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Adaptive behaviour requires that we monitor the changing environment, and, when needed, re-interpret our priorities, and re-evaluate our plans for action. This complex ability matures slowly, is deployed differently at different stages of life, and is impaired in disorders of thought and behaviour.

To study adaptive behaviour in our lab, we combine neuroimaging and behavioural methods with computational modelling. We focus on the remodelling of brain circuitry as we mature, especially during adolescence.

In recent work we integrate structural and functional connectivity with dynamical analysis methods to understand flexible behaviour at multiple time-scales, including what apsects are challenged in disorder (e.g. in ADHD, autism, or depression).

This approach enables us to study experience-bound moment-to-moment changes in brain and behaviour, as well as the interaction of these changes with slower maturational processes over development.

Scroll down to explore some of our current and past research projects, or click on a link below:

INDIE

SERE

HAVEN

Learning what to learn

BBCEO

INDIE

The INDIE study aims to understand how fluctuations in brain and body physiology affect the cognitive and emotional development of young people during adolescence.

Purpose of the study

The INDIE study seeks to understand how the neurobiological, cognitive, and emotional maturation of young people is influenced by the marked and volatile changes in physiology that ignite with puberty. This will help develop strategies about how to help young people thrive during this important developmental period, and how to better support those at risk of psychopathology.

Previous research has shown that hormone changes during the teenage years are associated with changes in the structure, organisation, and function of the brain. At the same time, young people experience many developmentally important changes, such as increased lability in mood, age-specific changes in sleep quality and sleep physiology, and challenges in regulating emotion. However, we do not yet understand the mechanisms that link the changes in hormone and brain physiology with the behavioural, cognitive, and emotional profile of adolescence. For example, we don’t understand how the very prominent fluctuations in physiology (for example during the menstrual cycle) may be driving maturation in this age range.

The INDIE study uses brain imaging and measures of physiology, mood, sleep, cognition, and physical activity, to synthesise a detailed picture of the interplay between experience, physiology, and development. We work with young people and their parents and carers, as well as with teachers and other educators, clinicians and mental health practitioners. Together we design, interprete, and make use of our research.

Contact the INDIE study team to find out more, including ways in which you can get involved.

SERE

The SERE study assesses the reliability of behavioural flexibility measures as indexed either by measuring task performance, or by computational models of latent factors contributing to performance.

Purpose of the study

The study of learning and decision-making processes in psychology and neuroscience typically relies on the use of conditioning tasks to assay behaviour. These include instrumental conditioning tasks where subjects learn through experience the relevant associations between actions and outcomes, such as pulling a slot machine lever to win money. These associations either increase or decrease the likelihood of a given action in the future, depending on whether the outcome was rewarding or punishing. However, these associations also need to be updated flexibly for an individual to respond adaptively to dynamic and changing environments.

This complex competence can be assessed in the lab using behavioural tasks and measuring aspects of performance, such as how quickly people shoft away from a previously succesful action when it stops being rewarded. We can also use computational models that try to disentangle the different processes that underpin successful performance, but it is not well understood whether such models are reliable across different participants, or within the same participant over time.

In SERE, we use repeated testing and reinforcement learning models to assess the extent of this reliability and the usefulness of these paradigms for studies of behavioural or physiological change over the timescale of weeks.

Williams, B., FitzGibbon, L., Brady, D., & Christakou, A. (2025). Sample size matters when estimating test–retest reliability of behaviour. Behavior Research Methods, 57(4), 123. https://doi.org/10.3758/s13428-025-02599-1

Intraclass correlation coefficients (ICCs) are a commonly used metric in test–retest reliability research to assess a measure’s ability to quantify systematic between-subject differences. However, estimates of between-subject differences are also influenced by factors including within-subject variability, random errors, and measurement bias. Here, we use data collected from a large online sample (N = 150) to (1) quantify test–retest reliability of behavioural and computational measures of reversal learning using ICCs, and (2) use our dataset as the basis for a simulation study investigating the effects of sample size on variance component estimation and the association between estimates of variance components and ICC measures. In line with previously published work, we find reliable behavioural and computational measures of reversal learning, a commonly used assay of behavioural flexibility. Reliable estimates of between-subject, within-subject (across-session), and error variance components for behavioural and computational measures (with ± .05 precision and 80% confidence) required sample sizes ranging from 10 to over 300 (behavioural median N: between-subject = 167, within-subject = 34, error = 103; computational median N: between-subject = 68, within-subject = 20, error = 45). These sample sizes exceed those often used in reliability studies, suggesting that sample sizes larger than are commonly used for reliability studies (circa 30) are required to robustly estimate reliability of task performance measures. Additionally, we found that ICC estimates showed highly positive and highly negative correlations with between-subject and error variance components, respectively, as might be expected, which remained relatively stable across sample sizes. However, ICC estimates were weakly or not correlated with within-subject variance, providing evidence for the importance of variance decomposition for reliability studies.

HAVEN

The HAVEN study aims to investigate whether the way our blood naturally clots can affect the health of the blood vessels around the body and in the brain, and how this relates to cognitive function in older life.

Purpose of the study

Previous research has shown that cardiovascular health conditions (like high blood pressure, heart disease, and diabetes) are linked to brain health and cognitive function in older adults. There is some evidence that certain regions of the brain that are involved in memory may be particularly affected. However, we do not yet know exactly how blood vessel health can affect the brain. In particular, we don’t know whether overall cardiovascular health affects only the blood vessels in the brain, the brain cells, or the ability for blood vessels and brain cells to work together in a co-ordinated way.

This research study will investigate these relationships. One of our goals is to see if there are substances in the blood that can help to identify and protect individuals at risk of developing brain health problems in later life.

Rossetti, G. M. K., Dunster, J. L., Sohail, A., Williams, B., Cox, K. M., Rawlings, S., Jewett, E., Benford, E., Lovegrove, J. A., Gibbins, J. M., & Christakou, A. (2025). Evidence for control of cerebral neurovascular function by circulating platelets in healthy older adults. The Journal of Physiology, 603(11), 3379–3404. https://doi.org/10.1113/JP288405

Platelets play a vital role in preventing haemorrhage through haemostasis, but complications arise when platelets become overly reactive, leading to pathophysiology such as atherothrombosis. Elevated haemostatic markers are linked to dementia and predict its onset in long-term studies. Despite epidemiological evidence, the mechanism linking haemostasis with early brain pathophysiology remains unclear. Here, we aimed to determine whether a mechanistic association exists between platelet function and cerebral neurovascular function in 52 healthy mid- to older-age adults. To do this, we combined, for the first time, magnetic resonance imaging of cerebral neurovascular function, peripheral vascular physiology and in vitro platelet assaying. We show an association between platelet reactivity and cerebral neurovascular function that is both independent of vascular reactivity and mechanistically specific: Distinct platelet signalling mechanisms (ADP, collagen-related peptide, thrombin receptor activator peptide 6) were associated with different physiological components of the haemodynamic response to neuronal (visual) stimulation (full-width half-maximum, time to peak, area under the curve), an association that was not mediated by peripheral vascular effects. This finding challenges the previous belief that systemic vascular health determines the vascular component of cerebral neurovascular function, highlighting a specific link between circulating platelets and the neurovascular unit. Because altered cerebral neurovascular function marks the initial stages of neurodegenerative pathophysiology, understanding this novel association is now imperative, with the potential to lead to a significant advancement in our comprehension of early dementia pathophysiology.

Contact the HAVEN study team to find out more, including ways in which you can get involved.

Learning what to learn

This study examines how the cholinergic modulation of the human basal ganglia influences adaptive behaviour, using functional, structural, and neurochemical imaging of reinforcement learning.

Bell, T., Lindner, M., Langdon, A., Mullins, P. G., & Christakou, A. (2019). Regional Striatal Cholinergic Involvement in Human Behavioral Flexibility. Journal of Neuroscience, 39(29), 5740–5749. https://doi.org/10.1523/JNEUROSCI.2110-18.2019

Animal studies have shown that the striatal cholinergic system plays a role in behavioral flexibility but, until recently, this system could not be studied in humans due to a lack of appropriate noninvasive techniques. Using proton magnetic resonance spectroscopy, we recently showed that the concentration of dorsal striatal choline (an acetylcholine precursor) changes during reversal learning (a measure of behavioral flexibility) in humans. The aim of the present study was to examine whether regional average striatal choline was associated with reversal learning. A total of 22 participants (mean age = 25.2 years, range = 18–32 years, 13 female) reached learning criterion in a probabilistic learning task with a reversal component. We measured choline at rest in both the dorsal and ventral striatum using magnetic resonance spectroscopy. Task performance was described using a simple reinforcement learning model that dissociates the contributions of positive and negative prediction errors to learning. Average levels of choline in the dorsal striatum were associated with performance during reversal, but not during initial learning. Specifically, lower levels of choline in the dorsal striatum were associated with a lower number of perseverative trials. Moreover, choline levels explained interindividual variance in perseveration over and above that explained by learning from negative prediction errors. These findings suggest that the dorsal striatal cholinergic system plays an important role in behavioral flexibility, in line with evidence from the animal literature and our previous work in humans. Additionally, this work provides further support for the idea of measuring choline with magnetic resonance spectroscopy as a noninvasive way of studying human cholinergic neurochemistry.SIGNIFICANCE STATEMENT Behavioral flexibility is a crucial component of adaptation and survival. Evidence from the animal literature shows that the striatal cholinergic system is fundamental to reversal learning, a key paradigm for studying behavioral flexibility, but this system remains understudied in humans. Using proton magnetic resonance spectroscopy, we showed that choline levels at rest in the dorsal striatum are associated with performance specifically during reversal learning. These novel findings help to bridge the gap between animal and human studies by demonstrating the importance of cholinergic function in the dorsal striatum in human behavioral flexibility. Importantly, the methods described here cannot only be applied to furthering our understanding of healthy human neurochemistry, but also to extending our understanding of cholinergic disorders.

Bell, T., Langdon, A., Lindner, M., Lloyd, W., & Christakou, A. (2019). Orbitofrontal and Thalamic Influences on Striatal Involvement in Human Reversal Learning. bioRxiv. https://doi.org/10.1101/246371

Cognitive flexibility is crucial for adaptation and is disrupted in neuropsychiatric disorders and psychopathology. Human studies of flexibility using reversal learning tasks typically contrast error trials before and after reversal, which provides little information about the mechanisms that support learning and expressing a new response. However, animal studies suggest a specific role in this latter process for the connections between the dorsal striatum and the centromedian parafascicular (CM-Pf) thalamus, a system which may recruit the striatal cholinergic interneurons, but which is not well understood in humans. This study investigated the role of this system in human probabilistic reversal learning, specifically with respect to learning a new response strategy, contrasting its function to that of the better understood orbitoftontal-striatal systems. Using psychophysiological interaction (PPI) analysis of functional magnetic resonance imaging (fMRI) data we show that connectivity between the striatum and both the lateral orbitofrontal cortex (lOFC) and CM-Pf pathways increased during reversal, but not initial learning. However, while the strength of lOFC-striatal connectivity was associated with the speed of the reversal, the strength of CM-Pf-striatal connectivity was associated specifically with the quality of the reversal (reduced regressive errors). These findings expand our understanding of flexibility mechanisms in the human brain, bridging the gap with animal studies of this system.

Bell, T., Lindner, M., Mullins, P. G., & Christakou, A. (2018). Functional neurochemical imaging of the human striatal cholinergic system during reversal learning. European Journal of Neuroscience, 47(10), 1184–1193. https://doi.org/10.1111/ejn.13803

Animal studies have shown that acetylcholine (ACh) levels in the dorsal striatum play a role in reversal learning. However, this has not been studied in humans due to a lack of appropriate non-invasive techniques. Proton magnetic resonance spectroscopy (1H-MRS) can be used to measure metabolite levels in humans in vivo. Although it cannot be used to study ACh directly, 1H-MRS can be used to study choline, an ACh precursor, which is linked to activity-dependent ACh release. The aim of this study was to use functional-1H-MRS (fMRS) to measure changes in choline levels in the human dorsal striatum during performance of a probabilistic reversal learning task. We demonstrate a task-dependent decrease in choline, specifically during reversal, but not initial, learning. We interpret this to reflect a sustained increase in ACh levels, which is in line with findings from the animal literature. This task-dependent change was specific to choline and was not observed in control metabolites. These findings provide support for the use of fMRS in the in vivo study of the human cholinergic system.

Lindner, M., Bell, T., Iqbal, S., Mullins, P. G., & Christakou, A. (2017). In vivo functional neurochemistry of human cortical cholinergic function during visuospatial attention. PLOS ONE, 12(2), e0171338. https://doi.org/10.1371/journal.pone.0171338

Cortical acetylcholine is involved in key cognitive processes such as visuospatial attention. Dysfunction in the cholinergic system has been described in a number of neuropsychiatric disorders. Levels of brain acetylcholine can be pharmacologically manipulated, but it is not possible to directly measure it in vivo in humans. However, key parts of its biochemical cascade in neural tissue, such as choline, can be measured using magnetic resonance spectroscopy (MRS). There is evidence that levels of choline may be an indirect but proportional measure of acetylcholine availability in brain tissue. In this study, we measured relative choline levels in the parietal cortex using functional (event-related) MRS (fMRS) during performance of a visuospatial attention task, with a modelling approach verified using simulated data. We describe a task-driven interaction effect on choline concentration, specifically driven by contralateral attention shifts. Our results suggest that choline MRS has the potential to serve as a proxy of brain acetylcholine function in humans.

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In collaboration with the John Madejski Centre for Reputation and the CEOs of large international organisations, we ask what aspects of disposition, brain and behaviour characterise extraordinary leaders.

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