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Hypotheses and beliefs guide credit assignment – the process of determining which previous events or actions caused an outcome. Adaptive hypothesis formation and testing are crucial in uncertain and changing environments in which associations and meanings are volatile. Despite primates’ abilities to form and test hypotheses, establishing what is causally responsible for the occurrence of particular outcomes remains a fundamental challenge for credit assignment and learning. Hypotheses about what surprises are due to stochasticity inherent in an environment as opposed to real, systematic changes are necessary for identifying the environment’s predictive features, but are often hard to test. We review evidence that two highly interconnected frontal cortical regions, anterior cingulate cortex and ventrolateral prefrontal area 47/12o, provide a biological substrate for linking two crucial components of hypothesis-formation and testing: the control of information seeking and credit assignment. Neuroimaging, targeted disruptions, and neurophysiological studies link an anterior cingulate – 47/12o circuit to generation of exploratory behaviour, non-instrumental information seeking, and interpretation of subsequent feedback in the service of credit assignment. Our observations support the idea that information seeking and credit assignment are linked at the level of neural circuits and explain why this circuit is important for ensuring behaviour is flexible and adaptive.

Contains fulltext : 230049.pdf (Publisher’s version ) (Closed access) Comparative neuroscience is entering the era of big data. New high-throughput methods and data-sharing initiatives have resulted in the availability of large, digital data sets containing many types of data from ever more species. Here, we present a framework for exploiting the new possibilities offered. The multimodality of the data allows vertical translations, which are comparisons of different aspects of brain organization within a single species and across scales. Horizontal translations compare particular aspects of brain organization across species, often by building abstract feature spaces. Combining vertical and horizontal translations allows for more sophisticated comparisons, including relating principles of brain organization across species by contrasting horizontal translations, and for making formal predictions of unobtainable data based on observed results in a model species. 18 p.

People and other animals learn the values of choices by observing the contingencies between them and their outcomes. However, decisions are not guided by choice-linked reward associations alone; macaques also maintain a memory of the general, average reward rate – the global reward state – in an environment. Remarkably, global reward state affects the way that each choice outcome is valued and influences future decisions so that the impact of both choice success and failure is different in rich and poor environments. Successful choices are more likely to be repeated but this is especially the case in rich environments. Unsuccessful choices are more likely to be abandoned but this is especially likely in poor environments. Functional magnetic resonance imaging (fMRI) revealed two distinct patterns of activity, one in anterior insula and one in the dorsal raphe nucleus, that track global reward state as well as specific outcome events., Wittmann and colleagues show that not only single outcome events but also the global reward state (GRS) impact learning in macaques; low GRS drives explorative choices. Analyses of macaque BOLD signal reveals that GRS impacts activity in the anterior insula as well as the dorsal raphe nucleus.

The decision that it is worth doing something rather than nothing is a core yet understudied feature of voluntary behaviour. Here we study “willingness to act”, the probability of making a response given the context. Human volunteers encountered opportunities to make effortful actions in order to receive rewards, while watching a movie inside a 7 T MRI scanner. Reward and other context features determined willingness-to-act. Activity in the habenula tracked trial-by-trial variation in participants’ willingness-to-act. The anterior insula encoded individual environment features that determined this willingness. We identify a multi-layered network in which contextual information is encoded in the anterior insula, converges on the habenula, and is then transmitted to the supplementary motor area, where the decision is made to either act or refrain from acting via the nigrostriatal pathway., A crucial component of voluntary behaviour is deciding that it is worth doing something rather than nothing. Here the authors show the brain network that encodes this decision, which includes the habenula and anterior insula.

Contains fulltext : 237221.pdf (Publisher’s version ) (Open Access) The macaque middle superior temporal sulcus shares functional properties with the human temporoparietal junction supporting mentalizing. The ability to attribute thoughts to others, also called theory of mind (TOM), has been extensively studied in humans; however, its evolutionary origins have been challenged. Computationally, the basis of TOM has been interpreted within the predictive coding framework and associated with activity in the temporoparietal junction (TPJ). Here, we revealed, using a nonlinguistic task and functional magnetic resonance imaging, that activity in a region of the macaque middle superior temporal cortex was specifically modulated by the predictability of social situations. As in human TPJ, this region could be distinguished from other temporal regions involved in face processing. Our result suggests the existence of a precursor for the TOM ability in the last common ancestor of human and Old World monkeys. 11 p.

Significance Oscillatory activity is prominent in the brain, and one hypothesis is that it is, in part, due to the nature of coupling or interaction patterns between brain areas. We tested this hypothesis by manipulating the strength of coupling between two brain regions (ventral premotor cortex, PMv, and motor cortex, M1) in two directions (increase or decrease) while carefully controlling for the impact each manipulation had on activity in each area. We looked at the PMv–M1 connection because it is the major cortical route by which prefrontal cortex might influence, inhibit, and curtail action-related activity in M1. Manipulating PMv–M1 coupling in accordance with Hebbian-like spike-timing–dependent plasticity resulted in changes in beta and theta frequencies linked to action control., The origins of oscillatory activity in the brain are currently debated, but common to many hypotheses is the notion that they reflect interactions between brain areas. Here, we examine this possibility by manipulating the strength of coupling between two human brain regions, ventral premotor cortex (PMv) and primary motor cortex (M1), and examine the impact on oscillatory activity in the motor system measurable in the electroencephalogram. We either increased or decreased the strength of coupling while holding the impact on each component area in the pathway constant. This was achieved by stimulating PMv and M1 with paired pulses of transcranial magnetic stimulation using two different patterns, only one of which increases the influence exerted by PMv over M1. While the stimulation protocols differed in their temporal patterning, they were comprised of identical numbers of pulses to M1 and PMv. We measured the impact on activity in alpha, beta, and theta bands during a motor task in which participants either made a preprepared action (Go) or withheld it (No-Go). Augmenting cortical connectivity between PMv and M1, by evoking synchronous pre- and postsynaptic activity in the PMv–M1 pathway, enhanced oscillatory beta and theta rhythms in Go and No-Go trials, respectively. Little change was observed in the alpha rhythm. By contrast, diminishing the influence of PMv over M1 decreased oscillatory beta and theta rhythms in Go and No-Go trials, respectively. This suggests that corticocortical communication frequencies in the PMv–M1 pathway can be manipulated following Hebbian spike-timing–dependent plasticity.

Humans learn about the environment either directly by interacting with it or indirectly by seeking information about it from social sources such as conspecifics. The degree of confidence in the information obtained through either route should determine the impact that it has on adapting and changing behaviour. We examined whether and how behavioural and neural computations differ during non-social learning as opposed to learning from social sources. Trial-wise confidence judgments about non-social and social information sources offered a window into this learning process. Despite matching exactly the statistical features of social and non-social conditions, confidence judgments were more accurate and less changeable when they were made about social as opposed to non-social information sources. In addition to subjective reports of confidence, differences were also apparent in the Bayesian estimates of participants’ subjective beliefs. Univariate activity in dorsomedial prefrontal cortex (dmPFC) and posterior temporo-parietal junction (pTPJ) more closely tracked confidence about social as opposed to non-social information sources. In addition, the multivariate patterns of activity in the same areas encoded identities of social information sources compared to non-social information sources.

Learning the structure of the world can be driven by reinforcement but also occurs incidentally through experience. Reinforcement learning theory has provided insight into how prediction errors drive updates in beliefs but less attention has been paid to the knowledge resulting from such learning. Here we contrast associative structures formed through reinforcement and experience of task statistics. BOLD neuroimaging in human volunteers demonstrates rigid representations of rewarded sequences in temporal pole and posterior orbito-frontal cortex, which are constructed backwards from reward. By contrast, medial prefrontal cortex and a hippocampal-amygdala border region carry reward-related knowledge but also flexible statistical knowledge of the currently relevant task model. Intriguingly, ventral striatum encodes prediction error responses but not the full RL- or statistically derived task knowledge. In summary, representations of task knowledge are derived via multiple learning processes operating at different time scales that are associated with partially overlapping and partially specialized anatomical regions., Associative learning occurs through reinforcement mechanisms as well as incidentally through experience of statistical relationships. Here, the authors report that these two learning processes are associated with specialized anatomical regions that operate at different time scales.

There has been debate about whether addition of an irrelevant distractor option to an otherwise binary decision influences which of the two choices is taken. We show that disparate views on this question are reconciled if distractors exert two opposing but not mutually exclusive effects. Each effect predominates in a different part of decision space: 1) a positive distractor effect predicts high-value distractors improve decision-making; 2) a negative distractor effect, of the type associated with divisive normalisation models entails decreased accuracy with increased distractor values. Here, we demonstrate both distractor effects and show disruption of medial intraparietal area (MIP) by transcranial magnetic stimulation (TMS) increases positive distractor effects at the expense of negative distractor effects. Furthermore, individuals with larger MIP volumes are also less susceptible to the disruption induced by TMS. These findings also demonstrate a causal link between MIP and the impact of distractors on decision-making.

While traditional economic models assume that agents are self-interested, humans and most non-human primates are social species. Therefore, many of decisions they make require the integration of information about other social agents. This study asks to what extent information about social status and the social context in which decisions are taken impact on reward-guided decisions in rhesus macaques. We tested 12 monkeys of varying dominance status in several experimental versions of a two-choice task in which reward could be delivered to self only, only another monkey, both the self and another monkey, or neither. Results showed dominant animals were more prone to make prosocial choices than subordinates, but only when the decision was between a reward for self only and a reward for both self and other. If the choice was between a reward for self only and a reward for other only, no animal expressed altruistic behaviour. Finally, prosocial choices were true social decisions as they were strikingly reduced when the social partner was replaced by a non-social object. These results showed that as in humans, rhesus macaques' social decisions are adaptive and modulated by social status and the cost associated with being prosocial. This article is part of the theme issue ‘Existence and prevalence of economic behaviours among non-human primates’.

Contains fulltext : 228321.pdf (Publisher’s version ) (Closed access) Neural mechanisms that mediate the ability to make value-guided decisions have received substantial attention in humans and animals. Experiments in animals typically involve long training periods. By contrast, choices in the real world often need to be made between new options spontaneously. It is therefore possible that the neural mechanisms targeted in animal studies differ from those required for new decisions, which are typical of human imaging studies. Here we show that the primate medial frontal cortex (MFC) is involved in making new inferential choices when the options have not been previously experienced. Macaques spontaneously inferred the values of new options via similarities with the component parts of previously encountered options. Functional magnetic resonance imaging (fMRI) suggested that this ability was mediated by the MFC, which is rarely investigated in monkeys; MFC activity reflected different processes of comparison for unfamiliar and familiar options. Multidimensional representations of options in the MFC used a coding scheme resembling that of grid cells, which is well known in spatial navigation, to integrate dimensions in this non-physical space during novel decision-making. By contrast, the orbitofrontal cortex held specific object-based value representations. In addition, minimally invasive ultrasonic disruption of MFC, but not adjacent tissue, altered the estimation of novel choice values. 5 p.

Several studies have established specific relationships between White Matter (WM) and behaviour. However, these studies have typically focussed on fractional anisotropy (FA), a neuroimaging metric that is sensitive to multiple tissue properties, making it difficult to identify what biological aspects of WM may drive such relationships. Here, we carry out a pre-registered assessment of WM-behaviour relationships in 50 healthy individuals across multiple behavioural and anatomical domains, and complementing FA with myelin-sensitive quantitative MR modalities (MT, R1, R2*).Surprisingly, we only find support for predicted relationships between FA and behaviour in one of three pre-registered tests. For one behavioural domain, where we failed to detect an FA-behaviour correlation, we instead find evidence for a correlation between behaviour and R1. This hints that multimodal approaches are able to identify a wider range of WM-behaviour relationships than focusing on FA alone.To test whether a common biological substrate such as myelin underlies WM-behaviour relationships, we then ran joint multimodal analyses, combining across all MRI parameters considered. No significant multimodal signatures were found and power analyses suggested that sample sizes of 40 to 200 may be required to detect such joint multimodal effects, depending on the task being considered.These results demonstrate that FA-behaviour relationships from the literature can be replicated, but may not be easily generalisable across domains. Instead, multimodal microstructural imaging may be best placed to detect a wider range of WM-behaviour relationships, as different MRI modalities provide distinct biological sensitivities. Our findings highlight a broad heterogeneity in WM’s relationship with behaviour, suggesting that variable biological effects may be shaping their interaction.HighlightsPre-registered testing of microstructural imaging across modalities (FA, MT, R1, R2*) to test WM-behaviour relationships.Partial support for FA-behaviour relationships hypothesised based on previous literature.Multimodal approaches can help detect WM-behaviour relationships that are not detected with FA alone.Sample sizes of 40 to 200 may be needed to detect myelin-behaviour relationships in joint multimodal analyses.Variable biological effects may be shaping WM-behaviour relationships.

Contains fulltext : 235985.pdf (Publisher’s version ) (Open Access) To navigate social environments, people must simultaneously hold representations about their own and others' abilities. During self-other mergence, people estimate others' abilities not only on the basis of the others' past performance, but the estimates are also influenced by their own performance. For example, if we perform well, we overestimate the abilities of those with whom we are co-operating and underestimate competitors. Self-other mergence is associated with specific activity patterns in the dorsomedial prefrontal cortex (dmPFC). Using a combination of non-invasive brain stimulation, functional magnetic resonance imaging, and computational modeling, we show that dmPFC neurostimulation silences these neural signatures of self-other mergence in relation to estimation of others' abilities. In consequence, self-other mergence behavior increases, and our assessments of our own performance are projected increasingly onto other people. This suggests an inherent tendency to form interdependent social representations and a causal role of the dmPFC in separating self and other representations. 9 p.

Description, Noninvasive ultrasound stimulation of primate area 47/12o disrupts credit assignment–related behavior and neural activity., Credit assignment is the association of specific instances of reward to the specific events, such as a particular choice, that caused them. Without credit assignment, choice values reflect an approximate estimate of how good the environment was when the choice was made—the global reward state—rather than exactly which outcome the choice caused. Combined transcranial ultrasound stimulation (TUS) and functional magnetic resonance imaging in macaques demonstrate credit assignment–related activity in prefrontal area 47/12o, and when this signal was disrupted with TUS, choice value representations across the brain were impaired. As a consequence, behavior was no longer guided by choice value, and decision-making was poorer. By contrast, global reward state–related activity in the adjacent anterior insula remained intact and determined decision-making after prefrontal disruption.

Brain perturbation studies allow detailed causal inferences of behavioral and neural processes. Because the combination of brain perturbation methods and neural measurement techniques is inherently challenging, research in humans has predominantly focused on non-invasive, indirect brain perturbations, or neurological lesion studies. Non-human primates have been indispensable as a neurobiological system that is highly similar to humans while simultaneously being more experimentally tractable, allowing visualization of the functional and structural impact of systematic brain perturbation. This review considers the state of the art in non-human primate brain perturbation with a focus on approaches that can be combined with neuroimaging. We consider both non-reversible (lesions) and reversible or temporary perturbations such as electrical, pharmacological, optical, optogenetic, chemogenetic, pathway-selective, and ultrasound based interference methods. Method-specific considerations from the research and development community are offered to facilitate research in this field and support further innovations. We conclude by identifying novel avenues for further research and innovation and by highlighting the clinical translational potential of the methods. ispartof: NEUROIMAGE vol:235 ispartof: location:United States status: published

Environments furnish multiple information sources for making predictions about future events. Here we use behavioural modelling and functional magnetic resonance imaging to describe how humans select predictors that might be most relevant. First, during early encounters with potential predictors, participants’ selections were explorative and directed towards subjectively uncertain predictors (positive uncertainty effect). This was particularly the case when many future opportunities remained to exploit knowledge gained. Then, preferences for accurate predictors increased over time, while uncertain predictors were avoided (negative uncertainty effect). The behavioural transition from positive to negative uncertainty-driven selections was accompanied by changes in the representations of belief uncertainty in ventromedial prefrontal cortex (vmPFC). The polarity of uncertainty representations (positive or negative encoding of uncertainty) changed between exploration and exploitation periods. Moreover, the two periods were separated by a third transitional period in which beliefs about predictors’ accuracy predominated. The vmPFC signals a multiplicity of decision variables, the strength and polarity of which vary with behavioural context. Trudel et al. find that the ventromedial prefrontal cortex carries multiple decision variables, the strength and polarity of which vary according to their relevance to the context of exploration, exploitation and the transition between these states.

Summary More than one type of probability must be considered when making decisions. It is as necessary to know one’s chance of performing choices correctly as it is to know the chances that desired outcomes will follow choices. We refer to these two choice contingencies as internal and external probability. Neural activity across many frontal and parietal areas reflected internal and external probabilities in a similar manner during decision-making. However, neural recording and manipulation approaches suggest that one area, the anterior lateral prefrontal cortex (alPFC), is highly specialized for making prospective, metacognitive judgments on the basis of internal probability; it is essential for knowing which decisions to tackle, given its assessment of how well they will be performed. Its activity predicted prospective metacognitive judgments, and individual variation in activity predicted individual variation in metacognitive judgments. Its disruption altered metacognitive judgments, leading participants to tackle perceptual decisions they were likely to fail., Highlights • People prospectively estimate their “internal probability” of deciding correctly • Prefrontal area, alPFC, accumulates internal probability information • alPFC disruption impairs prospective metacognition but not perceptual decisions • alPFC is crucial for estimating performance prior to tackling a perceptual decision, Miyamoto et al. found that activity in the anterior lateral prefrontal cortex (alPFC; area 47) reflects accumulation of information for prospective metacognitive decisions and predicts prospective metacognitive performance. Disruption of the alPFC by transcranial magnetic stimulation impairs accurate estimation of the probability of success prior to tackling difficult decisions with perceptual ambiguity.

International audience; The value of a third potential option or distractor can alter the way in which decisions are made between two other options. Two hypotheses have received empirical support: that a high value distractor improves the accuracy with which decisions between two other options are made and that it impairs accuracy. Recently, however, it has been argued that neither observation is replicable. Inspired by neuroimaging data showing that high value distractors have different impacts on prefrontal and parietal regions, we designed a dual route decision-making model that mimics the neural signals of these regions. Here we show in the dual route model and empirical data that both enhancement and impairment effects are robust phenomena but predominate in different parts of the decision space defined by the options’ and the distractor’s values. However, beyond these constraints, both effects co-exist under similar conditions. Moreover, both effects are robust and observable in six experiments.

SummaryOscillatory activity may reflect interactions between brain areas[1]. Here we tested whether inducing corticocortical plasticity in a specific set of connections changes oscillatory activity and cortico-cortical interactions and, if this is the case, whether the changes manifest in a manner that is behaviour state-dependent. We either increased or decreased the influence of activity in human ventral premotor cortex (PMv) over activity in primary motor cortex (M1) using cortico-cortical paired associative stimulation (ccPAS)[2, 3]. Before and after stimulation participants performed a Go/No-Go task. While M1 TMS pulses revealed the excitatory state of the motor system at specific time points, the electroencephalogram (EEG) revealed the evolution of oscillatory activity dynamics in the motor system over several hundreds of milliseconds before, during, and after each movement. Augmenting cortical connectivity between PMv and M1, by evoking synchronous pre- and postsynaptic activity in the PMv-M1 pathways, led to a state-dependent modulation of the causal influence of PMv over M1, and at the same time, enhanced oscillatory beta and theta rhythms in Go and No-Go trials, respectively. No changes were observed in the alpha rhythm. The plasticity induction effect was dependent on PMv-M1 stimulation order; the opposite patterns of results were observed after an equal amount of stimulation of PMv and M1 but applied in a temporal pattern that did not augment PMv’s influence over M1. These results are consistent with Hebbian principles of synaptic plasticity[4] and show that artificial manipulation of cortico-cortical connectivity produces state-dependent functional changes in the spectral fingerprints of the motor circuit.

Significance Decision-making studies often focus on brain mechanisms for selecting between goals and actions; however, another important, and often neglected, aspect of decision-making in humans concerns whether, at any given point in time, it is worth making any action at all. We showed that a considerable portion of the variance in when voluntary actions are emitted can be explained by a simple model that that takes into account key features of the current environment. By using ultrahigh-field MRI we identified a multilayered circuit in the human brain originating far beyond the medial frontal areas typically linked to human voluntary action starting in the basal forebrain and brain stem, converging in the dopaminergic midbrain, and only then projecting to striatum and cortex., Decisions about when to act are critical for survival in humans as in animals, but how a desire is translated into the decision that an action is worth taking at any particular point in time is incompletely understood. Here we show that a simple model developed to explain when animals decide it is worth taking an action also explains a significant portion of the variance in timing observed when humans take voluntary actions. The model focuses on the current environment’s potential for reward, the timing of the individual’s own recent actions, and the outcomes of those actions. We show, by using ultrahigh-field MRI scanning, that in addition to anterior cingulate cortex within medial frontal cortex, a group of subcortical structures including striatum, substantia nigra, basal forebrain (BF), pedunculopontine nucleus (PPN), and habenula (HB) encode trial-by-trial variation in action time. Further analysis of the activity patterns found in each area together with psychophysiological interaction analysis and structural equation modeling suggested a model in which BF integrates contextual information that will influence the decision about when to act and communicates this information, in parallel with PPN and HB influences, to nigrostriatal circuits. It is then in the nigrostriatal circuit that action initiation per se begins.

Social behaviour is coordinated by a network of brain regions, including those involved in the perception of social stimuli and those involved in complex functions like inferring perceptual and mental states and controlling social interactions. The properties and function of many of these regions in isolation is relatively well understood but little is known about how these regions interact whilst processing dynamic social interactions. To investigate whether social network connectivity is modulated by social context we collected fMRI data from monkeys viewing “affiliative”, “aggressive”, or “ambiguous” social interactions. We show activation relating to the perception of social interactions along both banks of the superior temporal sulcus, parietal, medial and lateral PFC and caudate nucleus. Within this network we demonstrate that fronto-temporal connectivity are significantly modulated by social context. Crucially, we link the observation of specific behaviours to changes in connectivity within our network. Viewing aggressive or affiliative behaviour was associated with a limited increase in temporo-temporal and premotor-temporal connectivity respectively. By contrast, viewing ambiguous interactions was associated with a pronounced increase in cingulate-cingulate, temporo-temporal, and cingulate-temporal connectivity. We hypothesise that this widespread network synchronisation occurs when cingulate and temporal areas coordinate their activity when more difficult social inferences are made.

Contains fulltext : 217200.pdf (Publisher’s version ) (Closed access) Nonhuman primate neuroimaging is on the cusp of a transformation, much in the same way its human counterpart was in 2010, when the Human Connectome Project was launched to accelerate progress. Inspired by an open data-sharing initiative, the global community recently met and, in this article, breaks through obstacles to define its ambitions. 4 p.

Studies of selective attention typically consider the role of task goals or physical salience, but recent work has shown that attention can also be captured by previously reward-associated stimuli, even if they are currently task-irrelevant. One theory underlying this value-driven attentional capture (VDAC) is that reward-associated stimulus representations may undergo plasticity in sensory cortex, thereby automatically capturing attention during early processing. To test this, we used magnetoencephalography to probe whether stimulus location and identity representations in sensory cortex are modulated by reward learning. We furthermore investigated the time-course of these neural effects, and their relationship to behavioural VDAC. Male and female human participants first learned stimulus-reward associations. Next, we measured VDAC in a separate task by presenting these stimuli in the absence of reward contingency, and probing their effects on the processing of separate target stimuli presented at different time lags. Using time-resolved multivariate pattern analysis, we found that learned value modulated the spatial selection of previously rewarded stimuli in posterior visual and parietal cortex from ∼260ms after stimulus onset. This value modulation was related to the strength of participants’ behavioural VDAC effect and persisted into subsequent target processing. Furthermore, we found a spatially invariant value signal from ∼340ms. Importantly, learned value did not influence cortical signatures of early processing (i.e., earlier than ∼200ms), nor did it influence the decodability of the identity of previously rewarded stimuli. Our results suggest that VDAC is underpinned by learned value signals which modulate spatial selection throughout posterior visual and parietal cortex. We further suggest that VDAC can occur in the absence of changes in early visual processing in cortex.Significance statementAttention is our ability to focus on relevant information at the expense of irrelevant information. It can be affected by previously learned but currently irrelevant stimulus-reward associations, a phenomenon termed “value-driven attentional capture” (VDAC). The neural mechanisms underlying VDAC remain unclear. It has been speculated that reward learning induces visual cortical plasticity which modulates early visual processing to capture attention. Although we find that learned value modulates spatial signals in visual cortical areas, an effect which correlates with VDAC, we find no relevant signatures of changes in early visual processing in cortex.

Summary The medial frontal cortex has been linked to voluntary action, but an explanation of why decisions to act emerge at particular points in time has been lacking. We show that, in macaques, decisions about whether and when to act are predicted by a set of features defining the animal’s current and past context; for example, respectively, cues indicating the current average rate of reward and recent previous voluntary action decisions. We show that activity in two brain areas—the anterior cingulate cortex and basal forebrain—tracks these contextual factors and mediates their effects on behavior in distinct ways. We use focused transcranial ultrasound to selectively and effectively stimulate deep in the brain, even as deep as the basal forebrain, and demonstrate that alteration of activity in the two areas changes decisions about when to act., Highlights • Likelihood and timing of voluntary action in macaques can be partially predicted • Recent experience and present context influence when voluntary action occurs • A basal forebrain-cingulate circuit mediated effects of these factors on behavior • Stimulation of this circuit by ultrasound changed decisions about when to act, Deciding when to act is crucial for animals’ survival. Khalighinejad et al. used neuroimaging and ultrasound to identify a basal forebrain-cingulate circuit that tracks contextual factors in animals’ environments and mediates their effects on animals’ decisions about when to act.

The survival of an organism depends on the ability to make adaptive decisions to achieve the needs of the organism: where to get food, who to mate with, and how to evade predators. Decision-making is a term used to describe a collection of behavioral and/or computational functions that guide the selection of an option amongst a set of alternatives. Some of these functions may include calculating the costs and benefits of a particular action, evaluating differences in value of each of the alternative outcomes and the likelihood of receiving a particular outcome, using past experiences to generate predictions or expectations about action-outcome associations, and/or integration of past experiences to make novel inferences that can be used in new environments. There is considerable interest in understanding the neurobiological mechanisms that mediate these decision-making functions and recent advances in behavioral approaches, neuroscience techniques, and neuroimaging measures have begun to develop mechanistic links between biology, reward, and decision making. This multidisciplinary work holds great promise for elucidating the biological mechanisms mediating decision-making deficits in normal and abnormal states. The multidisciplinary studies included in this Collection provide new insights into the neuroscience of decision making and reward.

Contains fulltext : 201971.pdf (Publisher’s version ) (Open Access) The causal role of an area within a neural network can be determined by interfering with its activity and measuring the impact. Many current reversible manipulation techniques have limitations preventing their application, particularly in deep areas of the primate brain. Here, we demonstrate that a focused transcranial ultrasound stimulation (TUS) protocol impacts activity even in deep brain areas: a subcortical brain structure, the amygdala (experiment 1), and a deep cortical region, the anterior cingulate cortex (ACC, experiment 2), in macaques. TUS neuromodulatory effects were measured by examining relationships between activity in each area and the rest of the brain using functional magnetic resonance imaging (fMRI). In control conditions without sonication, activity in a given area is related to activity in interconnected regions, but such relationships are reduced after sonication, specifically for the targeted areas. Dissociable and focal effects on neural activity could not be explained by auditory confounds. 14 p.

To understand brain circuits it is necessary both to record and manipulate their activity. Transcranial ultrasound stimulation (TUS) is a promising non-invasive brain stimulation technique. To date, investigations report short-lived neuromodulatory effects, but to deliver on its full potential for research and therapy, ultrasound protocols are required that induce longer-lasting ‘offline’ changes. Here, we present a TUS protocol that modulates brain activation in macaques for more than one hour after 40 s of stimulation, while circumventing auditory confounds. Normally activity in brain areas reflects activity in interconnected regions but TUS caused stimulated areas to interact more selectively with the rest of the brain. In a within-subject design, we observe regionally specific TUS effects for two medial frontal brain regions – supplementary motor area and frontal polar cortex. Independently of these site-specific effects, TUS also induced signal changes in the meningeal compartment. TUS effects were temporary and not associated with microstructural changes., eLife digest Ultrasound is well known for making visible what is hidden, for example, when giving parents a glimpse of their child before birth. But researchers are now using these high-frequency sound waves – beyond the range of human hearing – for a wholly different purpose: to manipulate the activity of the brain. Conventional brain stimulation techniques use electric currents or magnetic fields to alter brain activity. These techniques, however, have limitations. They can only reach the surface of the brain and are not particularly precise. By contrast, beams of ultrasound can be focused at a millimetre scale, even deep within the brain. Ultrasound thus has the potential to provide new insights into how the brain works. Most studies of ultrasound stimulation have looked at what happens to the brain during the stimulation itself. But could ultrasound also induce longer-lasting changes in brain activity? Changes that persist after the stimulation has ended would be valuable for research. They would also make it more likely that we could use ultrasound to treat brain disorders by changing brain activity. Verhagen, Gallea et al. used a brain scanner to measure brain activity in macaque monkeys after ultrasound stimulation. The results showed that 40 seconds of repetitive ultrasound changed brain activity for up to two hours. Ultrasound caused the stimulated brain area to interact more selectively with the rest of the brain. Notably, only the stimulated area changed its activity in this way. This helps rule out the possibility that the changes reflect non-specific effects. If the monkeys had been able to hear the ultrasound, for example, it would have changed the activity of the parts of the brain related to hearing. Most important of all, the changes were reversible and did not harm the brain. The results of Verhagen, Gallea et al. show that repetitive ultrasound can induce long-lasting alterations in brain activity. It can target areas deep within the brain, including those that are out of reach with other techniques. If this procedure also shows longer-lasting effects in people, it could yield valuable insights into the links between brain and behaviour. It could also help us develop new treatments for neurological and psychiatric disorders.

The neural mechanisms mediating sensory-guided decision-making have received considerable attention, but animals often pursue behaviors for which there is currently no sensory evidence. Such behaviors are guided by internal representations of choice values that have to be maintained even when these choices are unavailable. We investigated how four macaque monkeys maintained representations of the value of counterfactual choices—choices that could not be taken at the current moment but which could be taken in the future. Using functional magnetic resonance imaging, we found two different patterns of activity co-varying with values of counterfactual choices in a circuit spanning the hippocampus, the anterior lateral prefrontal cortex and the anterior cingulate cortex. Anterior cingulate cortex activity also reflected whether the internal value representations would be translated into actual behavioral change. To establish the causal importance of the anterior cingulate cortex for this translation process, we used a novel technique, transcranial focused ultrasound stimulation, to reversibly disrupt anterior cingulate cortex activity. Fouragnan et al. used neuroimaging and ultrasound neuromodution in non-human primates to demonstrate the causal role of the anterior cingulate cortex in translating counterfactual values in future choices.

Summary Non-human primate neuroimaging is a rapidly growing area of research that promises to transform and scale translational and cross-species comparative neuroscience. Unfortunately, the technological and methodological advances of the past two decades have outpaced the accrual of data, which is particularly challenging given the relatively few centers that have the necessary facilities and capabilities. The PRIMatE Data Exchange (PRIME-DE) addresses this challenge by aggregating independently acquired non-human primate magnetic resonance imaging (MRI) datasets and openly sharing them via the International Neuroimaging Data-sharing Initiative (INDI). Here, we present the rationale, design, and procedures for the PRIME-DE consortium, as well as the initial release, consisting of 25 independent data collections aggregated across 22 sites (total = 217 non-human primates). We also outline the unique pitfalls and challenges that should be considered in the analysis of non-human primate MRI datasets, including providing automated quality assessment of the contributed datasets., Highlights • Openly shared, large non-human primate neuroimaging data resource • Multiple imaging modalities contributed from investigators around the world • Quality assessments of the dataset • Discussed pitfalls and challenges in analyzing the non-human primate MRI data, The PRIMatE Data Exchange (PRIME-DE) consortium is an open science resource for the neuroimaging community aiming to facilitate efforts to map the non-human primate connectome. It aggregates and shares anatomical, functional, and diffusion MRI datasets from laboratories throughout the world.

Introduction Mood instability is a prominent feature of bipolar disorder (BD) and other affective disorders [1]. Recent research has begun to highlight a strong association between mood instability and cognitive processing, particularly within the decision-making and reward-processing domain, suggesting the ability for mood to bias perception of reward and loss, and to induce risk-taking behaviour [2,3]. However, whilst this has provided an interesting first-line understanding of the phenotypic nature of BD, research to date has failed to explore the complexities of this relationship over a longitudinal basis. Modern technologies, such as remote online platforms, can address this issue by using high frequency and prospective monitoring. This is particularly important given the dynamic nature of mood instability [4] and the expanding need to understand its underlying neural mechanisms in order to develop new and better-suited targets for treatment [1]. Aims Given the emergence of new technologies and the ubiquity of internet access, we aimed to assess whether remote monitoring can capture dynamic mood instability in individuals showing dimensions of BD as measured by the Mood Disorder Questionnaire (MDQ) screening tool, and whether such instability is reflected in risk-taking behaviour in a longitudinal decision-making and reward-processing task. Methods Remote mood and cognitive monitoring over 10 weeks, as part of the Cognition and Mood Evolution across Time (COMET) study. We analysed data from 37 participants scoring >7 on the MDQ (high MDQ group) and 35 matched controls (MDQ Results The high MDQ group showed greater variability in their PANAS positive affect, F (1)=10.56, p F (1)=15.01, p F (1)=14.46, p Whilst the high MDQ participants did not show a significant bias towards riskier decisions in the gambling task in these preliminary analyses, all participants appeared to make less risky choices, F (5.00)=7.42, p F (4.81)=2.50, p Conclusions Longitudinal daily remote mood monitoring captures mood instability in individuals showing dimensions of BD. Concurrent monitoring of cognition, particularly within the reward processing domain, suggests a pattern of dynamic decision-making and warrants further sophisticated analyses to better elucidate the cognitive underpinnings of such mood instability. Nevertheless, findings add to the increasing evidence for mood instability as a marker for BD, and suggest the efficacy of remote monitoring as a modern phenotyping technology in prospectively assessing mood instability and associated cognition. This will aid in the search for biomarkers that can be used in determining the effectiveness of current treatments and in the development of novel therapeutic targets.

Contains fulltext : 150234.pdf (Publisher’s version ) (Closed access) The great promise of comparative neuroscience is to understand why brains differ by investigating the relations between variations in the organization of different brains, their evolutionary history, and their current ecological niche. For this approach to be successful, the organization of different brains needs to be quantifiable. Here, we present an approach to formally comparing the connectivity of different cortical areas across different brains. We exploit the fact that cortical regions can be characterized by the unique pattern of connectivity, the so-called connectivity fingerprint. By comparing connectivity fingerprints between cortical areas in the human and non-human primate brain we can identify between-species homologs, but also illustrate that is driving differences between species. We illustrate the approach by comparing the organization of the frontal cortex between humans and macaques, showing general similarities combined with some differences in the lateral frontal pole. 8 p.

Non-human primate neuroimaging is a rapidly growing area of research that promises to transform and scale translational and cross-species comparative neuroscience.Unfortunately, the technological and methodological advances of the past two decades have outpaced the accrual of data, which is particularly challenging given the relatively few centers that have the necessary facilities and capabilities. The PRIMate Data Exchange (PRIME-DE) addresses this challenge by aggregating independently acquired non-human primate magnetic resonance imaging (MRI) datasets and openly sharing them via the International Neuroimaging Data-sharing Initiative (INDI). Here, we present the rationale, design and procedures for the PRIME-DE consortium, as well as the initial release, consisting of 13 independent data collections aggregated across 11 sites (total = 98 macaque monkeys). We also outline the unique pitfalls and challenges that should be considered in the analysis of the non-human primate MRI datasets, including providing automated quality assessment of the contributed datasets.

The orbitofrontal cortex is critical for goal-directed behavior. Recent work in macaques has suggested the lateral orbitofrontal cortex (lOFC) is relatively more concerned with assignment of credit for rewards to particular choices during value-guided learning, whereas the medial orbitofrontal cortex (often referred to as ventromedial prefrontal cortex in humans; vmPFC/mOFC) is involved in constraining the decision to the relevant options. We examined whether people with damage restricted to subregions of prefrontal cortex showed the patterns of impairment observed in prior investigations of the effects of lesions to homologous regions in macaques. Groups of patients with either lOFC (predominantly right hemisphere), mOFC/vmPFC, or dorsomedial prefrontal (DMF), and a comparison group of healthy age- and education-matched controls performed a probabilistic 3-choice decision-making task. We report anatomically specific patterns of impairment. We found that credit assignment, as indexed by the normal influence of contingent relationships between choice and reward, is reduced in lOFC patients compared with Controls and mOFC/vmPFC patients. Moreover, the effects of reward contingency on choice were similar for patients with lesions in DMF or mOFC/vmPFC, compared with Controls. By contrast, mOFC/vmPFC-lesioned patients made more stochastic choices than Controls when the decision was framed by valuable distracting alternatives, suggesting that value comparisons were no longer independent of irrelevant options. Once again, there was evidence of regional specialization: patients with lOFC lesions were unimpaired relative to Controls. As in macaques, human lOFC and mOFC/vmPFC are necessary for contingent learning and value-guided decision-making, respectively. SIGNIFICANCE STATEMENT The lateral and medial regions of the orbitofrontal cortex are cytoarchitectonically distinct and have different anatomical connections. Previous investigations in macaques have shown these anatomical differences are accompanied by functional specialization for learning and decision-making. Here, for the first time, we test the predictions made by macaque studies in an experiment with humans with frontal lobe lesions, asking whether behavioral impairments can be linked to lateral or medial orbitofrontal cortex. Using equivalent tasks and computational analyses, our findings broadly replicate the pattern reported after selective lesions in monkeys. Patients with lateral orbitofrontal damage had impaired credit assignment, whereas damage to medial orbitofrontal cortex meant that patients were more likely to be distracted by irrelevant options.

Decisions are based on value expectations derived from experience. We show that dorsal anterior cingulate cortex and three other brain regions hold multiple representations of choice value based on different timescales of experience organized in terms of systematic gradients across the cortex. Some parts of each area represent value estimates based on recent reward experience while others represent value estimates based on experience over the longer term. The value estimates within these areas interact with one another according to their temporal scaling. Some aspects of the representations change dynamically as the environment changes. The spectrum of value estimates may act as a flexible selection mechanism for combining experience-derived value information with other aspects of value to allow flexible and adaptive decisions in changing environments., Activity in dorsal anterior cingulate cortex (dACC) dynamically tracks the value of the choice after every outcome. Here the authors report that dACC represents topographic maps of value estimates for different learning rates and interacts with similar maps in other areas at the time of the decision.

Dorsal anterior cingulate cortex (dACC) mediates updating and maintenance of cognitive models of the world used to drive adaptive reward-guided behavior. We investigated the neurochemical underpinnings of this process. We used magnetic resonance spectroscopy in humans, to measure levels of glutamate and GABA in dACC. We examined their relationship to neural signals in dACC, measured with fMRI, and cognitive task performance. Both inhibitory and excitatory neurotransmitters in dACC were predictive of the strength of neural signals in dACC and behavioral adaptation. Glutamate levels were correlated, first, with stronger neural activity representing information to be learnt about the tasks’ costs and benefits and, second, greater use of this information in the guidance of behavior. GABA levels were negatively correlated with the same neural signals and the same indices of behavioral influence. Our results suggest that glutamate and GABA in dACC affect the encoding and use of past experiences to guide behavior. DOI: http://dx.doi.org/10.7554/eLife.20365.001

Summary Sometimes when a choice is made, the outcome is not guaranteed and there is only a probability of its occurrence. Each individual’s attitude to probability, sometimes called risk proneness or aversion, has been assumed to be static. Behavioral ecological studies, however, suggest such attitudes are dynamically modulated by the context an organism finds itself in; in some cases, it may be optimal to pursue actions with a low probability of success but which are associated with potentially large gains. We show that human subjects rapidly adapt their use of probability as a function of current resources, goals, and opportunities for further foraging. We demonstrate that dorsal anterior cingulate cortex (dACC) carries signals indexing the pressure to pursue unlikely choices and signals related to the taking of such choices. We show that dACC exerts this control over behavior when it, rather than ventromedial prefrontal cortex, interacts with posterior cingulate cortex., Highlights • Against common belief, risk preference is not fixed but is dynamically updated • Environments exert varying “risk pressure” tracked by ACC • Risk-related values and behavior are then regulated by ACC • Two mechanisms regulate competition for control of behavior between ACC and vmPFC, The propensity to take risks has been considered a fixed personality trait. By contrast, Kolling et al. show that people modulate their degree of risk taking from moment to moment and that this ability is related to a suite of signals in the anterior cingulate cortex.

Top–down control is critical to select goal-directed actions in changeable environments, particularly when several conflicting options compete for selection. In humans, this control system is thought to involve an inhibitory mechanism that suppresses the motor representation of unwanted responses to favor selection of the most appropriate action. Here, we aimed to evaluate the role of a region of the medial frontal cortex, the pre-SMA, in this form of inhibition by using a double coil TMS protocol combining repetitive TMS (rTMS) over the pre-SMA and a single-pulse TMS over the primary motor cortex (M1) during a visuomotor task that required participants to choose between a left or right button press according to an imperative cue. M1 stimulation allowed us to assess changes in motor excitability related to selected and nonselected (unwanted) actions, and rTMS was used to produce transient disruption of pre-SMA functioning. We found that when rTMS was applied over pre-SMA, inhibition of the nonselected movement representation was reduced. Importantly, this effect was only observed when the imperative cue produced a substantial amount of competition between the response alternatives. These results are consistent with previous studies pointing to a role of pre-SMA in competition resolution. In addition, our findings indicate that this function of pre-SMA involves the control of inhibitory influences directed at unwanted action representations.