Showing papers by "Raymond J. Dolan published in 2015"
TL;DR: It is demonstrated that higher presynaptic dopamine in human ventral striatum is associated with more pronounced model-based behavioral control, as well as an enhanced coding ofmodel-based signatures in lateral prefrontal cortex and diminished coding of model-free learning signals in ventral Striatum.
Abstract: Dual system theories suggest that behavioral control is parsed between a deliberative “model-based” and a more reflexive “model-free” system. A balance of control exerted by these systems is thought to be related to dopamine neurotransmission. However, in the absence of direct measures of human dopamine, it remains unknown whether this reflects a quantitative relation with dopamine either in the striatum or other brain areas. Using a sequential decision task performed during functional magnetic resonance imaging, combined with striatal measures of dopamine using [18F]DOPA positron emission tomography, we show that higher presynaptic ventral striatal dopamine levels were associated with a behavioral bias toward more model-based control. Higher presynaptic dopamine in ventral striatum was associated with greater coding of model-based signatures in lateral prefrontal cortex and diminished coding of model-free prediction errors in ventral striatum. Thus, interindividual variability in ventral striatal presynaptic dopamine reflects a balance in the behavioral expression and the neural signatures of model-free and model-based control. Our data provide a novel perspective on how alterations in presynaptic dopamine levels might be accompanied by a disruption of behavioral control as observed in aging or neuropsychiatric diseases such as schizophrenia and addiction.
220 citations
TL;DR: A neurobiological dysfunction related to reward prediction that transcended disorder categories and was related to measures of depressed mood is demonstrated and underline the potential of a dimensional approach in psychiatry and strengthen the hypothesis that neurobiology research in psychiatric disorders can be targeted at core mechanisms that are likely to be implicated in a range of clinical entities.
Abstract: Rationale
A dimensional approach in psychiatry aims to identify core mechanisms of mental disorders across nosological boundaries.
172 citations
TL;DR: It is demonstrated that human subjects infer both optimal policies and the precision of those inferences, and thus support the notion that humans perform hierarchical probabilistic Bayesian inference.
Abstract: Dopamine plays a key role in learning; however, its exact function in decision making and choice remains unclear. Recently, we proposed a generic model based on active (Bayesian) inference wherein dopamine encodes the precision of beliefs about optimal policies. Put simply, dopamine discharges reflect the confidence that a chosen policy will lead to desired outcomes. We designed a novel task to test this hypothesis, where subjects played a “limited offer” game in a functional magnetic resonance imaging experiment. Subjects had to decide how long to wait for a high offer before accepting a low offer, with the risk of losing everything if they waited too long. Bayesian model comparison showed that behavior strongly supported active inference, based on surprise minimization, over classical utility maximization schemes. Furthermore, midbrain activity, encompassing dopamine projection neurons, was accurately predicted by trial-by-trial variations in model-based estimates of precision. Our findings demonstrate that human subjects infer both optimal policies and the precision of those inferences, and thus support the notion that humans perform hierarchical probabilistic Bayesian inference. In other words, subjects have to infer both what they should do as well as how confident they are in their choices, where confidence may be encoded by dopaminergic firing.
165 citations
Journal Article•
TL;DR: This paper found that most people valued others' pain more than their own pain, and this "hyperaltruistic" valuation was linked to slower responding when making decisions that affected others, consistent with an engagement of deliberative processes in moral decision making.
Abstract: Significance Concern for the welfare of others is a key component of moral decision making and is disturbed in antisocial and criminal behavior. However, little is known about how people evaluate the costs of others’ suffering. Past studies have examined people’s judgments in hypothetical scenarios, but there is evidence that hypothetical judgments cannot accurately predict actual behavior. Here we addressed this issue by measuring how much money people will sacrifice to reduce the number of painful electric shocks delivered to either themselves or an anonymous stranger. Surprisingly, most people sacrifice more money to reduce a stranger’s pain than their own pain. This finding may help us better understand how people resolve moral dilemmas that commonly arise in medical, legal, and political decision making. Concern for the suffering of others is central to moral decision making. How humans evaluate others’ suffering, relative to their own suffering, is unknown. We investigated this question by inviting subjects to trade off profits for themselves against pain experienced either by themselves or an anonymous other person. Subjects made choices between different amounts of money and different numbers of painful electric shocks. We independently varied the recipient of the shocks (self vs. other) and whether the choice involved paying to decrease pain or profiting by increasing pain. We built computational models to quantify the relative values subjects ascribed to pain for themselves and others in this setting. In two studies we show that most people valued others’ pain more than their own pain. This was evident in a willingness to pay more to reduce others’ pain than their own and a requirement for more compensation to increase others’ pain relative to their own. This ‟hyperaltruistic” valuation of others’ pain was linked to slower responding when making decisions that affected others, consistent with an engagement of deliberative processes in moral decision making. Subclinical psychopathic traits correlated negatively with aversion to pain for both self and others, in line with reports of aversive processing deficits in psychopathy. Our results provide evidence for a circumstance in which people care more for others than themselves. Determining the precise boundaries of this surprisingly prosocial disposition has implications for understanding human moral decision making and its disturbance in antisocial behavior.
163 citations
TL;DR: Boosting dopamine levels using levodopa (l-DOPA) as human subjects made economic decisions and repeatedly reported their momentary happiness shows an effect on both choices and happiness.
Abstract: The neuromodulator dopamine has a well established role in reporting appetitive prediction errors that are widely considered in terms of learning. However, across a wide variety of contexts, both phasic and tonic aspects of dopamine are likely to exert more immediate effects that have been less well characterized. Of particular interest is dopamine's influence on economic risk taking and on subjective well-being, a quantity known to be substantially affected by prediction errors resulting from the outcomes of risky choices. By boosting dopamine levels using levodopa (l-DOPA) as human subjects made economic decisions and repeatedly reported their momentary happiness, we show here an effect on both choices and happiness. Boosting dopamine levels increased the number of risky options chosen in trials involving potential gains but not trials involving potential losses. This effect could be better captured as increased Pavlovian approach in an approach-avoidance decision model than as a change in risk preferences within an established prospect theory model. Boosting dopamine also increased happiness resulting from some rewards. Our findings thus identify specific novel influences of dopamine on decision making and emotion that are distinct from its established role in learning.
161 citations
TL;DR: An active inference scheme for solving Markov decision processes is extended to include learning, and it is shown that simulated dopamine dynamics strongly resemble those actually observed during instrumental conditioning.
Abstract: Temporal difference learning models propose phasic dopamine signaling encodes reward prediction errors that drive learning. This is supported by studies where optogenetic stimulation of dopamine neurons can stand in lieu of actual reward. Nevertheless, a large body of data also shows that dopamine is not necessary for learning, and that dopamine depletion primarily affects task performance. We offer a resolution to this paradox based on an hypothesis that dopamine encodes the precision of beliefs about alternative actions, and thus controls the outcome-sensitivity of behavior. We extend an active inference scheme for solving Markov decision processes to include learning, and show that simulated dopamine dynamics strongly resemble those actually observed during instrumental conditioning. Furthermore, simulated dopamine depletion impairs performance but spares learning, while simulated excitation of dopamine neurons drives reward learning, through aberrant inference about outcome states. Our formal approach provides a novel and parsimonious reconciliation of apparently divergent experimental findings.
95 citations
TL;DR: It is shown that mPFC encodes agent-independent representations of subjective value, such that prediction errors simultaneously update multiple agents’ value representations, shedding mechanistic light on complex human processes such as the powerful influence of social interaction on beliefs and preferences.
91 citations
TL;DR: It is shown that, as age increases, working memory performance is compromised more by distractors presented during WM maintenance than distractor presented during encoding, and the ability to exclude distraction at encoding is a better predictor of WMC in the absence of distraction.
Abstract: A weakened ability to effectively resist distraction is a potential basis for reduced working memory capacity (WMC) associated with healthy aging. Exploiting data from 29,631 users of a smartphone game, we show that, as age increases, working memory (WM) performance is compromised more by distractors presented during WM maintenance than distractors presented during encoding. However, with increasing age, the ability to exclude distraction at encoding is a better predictor of WMC in the absence of distraction. A significantly greater contribution of distractor filtering at encoding represents a potential compensation for reduced WMC in older age.
89 citations
TL;DR: Dissociable effects of the serotonin reuptake inhibitor citalopram and the dopamine precursor levodopa on decisions to inflict pain on oneself and others for financial gain and evidence for dose dependency of these effects are found.
88 citations
TL;DR: Suboptimal or pathological behaviour does not speak against understanding behaviour in terms of (Bayes optimal) inference, but rather calls for a more refined understanding of the subject’s generative model upon which their (optimal) Bayesian inference is based.
87 citations
TL;DR: It is argued that an informational account predicts a surprising tendency to conform, and how normative influences fit into this framework and interact with social influences is detailed.
TL;DR: It is shown that manipulating expected precision strongly affects how much information an agent characteristically samples, and thus provides a possible link between impulsivity and dopaminergic dysfunction.
Abstract: Deciding how much evidence to accumulate before making a decision is a problem we and other animals often face, but one that is not completely understood. This issue is particularly important because a tendency to sample less information often known as reflection impulsivity is a feature in several psychopathologies, such as psychosis. A formal understanding of information sampling may therefore clarify the computational anatomy of psychopathology. In this theoretical letter, we consider evidence accumulation in terms of active Bayesian inference using a generic model of Markov decision processes. Here, agents are equipped with beliefs about their own behavior-in this case, that they will make informed decisions. Normative decision making is then modeled using variational Bayes to minimize surprise about choice outcomes. Under this scheme, different facets of belief updating map naturally onto the functional anatomy of the brain at least at a heuristic level. Of particular interest is the key role played by the expected precision of beliefs about control, which we have previously suggested may be encoded by dopaminergic neurons in the midbrain. We show that manipulating expected precision strongly affects how much information an agent characteristically samples, and thus provides a possible link between impulsivity and dopaminergic dysfunction. Our study therefore represents a step toward understanding evidence accumulation in terms of neurobiologically plausible Bayesian inference and may cast light on why this process is disordered in psychopathology.
TL;DR: It is shown that human decision-making is better explained by surprise minimization compared to utility maximization, and a limitation of purely economic motivations in explaining choice behavior is highlighted and the importance of belief-based motivations is emphasized.
Abstract: Classical economic models are predicated on the idea that the ultimate aim of choice is to maximize utility or reward. In contrast, an alternative perspective highlights the fact that adaptive behavior requires agents' to model their environment and minimize surprise about the states they frequent. We propose that choice behavior can be more accurately accounted for by surprise minimization compared to reward or utility maximization alone. Minimizing surprise makes a prediction at variance with expected utility models; namely, that in addition to attaining valuable states, agents attempt to maximize the entropy over outcomes and thus 'keep their options open'. We tested this prediction using a simple binary choice paradigm and show that human decision-making is better explained by surprise minimization compared to utility maximization. Furthermore, we replicated this entropy-seeking behavior in a control task with no explicit utilities. These findings highlight a limitation of purely economic motivations in explaining choice behavior and instead emphasize the importance of belief-based motivations.
TL;DR: It is concluded that subtle differences in local rather than long-range tracts in the ventral temporal lobe are more likely associated with developmental prosopagnosia.
TL;DR: It is shown that cognitive load does not impair model-based reasoning if subjects receive prior training on the task, and this finding is replicated across two studies and a variety of analysis methods.
Abstract: Model-based and model-free reinforcement learning (RL) have been suggested as algorithmic realizations of goal-directed and habitual action strategies. Model-based RL is more flexible than model-free but requires sophisticated calculations using a learnt model of the world. This has led model-based RL to be identified with slow, deliberative processing, and model-free RL with fast, automatic processing. In support of this distinction, it has recently been shown that model-based reasoning is impaired by placing subjects under cognitive load--a hallmark of non-automaticity. Here, using the same task, we show that cognitive load does not impair model-based reasoning if subjects receive prior training on the task. This finding is replicated across two studies and a variety of analysis methods. Thus, task familiarity permits use of model-based reasoning in parallel with other cognitive demands. The ability to deploy model-based reasoning in an automatic, parallelizable fashion has widespread theoretical implications, particularly for the learning and execution of complex behaviors. It also suggests a range of important failure modes in psychiatric disorders.
TL;DR: Three classes of failure modes arising in computational neuroscience stem from abnormalities in the framing of problems or tasks, from the mechanisms of cognition used to solve the tasks, or from the historical data available from the environment.
Abstract: Psychiatric disorders profoundly impair many aspects of decision making. Poor choices have negative consequences in the moment and make it very hard to navigate complex social environments. Computational neuroscience provides normative, neurobiologically informed descriptions of the components of decision making that serve as a platform for a principled exploration of dysfunctions. Here, we identify and discuss three classes of failure modes arising in these formalisms. They stem from abnormalities in the framing of problems or tasks, from the mechanisms of cognition used to solve the tasks, or from the historical data available from the environment.
TL;DR: Surprisingly, the results suggest that the vmPFC drives the hippocampus during the generation and processing of mismatch signals, providing new evidence that the hippocampal–vmPFC circuit is engaged during novelty processing, which has implications for emerging theories regarding the role of VMPFC in memory.
TL;DR: The short-time evolution of neural representations of indirect objects retrieved during reward-learning about direct objects are examined using the spatiotemporal precision of magnetoencephalography to suggest the temporal structure within retrieved neural representations may be key to their function.
Abstract: Seeing an object triggers a complex and carefully orchestrated dance of brain activity. The spatial pattern of the brain activity encoding the object can change multiple times even within the first second of seeing the object. These rapid changes appear to be a core feature of how the brain understands and processes objects. Yet little is known about how these patterns unfold through time when we remember an object. Remembering, or retrieving information about objects, is how we use our knowledge of the world to make good decisions. It is not clear whether, during remembering, there are rapid changes in the patterns similar to those that happen when directly seeing an object. Mapping brain activity during remembering could help us understand how stored information can guide decisions. Using recently developed methods in brain imaging and statistics, Kurth-Nelson et al. found that two distinct patterns of brain activity appeared when viewing particular objects. One occurred around 200 milliseconds after viewing an object, and the other appeared a bit later, by about 400 milliseconds. Later, when remembering the object, these patterns reappeared in the brain, but at different points in time. Furthermore, these two patterns had distinct roles in learning associated with the objects to guide later decisions. This work shows that rapid changes in the pattern of neuronal activity are central to how stored information is retrieved and used to make decisions.
TL;DR: Comparative analyses reveal that central complex and basal ganglia circuitries share comparable lineage relationships within clusters of functionally integrated neurons, suggesting evolutionarily conserved computational mechanisms for action selection in insects and vertebrates.
Abstract: Survival and reproduction entail the selection of adaptive behavioural repertoires. This selection manifests as phylogenetically acquired activities that depend on evolved nervous system circuitries. Lorenz and Tinbergen already postulated that heritable behaviours and their reliable performance are specified by genetically determined programs. Here we compare the functional anatomy of the insect central complex and vertebrate basal ganglia to illustrate their role in mediating selection and maintenance of adaptive behaviours. Comparative analyses reveal that central complex and basal ganglia circuitries share comparable lineage relationships within clusters of functionally integrated neurons. These clusters are specified by genetic mechanisms that link birth time and order to their neuronal identities and functions. Their subsequent connections and associated functions are characterized by similar mechanisms that implement dimensionality reduction and transition through attractor states, whereby spatially organized parallel-projecting loops integrate and convey sensorimotor representations that select and maintain behavioural activity. In both taxa, these neural systems are modulated by dopamine signalling that also mediates memory-like processes. The multiplicity of similarities between central complex and basal ganglia suggests evolutionarily conserved computational mechanisms for action selection. We speculate that these may have originated from ancestral ground pattern circuitries present in the brain of the last common ancestor of insects and vertebrates.
TL;DR: The findings indicate that the dynamics of neuronal activity in the human PPC during perceptual decision-making recapitulate those observed in the macaque, and in so doing they link observations from primate electrophysiology and human choice behaviour.
TL;DR: Findings from a response inhibition task that allowed us to index proactive and reactive inhibitory self-control in a large community sample suggest that reactive and proactive inhibitory control partially rely on distinct neural substrates that are differentially sensitive to age-related change.
Abstract: One expression of executive control involves proactive preparation for future events, and this contrasts with stimulus driven reactive control exerted in response to events. Here we describe findings from a response inhibition task, delivered using a smartphone-based platform, that allowed us to index proactive and reactive inhibitory self-control in a large community sample (n = 12,496). Change in stop-signal reaction time (SSRT) when participants are provided with advance information about an upcoming trial, compared to when they are not, provides a measure of proactive control while SSRT in the absence of advance information provides a measure of reactive control. Both forms of control rely on overlapping frontostriatal pathways known to deteriorate in healthy aging, an age-related decline that occurs at an accelerated rate in men compared to women. Here we ask whether these patterns of age-related decline are reflected in similar changes in proactive and reactive inhibitory control across the lifespan. As predicted, we observed a decline in reactive control with natural aging, with a greater rate of decline in men compared to women (~10 ms versus ~8 ms per decade of adult life). Surprisingly, the benefit of preparation, i.e. proactive control, did not change over the lifespan and women showed superior proactive control at all ages compared to men. Our results suggest that reactive and proactive inhibitory control partially rely on distinct neural substrates that are differentially sensitive to age-related change.
TL;DR: This is the first direct demonstration that human amygdala lesions impair prioritisation of threatening faces, providing evidence that this structure has a causal role in responding to imminent danger.
TL;DR: A novel approach to analyzing simultaneous EEG-fMRI that allows to dissociate the individual time courses of brain regions is used, and it is found that vmPFC and dmPFC have distinguishable time courses and time-frequency patterns.
Abstract: In decision making, dorsal and ventral medial prefrontal cortex show a sensitivity to key decision variables, such as reward prediction errors. It is unclear whether these signals reflect parallel processing of a common synchronous input to both regions, for example from mesocortical dopamine, or separate and consecutive stages in reward processing. These two perspectives make distinct predictions about the relative timing of feedback-related activity in each of these regions, a question we address here. To reconstruct the unique temporal contribution of dorsomedial (dmPFC) and ventromedial prefrontal cortex (vmPFC) to simultaneously measured EEG activity in human subjects, we developed a novel trialwise fMRI-informed EEG analysis that allows dissociating correlated and overlapping sources. We show that vmPFC uniquely contributes a sustained activation profile shortly after outcome presentation, whereas dmPFC contributes a later and more peaked activation pattern. This temporal dissociation is expressed mainly in the alpha band for a vmPFC signal, which contrasts with a theta based dmPFC signal. Thus, our data show reward-related vmPFC and dmPFC responses have distinct time courses and unique spectral profiles, findings that support distinct functional roles in a reward-processing network.
TL;DR: An experiment involving the dynamic consumption over approximately 15 minutes of a limited budget of relief from moderately painful stimuli shows that the consumption choices are consistent with a combination of simple heuristics involving early-spending, spreading or saving of relief until the end, with subjects predominantly exhibiting the last two.
Abstract: Humans frequently need to allocate resources across multiple time-steps. Economic theory proposes that subjects do so according to a stable set of intertemporal preferences, but the computational demands of such decisions encourage the use of formally less competent heuristics. Few empirical studies have examined dynamic resource allocation decisions systematically. Here we conducted an experiment involving the dynamic consumption over approximately 15 minutes of a limited budget of relief from moderately painful stimuli. We had previously elicited the participants’ time preferences for the same painful stimuli in one-off choices, allowing us to assess self-consistency. Participants exhibited three characteristic behaviors: saving relief until the end, spreading relief across time, and early spending, of which the last was markedly less prominent. The likelihood that behavior was heuristic rather than normative is suggested by the weak correspondence between one-off and dynamic choices. We show that the consumption choices are consistent with a combination of simple heuristics involving early-spending, spreading or saving of relief until the end, with subjects predominantly exhibiting the last two.
TL;DR: It is argued that a psychiatry informed by computational neuroscience, computational psychiatry, can obviate this danger of research into the biological basis of emotional and motivational disorders by rendering obsolete the polarity between biological and psychosocial conceptions of illness.
Abstract: Research into the biological basis of emotional and motivational disorders is in danger of riding roughshod over a patient-centered psychiatry and falling into the dualist errors of the past, i.e., by treating mind and brain as conceptually distinct. We argue that a psychiatry informed by computational neuroscience, computational psychiatry, can obviate this danger. Through a focus on the reasoning processes by which humans attempt to maximize reward (and minimize punishment), and how such reasoning is expressed neurally, computational psychiatry can render obsolete the polarity between biological and psychosocial conceptions of illness. Here, the term 'psychological' comes to refer to information processing performed by biological agents, seen in light of underlying goals. We reflect on the implications of this perspective for a definition of mental disorder, including what is entailed in asserting that a particular disorder is 'biological' or 'psychological' in origin. We propose that a computational approach assists in understanding the topography of mental disorder, while cautioning that the point at which eccentric reasoning constitutes disorder often remains a matter of cultural judgment.
TL;DR: These findings confirm theoretical predictions of a sensory modulation prior to self-generated sensations and support the idea that a sensory prediction is generated in parallel to motor output (Walsh and Haggard 2010), before an efference copy becomes available.
Abstract: Sensory consequences of one's own actions are perceived as less intense than identical, externally generated stimuli. This is generally taken as evidence for sensory prediction of action consequences. Accordingly, recent theoretical models explain this attenuation by an anticipatory modulation of sensory processing prior to stimulus onset (Roussel et al. 2013) or even action execution (Brown et al. 2013). Experimentally, prestimulus changes that occur in anticipation of self-generated sensations are difficult to disentangle from more general effects of stimulus expectation, attention and task load (performing an action). Here, we show that an established manipulation of subjective agency over a stimulus leads to a predictive modulation in sensory cortex that is independent of these factors. We recorded magnetoencephalography while subjects performed a simple action with either hand and judged the loudness of a tone caused by the action. Effector selection was manipulated by subliminal motor priming. Compatible priming is known to enhance a subjective experience of agency over a consequent stimulus (Chambon and Haggard 2012). In line with this effect on subjective agency, we found stronger sensory attenuation when the action that caused the tone was compatibly primed. This perceptual effect was reflected in a transient phase-locked signal in auditory cortex before stimulus onset and motor execution. Interestingly, this sensory signal emerged at a time when the hemispheric lateralization of motor signals in M1 indicated ongoing effector selection. Our findings confirm theoretical predictions of a sensory modulation prior to self-generated sensations and support the idea that a sensory prediction is generated in parallel to motor output (Walsh and Haggard 2010), before an efference copy becomes available.
TL;DR: A novel type of functional division between the hippocampus and the basal ganglia in the motivational regulation of long-term memory consolidation, which favors remembering events that are worth acting for is indicated.
Abstract: The expectation of reward is known to enhance a consolidation of long-term memory for events. We tested whether this effect is driven by positive valence or action requirements tied to expected reward. Using a functional magnetic resonance imaging (fMRI) paradigm in young adults, novel images predicted gain or loss outcomes, which in turn were either obtained or avoided by action or inaction. After 24 h, memory for these images reflected a benefit of action as well as a congruence of action requirements and valence, namely, action for reward and inaction for avoidance. fMRI responses in the hippocampus, a region known to be critical for long-term memory function, reflected the anticipation of inaction. In contrast, activity in the putamen mirrored the congruence of action requirement and valence, whereas other basal ganglia regions mirrored overall action benefits on long-lasting memory. The findings indicate a novel type of functional division between the hippocampus and the basal ganglia in the motivational regulation of long-term memory consolidation, which favors remembering events that are worth acting for.
TL;DR: The data indicate that, given concern for others, the fundamental principle of diminishing marginal utility motivates spreading costs across individuals, and a model incorporating this assumption outperformed existing models of social utility in explaining the data.
Abstract: People show empathic responses to others' pain, yet how they choose to apportion pain between themselves and others is not well understood. To address this question, we observed choices to reapportion social allocations of painful stimuli and, for comparison, also elicited equivalent choices with money. On average people sought to equalize allocations of both pain and money, in a manner which indicated that inequality carried an increasing marginal cost. Preferences for pain were more altruistic than for money, with several participants assigning more than half the pain to themselves. Our data indicate that, given concern for others, the fundamental principle of diminishing marginal utility motivates spreading costs across individuals. A model incorporating this assumption outperformed existing models of social utility in explaining the data. By implementing selected allocations for real, we also found that while inequality per se did not influence pain perception, altruistic behavior had an intrinsic analgesic effect for the recipient.
TL;DR: A computational model which involves tuning motivational arousal to the appraised stressing condition provides a causal explanation of the shift from active to passive coping strategies, i.e. from a condition characterised by high motivational arousal, required to deal with a situation appraised as stressful, to a conditioncharacterised by emotional and motivational withdrawal, required when the stressful situation is appraising as uncontrollable/unavoidable.
Abstract: Appraisal of a stressful situation and the possibility to control or avoid it is thought to involve frontal-cortical mechanisms. The precise mechanism underlying this appraisal and its translation into effective stress coping (the regulation of physiological and behavioural responses) are poorly understood. Here, we propose a computational model which involves tuning motivational arousal to the appraised stressing condition. The model provides a causal explanation of the shift from active to passive coping strategies, i.e. from a condition characterised by high motivational arousal, required to deal with a situation appraised as stressful, to a condition characterised by emotional and motivational withdrawal, required when the stressful situation is appraised as uncontrollable/unavoidable. The model is motivated by results acquired via microdialysis recordings in rats and highlights the presence of two competing circuits dominated by different areas of the ventromedial prefrontal cortex: these are shown having opposite effects on several subcortical areas, affecting dopamine outflow in the striatum, and therefore controlling motivation. We start by reviewing published data supporting structure and functioning of the neural model and present the computational model itself with its essential neural mechanisms. Finally, we show the results of a new experiment, involving the condition of repeated inescapable stress, which validate most of the model’s predictions.
TL;DR: A novel within-subject psychopharmacological and combined functional neuroimaging paradigm is used, investigating the interaction between hedonic salience, dopamine, and response set shifting, distinct from effects on action learning or motor execution.
Abstract: Dopamine is implicated in multiple functions, including motor execution, action learning for hedonically salient outcomes, maintenance, and switching of behavioral response set. Here, we used a novel within-subject psychopharmacological and combined functional neuroimaging paradigm, investigating the interaction between hedonic salience, dopamine, and response set shifting, distinct from effects on action learning or motor execution. We asked whether behavioral performance in response set shifting depends on the hedonic salience of reversal cues, by presenting these as null (neutral) or salient (monetary loss) outcomes. We observed marked effects of reversal cue salience on set-switching, with more efficient reversals following salient loss outcomes. l-Dopa degraded this discrimination, leading to inappropriate perseveration. Generic activation in thalamus, insula, and striatum preceded response set switches, with an opposite pattern in ventromedial prefrontal cortex (vmPFC). However, the behavioral effect of hedonic salience was reflected in differential vmPFC deactivation following salient relative to null reversal cues. l-Dopa reversed this pattern in vmPFC, suggesting that its behavioral effects are due to disruption of the stability and switching of firing patterns in prefrontal cortex. Our findings provide a potential neurobiological explanation for paradoxical phenomena, including maintenance of behavioral set despite negative outcomes, seen in impulse control disorders in Parkinson's disease.