L to identify relapse. Together these observations suggest that measurement of Flt3L provides a non-invasive estimate of progenitor cell mass in most patients with AML, with the potential to inform clinical decisions.\n\nGraphical abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=151 HEIGHT=200 SRC=\"FIGDIR/small/588319_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (21K):\norg.highwire.dtl.DTLVardef@132f3f3org.highwire.dtl.DTLVardef@2e033eorg.highwire.dtl.DTLVardef@d70598org.highwire.dtl.DTLVardef@b0648a_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2019

Early patterns of functional brain development associated with autism spectrum disorder in tuberous sclerosis complex.

Lay AbstractAround half of infants with tuberous sclerosis complex (TSC) develop autism. Here, using EEG, we find that there is a reduction in communication between brain regions during infancy in TSC, and that the infants who show the largest reductions are those who later develop autism. Being able to identify infants who show early signs of disrupted brain development may improve the timing of early prediction and interventions in TSC, and also help us to understand how early brain changes lead to autism.\n\nAbstractTuberous sclerosis complex (TSC) is a rare genetic disorder that confers a high risk for autism spectrum disorders (ASD), with behavioral predictors of ASD emerging early in life. Deviations in structural and functional neuronal connectivity are highly implicated in both TSC and ASD.\n\nFor the first time, we explore whether electroencephalographic (EEG) measures of network function precede or predict the emergence of ASD in TSC. We determine whether altered brain function (1) is present in infancy in TSC, (2) differentiates infants with TSC based on ASD diagnostic status, and (3) is associated with later cognitive function.\n\nWe studied 35 infants with TSC (N=35), and a group of typically developing infants (n=20) at 12 and 24 months of age. Infants with TSC were later subdivided into ASD and non-ASD groups based on clinical evaluation. We measured features of spontaneous alpha oscillations (6-12Hz) that are closely associated with neural network development: alpha power, alpha phase coherence (APC) and peak alpha frequency (PAF).\n\nInfants with TSC demonstrated reduced interhemispheric APC compared to controls at 12 months of age, and these differences were found to be most pronounced at 24 months in the infants who later developed ASD. Across all infants, PAF at 24 months was associated with verbal and non-verbal cognition at 36 months.\n\nAssociations between early network function and later neurodevelopmental and cognitive outcomes highlight the potential utility of early scalable EEG markers to identify infants with TSC requiring additional targeted intervention initiated very early in life.

neuroscience↗

bioRxiv2018

A re-examination of responding on ratio and regulated-probability interval schedules

The higher response rates observed on ratio than on matched interval reward schedules has been attributed to the differential reinforcement of longer inter-response times (IRTs) on the interval contingency. Some data, however, seem to contradict this hypothesis, showing that the difference is still observed when the role of IRT reinforcement is neutralized by using a regulated-probability interval schedule (RPI). Given the mixed evidence for these predictions, we re-examined this hypothesis by training three groups of rats to lever press under ratio, interval and RPI schedules across two phases while matching reward rates within triads. At the end of the first phase, the master ratio and RPI groups responded at similar rates. In the second phase, an interval group yoked to the same master ratio group of the first phase responded at a lower rate than the RPI group. Post-hoc analysis showed comparable reward rates for master and yoked schedules. The experienced response-outcome rate correlations were likewise similar, and approached zero as training progressed. We discuss these results in terms of dual-system theories of instrumental conditioning.

animal behavior and cognition↗