Showing papers by "Raymond J. Dolan published in 2018"

Adolescent Tuning of Association Cortex in Human Structural Brain Networks.

Abstract: Motivated by prior data on local cortical shrinkage and intracortical myelination, we predicted age-related changes in topological organization of cortical structural networks during adolescence. We estimated structural correlation from magnetic resonance imaging measures of cortical thickness at 308 regions in a sample of N = 297 healthy participants, aged 14-24 years. We used a novel sliding-window analysis to measure age-related changes in network attributes globally, locally and in the context of several community partitions of the network. We found that the strength of structural correlation generally decreased as a function of age. Association cortical regions demonstrated a sharp decrease in nodal degree (hubness) from 14 years, reaching a minimum at approximately 19 years, and then levelling off or even slightly increasing until 24 years. Greater and more prolonged age-related changes in degree of cortical regions within the brain network were associated with faster rates of adolescent cortical myelination and shrinkage. The brain regions that demonstrated the greatest age-related changes were concentrated within prefrontal modules. We conclude that human adolescence is associated with biologically plausible changes in structural imaging markers of brain network organization, consistent with the concept of tuning or consolidating anatomical connectivity between frontal cortex and the rest of the connectome.

Locus coeruleus integrity in old age is selectively related to memories linked with salient negative events.

Abstract: The locus coeruleus (LC) is the principal origin of noradrenaline in the brain. LC integrity varies considerably across healthy older individuals, and is suggested to contribute to altered cognitive functions in aging. Here we test this hypothesis using an incidental memory task that is known to be susceptible to noradrenergic modulation. We used MRI neuromelanin (NM) imaging to assess LC structural integrity and pupillometry as a putative index of LC activation in both younger and older adults. We show that older adults with reduced structural LC integrity show poorer subsequent memory. This effect is more pronounced for emotionally negative events, in accord with a greater role for noradrenergic modulation in encoding salient or aversive events. In addition, we found that salient stimuli led to greater pupil diameters, consistent with increased LC activation during the encoding of such events. Our study presents novel evidence that a decrement in noradrenergic modulation impacts on specific components of cognition in healthy older adults. The findings provide a strong motivation for further investigation of the effects of altered LC integrity in pathological aging.

Cohort Profile: The NSPN 2400 Cohort: a developmental sample supporting the Wellcome Trust NeuroScience in Psychiatry Network.

Abstract: This study was supported by the Neuroscience in Psychiatry Network, a strategic award from the Wellcome Trust to the University of Cambridge and University College London (095844/Z/11/Z). Additional support was provided by the National Institute for Health (NIHR) Research Cambridge Biomedical Research Centre, the NIHR Collaboration for Leadership in Applied Health Research & Care East of England, and the Medical Research Council (MRC)/Wellcome Trust Behavioural and Clinical Neuroscience Institute.

Dopaminergic basis for signaling belief updates, but not surprise, and the link to paranoia

Abstract: Distinguishing between meaningful and meaningless sensory information is fundamental to forming accurate representations of the world. Dopamine is thought to play a central role in processing the meaningful information content of observations, which motivates an agent to update their beliefs about the environment. However, direct evidence for dopamine’s role in human belief updating is lacking. We addressed this question in healthy volunteers who performed a model-based fMRI task designed to separate the neural processing of meaningful and meaningless sensory information. We modeled participant behavior using a normative Bayesian observer model and used the magnitude of the model-derived belief update following an observation to quantify its meaningful information content. We also acquired PET imaging measures of dopamine function in the same subjects. We show that the magnitude of belief updates about task structure (meaningful information), but not pure sensory surprise (meaningless information), are encoded in midbrain and ventral striatum activity. Using PET we show that the neural encoding of meaningful information is negatively related to dopamine-2/3 receptor availability in the midbrain and dexamphetamine-induced dopamine release capacity in the striatum. Trial-by-trial analysis of task performance indicated that subclinical paranoid ideation is negatively related to behavioral sensitivity to observations carrying meaningful information about the task structure. The findings provide direct evidence implicating dopamine in model-based belief updating in humans and have implications for understating the pathophysiology of psychotic disorders where dopamine function is disrupted.

Change, stability, and instability in the Pavlovian guidance of behaviour from adolescence to young adulthood

Abstract: Pavlovian influences are important in guiding decision-making across health and psychopathology. There is an increasing interest in using concise computational tasks to parametrise such influences in large populations, and especially to track their evolution during development and changes in mental health. However, the developmental course of Pavlovian influences is uncertain, a problem compounded by the unclear psychometric properties of the relevant measurements. We assessed Pavlovian influences in a longitudinal sample using a well characterised and widely used Go-NoGo task. We hypothesized that the strength of Pavlovian influences and other ‘psychomarkers’ guiding decision-making would behave like traits. As reliance on Pavlovian influence is not as profitable as precise instrumental decision-making in this Go-NoGo task, we expected this influence to decrease with higher IQ and age. Additionally, we hypothesized it would correlate with expressions of psychopathology. We found that Pavlovian effects had weak temporal stability, while model-fit was more stable. In terms of external validity, Pavlovian effects decreased with increasing IQ and experience within the task, in line with normative expectations. However, Pavlovian effects were poorly correlated with age or psychopathology. Thus, although this computational construct did correlate with important aspects of development, it does not meet conventional requirements for tracking individual development. We suggest measures that might improve psychometric properties of task-derived Pavlovian measures for future studies.

Beta-Blocker Propranolol Modulates Decision Urgency During Sequential Information Gathering.

Abstract: Arbitrating between timely choice and extended information gathering is critical for effective decision making. Aberrant information gathering behavior is thought to be a feature of psychiatric disorders such as schizophrenia and obsessive-compulsive disorder, but we know little about the underlying neurocognitive control mechanisms. In a double-blind, placebo-controlled drug study involving 60 healthy human subjects (30 female), we examined the effects of noradrenaline and dopamine antagonism on information gathering during performance of an information sampling task. We show that modulating noradrenaline function with 40 mg of the β-blocker propranolol leads to decreased information gathering behavior. Modulating dopamine function via a single dose of 400 mg of amisulpride revealed some effects that were intermediate between those of propranolol and placebo. Using a Bayesian computational model, we show that sampling behavior is best explained by inclusion of a nonlinear urgency signal that promotes commitment to an early decision. Noradrenaline blockade promotes the expression of this decision-related urgency signal during information gathering. We discuss the findings with respect to psychopathological conditions that are linked to aberrant information gathering.SIGNIFICANCE STATEMENT Knowing when to stop gathering information and commit to a choice option is nontrivial. This is an important element in arbitrating between information gain and energy conservation. In this double-blind, placebo-controlled drug study, we investigated the role of catecholamines noradrenaline and dopamine on sequential information gathering. We found that blockade of noradrenaline led to a decrease in information gathering. Dopamine blockade showed an intermediate, but nonsignificant, effect. Using a Bayesian computational model, we show that this noradrenaline effect is driven by increased decision urgency, a signal that reflects an escalating subjective cost of sampling. The observation that noradrenaline modulates decision urgency suggests new avenues for treating patients that show information gathering deficits.

Neural activity and fundamental learning, motivated by monetary loss and reward, are intact in mild to moderate major depressive disorder.

Abstract: Introduction Reduced motivation is an important symptom of major depression, thought to impair recovery by reducing opportunities for rewarding experiences. We characterized motivation for monetary outcomes in depressed outpatients (N = 39, 22 female) and controls (N = 22, 11 female) in terms of their effectiveness in seeking rewards and avoiding losses. We assessed motivational function during learning of associations between stimuli and actions, as well as when learning was complete. We compared the activity within neural circuits underpinning these behaviors between depressed patients and controls. Methods We used a Go/No-Go task that assessed subjects’ abilities in learning to emit or withhold actions to obtain monetary rewards or avoid losses. We derived motivation-relevant parameters of behavior (learning rate, Pavlovian bias, and motivational influence of gains and losses). After learning, participants performed the task during functional magnetic resonance imaging (fMRI). We compared neural activation during anticipation of action emission vs. action inhibition, and for actions performed to obtain rewards compared to actions that avoid losses. Results Depressed patients showed a similar Pavlovian bias to controls and were equivalent in terms of withholding action to gain rewards and emitting action to avoid losses, behaviors that conflict with well-described Pavlovian tendencies to approach rewards and avoid losses. Patients were not impaired in overall performance or learning and showed no abnormal neural responses, for example in bilateral midbrain or striatum. We conclude that basic mechanisms subserving motivated learning are thus intact in moderate depression. Implications Therapeutically, the intact mechanisms identified here suggest that learning-based interventions may be particularly effective in encouraging recovery. Etiologically, our results suggest that the severe motivational deficits clinically observed in depression are likely to have complex origins, possibly related to an impairment in the representation of future states necessary for long-term planning.

The impact of traumatic stress on Pavlovian biases.

Abstract: Background Disturbances in Pavlovian valuation systems are reported to follow traumatic stress exposure. However, motivated decisions are also guided by instrumental mechanisms, but to date the effect of traumatic stress on these instrumental systems remain poorly investigated. Here, we examine whether a single episode of severe traumatic stress influences flexible instrumental decisions through an impact on a Pavlovian system. Methods Twenty-six survivors of the 2011 Norwegian terror attack and 30 matched control subjects performed an instrumental learning task in which Pavlovian and instrumental associations promoted congruent or conflicting responses. We used reinforcement learning models to infer how traumatic stress affected learning and decision-making. Based on the importance of dorsal anterior cingulate cortex (dACC) for cognitive control, we also investigated if individual concentrations of Glx (=glutamate + glutamine) in dACC predicted the Pavlovian bias of choice. Results Survivors of traumatic stress expressed a greater Pavlovian interference with instrumental action selection and had significantly lower levels of Glx in the dACC. Across subjects, the degree of Pavlovian interference was negatively associated with dACC Glx concentrations. Conclusions Experiencing traumatic stress appears to render instrumental decisions less flexible by increasing the susceptibility to Pavlovian influences. An observed association between prefrontal glutamatergic levels and this Pavlovian bias provides novel insight into the neurochemical basis of decision-making, and suggests a mechanism by which traumatic stress can impair flexible instrumental behaviours.

Hypotheses About the Relationship of Cognition With Psychopathology Should be Tested by Embedding Them Into Empirical Priors

Abstract: Mechanistic hypotheses about psychiatric disorders are increasingly formalized as computational models. Model parameters, characterizing for example decision-making biases, are hypothesized to correlate with clinical constructs. This is promising (Moutoussis et al., 2016), but here we comment that techniques used in the literature tominimize noise in parameter estimationmay not be helpful. In addition, we point out related pitfalls whichmay lead to questionable research practices (Sijtsma, 2015). We advocate incorporating cross-domain, e.g., psychopathology-cognition relationships into the parameter inference itself. Maximum-likelihood techniques often provide noisy parameter estimates, in the sense of total error over an experimental group. In addition, in large studies brief tasks are often used, providing little data per participant. However, individual parameter estimation can be improved by using empirical priors (Efron, 2012). Here, parameter estimates are informed by, or conditioned upon, the population distribution that a case comes from. For an individual j with parameters θ j coming from a population distribution ppop:

Magnetoencephalography decoding reveals structural differences within integrative decision processes

Abstract: When confronted with complex inputs consisting of multiple elements, humans use various strategies to integrate the elements quickly and accurately. For instance, accuracy may be improved by processing elements one at a time1-4 or over extended periods5-8; speed can increase if the internal representation of elements is accelerated9,10. However, little is known about how humans actually approach these challenges because behavioural findings can be accounted for by multiple alternative process models11 and neuroimaging investigations typically rely on haemodynamic signals that change too slowly. Consequently, to uncover the fast neural dynamics that support information integration, we decoded magnetoencephalographic signals that were recorded as human subjects performed a complex decision task. Our findings reveal three sources of individual differences in the temporal structure of the integration process-sequential representation, partial reinstatement and early computation-each having a dissociable effect on how subjects handled problem complexity and temporal constraints. Our findings shed new light on the structure and influence of self-determined neural integration processes.

Decreased value-sensitivity in schizophrenia

Abstract: Pathophysiology in schizophrenia has been linked to aberrant incentive salience, namely the dysfunctional processing of value linked to abnormal dopaminergic activity. In line with this, recent studies showed impaired learning of value in schizophrenia. However, how value is used to guide behaviour independently from learning, as in risky choice, has rarely been examined in this disorder. We studied value-guided choice under risk in patients with schizophrenia and in controls using a task requiring a choice between a certain monetary reward, varying trial-by-trial, and a gamble offering an equal probability of getting double this certain amount or nothing. We observed that patients compared to controls exhibited reduced sensitivity to values, implying that their choices failed to flexibly adapt to the specific values on offer. Moreover, the degree of this value sensitivity inversely correlated with aberrant salience experience, suggesting that the inability to tune choice to value may be a key element of aberrant salience in the illness. Our results help clarify the cognitive mechanisms underlying improper attribution of value in schizophrenia and may thus inform cognitive interventions aimed at reinstating value sensitivity in patients.

Age-dependent Pavlovian biases influence motor decision-making.

Abstract: Motor decision-making is an essential component of everyday life which requires weighing potential rewards and punishments against the probability of successfully executing an action. To achieve this, humans rely on two key mechanisms; a flexible, instrumental, value-dependent process and a hardwired, Pavlovian, value-independent process. In economic decision-making, age-related decline in risk taking is explained by reduced Pavlovian biases that promote action toward reward. Although healthy ageing has also been associated with decreased risk-taking in motor decision-making, it is currently unknown whether this is a result of changes in Pavlovian biases, instrumental processes or a combination of both. Using a newly established approach-avoidance computational model together with a novel app-based motor decision-making task, we measured sensitivity to reward and punishment when participants (n = 26,532) made a 'go/no-go' motor gamble based on their perceived ability to execute a complex action. We show that motor decision-making can be better explained by a model with both instrumental and Pavlovian parameters, and reveal age-related changes across punishment- and reward-based instrumental and Pavlovian processes. However, the most striking effect of ageing was a decrease in Pavlovian attraction towards rewards, which was associated with a reduction in optimality of choice behaviour. In a subset of participants who also played an independent economic decision-making task (n = 17,220), we found similar decision-making tendencies for motor and economic domains across a majority of age groups. Pavlovian biases, therefore, play an important role in not only explaining motor decision-making behaviour but also the changes which occur through normal ageing. This provides a deeper understanding of the mechanisms which shape motor decision-making across the lifespan.

Agent-specific learning signals for self-other distinction during mentalising.

Abstract: Humans have a remarkable ability to simulate the minds of others. How the brain distinguishes between mental states attributed to self and mental states attributed to someone else is unknown. Here, we investigated how fundamental neural learning signals are selectively attributed to different agents. Specifically, we asked whether learning signals are encoded in agent-specific neural patterns or whether a self–other distinction depends on encoding agent identity separately from this learning signal. To examine this, we tasked subjects to learn continuously 2 models of the same environment, such that one was selectively attributed to self and the other was selectively attributed to another agent. Combining computational modelling with magnetoencephalography (MEG) enabled us to track neural representations of prediction errors (PEs) and beliefs attributed to self, and of simulated PEs and beliefs attributed to another agent. We found that the representational pattern of a PE reliably predicts the identity of the agent to whom the signal is attributed, consistent with a neural self–other distinction implemented via agent-specific learning signals. Strikingly, subjects exhibiting a weaker neural self–other distinction also had a reduced behavioural capacity for self–other distinction and displayed more marked subclinical psychopathological traits. The neural self–other distinction was also modulated by social context, evidenced in a significantly reduced decoding of agent identity in a nonsocial control task. Thus, we show that self–other distinction is realised through an encoding of agent identity intrinsic to fundamental learning signals. The observation that the fidelity of this encoding predicts psychopathological traits is of interest as a potential neurocomputational psychiatric biomarker.

Personality dimensions emerging during adolescence and young adulthood are underpinned by a single latent trait indexing impairment in social functioning

Abstract: Personality with stable behavioural traits emerges in the adolescent and young adult years. Models of putatively distinct, but correlated, personality traits have been developed to describe behavioural styles including schizotypal, narcissistic, callous-unemotional, negative emotionality, antisocial and impulsivity traits. These traits have influenced the classification of their related personality disorders. We tested if a bifactor model fits the data better than correlated-factor and orthogonal-factor models and subsequently validated the obtained factors with mental health measures and treatment history. A set of self-report questionnaires measuring the above traits together with measures of mental health and service use were collected from a volunteer community sample of adolescents and young adults aged 14 to 25 years (N = 2443). Results: The bifactor model with one general and four specific factors emerged in exploratory analysis, which fit data better than models with correlated or orthogonal factors. The general factor showed high reliability and validity. The findings suggest that a selected range of putatively distinct personality traits is underpinned by a general latent personality trait that may be interpreted as a severity factor, with higher scores indexing more impairment in social functioning. The results are in line with ICD-11, which suggest an explicit link between personality disorders and compromised interpersonal or social function. The obtained general factor was akin to the overarching dimension of personality functioning (describing one’s relation to the self and others) proposed by DSM-5 Section III.

Learning Contextual Reward Expectations for Value Adaptation.

Abstract: Substantial evidence indicates that subjective value is adapted to the statistics of reward expected within a given temporal context. However, how these contextual expectations are learned is poorly understood. To examine such learning, we exploited a recent observation that participants performing a gambling task adjust their preferences as a function of context. We show that, in the absence of contextual cues providing reward information, an average reward expectation was learned from recent past experience. Learning dependent on contextual cues emerged when two contexts alternated at a fast rate, whereas both cue-independent and cue-dependent forms of learning were apparent when two contexts alternated at a slower rate. Motivated by these behavioral findings, we reanalyzed a previous fMRI data set to probe the neural substrates of learning contextual reward expectations. We observed a form of reward prediction error related to average reward such that, at option presentation, activity in ventral tegmental area/substantia nigra and ventral striatum correlated positively and negatively, respectively, with the actual and predicted value of options. Moreover, an inverse correlation between activity in ventral tegmental area/substantia nigra (but not striatum) and predicted option value was greater in participants showing enhanced choice adaptation to context. The findings help understanding the mechanisms underlying learning of contextual reward expectation.

Risk preference and choice stochasticity during decisions for other people

Abstract: In several contexts, such as finance and politics, people make choices that are relevant for others but irrelevant for oneself. Focusing on decision-making under risk, we compared monetary choices made for one’s own interest with choices made on behalf of an anonymous individual. Consistent with the previous literature, other-interest choices were characterized by an increased gambling propensity. We also investigated choice stochasticity, which captures how much decisions vary in similar conditions. An aspect related to choice stochasticity is how much decisions are tuned to the option values, and we found that this was higher during self-interest than during other-interest choices. This effect was observed only in individuals who reported a motivation to distribute rewards unequally, suggesting that it may (at least partially) depend on a motivation to make accurate decisions for others. Our results indicate that, during decision-making under risk, choices for other people are characterized by a decreased tuning to the values of the options, in addition to enhanced risk seeking.

Are you sure about that? On the origins of confidence in concept learning

Abstract: Humans possess a rich repertoire of abstract concepts about which they can often judge their confidence. These judgements help guide behaviour, but the mechanisms underlying them are still poorly understood. Here, we examine the evolution of people’s sense of confidence as they engage in probabilistic concept learning. Participants learned a continuous function of four continuous features, reporting their predictions and confidence about these predictions. Participants indeed had insight into their uncertainties: confidence was correlated with the accuracy of predictions, increasing as learning progressed. There were substantial individual differences. In contrast to many classical models that try to explain only the predictions, we formalized human function learning in Bayesian terms as Gaussian process inference. This model generates posterior distributions, allowing us to link predictions and confidence judgements. Gaussian process inference well matched participants’ predictions, and also the confidence judgements of metacognitively competent participants. Our results show that human confidence judgements during learning are tied to uncertainty, suggesting that concept learning is fundamentally probabilistic.

Schizotypy-related magnetization of cortex in healthy adolescence is co-located with expression of schizophrenia risk genes

Abstract: Background: Genetic risk is thought to drive clinical variation on a spectrum of schizophrenia-like traits but the underlying changes in brain structure that mechanistically link genomic variation to schizotypal experience and behaviour are unclear. Methods: We assessed schizotypy using a self-reported questionnaire, and measured magnetization transfer (MT), as a putative micro-structural MRI marker of intra-cortical myelination, in 68 brain regions, in 248 healthy young people (aged 14-25 years). We used normative adult brain gene expression data, and partial least squares (PLS) analysis, to find the weighted gene expression pattern that was most co-located with the cortical map of schizotypy-related magnetization (SRM). Results: Magnetization was significantly correlated with schizotypy in bilateral posterior cingulate cortex and precuneus (and for disorganized schizotypy also in medial prefrontal cortex; all FDR-corrected P < 0.05), which are regions of the default mode network specialized for social and memory functions. The genes most positively weighted on the whole genome expression map co-located with SRM were enriched for genes that were significantly down-regulated in two prior case-control histological studies of brain gene expression in schizophrenia. Conversely, the most negatively weighted genes were enriched for genes that were transcriptionally up-regulated in schizophrenia. Positively weighted (down-regulated) genes were enriched for neuronal, specifically inter-neuronal, affiliations and coded a network of proteins comprising a few highly interactive -hubs- such as parvalbumin and calmodulin. Conclusions: Microstructural MRI maps of intracortical magnetization can be linked to both the behavioural traits of schizotypy and to prior histological data on dysregulated gene expression in schizophrenia.

Compulsivity and impulsivity are linked to distinct aberrant developmental trajectories of fronto-striatal myelination

Abstract: The transition from adolescence into adulthood is a period where rapid brain development coincides with a greatly enhanced incidence of psychiatric disorder. The precise developmental brain changes that might account for this emergent psychiatric symptomatology remains obscure. Capitalising on a unique longitudinal dataset, that includes in-vivo myelin-sensitive magnetization transfer (MT) MRI, we show this transition period is characterised by brain-wide growth in MT, within both gray matter and adjacent juxta-cortical white matter. The expression of common developmental psychiatric risk symptomatology in this otherwise healthy population, namely compulsivity and impulsivity, was tied to regionally specific aberrant unfolding of these MT trajectories. This was most marked in superior frontal/cingulate cortex for compulsivity, and in inferior frontal/insular cortex for impulsivity. The findings highlight a brain developmental linkage for emergent psychiatric risk features, evident in regionally specific perturbations in the expansion of MT-related myelination.

Better than expected: The influence of option expectations during decision-making

Abstract: Our choices often arise from a consideration of options presented in a sequence (e.g. the products in a supermarket row). However, whether the precise sequential order of option presentation affects decision-making remains poorly understood. A recent model of choice proposes that, in a set of options presented sequentially, those that are better than expected will be perceived as more valuable, even when options are objectively equivalent within the set. Inspired by this proposal, we devised a novel decision-making task where we manipulated the order of option presentation together with expectations about option value. Even when we compared trials that were exactly equivalent except for option order, we observed a striking preference for options that were better than expected. Our findings show that expectations about options affect which option will be favoured within a sequence, an influence which is manifested as a preference for better-than-expected options. The findings have potential practical implications, as for example they may help policymakers in devising nudge strategies that rely on ad hoc option orders.

Neural substrates of norm compliance in perceptual decisions.

Abstract: Societal norms exert a powerful influence on our decisions. Behaviours motivated by norms, however, do not always concur with the responses mandated by decision relevant information potentially generating a conflict. To probe the interplay between normative and informational influences, we examined how prosocial norms impact on perceptual decisions subjects made in the context of a simultaneous presentation of social information. Participants displayed a bias in their perceptual decisions towards that mandated by social information. However, normative prescriptions modulated this bias bi-directionally depending on whether norms mandated a decision in accord or contrary to the contextual social information. At a neural level, the addition of a norms increased activity in prefrontal cortex and modulated functional connectivity between prefrontal and parietal areas. The bi-directional effect of our norms was captured by differential activations when participants decided against the social information. When norms indicated a decision in line with social information, non-compliance modulated lateral prefrontal cortex activity. By contrast, when norms mandated a decision against social information norm compliance increased activity in the anterior cingulate cortex. Hence, social norms changed the balance between a reliance on perceptual and social information by modulating brain activity in regions associated with response inhibition and conflict monitoring.

Noradrenaline modulates decision urgency during sequential information gathering

Abstract: Arbitrating between timely choice and extended information gathering is critical in effective decision making. Aberrant information gathering behaviour is said to be a feature of psychiatric disorders such as schizophrenia and obsessive-compulsive disorder. We know little about the neurocognitive control mechanisms that drive such information gathering. In a double-blind placebo-controlled drug study with 60 healthy humans (30 female), we examined the effects of noradrenaline and dopamine antagonism on information gathering. We show that modulating noradrenaline function with propranolol leads to decreased information gathering behaviour and this contrasts with no effect following a modulation of dopamine function. Using a Bayesian computational model, we show sampling behaviour is best explained when including an urgency signal that promotes commitment to an early decision. We demonstrate that noradrenaline blockade promotes the expression of this decision-related urgency signal during information gathering. We discuss the findings with respect to psychopathological conditions that are linked to aberrant information gathering.

Noradrenaline modulates decision urgency during sequential information gathering

Abstract: Arbitrating between timely choice and extended information gathering is critical in effective decision making. Aberrant information gathering behaviour is said to be a feature of psychiatric disorders such as schizophrenia and obsessive-compulsive disorder. We know little about the neurocognitive control mechanisms that drive such information gathering. In a double-blind placebo-controlled drug study with 60 healthy humans (30 female), we examined the effects of noradrenaline and dopamine antagonism on information gathering. We show that modulating noradrenaline function with propranolol leads to decreased information gathering behaviour and this contrasts with no effect following a modulation of dopamine function. Using a Bayesian computational model, we show sampling behaviour is best explained when including an urgency signal that promotes commitment to an early decision. We demonstrate that noradrenaline blockade promotes the expression of this decision-related urgency signal during information gathering. We discuss the findings with respect to psychopathological conditions that are linked to aberrant information gathering.

Sparse PLS hyper-parameters optimisation for investigating brain-behaviour relationships

Abstract: Unsupervised learning approaches, such as Partial Least Squares, can be used to investigate relationships between multiple sources of data, such as neuroimaging and behavioural data. In cases of high-dimensional datasets with limited number of examples (e.g. neuroimaging data) there is a need for regularisation to enable the solution of the ill-posed problem and prevent overfitting. Different approaches have been proposed to optimise the regularisation parameters in unsupervised models, however, so far, there has been no comparison between the different approaches using the same data. In this work, two optimisation frameworks (i.e. a permutation and a train/test framework) were compared using sparse PLS to investigate associations between brain connectivity and behaviour data. Both frameworks were able to identify at least one brain-behaviour associative effect. A second brain-behaviour effect was only found using the train/test framework. More importantly, the results show that the multivariate associative effects found with the train/test framework generalise better to new data, suggesting that results based on the permutation framework should be carefully interpreted.

Brain-behaviour modes of covariation in healthy and clinically depressed young people

Abstract: Understanding how variations in dimensions of psychometrics, IQ and demographics relate to changes in brain connectivity during the critical developmental period of adolescence and early adulthood is a major challenge. This has particular relevance for mental health disorders where a failure to understand these links might hinder the development of better diagnostic approaches and therapeutics. Here, we investigated this question in 306 adolescents and young adults (14-24y, 25 clinically depressed) using a multivariate statistical framework, based on canonical correlation analysis (CCA). By linking individual functional brain connectivity profiles to self-report questionnaires, IQ and demographic data we identified two distinct modes of covariation. The first mode mapped onto an externalization/internalization axis and showed a strong association with sex. The second mode mapped onto a well-being/distress axis independent of sex. Interestingly, both modes showed an association with age. Crucially, the changes in functional brain connectivity associated with changes in these phenotypes showed marked developmental effects. The findings point to a role for the default mode, frontoparietal and limbic networks in psychopathology and depression.