Biology subjects

Mason, L.

Publications and source records attributed to Mason, L..

12 recordsLinked to original sources

bioRxiv2026

Serotonin reuptake inhibition rapidly enhances affect-reward coupling and improves mood over time

Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed antidepressants, yet the mechanisms linking their rapid neurobiological effects to more gradual improvements in mood remain unclear. Computational accounts in which mood reflects the integration of reward outcome and reward prediction errors (RPEs) offer a compelling framework for examining SSRI effects, but reliance on laboratory tasks poses a major translational gap, both in timescale and ecological validity. We address this gap by examining the impact of SSRIs on affect-reward dynamics over a clinically relevant timescale using real-world rewards. Across 11 days, 66 healthy participants (n=37 receiving the SSRI citalopram) completed repeated ecological momentary assessments (EMA) of mood and goal-directed activities (up to 8 per day, totaling 3,542 surveys). By probing anticipated reward (pre-activity) and consummatory reward (post-activity), we derived real-world RPEs to test whether SSRIs amplify RPE impacts on momentary mood. Mixed-effects modelling showed that citalopram rapidly amplified the impact of reward outcome and RPEs on momentary mood, and predicted later increases in positive mood. Citalopram also selectively attenuated the impact of negative mood on expectations for future reward. These findings suggest that SSRIs modulate the bidirectional coupling between mood and reward processes in daily life, consistent with a positive feedback loop that could underpin the gradual mood improvement observed for antidepressant treatment. More broadly, our results highlight the utility of EMA as a highly sensitive real-world assay of early pharmacological effects on mood-reward dynamics.

neuroscience↗

bioRxiv2025

Crossmodal attention develops in the first year of life: Cortical signatures of tactile to visual exogenous spatial cuing at 8 but not 5 months of age

Adults are able to orient their attention between different (often fleeting) sensory cues that present to different senses ("crossmodal attention"), but we cannot assume that this is the case in early life. Here we report the findings of a study in which we probed the presence of tactile to visual crossmodal links in spatial attention using event related potentials (ERP) gathered from the scalp electroencephalograms (EEG) of 5-(n = 19) and 8-month-old (n = 19) infants. Whilst recording EEG, we presented 5- and 8month-old participants with vibrotactile stimuli on one of their hands, followed by visual stimuli on the same (Congruent) or the opposite (Incongruent) hand, or no touch at all (No probe). During the presentation of these stimuli the infants eyes were oriented centrally. We subtracted No probe trials from Congruent and Incongruent trials to yield visual evoked potentials (VEPs) free from the influence of prior somatosensory processing. Comparably to prior findings in adults, 8-month-olds first negative component of the VEP was enhanced in the hemisphere ipsilateral to the probe when the visual probe was spatially congruent with the tactile cue. No crossmodal effect was observed in the 5-month-olds, indicating developments in the crossmodal coordination of attention in the first year of life.

neuroscience↗

bioRxiv2025

Cortical Excitability during Fixations Drives Frequency-Specific Neural Activity in Children and Adults

Extensive previous research has examined how neuronal oscillations support basic cognitive processes, from early development into adulthood. However, the question of how these oscillations originate and are maintained remains relatively underexplored. Here, we examine how transient increases in cortical excitability that occur time-locked to the offsets of spontaneous eye movements associate with frequency-specific neural activity, and how these relationships change over development and between contexts (social vs non-social). We examine two datasets of combined EEG and eye-tracking data from 24-month-old children (N=114) and adults (N=108) while they watched stimuli that were either social (an actor singing nursery rhythms) or non-social (dynamic toys). EEG data was time-locked to the offsets of eye movements and analysed using a spectrum of methods designed to highlight the progression of various neural signals across time, frequency, and space (topography). Fixation-related potentials (FRPs) manifest as a differentiable combination of eye movement-related artifact and genuine neural activity. Child FRPs are slower and unfold over longer time periods, which manifests as differences in the frequency domain. Even after removing artifact, dipoles associated with fixation-related P1 and N170 components manifest as Theta activity over fronto-central areas, along with activity in other frequencies, in children but not adults. Data sections where no fixation-related potentials are present show strongly attenuated oscillatory activity. Our results show that a variety of previously documented developmental effects in the frequency domain may be better understood as fine-grained, movement-induced brain states.

animal behavior and cognition↗

bioRxiv2025

Epigenome-wide analysis reveals novel DNA methylation signatures significantly associated with the infant pupillary light reflex, a candidate intermediate phenotype for autism.

Autism is a highly heterogeneous neurodevelopmental condition, currently diagnosed based on behavioural characteristics. Candidate early intermediate phenotypes, such as the Pupillary Light Reflex (PLR), a reflexive constriction of the pupil in response to increased optical luminance, may provide insights into etiological factors and potential biomarkers, such as DNA methylation (DNAm), involved in the emergence of autism. We conducted epigenome-wide DNAm association analyses of 9-, 14-, 24-month PLR onset latency and constriction amplitude in a sample of 51 infants enriched for autism family history, using buccal DNA collected at 9-months. Our epigenome-wide analysis (EWAS) identified four stringently significant differentially methylated probes (p < 2.4 x 10-7) associated with cross-section PLR latency measurements at 14- and 24-months, and with 14-to 24-month PLR latency developmental change. Differentially methylated probes associated with PLR amplitude were identified, but at a less stringent discovery threshold (p < 5 x 10-5). Our region analyses identified several significant differentially methylated regions associated with both PLR latency and amplitude Downstream exploratory pathway analysis identified enrichment for multiple developmental biological processes, as well as several susceptibility genes to autism and related neurodevelopmental conditions including NR4A2, HNRNPU and NAV2. Our findings provide novel insight into the role of DNAm in PLR development and illuminate biological mechanisms underpinning altered PLR in infancy in emerging autism.

neuroscience↗

bioRxiv2024

Mood impacts confidence through biased learning of reward likelihood

Mood disturbances are accompanied by marked and apparently non-rational changes in self-efficacy and goal-directed behaviour, yet the mechanisms linking affective states to these fluctuations remain unclear. Here we tested whether mood biases confidence in reward-based decision-making and whether this is amplified by trait instability in mood and self-efficacy. By formalising both confidence and mood within a computational model of reward learning, we adjudicated between two accounts of these clinically relevant effects: mood imposing a direct, evidence-independent shift in confidence, or mood distorting the accumulation of reward learning signals from which confidence is then rationally inferred. Across two independent studies--a laboratory experiment (n = 35) and a preregistered online replication (n = 106)--participants completed a reinforcement-learning task with mood manipulation and repeated confidence ratings. Mood systematically biased confidence without affecting objective accuracy. Critically, this effect accumulated gradually across learning rather than emerging immediately after mood induction, even as mood itself returned toward baseline. These dynamics were captured by a computational model in which mood biases the accumulation of reward probability estimates. A single mood-bias parameter accounted for shifts in confidence, biased valuation of stimuli learned under different mood states, and amplification of these effects in individuals with elevated hypomanic traits. These findings suggest that disturbances in confidence arise from mood-biased learning signals, providing a mechanistic account linking these distortions to disrupted goal pursuit and self-efficacy in mood disorders.

neuroscience↗

bioRxiv2024

Qualitative EEG abnormalities signal a shift towards inhibition-dominated brain networks. Results from the EU-AIMS LEAP studies

Qualitative EEG abnormalities are common in Autism Spectrum Disorder (ASD) and hypothesized to reflect disrupted excitation/inhibition balance. To test this, we recently introduced a functional measure of network-level E/I ratio (fE/I). Here, we applied fE/I and other EEG measures to alpha oscillations from source-reconstructed data in the EU-AIMS dataset (267 ASD, 209 controls). We analyzed these measures alongside qualitative EEG abnormalities ranging from slowing of activity to epileptiform patterns, aiming to replicate the findings from the SPACE-BAMBI study. EEG abnormalities were rare in adults and could not be statistically assessed. ASD children-adolescents with EEG abnormalities exhibited lower relative alpha power and fE/I compared to those without. However, EEG-abnormality scoring did not stratify the behavioral heterogeneity of ASD using clinical measures. Surprisingly, several controls also exhibited qualitative EEG abnormalities with a strikingly similar anatomical distribution of reduced fE/I, suggesting a shift towards inhibition-dominated network dynamics in sensory processing regions. The robustness of this association between EEG abnormalities and reduced fE/I was further supported by re-analysis of the SPACE-BAMBI study in source space. Stratification by the presence of EEG abnormalities and their effects on network activity may help understand neurodevelopmental physiological heterogeneity and the difficulties in implementing E/I targeting treatments in unselected cohorts.

neuroscience↗

bioRxiv2023

Misperceiving momentum: computational mechanisms of biased striatal reward prediction errors in bipolar disorder

BackgroundDysregulated reward processing and mood instability are core features of bipolar disorder that have largely been considered separately, and with contradictory findings. We sought to test a mechanistic account that proposes that, in bipolar disorder, there is an excessive tendency to enter recursive cycles in which reward perception is biased by signals that the environment might be changing for the better or worse. MethodsParticipants completed a probabilistic reward task with functional Magnetic Resonance Imaging. Using an influential computational model, we ascertained whether participants with bipolar disorder (n = 21) show greater striatal tracking of momentum-biased reward prediction errors (RPEs) than healthy controls (n = 21). We conducted psychophysiological interaction analyses to quantify the degree to which each group modulated functional connectivity between the ventral striatum and left anterior insula in response to fluctuations in momentum. ResultsIn the bipolar disorder group, but not controls, the momentum-biased RPE model accounted for significant additional variance in ventral striatal activity beyond a standard mode of veridical RPEs. Compared to controls, the bipolar disorder group exhibited lower ventral striatal-left insular functional connectivity modulated by momentum-biased RPE. Moreover, this reduction in connectivity was more pronounced as a function of current manic symptoms. ConclusionsConsistent with an existing theory, we found evidence that bipolar disorder is associated with a tendency for momentum to excessively bias striatal tracking of RPE signals. We identify impaired striatal-insular connectivity as a possible locus for this propensity. We argue that computational psychiatric approaches that examine momentary shifts in reward and mood dynamics have strong potential for new mechanistic insights and targets for intervention.

neuroscience↗

bioRxiv2023

The role of serotonin and of perceived social differences in infering the motivation of others

Attributing motives to others is a crucial aspect of mentalizing, can be biased by prejudice, and also is affected by common psychiatric disorders. It is therefore important to understand in depth the mechanisms underpinning it. Toward improving models of mentalizing motives, we hypothesized that people quickly infer whether others motives are likely beneficial or detrimental, then refine their judgment ( Classify-refine). To test this, we used a modified Dictator game, a game theoretic task, where participants judged the likelihood of intent to harm vs. self-interest in economic decisions. Toward testing the role of serotonin in judgments of intent to harm, we delivered the task in a week-long, placebo vs. Citalopram study. Computational model comparison provided clear evidence for the superiority of Classify-refine models over traditional ones, strongly supporting the central hypothesis. Further, while Citalopram helped refine attributions about motives through learning, it did not induce more positive initial inferences about others motives. Finally, model comparison indicated a minimal role for racial bias within economic decisions for the large majority of our sample. Overall, these results support a proposal that classify-refine social cognition is adaptive, although relevant mechanisms of Serotonergic antidepressant action will need to be studied over longer time spans.

neuroscience↗

bioRxiv2023

Objective assessment of visual attention in toddlerhood

Visual attention is an important mechanism through which children learn about their environment, and individual differences could substantially shape later development. Eyetracking provides a sensitive and scalable tool for assessing visual attention that has potential for objective assessment of child development, but to date the majority of studies are small and replication attempts are rare. This study investigates the feasibility of a comprehensive eye-tracking assessment of visual attention and introduces a shared data resource for the scientific community. Data from eight eyetracking tasks were collected from 350 term-born (166 females) 18-month-olds recruited as neonates http://www.developingconnectome.org/). Analyses showed expected condition effects for seven of eight tasks (p-values from <.001 to .04), an important indication of replicability. Consistent with some theoretical models of visual attention, structural equation modelling indicated participants performance could be explained by two factors representing social and non-social attention. Comprehensive eye-tracking batteries can objectively measure individual differences in core components of visual attention in large-scale toddlerhood studies. This is the first large-scale comprehensive study to present high-quality normative eye-tracking data from a large task battery in toddlers and make them freely available to the scientific community.

neuroscience↗

bioRxiv2021

Excitatory/inhibitory imbalance in autism: the role of glutamate and GABA gene-sets in symptoms and cortical brain structure

BackgroundThe excitatory/inhibitory (E/I) imbalance hypothesis posits that an imbalance between excitatory (glutamatergic) and inhibitory (GABAergic) mechanisms underlies the behavioral characteristics of autism spectrum disorder (autism). However, how E/I imbalance arises and how it may differ across autism symptomatology and brain regions is not well understood. MethodsWe used innovative analysis methods - combining competitive gene-set analysis and gene-expression profiles in relation to cortical thickness (CT)- to investigate the relationship between genetic variance, brain structure and autism symptomatology of participants from the EU-AIMS LEAP cohort (autism=360, male/female=259/101; neurotypical control participants=279, male/female=178/101) aged 6 to 30 years. Competitive gene-set analysis investigated associations between glutamatergic and GABAergic signaling pathway gene-sets and clinical measures, and CT. Additionally, we investigated expression profiles of the genes within those sets throughout the brain and how those profiles relate to differences in CT between autistic and neurotypical control participants in the same regions. ResultsThe glutamate gene-set was associated with all autism symptom severity scores on the Autism Diagnostic Observation Schedule-2 (ADOS-2) and the Autism Diagnostic Interview-Revised (ADI-R) within the autistic group, while the GABA set was associated with sensory processing measures (using the SSP subscales) across all participants. Brain regions with greater gene expression of both glutamate and GABA genes showed greater differences in CT between autistic and neurotypical control participants. ConclusionsOur results suggest crucial roles for glutamate and GABA genes in autism symptomatology as well as CT, where GABA is more strongly associated with sensory processing and glutamate more with autism symptom severity.

neuroscience↗

bioRxiv2020

Attenuated Anticipation of Social and Monetary Rewards in Autism Spectrum Disorders

BackgroundReward processing has been proposed to underpin atypical social behavior, a core feature of autism spectrum disorder (ASD). However, previous neuroimaging studies have yielded inconsistent results regarding the specificity of atypicalities for social rewards in ASD. Utilizing a large sample, we aimed to assess altered reward processing in response to reward type (social, monetary) and reward phase (anticipation, delivery) in ASD. MethodsFunctional magnetic resonance imaging during social and monetary reward anticipation and delivery was performed in 212 individuals with ASD (7.6-30.5 years) and 181 typically developing (TD) participants (7.6-30.8 years). ResultsAcross social and monetary reward anticipation, whole-brain analyses (p<0.05, family-wise error-corrected) showed hypoactivation of the right ventral striatum (VS) in ASD. Further, region of interest (ROI) analysis across both reward types yielded hypoactivation in ASD in both the left and right VS. Across delivery of social and monetary reward, hyperactivation of the VS in individuals with ASD did not survive correction for multiple comparisons. Reward type by diagnostic group interactions, and a dimensional analysis of autism trait scores were not significant during anticipation or delivery. Levels of attention-deficit/hyperactivity disorder (ADHD) symptoms did not affect reward processing in ASD. ConclusionsOur results do not support current theories linking atypical social interaction in ASD to specific alterations in processing of social rewards. Instead, they point towards a generalized hypoactivity of VS in ASD during anticipation of both social and monetary rewards. We suggest that this indicates attenuated subjective reward value in ASD independent of social content and ADHD symptoms.

neuroscience↗

bioRxiv2020

Differential functional neural circuitry behind autism subtypes with marked imbalance between social-communicative and restricted repetitive behavior symptom domains

Social-communication (SC) and restricted repetitive behaviors (RRB) are autism diagnostic symptom domains. SC and RRB severity can markedly differ within and between individuals and may be underpinned by different neural circuitry and genetic mechanisms. Modeling SC-RRB balance could help identify how neural circuitry and genetic mechanisms map onto such phenotypic heterogeneity. Here we developed a phenotypic stratification model that makes highly accurate (97-99%) out-of-sample SC=RRB, SC>RRB, and RRB>SC subtype predictions. Applying this model to resting state fMRI data from the EU-AIMS LEAP dataset (n=509), we find that while the phenotypic subtypes share many commonalities in terms of intrinsic functional connectivity, they also show replicable differences within some networks compared to a typically-developing group (TD). Specifically, the somatomotor network is hypoconnected with perisylvian circuitry in SC>RRB and visual association circuitry in SC=RRB. The SC=RRB subtype show hyperconnectivity between medial motor and anterior salience circuitry. Genes that are highly expressed within these networks show a differential enrichment pattern with known autism-associated genes, indicating that such circuits are affected by differing autism-associated genomic mechanisms. These results suggest that SC-RRB imbalance subtypes share many commonalities, but also express subtle differences in functional neural circuitry and the genomic underpinnings behind such circuitry.

neuroscience↗