Biology subjects

Harmer, C. J.

Publications and source records attributed to Harmer, C. J..

8 recordsLinked to original sources

bioRxiv2026

Acute and cumulative light exposure differentially influence mood in healthy adults

Light influences mood in both clinical and experimental settings, yet it remains unclear how ambient light exposure relates to mood in daily life, which dimensions of mood are most sensitive to light and over what timescales these associations emerge. Here, we combined continuous personal light monitoring using wearable light sensors with repeated assessments of multiple dimensions of mood and affect, including self-reported mood ratings and cognitive measures of affective bias, alongside physiological monitoring in 49 healthy adults living under naturalistic conditions. Brighter light was consistently associated with more positive self-reported mood. Associations emerged over distinct temporal windows, with greater melanopic irradiance during the preceding 30 min associated with increased feelings of energy. Importantly, this association remained significant after accounting for alertness, physical activity and sleep-related covariates, suggesting that it is not solely explained by the established alerting effects of light. In contrast, several positive mood dimensions, including happiness, feeling accompanied, enjoyment, motivation and relaxation, were associated with light accumulated over longer periods (60-240 min). Furthermore, happiness, feeling accompanied, enjoyment and relaxation, but not energy, were also associated with greater cumulative daily exposure to light above 250 lux melanopic equivalent daylight illuminance (EDI), a threshold proposed to support healthy daytime light exposure. Behavioural measures of affective bias showed no robust associations with light exposure. Together, these findings indicate that everyday light exposure is associated with distinct dimensions of mood over different timescales, highlighting a complex relationship between light and affect in daily life. Significance StatementLight is a promising target for improving mental health, yet little is known about how everyday light exposure relates to mood outside laboratory and clinical settings. Using wearable light sensors and repeated mood assessments in healthy adults living under naturalistic conditions, we show that different dimensions of mood are linked to light exposure over distinct timescales, from recent exposure to cumulative light history. Importantly, the association between recent light exposure and feelings of energy remained independent of physical activity and sleep-related factors. These findings demonstrate that effects of light on mood are dynamic and multidimensional, highlighting the need to move beyond simple measures of total light exposure and informing future efforts to design healthier light environments that support emotional wellbeing.

neuroscience↗

bioRxiv2026

Ketamine attenuates habenula activity in response to aversive outcomes during Pavlovian learning

Ketamine is an NMDA receptor antagonist with rapid-antidepressant properties when administered at a sub-anesthetic dose. Preclinical models indicate that a direct injection of ketamine into lateral habenula (Hb), a small midbrain structure with an evolutionarily preserved role in aversive learning across mammals, can rapidly relieve depression-like behavior. However, there is limited evidence to explain how ketamine acts on the function of the human habenula. In a translational computational neuroscience study, 70 healthy adult volunteers were randomised in a 1:1 ratio to receive ketamine or placebo (NaCl 0.9%). We used an aversive Pavlovian conditioning paradigm combined with 7-Tesla functional neuroimaging to show that ketamine attenuates habenula response during aversive stimuli expectations and outcomes 24 hours post-infusion. We further present preliminary evidence suggesting that when aversive learning occurs after ketamine infusion, reduced habenula activity during the learning process may lead to downstream effects that diminish the aversive impact of negative affective memories. These findings provide translational support for preclinical models of ketamines mechanisms in humans.

neuroscience↗

bioRxiv2025

Synaptic histamine shapes the neurocomputational dynamics of human learning

Histamine was the first canonical monoamine identified in the mammalian brain 1-6, yet arguably remains the least understood in its mechanistic contributions to human behaviour. Using a first-in-class causal probe (H3R inverse agonist pitolisant), we show how increased synaptic histamine shapes offline and online temporal-hippocampal dynamics, sustaining learning-related activity and polarising retrieval computations. At a broader level, elevated histamine adaptively shifts neurocomputational strategy under high cognitive load, while stabilising value updates during aversive reinforcement learning. These findings uncover a mechanistically grounded influence of this underexplored system on human neurocomputation, supporting its therapeutic potential in psychiatry.

neuroscience↗

bioRxiv2023

Beta and theta oscillations track effort and previous reward in human basal ganglia and prefrontal cortex during decision making

Choosing whether to exert effort to obtain rewards is fundamental to human motivated behavior. However, the neural dynamics underlying the evaluation of reward and effort in humans is poorly understood. Here, we investigate this with chronic intracranial recordings from prefrontal cortex (PFC) and basal ganglia (BG; subthalamic nuclei and globus pallidus) in people with Parkinsons disease performing a decision-making task with offers that varied in levels of reward and physical effort required. This revealed dissociable neural signatures of reward and effort, with BG beta (12-20 Hz) oscillations tracking subjective effort on a single trial basis and PFC theta (4-7 Hz) signaling previous trial reward. Stimulation of PFC increased overall acceptance of offers in addition to increasing the impact of reward on choices. This work uncovers oscillatory mechanisms that guide fundamental decisions to exert effort for reward across BG and PFC, as well as supporting a causal role of PFC for such choices.

neuroscience↗

bioRxiv2023

Direct serotonin release in humans shapes decision computations within aversive environments

The role of serotonin in human behaviour is critically informed by approaches which allow in vivo modification of synaptic serotonin. However, characterising the effects of increased serotonin signalling in human models of behaviour is challenging given the limitations of available experimental probes (e.g., SSRIs). Here we use a now accessible approach to directly increase synaptic serotonin in humans - a selective serotonin releasing agent - and examine its influence on domains of behaviour historically considered core functions of serotonin. Computational techniques including reinforcement learning and drift diffusion modelling were fit to observed behaviour. Reinforcement learning models revealed that increased synaptic serotonin reduced sensitivity specifically for outcomes in aversive but not appetitive contexts. Furthermore, increasing synaptic serotonin enhanced behavioural inhibition, and shifted bias towards impulse control during exposure to aversive emotional probes. These effects were seen in the context of overall improvements in memory for neutral verbal information. Our findings highlight the direct effects of increased synaptic serotonin on human behaviour, underlining its critical role in guiding decision-making within aversive and neutral contexts, and offering broad implications for longstanding theories of central serotonin function.

neuroscience↗

bioRxiv2021

Value-based decision-making between affective memories

Affective biases can influence how past events are recalled from memory. However, the mechanisms underlying how discrete affective events shape memory formation and subsequent recall are not well understood. Further understanding this is important given the central role of negative biases in affective memory recall in depression and antidepressant drug action. In order to capture cognitive processes associated with affective memory formation and recall, we studied value-based decision-making between affective memories in two within-subject experiments (n=45 and n=74). Our findings suggest that discrete affective events, created by large magnitude Wheel of Fortune (WoF) outcomes, influence affective memory formation processes during reinforcement-learning (RL). After 24 hours, we show that healthy volunteers display stable preferences during value-based recall of affective memories in a binary decision-making task. Computational modelling of these preferences demonstrated a positive bias during value-based recall, induced by previously winning in the WoF. We further showed that value-based decision-making between affective memories engages the pupil-linked central arousal systems, leading to pupil constriction prior to, and differential pupil dilation after the decision onset depending on the valence of the chosen options. Taken together, we demonstrate that mechanisms underlying human affective memory systems can be described by RL and probability weighting models. This approach could be used as a translational assay to study the effects of novel antidepressants.

neuroscience↗

bioRxiv2019

Pupillary correlates of computations underlying human responder behaviour in the Ultimatum Game

Negotiating with others about how finite resources should be distributed is an important aspect of human social life. However, little is known about mechanisms underlying human social-interactive decision-making. Here, we report results from a novel iterative Ultimatum Game (UG) task, in which the proposers facial emotions and offer amounts were sampled probabilistically based on the participants decisions, creating a gradually evolving social-interactive decision-making environment. Our model-free results confirm the prediction that both the proposers facial emotions and the offer amount influence human choice behaviour. These main effects demonstrate that biases in facial emotion recognition also contribute to violations of the Rational Actor model (i.e. all offers should be accepted). Model-based analyses extend these findings, indicating that participants decisions are guided by an aversion to inequality in the UG. We highlight that the proposers facial responses to participant decisions dynamically modulate how human decision-makers perceive self-other inequality, relaxing its otherwise negative influence on decision values. In iterative games, this cognitive model underlies how offers initially rejected can gradually become more acceptable under increasing affective load, and accurately predicts 86% of participant decisions. Activity of the central arousal systems, assessed by measuring pupil size, encode a key element of this model: proposers affective reactions in response to participant decisions. Taken together, our results demonstrate that, under affective load, participants aversion to inequality is a malleable cognitive process which is modulated by the activity of the pupil-linked central arousal systems.

neuroscience↗

bioRxiv2018

Effects of Attentional Bias Modification on Residual Symptoms in depression. A Randomized Controlled Trial.

BackgroundFollowing treatment, many depressed patients have significant residual symptoms. However, large randomised controlled trials (RCT) in this population are lacking. When Attention bias modification training (ABM) leads to more positive emotional biases, associated changes in clinical symptoms have been reported. A broader and more transparent picture of the true advantage of ABM based on larger and more stringent clinical trials have been requested.\n\nAimsTo evaluate the early effect of two weeks ABM training on blinded clinician-rated and self-reported residual symptoms, and whether changes towards more positive attentional biases (AB) would be associated with symptom reduction.\n\nMethodA total of 321 patients with a history of depression were included in a preregistered randomized controlled double-blinded trial. Patients were randomised to an emotional ABM paradigm over fourteen days or a closely matched control condition. Symptoms based on the Hamilton Rating Scale for Depression (HRSD) and Beck Depression Inventory II (BDI-II) were obtained at baseline and after ABM training.\n\nResultsABM training led to significantly greater decrease in clinician-rated symptoms of depression as compared to the control condition. No differences between ABM and placebo were found for self-reported symptoms. ABM induced a change of AB towards relatively more positive stimuli associated with greater symptom reduction.\n\nConclusionThe current study demonstrates that ABM produces early changes in both AB and blinded clinician-rated depressive symptoms. ABM may have practical potential in the treatment of residual depression.\n\nClinicalTrials.gov ID: NCT02658682

clinical trials↗