Showing papers by "Raymond J. Dolan published in 2016"
TL;DR: It is concluded that normative human brain maturation involves a genetically patterned process of consolidating anatomical network hubs and developmental variation of this consolidation process may be relevant both to normal cognitive and behavioral changes and the high incidence of schizophrenia during human brain adolescence.
Abstract: How does human brain structure mature during adolescence? We used MRI to measure cortical thickness and intracortical myelination in 297 population volunteers aged 14-24 y old. We found and replicated that association cortical areas were thicker and less myelinated than primary cortical areas at 14 y. However, association cortex had faster rates of shrinkage and myelination over the course of adolescence. Age-related increases in cortical myelination were maximized approximately at the internal layer of projection neurons. Adolescent cortical myelination and shrinkage were coupled and specifically associated with a dorsoventrally patterned gene expression profile enriched for synaptic, oligodendroglial- and schizophrenia-related genes. Topologically efficient and biologically expensive hubs of the brain anatomical network had greater rates of shrinkage/myelination and were associated with overexpression of the same transcriptional profile as cortical consolidation. We conclude that normative human brain maturation involves a genetically patterned process of consolidating anatomical network hubs. We argue that developmental variation of this consolidation process may be relevant both to normal cognitive and behavioral changes and the high incidence of schizophrenia during human brain adolescence.
401 citations
TL;DR: It is demonstrated that subjective estimates of uncertainty predict the dynamics of subjective and physiological stress responses, and the finding that stress responses are tuned to environmental uncertainty provides new insight into their generation and likely adaptive function.
Abstract: The effects of stress are frequently studied, yet its proximal causes remain unclear. Here we demonstrate that subjective estimates of uncertainty predict the dynamics of subjective and physiological stress responses. Subjects learned a probabilistic mapping between visual stimuli and electric shocks. Salivary cortisol confirmed that our stressor elicited changes in endocrine activity. Using a hierarchical Bayesian learning model, we quantified the relationship between the different forms of subjective task uncertainty and acute stress responses. Subjective stress, pupil diameter and skin conductance all tracked the evolution of irreducible uncertainty. We observed a coupling between emotional and somatic state, with subjective and physiological tuning to uncertainty tightly correlated. Furthermore, the uncertainty tuning of subjective and physiological stress predicted individual task performance, consistent with an adaptive role for stress in learning under uncertain threat. Our finding that stress responses are tuned to environmental uncertainty provides new insight into their generation and likely adaptive function.
213 citations
TL;DR: It is proposed that mood represents the overall momentum of recent outcomes, and its biasing influence on the perception of outcomes ‘corrects’ learning to account for environmental dependencies.
209 citations
TL;DR: It is concluded that topologically integrative hubs, mediating long-distance connections between modules, are more costly in terms of mitochondrial glucose metabolism.
Abstract: Human functional magnetic resonance imaging (fMRI) brain networks have a complex topology comprising integrative components, e.g. long-distance inter-modular edges, that are theoretically associated with higher biological cost. Here, we estimated intra-modular degree, inter-modular degree and connection distance for each of 285 cortical nodes in multi-echo fMRI data from 38 healthy adults. We used the multivariate technique of partial least squares (PLS) to reduce the dimensionality of the relationships between these three nodal network parameters and prior microarray data on regional expression of 20 737 genes. The first PLS component defined a transcriptional profile associated with high intra-modular degree and short connection distance, whereas the second PLS component was associated with high inter-modular degree and long connection distance. Nodes in superior and lateral cortex with high inter-modular degree and long connection distance had local transcriptional profiles enriched for oxidative metabolism and mitochondria, and for genes specific to supragranular layers of human cortex. In contrast, primary and secondary sensory cortical nodes in posterior cortex with high intra-modular degree and short connection distance had transcriptional profiles enriched for RNA translation and nuclear components. We conclude that, as predicted, topologically integrative hubs, mediating long-distance connections between modules, are more costly in terms of mitochondrial glucose metabolism.This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'.
189 citations
TL;DR: It is found that increasing time pressure led to shallower goal-directed planning, suggesting that a speed-accuracy tradeoff controls the depth of planning with deeper search leading to more accurate evaluation, at the cost of slower decision-making.
Abstract: Behavioral and neural evidence reveal a prospective goal-directed decision process that relies on mental simulation of the environment, and a retrospective habitual process that caches returns previously garnered from available choices. Artificial systems combine the two by simulating the environment up to some depth and then exploiting habitual values as proxies for consequences that may arise in the further future. Using a three-step task, we provide evidence that human subjects use such a normative plan-until-habit strategy, implying a spectrum of approaches that interpolates between habitual and goal-directed responding. We found that increasing time pressure led to shallower goal-directed planning, suggesting that a speed-accuracy tradeoff controls the depth of planning with deeper search leading to more accurate evaluation, at the cost of slower decision-making. We conclude that subjects integrate habit-based cached values directly into goal-directed evaluations in a normative manner.
148 citations
TL;DR: Recorded magnetoencephalography while human subjects performed a novel non-spatial reasoning task and found that spontaneous fast sequential representation of states can be measured non-invasively in humans, and these sequences may be a fundamental feature of neural computation across tasks.
146 citations
TL;DR: Modulated excitation/inhibition balance with transcranial direct current stimulation is modulated and it is shown that reducing GABA allows cortical associations to be re-expressed, suggesting that in humans associative memories are stored in balanced excitatory-inhibitory ensembles that lie dormant unless latent inhibitory connections are unmasked.
123 citations
TL;DR: It is proposed that ADHD is caused by impaired gain modulation in systems that generate this phenotypic increased behavioural variability, and how this variable behaviour might be implemented at a neural level through catecholamine influences on corticostriatal loops.
99 citations
TL;DR: Using a novel approach-avoidance computational model, a Pavlovian attraction to potential reward declined with age, suggesting that age-related decline in this neuromodulator could lead to the observed decrease in risk taking.
83 citations
TL;DR: This work hypothesized that this preference of advance information arises because reward prediction errors carried by such information can boost the level of anticipation, and formulated this proposal in a reinforcement-learning model.
Abstract: When people anticipate uncertain future outcomes, they often prefer to know their fate in advance. Inspired by an idea in behavioral economics that the anticipation of rewards is itself attractive, we hypothesized that this preference of advance information arises because reward prediction errors carried by such information can boost the level of anticipation. We designed new empirical behavioral studies to test this proposal, and confirmed that subjects preferred advance reward information more strongly when they had to wait for rewards for a longer time. We formulated our proposal in a reinforcement-learning model, and we showed that our model could account for a wide range of existing neuronal and behavioral data, without appealing to ambiguous notions such as an explicit value for information. We suggest that such boosted anticipation significantly drives risk-seeking behaviors, most pertinently in gambling.
80 citations
TL;DR: It is demonstrated that people differ in how they learn to avoid pain, with some individuals refraining from actions that resulted in painful outcomes, whereas others favor actions that helped prevent pain.
Abstract: Pain is an elemental inducer of avoidance. Here, we demonstrate that people differ in how they learn to avoid pain, with some individuals refraining from actions that resulted in painful outcomes, whereas others favor actions that helped prevent pain. These individual biases were best explained by differences in learning from outcome prediction errors and were associated with distinct forms of striatal responses to painful outcomes. Specifically, striatal responses to pain were modulated in a manner consistent with an aversive prediction error in individuals who learned predominantly from pain, whereas in individuals who learned predominantly from success in preventing pain, modulation was consistent with an appetitive prediction error. In contrast, striatal responses to success in preventing pain were consistent with an appetitive prediction error in both groups. Furthermore, variation in striatal structure, encompassing the region where pain prediction errors were expressed, predicted participants’ predominant mode of learning, suggesting the observed learning biases may reflect stable individual traits. These results reveal functional and structural neural components underlying individual differences in avoidance learning, which may be important contributors to psychiatric disorders involving pathological harm avoidance behavior.
TL;DR: Using functional magnetic-resonance imaging in humans, it is shown that dopamine-rich midbrain regions encode shifts in beliefs whereas surprise is encoded in prefrontal regions, including the pre-supplementary motor area and dorsal cingulate cortex.
TL;DR: This study presents the first network-based account of how face selectivity arises in the human brain and suggests a novel view on the relevance of feedforward projection from EVC to posterior occipitotemporal face areas in generating cortical faceSelectivity and differences in face recognition ability.
Abstract: Face processing is mediated by interactions between functional areas in the occipital and temporal lobe, and the fusiform face area (FFA) and anterior temporal lobe play key roles in the recognition of facial identity. Individuals with developmental prosopagnosia (DP), a lifelong face recognition impairment, have been shown to have structural and functional neuronal alterations in these areas. The present study investigated how face selectivity is generated in participants with normal face processing, and how functional abnormalities associated with DP, arise as a function of network connectivity. Using functional magnetic resonance imaging and dynamic causal modeling, we examined effective connectivity in normal participants by assessing network models that include early visual cortex (EVC) and face-selective areas and then investigated the integrity of this connectivity in participants with DP. Results showed that a feedforward architecture from EVC to the occipital face area, EVC to FFA, and EVC to posterior superior temporal sulcus (pSTS) best explained how face selectivity arises in both controls and participants with DP. In this architecture, the DP group showed reduced connection strengths on feedforward connections carrying face information from EVC to FFA and EVC to pSTS. These altered network dynamics in DP contribute to the diminished face selectivity in the posterior occipitotemporal areas affected in DP. These findings suggest a novel view on the relevance of feedforward projection from EVC to posterior occipitotemporal face areas in generating cortical face selectivity and differences in face recognition ability.
SIGNIFICANCE STATEMENT Areas of the human brain showing enhanced activation to faces compared to other objects or places have been extensively studied. However, the factors leading to this face selectively have remained mostly unknown. We show that effective connectivity from early visual cortex to posterior occipitotemporal face areas gives rise to face selectivity. Furthermore, people with developmental prosopagnosia, a lifelong face recognition impairment, have reduced face selectivity in the posterior occipitotemporal face areas and left anterior temporal lobe. We show that this reduced face selectivity can be predicted by effective connectivity from early visual cortex to posterior occipitotemporal face areas. This study presents the first network-based account of how face selectivity arises in the human brain.
TL;DR: Depression is associated with an abnormal influence of emotional reactions on decision-making in a way that may predict recovery over the follow-up period of the illness.
Abstract: BACKGROUND: Changes in reflexive emotional responses are hallmarks of depression, but how emotional reflexes make an impact on adaptive decision-making in depression has not been examined formally. Using a Pavlovian-instrumental transfer (PIT) task, we compared the influence of affectively valenced stimuli on decision-making in depression and generalized anxiety disorder compared with healthy controls; and related this to the longitudinal course of the illness. METHOD: A total of 40 subjects with a current DSM-IV-TR diagnosis of major depressive disorder, dysthymia, generalized anxiety disorder, or a combination thereof, and 40 matched healthy controls performed a PIT task that assesses how instrumental approach and withdrawal behaviours are influenced by appetitive and aversive Pavlovian conditioned stimuli (CSs). Patients were followed up after 4-6 months. Analyses focused on patients with depression alone (n = 25). RESULTS: In healthy controls, Pavlovian CSs exerted action-specific effects, with appetitive CSs boosting active approach and aversive CSs active withdrawal. This action-specificity was absent in currently depressed subjects. Greater action-specificity in patients was associated with better recovery over the follow-up period. CONCLUSIONS: Depression is associated with an abnormal influence of emotional reactions on decision-making in a way that may predict recovery.
TL;DR: The results indicate that the influence of dopamine on choice behavior involves a specific modulation of the attractiveness of risky options—a finding with implications for understanding a range of reward-related psychopathologies including addiction.
TL;DR: A potential role for Pavlovian approach in biasing which information humans will choose to sample is investigated and its findings suggest information sampling biases reflect the expression of primitive, yet potentially ecologically adaptive, behavioral repertoires.
Abstract: Information sampling is often biased towards seeking evidence that confirms one’s prior beliefs. Despite such biases being a pervasive feature of human behavior, their underlying causes remain unclear. Many accounts of these biases appeal to limitations of human hypothesis testing and cognition, de facto evoking notions of bounded rationality, but neglect more basic aspects of behavioral control. Here, we investigated a potential role for Pavlovian approach in biasing which information humans will choose to sample. We collected a large novel dataset from 32,445 human subjects, making over 3 million decisions, who played a gambling task designed to measure the latent causes and extent of information-sampling biases. We identified three novel approach-related biases, formalized by comparing subject behavior to a dynamic programming model of optimal information gathering. These biases reflected the amount of information sampled (“positive evidence approach”), the selection of which information to sample (“sampling the favorite”), and the interaction between information sampling and subsequent choices (“rejecting unsampled options”). The prevalence of all three biases was related to a Pavlovian approach-avoid parameter quantified within an entirely independent economic decision task. Our large dataset also revealed that individual differences in the amount of information gathered are a stable trait across multiple gameplays and can be related to demographic measures, including age and educational attainment. As well as revealing limitations in cognitive processing, our findings suggest information sampling biases reflect the expression of primitive, yet potentially ecologically adaptive, behavioral repertoires. One such behavior is sampling from options that will eventually be chosen, even when other sources of information are more pertinent for guiding future action.
TL;DR: Evidence is found for taste uncertainty and for Bayesian taste updating in a novel, large community study of 14–24 year olds that assessed discounting behaviour, including decision variability, before and after participants observed another person’s choices.
Abstract: The weight with which a specific outcome feature contributes to preference quantifies a person's 'taste' for that feature. However, far from being fixed personality characteristics, tastes are plastic. They tend to align, for example, with those of others even if such conformity is not rewarded. We hypothesised that people can be uncertain about their tastes. Personal tastes are therefore uncertain beliefs. People can thus learn about them by considering evidence, such as the preferences of relevant others, and then performing Bayesian updating. If a person's choice variability reflects uncertainty, as in random-preference models, then a signature of Bayesian updating is that the degree of taste change should correlate with that person's choice variability. Temporal discounting coefficients are an important example of taste-for patience. These coefficients quantify impulsivity, have good psychometric properties and can change upon observing others' choices. We examined discounting preferences in a novel, large community study of 14-24 year olds. We assessed discounting behaviour, including decision variability, before and after participants observed another person's choices. We found good evidence for taste uncertainty and for Bayesian taste updating. First, participants displayed decision variability which was better accounted for by a random-taste than by a response-noise model. Second, apparent taste shifts were well described by a Bayesian model taking into account taste uncertainty and the relevance of social information. Our findings have important neuroscientific, clinical and developmental significance.
TL;DR: This work compared electrophysiological responses from two patients with distinct monogenic ion channelopathies and a large cohort of healthy controls to demonstrate the feasibility of assaying synaptic-level channel communication non-invasively, indicating a potential novel application as an adjunct for clinical assessments in neurological and psychiatric settings.
TL;DR: A novel gambling task that generated approach‐avoidance conflict while controlling for spatial processing implicates the anterior hippocampus in behavioral avoidance and choice monitoring, in a manner relevant to understanding its role in anxiety.
Abstract: The hippocampus plays a central role in the approach-avoidance conflict that is central to the genesis of anxiety. However, its exact functional contribution has yet to be identified. We designed a novel gambling task that generated approach-avoidance conflict while controlling for spatial processing. We fit subjects' behavior using a model that quantified the subjective values of choice options, and recorded neural signals using functional magnetic resonance imaging (fMRI). Distinct functional signals were observed in anterior hippocampus, with inferior hippocampus selectively recruited when subjects rejected a gamble, to a degree that covaried with individual differences in anxiety. The superior anterior hippocampus, in contrast, uniquely demonstrated value signals that were potentiated in the context of approach-avoidance conflict. These results implicate the anterior hippocampus in behavioral avoidance and choice monitoring, in a manner relevant to understanding its role in anxiety. Our findings highlight interactions between subregions of the hippocampus as an important focus for future study.
TL;DR: A multifaceted basis for choice behaviour with distinct mappings between components of this behaviour and value sensitive brain regions is highlighted, showing that activity in the VTA/SN reflected contextual reward statistics to the extent that context affected behaviour.
TL;DR: FMRI data during performance of a gambling task where blocks comprise values drawn from one of two different, but partially overlapping, reward distributions or contexts suggest that context-sensitive choice is driven by a brain circuit involving hippocampus and dopaminergic midbrain.
Abstract: Contextual influences on choice are ubiquitous in ecological settings. Current evidence suggests that subjective values are normalized with respect to the distribution of potentially available rewards. However, how this context-sensitivity is realised in the brain remains unknown. To address this, here we examine functional magnetic resonance imaging (fMRI) data during performance of a gambling task where blocks comprise values drawn from one of two different, but partially overlapping, reward distributions or contexts. At the beginning of each block (when information about context is provided), hippocampus is activated and this response is enhanced when contextual influence on choice increases. In addition, response to value in ventral tegmental area/substantia nigra (VTA/SN) shows context-sensitivity, an effect enhanced with an increased contextual influence on choice. Finally, greater response in hippocampus at block start is associated with enhanced context sensitivity in VTA/SN. These findings suggest that context-sensitive choice is driven by a brain circuit involving hippocampus and dopaminergic midbrain.
TL;DR: A novel social decision task combined with computational modelling shows that a participant's subjective emotional state reflects not only the impact of rewards they themselves receive, but also the rewards received by a social partner.
Abstract: Although social comparison is a known determinant of overall life satisfaction, it is not clear how it affects moment-to-moment variation in subjective emotional state. Using a novel social decision task combined with computational modelling, we show that a participant's subjective emotional state reflects not only the impact of rewards they themselves receive, but also the rewards received by a social partner. Unequal outcomes, whether advantageous or disadvantageous, reduce average momentary happiness. Furthermore, the relative impacts of advantageous and disadvantageous inequality on momentary happiness at the individual level predict a subject's generosity in a separate dictator game. These findings demonstrate a powerful social influence upon subjective emotional state, where emotional reactivity to inequality is strongly predictive of altruism in an independent task domain.
TL;DR: Support is found for the hypotheses that stress would lead to a non-selective increase in the expression of Pavlovian biases and that stress, as an aversive state, might specifically impact action production due to the Pavlovians linkage between inaction and aversive states.
Abstract: Stress interferes with instrumental learning. However, choice is also influenced by non-instrumental factors, most strikingly by biases arising from Pavlovian associations that facilitate action in pursuit of rewards and inaction in the face of punishment. Whether stress impacts on instrumental learning via these Pavlovian associations is unknown. Here, in a task where valence (reward or punishment) and action (go or no-go) were orthogonalised, we asked whether the impact of stress on learning was action or valence specific. We exposed 60 human participants either to stress (socially-evaluated cold pressor test) or a control condition (room temperature water). We contrasted two hypotheses: that stress would lead to a non-selective increase in the expression of Pavlovian biases; or that stress, as an aversive state, might specifically impact action production due to the Pavlovian linkage between inaction and aversive states. We found support for the second of these hypotheses. Stress specifically impaired learning to produce an action, irrespective of the valence of the outcome, an effect consistent with a Pavlovian linkage between punishment and inaction. This deficit in action-learning was also reflected in pupillary responses; stressed individuals showed attenuated pupillary responses to action, hinting at a noradrenergic contribution to impaired action-learning under stress.
TL;DR: This work draws attention to a growing literature finding greater discounting of delayed reward, an important aspect of impatience, across a range of psychiatric disorders and proposes these findings are best understood by considering the goals and motivation for discounting future reward.
Abstract: Impatience for reward is a facet of many psychiatric disorders. We draw attention to a growing literature finding greater discounting of delayed reward, an important aspect of impatience, across a range of psychiatric disorders. We propose these findings are best understood by considering the goals and motivation for discounting future reward. We characterize these as arising from either the opportunity costs of waiting or the uncertainty associated with delayed reward. We link specific instances of higher discounting in psychiatric disorder to heightened subjective estimates of either of these factors. We propose these costs are learned and represented based either on a flexible cognitive model of the world, an accumulation of previous experience, or through evolutionary specification. Any of these can be considered suboptimal for the individual if the resulting behavior results in impairments in personal and social functioning and/or in distress. By considering the neurochemical and neuroanatomical implementation of these processes, we illustrate how this approach can in principle unite social, psychological and biological conceptions of impulsive choice.
TL;DR: Greater average reward was associated with enhanced activity in dopaminergic midbrain to a degree that correlated with the relationship between average reward and pressing vigor, and an opposite pattern was observed in subgenual cingulate cortex, a region implicated in negative mood and motivational inhibition.
Abstract: Dopamine plays a key role in motivation. Phasic dopamine response reflects a reinforcement prediction error RPE, whereas tonic dopamine activity is postulated to represent an average reward that mediates motivational vigor. However, it has been hard to find evidence concerning the neural encoding of average reward that is uncorrupted by influences of RPEs. We circumvented this difficulty in a novel visual search task where we measured participants' button pressing vigor in a context where information underlying an RPE about future average reward was provided well before the average reward itself. Despite no instrumental consequence, participants' pressing force increased for greater current average reward, consistent with a form of Pavlovian effect on motivational vigor. We recorded participants' brain activity during task performance with fMRI. Greater average reward was associated with enhanced activity in dopaminergic midbrain to a degree that correlated with the relationship between average reward and pressing vigor. Interestingly, an opposite pattern was observed in subgenual cingulate cortex, a region implicated in negative mood and motivational inhibition. These findings highlight a crucial role for dopaminergic midbrain in representing aspects of average reward and motivational vigor.
TL;DR: Improved memory was linked to context-related activation of the DG/CA3 and SN/VTA, which may determine whether memories are improved by contextual reward.
TL;DR: A normative (Bayesian) account of how rewards map to incentive values is introduced, suggesting that incentive value is intrinsically context-dependent and influenced by context variability and by hierarchically nested contexts.
Abstract: Substantial evidence indicates that incentive value depends on an anticipation of rewards within a given context. However, the computations underlying this context sensitivity remain unknown. To address this question, we introduce a normative (Bayesian) account of how rewards map to incentive values. This assumes that the brain inverts a model of how rewards are generated. Key features of our account include (i) an influence of prior beliefs about the context in which rewards are delivered (weighted by their reliability in a Bayes-optimal fashion), (ii) the notion that incentive values correspond to precision-weighted prediction errors, (iii) and contextual information unfolding at different hierarchical levels. This formulation implies that incentive value is intrinsically context-dependent. We provide empirical support for this model by showing that incentive value is influenced by context variability and by hierarchically nested contexts. The perspective we introduce generates new empirical predictions that might help explaining psychopathologies, such as addiction.
TL;DR: A computational model of aversion is proposed that combines goal-directed and Pavlovian forms of control into a unifying framework in which their relative importance is regulated by factors such as threat distance and controllability.
TL;DR: The results implicate the subthalamic nucleus in a modulation of outcome value in experience-based learning and decision-making in Parkinson’s disease, suggesting a more pervasive role of the subhalic nucleus in the control of human decision- making than previously thought.
Abstract: Deep brain stimulation (DBS) of the subthalamic nucleus in Parkinson's disease is known to cause a subtle but important adverse impact on behaviour, with impulsivity its most widely reported manifestation. However, precisely which computational components of the decision process are modulated is not fully understood. Here we probe a number of distinct subprocesses, including temporal discount, outcome utility, instrumental learning rate, instrumental outcome sensitivity, reward-loss trade-offs, and perseveration. We tested 22 Parkinson's Disease patients both on and off subthalamic nucleus deep brain stimulation (STN-DBS), while they performed an instrumental learning task involving financial rewards and losses, and an inter-temporal choice task for financial rewards. We found that instrumental learning performance was significantly worse following stimulation, due to modulation of instrumental outcome sensitivity. Specifically, patients became less sensitive to decision values for both rewards and losses, but without any change to the learning rate or reward-loss trade-offs. However, we found no evidence that DBS modulated different components of temporal impulsivity. In conclusion, our results implicate the subthalamic nucleus in a modulation of outcome value in experience-based learning and decision-making in Parkinson's disease, suggesting a more pervasive role of the subthalamic nucleus in the control of human decision-making than previously thought.