Robust memory of face moral values is encoded in the human caudate tail: a simultaneous EEG-fMRI study.

Moral judgements about people based on their actions is a key component that guides social decision making. It is currently unknown how positive or negative moral judgments associated with a person's face are processed and stored in the brain for a long time. Here, we investigate the long-term memory of moral values associated with human faces using simultaneous EEG-fMRI data acquisition. Results show that only a few exposures to morally charged stories of people are enough to form long-term memories a day later for a relatively large number of new faces. Event related potentials (ERPs) showed a significant differentiation of remembered good vs bad faces over centerofrontal electrode sites (value ERP). EEG-informed fMRI analysis revealed a subcortical cluster centered on the left caudate tail (CDt) as a correlate of the face value ERP. Importantly neither this analysis nor a conventional whole-brain analysis revealed any significant coding of face values in cortical areas, in particular the fusiform face area (FFA). Conversely an fMRI-informed EEG source localization using accurate subject-specific EEG head models also revealed activation in the left caudate tail. Nevertheless, the detected caudate tail region was found to be functionally connected to the FFA, suggesting FFA to be the source of face-specific information to CDt. A further psycho-physiological interaction analysis also revealed task-dependent coupling between CDt and dorsomedial prefrontal cortex (dmPFC), a region previously identified as retaining emotional working memories. These results identify CDt as a main site for encoding the long-term value memories of faces in humans suggesting that moral value of faces activates the same subcortical basal ganglia circuitry involved in processing reward value memory for objects in primates.

Differential Roles of Key Brain Regions: Ventral Tegmental Area, Locus Coeruleus, Dorsal Raphe, Nucleus Accumbens, Caudate Nucleus, and Prefrontal Cortex in Regulating Response to Methylphenidate: Insights from Neuronal and Behavioral Studies in Freely Behaving Rats.

A total of 3102 neurons were recorded before and following acute and chronic methylphenidate (MPD) administration. Acute MPD exposure elicits mainly increases in neuronal and behavioral activity in dose-response characteristics. The response to chronic MPD exposure, as compared to acute 0.6, 2.5, or 10.0 mg/kg MPD administration, elicits electrophysiological and behavioral sensitization in some animals and electrophysiological and behavioral tolerance in others when the neuronal recording evaluations were performed based on the animals' behavioral responses, or amount of locomotor activity, to chronic MPD exposure. The majority of neurons recorded from those expressing behavioral sensitization responded to chronic MPD with further increases in firing rate as compared to the initial MPD responses. The majority of neurons recorded from animals expressing behavioral tolerance responded to chronic MPD with decreases in their firing rate as compared to the initial MPD exposures. Each of the six brain areas studied-the ventral tegmental area, locus coeruleus, dorsal raphe, nucleus accumbens, prefrontal cortex, and caudate nucleus (VTA, LC, DR, NAc, PFC, and CN)-responds significantly (p < 0.001) differently to MPD, suggesting that each one of the above brain areas exhibits different roles in the response to MPD. Moreover, this study demonstrates that it is essential to evaluate neuronal activity responses to psychostimulants based on the animals' behavioral responses to acute and chronic effects of the drug from several brain areas simultaneously to obtain accurate information on each area's role in response to the drug.

The tail of the caudate is sensitive to both gain and loss feedback during information integration categorization.

Although most category learning studies use feedback for training, little attention has been paid to how individuals utilize feedback implemented as gains or losses during categorization. We compared skilled categorization under three different conditions: Gain (earn points for correct answers), Gain and Loss (earn points for correct answers and lose points for wrong answers) and Correct or Wrong (accuracy feedback only). We also manipulated difficulty and point value, with near boundary stimuli having the highest number of points to win or lose, and stimuli far from the boundary having the lowest point value. We found that the tail of the caudate was sensitive to feedback condition, with highest activity when both Gain and Loss feedback were present and least activity when only Gain or accuracy feedback was present. We also found that activity across the caudate was affected by distance from the decision bound, with greatest activity for the near boundary high value stimuli, and lowest for far low value stimuli. Overall these results indicate that the tail of the caudate is sensitive not only to positive rewards but also to loss and punishment, consistent with recent animal research finding tail of the caudate activity in aversive learning.

Comparative Roles of the Caudate and Putamen in the Serial Order of Behavior: Effects of Striatal Glutamate Receptor Blockade on Variable versus Fixed Spatial Self-Ordered Sequencing in Marmosets.

Self-ordered sequencing is an important executive function involving planning and executing a series of steps to achieve goal-directed outcomes. The lateral frontal cortex is implicated in this behavior, but downstream striatal outputs remain relatively unexplored. We trained marmosets on a three-stimulus self-ordered spatial sequencing task using a touch-sensitive screen to explore the role of the caudate nucleus and putamen in random and fixed response arrays. By transiently blocking glutamatergic inputs to these regions, using intrastriatal CNQX microinfusions, we demonstrate that the caudate and putamen are both required for, but contribute differently to, flexible and fixed sequencing. CNQX into either the caudate or putamen impaired variable array accuracy, and infusions into both simultaneously elicited greater impairment. We demonstrated that continuous perseverative errors in variable array were caused by putamen infusions, likely due to interference with the putamen's established role in monitoring motor feedback. Caudate infusions, however, did not affect continuous errors, but did cause an upward trend in recurrent perseveration, possibly reflecting interference with the caudate's established role in spatial working memory and goal-directed planning. In contrast to variable array performance, while both caudate and putamen infusions impaired fixed array responding, the combined effects were not additive, suggesting possible competing roles. Infusions into either region individually, but not simultaneously, led to continuous perseveration. Recurrent perseveration in fixed arrays was caused by putamen, but not caudate, infusions. These results are consistent overall with a role of caudate in planning and flexible responding and the putamen in more rigid habitual or automatic responding.

Human striatal association megaclusters.

The striatum receives projections from multiple regions of the cerebral cortex consistent with the role of the basal ganglia in diverse motor, affective, and cognitive functions. Within the striatum, the caudate receives projections from association cortex, including multiple distinct regions of prefrontal cortex. Building on recent insights about the details of how juxtaposed cortical networks are specialized for distinct aspects of higher-order cognition, we revisited caudate organization using within-individual precision neuroimaging initially in two intensively scanned individuals (each scanned 31 times). Results revealed that the caudate has side-by-side regions that are coupled to at least five distinct distributed association networks, paralleling the organization observed in the cerebral cortex. We refer to these spatial groupings of regions as striatal association megaclusters. Correlation maps from closely juxtaposed seed regions placed within the megaclusters recapitulated the five distinct cortical networks, including their multiple spatially distributed regions. Striatal association megaclusters were explored in 15 additional participants (each scanned at least 8 times), finding that their presence generalizes to new participants. Analysis of the laterality of the regions within the megaclusters further revealed that they possess asymmetries paralleling their cortical counterparts. For example, caudate regions linked to the language network were left lateralized. These results extend the general notion of parallel specialized basal ganglia circuits with the additional discovery that, even within the caudate, there is fine-grained separation of multiple distinct higher-order networks that reflects the organization and lateralization found in the cerebral cortex.NEW & NOTEWORTHY An individualized precision neuroimaging approach reveals juxtaposed zones of the caudate that are coupled with five distinct networks in association cortex. The organization of these caudate zones recapitulates organization observed in the cerebral cortex and extends the notion of specialized basal ganglia circuits.

Visually evoked local field potential changes in the caudate nucleus are remarkably more frequent in awake, behaving cats than in anaesthetized animals.

Previous results show that halothane gas anaesthesia has a suppressive effect on the visually evoked single-cell activities in the feline caudate nucleus (CN). In this study, we asked whether the low-frequency neuronal signals, the local field potentials (LFP) are also suppressed in the CN of anaesthetized animals.To answer this question, we compared the LFPs recorded from the CN of two halothane-anaesthetized (1.0%), paralyzed, and two awake, behaving cats during static and dynamic visual stimulation. The behaving animals were trained to perform a visual fixation task.Our results denoted a lower proportion of significant power changes to visual stimulation in the CN of the anesthetized cats in each frequency range (from delta to beta) of the LFPs, except gamma. These differences in power changes were more obvious in static visual stimulation, but still, remarkable differences were found in dynamic stimulation, too. The largest differences were found in the alpha and beta frequency bands for static stimulation. Concerning dynamic stimulation, the differences were the biggest in the theta, alpha and beta bands.Similar to the single-cell activities, remarkable differences were found between the visually evoked LFP changes in the CN of the anaesthetized, paralyzed and awake, behaving cats. The halothane gas anaesthesia and the immobilization suppressed the significant LFP power alterations in the CN to both static and dynamic stimulation. These results suggest the priority of the application of behaving animals even in the analysis of the visually evoked low-frequency electric signals, the LFPs recorded from the CN.

Neural Representations of Post-Decision Accuracy and Reward Expectation in the Caudate Nucleus and Frontal Eye Field.

Performance monitoring that supports ongoing behavioral adjustments is often examined in the context of either choice confidence for perceptual decisions (i.e., "did I get it right?") or reward expectation for reward-based decisions (i.e., "what reward will I receive?"). However, our understanding of how the brain encodes these distinct evaluative signals remains limited because they are easily conflated, particularly in commonly used two-alternative tasks with symmetric rewards for correct choices. Previously we used a motion-discrimination task with asymmetric rewards to identify neural substrates of forming reward-biased perceptual decisions in the caudate nucleus (part of the striatum in the basal ganglia) and the frontal eye field (FEF, in prefrontal cortex). Here we leveraged this task design to partially decouple estimates of accuracy and reward expectation and examine their impacts on subsequent decisions and their representations in those two brain areas. We identified distinguishable representations of these two evaluative signals in individual caudate and FEF neurons, with regional differences in their distribution patterns and time courses. We observed that well-trained monkeys (both sexes) used both evaluative signals, infrequently but consistently, to adjust their subsequent decisions. We found further that these behavioral adjustments had reliable relationships with the neural representations of both evaluative signals in caudate, but not FEF. These results suggest that the cortico-striatal decision network may use diverse evaluative signals to monitor and adjust decision-making behaviors, adding to our understanding of the different roles that the FEF and caudate nucleus play in a diversity of decision-related computations.

Sex steroid hormones, the estrous cycle, and rapid modulation of glutamatergic synapse properties in the striatal brain regions with a focus on 17ß-estradiol and the nucleus accumbens.

The striatal brain regions encompassing the nucleus accumbens core (NAcc), shell (NAcs) and caudate-putamen (CPu) regulate cognitive functions including motivated behaviors, habit, learning, and sensorimotor action, among others. Sex steroid hormone sensitivity and sex differences have been documented in all of these functions in both normative and pathological contexts, including anxiety, depression and addiction. The neurotransmitter glutamate has been implicated in regulating these behaviors as well as striatal physiology, and there are likewise documented sex differences in glutamate action upon the striatal output neurons, the medium spiny neurons (MSNs). Here we review the available data regarding the role of steroid sex hormones such as 17ß-estradiol (estradiol), progesterone, and testosterone in rapidly modulating MSN glutamatergic synapse properties, presented in the context of the estrous cycle as appropriate. Estradiol action upon glutamatergic synapse properties in female NAcc MSNs is most comprehensively discussed. In the female NAcc, MSNs exhibit development period-specific sex differences and estrous cycle variations in glutamatergic synapse properties as shown by multiple analyses, including that of miniature excitatory postsynaptic currents (mEPSCs). Estrous cycle-differences in NAcc MSN mEPSCs can be mimicked by acute exposure to estradiol or an ERα agonist. The available evidence, or lack thereof, is also discussed concerning estrogen action upon MSN glutamatergic synapse in the other striatal regions as well as the underexplored roles of progesterone and testosterone. We conclude that there is strong evidence regarding estradiol action upon glutamatergic synapse function in female NAcs MSNs and call for more research regarding other hormones and striatal regions.

Anatomical and Functional Comparison of the Caudate Tail in Primates and the Tail of the Striatum in Rodents: Implications for Sensory Information Processing and Habitual Behavior.

The tail of the striatum (TS) is located at the caudal end in the striatum. Recent studies have advanced our knowledge of the anatomy and function of the TS but also raised questions about the differences between rodent and primate TS. In this review, we compare the anatomy and function of the TS in rodent and primate brains. The primate TS is expanded more caudally during brain development in comparison with the rodent TS. Additionally, five sensory inputs from the cortex and thalamus converge in the rodent TS, but this convergence is not observed in the primate TS. The primate TS, including the caudate tail and putamen tail, primarily receives inputs from the visual areas, implying a specialized function in processing visual inputs for action generation. This anatomical difference leads to further discussion of cellular circuit models to comprehend how the primate brain processes a wider range of complex visual stimuli to produce habitual behavior as compared with the rodent brain. Examining these differences and considering possible neural models may provide better understanding of the anatomy and function of the primate TS.

Chemogenetic Disconnection between the Orbitofrontal Cortex and the Rostromedial Caudate Nucleus Disrupts Motivational Control of Goal-Directed Action.

The orbitofrontal cortex (OFC) and its major downstream target within the basal ganglia-the rostromedial caudate nucleus (rmCD)-are involved in reward-value processing and goal-directed behavior. However, a causal contribution of the pathway linking these two structures to goal-directed behavior has not been established. Using the chemogenetic technology of designer receptors exclusively activated by designer drugs with a crossed inactivation design, we functionally and reversibly disrupted interactions between the OFC and rmCD in two male macaque monkeys. We injected an adeno-associated virus vector expressing an inhibitory designer receptor, hM4Di, into the OFC and contralateral rmCD, the expression of which was visualized in vivo by positron emission tomography and confirmed by postmortem immunohistochemistry. Functional disconnection of the OFC and rmCD resulted in a significant and reproducible loss of sensitivity to the cued reward value for goal-directed action. This decreased sensitivity was most prominent when monkeys had accumulated a certain amount of reward. These results provide causal evidence that the interaction between the OFC and the rmCD is needed for motivational control of action on the basis of the relative reward value and internal drive. This finding extends the current understanding of the physiological basis of psychiatric disorders in which goal-directed behavior is affected, such as obsessive-compulsive disorder.SIGNIFICANCE STATEMENT In daily life, we routinely adjust the speed and accuracy of our actions on the basis of the value of expected reward. Abnormalities in these kinds of motivational adjustments might be related to behaviors seen in psychiatric disorders such as obsessive-compulsive disorder. In the current study, we show that the connection from the orbitofrontal cortex to the rostromedial caudate nucleus is essential for motivational control of action in monkeys. This finding expands our knowledge about how the primate brain controls motivation and behavior and provides a particular insight into disorders like obsessive-compulsive disorder in which altered connectivity between the orbitofrontal cortex and the striatum has been implicated.

Fast and slow contributions to decision-making in corticostriatal circuits.

We make complex decisions using both fast judgments and slower, more deliberative reasoning. For example, during value-based decision-making, animals make rapid value-guided orienting eye movements after stimulus presentation that bias the upcoming decision. The neural mechanisms underlying these processes remain unclear. To address this, we recorded from the caudate nucleus and orbitofrontal cortex while animals made value-guided decisions. Using population-level decoding, we found a rapid, phasic signal in caudate that predicted the choice response and closely aligned with animals' initial orienting eye movements. In contrast, the dynamics in orbitofrontal cortex were more consistent with a deliberative system serially representing the value of each available option. The phasic caudate value signal and the deliberative orbitofrontal value signal were largely independent from each other, consistent with value-guided orienting and value-guided decision-making being independent processes.

Neural correlates of the inverse base rate effect.

The inverse base rate effect (IBRE) is a nonrational behavioral phenomenon in predictive learning. Canonically, participants learn that the AB stimulus compound leads to one outcome and that AC leads to another outcome, with AB being presented three times as often as AC. When subsequently presented with BC, the outcome associated with AC is preferentially selected, in opposition to the underlying base rates of the outcomes. The current leading explanation is based on error-driven learning. A key component of this account is prediction error, a concept previously linked to a number of brain areas including the anterior cingulate, the striatum, and the dorsolateral prefrontal cortex. The present work is the first fMRI study to directly examine the IBRE. Activations were noted in brain areas linked to prediction error, including the caudate body, the anterior cingulate, the ventromedial prefrontal cortex, and the right dorsolateral prefrontal cortex. Analyzing the difference in activations for singular key stimuli (B and C), as well as frequency matched controls, supports the predictions made by the error-driven learning account.

Functional connectivity between the caudate and medial prefrontal cortex reflects individual honesty variations in adults and children.

Deception emerges in early childhood and prevails in adults. Activation patterns in previous adults' task-state functional magnetic resonance imaging (fMRI), though sensitive to state honesty on a specific decision, are less reliable reflecting trait honesty. Besides of state honesty, most previous neuroimaging studies about dishonesty suffer the generalization problem due to the major focus on adults with children unexplored. To investigate honesty associated functional brain networks variations, 98 healthy adults (Age: 18-28 y.o.; 49 males and 49 females) were invited to participate in a resting-state functional magnetic resonance imaging (rfMRI) study (Study 1). We investigated how functional connections between the caudate and the medial prefrontal cortex (mPFC) change among adults who differ in self-reported trait honesty. Results showed that adults with higher trait honesty have increased functional connectivity from the caudate to the mPFC, which is identified as an honesty-related hub region in global brain connectivity analysis and connects more tightly to a wide range of brain regions including the amygdala. Study 2 compared functional connectivity between children with high vs. low lying frequencies (Age: 6-16 y.o.; 61 males and 39 females) based on a publicly accessible database of rfMRI. Consistent with findings in adults, increased functional connectivity from the caudate to the mPFC was found in less frequently lying children. Despite different honesty indicators of self-reported honesty trait in adults and parent-reported lying patterns in children, consistent findings have been noted in the two samples with regards to functional connectivity variations between reward-related and self-related brain regions. These findings suggest functional connectivity alterations between the caudate and the mPFC contribute to honesty variations in both adults and children.

Hippocampal and striatal responses during motor learning are modulated by prefrontal cortex stimulation.

While it is widely accepted that motor sequence learning (MSL) is supported by a prefrontal-mediated interaction between hippocampal and striatal networks, it remains unknown whether the functional responses of these networks can be modulated in humans with targeted experimental interventions. The present proof-of-concept study employed a multimodal neuroimaging approach, including functional magnetic resonance (MR) imaging and MR spectroscopy, to investigate whether individually-tailored theta-burst stimulation of the dorsolateral prefrontal cortex can modulate responses in the hippocampus and the basal ganglia during motor learning. Our results indicate that while stimulation did not modulate motor performance nor task-related brain activity, it influenced connectivity patterns within hippocampo-frontal and striatal networks. Stimulation also altered the relationship between the levels of gamma-aminobutyric acid (GABA) in the stimulated prefrontal cortex and learning-related changes in both activity and connectivity in fronto-striato-hippocampal networks. This study provides the first experimental evidence, to the best of our knowledge, that brain stimulation can alter motor learning-related functional responses in the striatum and hippocampus.

Functional parcellation of human and macaque striatum reveals human-specific connectivity in the dorsal caudate.

A wide homology between human and macaque striatum is often assumed as in both the striatum is involved in cognition, emotion and executive functions. However, differences in functional and structural organization between human and macaque striatum may reveal evolutionary divergence and shed light on human vulnerability to neuropsychiatric diseases. For instance, dopaminergic dysfunction of the human striatum is considered to be a pathophysiological underpinning of different disorders, such as Parkinson's disease (PD) and schizophrenia (SCZ). Previous investigations have found a wide similarity in structural connectivity of the striatum between human and macaque, leaving the cross-species comparison of its functional organization unknown. In this study, resting-state functional connectivity (RSFC) derived striatal parcels were compared based on their homologous cortico-striatal connectivity. The goal here was to identify striatal parcels whose connectivity is human-specific compared to macaque parcels. Functional parcellation revealed that the human striatum was split into dorsal, dorsomedial, and rostral caudate and ventral, central, and caudal putamen, while the macaque striatum was divided into dorsal, and rostral caudate and rostral, and caudal putamen. Cross-species comparison indicated dissimilar cortico-striatal RSFC of the topographically similar dorsal caudate. We probed clinical relevance of the striatal clusters by examining differences in their cortico-striatal RSFC and gray matter (GM) volume between patients (with PD and SCZ) and healthy controls. We found abnormal RSFC not only between dorsal caudate, but also between rostral caudate, ventral, central and caudal putamen and widespread cortical regions for both PD and SCZ patients. Also, we observed significant structural atrophy in rostral caudate, ventral and central putamen for both PD and SCZ while atrophy in the dorsal caudate was specific to PD. Taken together, our cross-species comparative results revealed shared and human-specific RSFC of different striatal clusters reinforcing the complex organization and function of the striatum. In addition, we provided a testable hypothesis that abnormalities in a region with human-specific connectivity, i.e., dorsal caudate, might be associated with neuropsychiatric disorders.

Prefronto-Striatal Structural Connectivity Mediates Adult Age Differences in Action Selection.

In complex everyday environments, action selection is critical for optimal goal-directed behavior. This refers to the process of choosing a proper action from the range of possible alternatives. The neural mechanisms underlying action selection and how these are affected by normal aging remain to be elucidated. In the present cross-sectional study, we studied processes of effector selection during a multilimb reaction time task in a lifespan sample of healthy human adults (N = 89; 20-75 years; 48 males, 41 females). Participants were instructed to react as quickly and accurately as possible to visually cued stimuli representing single-limb or combined upper and/or lower limb motions. Diffusion MRI was used to study structural connectivity between prefrontal and striatal regions as critical nodes for action selection. Behavioral findings revealed that increasing age was associated with slowing of action selection performance. At the neural level, aging had a negative impact on prefronto-striatal connectivity. Importantly, mediation analyses revealed that the negative association between action selection performance and age was mediated by prefronto-striatal connectivity, specifically the connections between left rostral medial frontal gyrus and left nucleus accumbens as well as right frontal pole and left caudate. These results highlight the potential role of prefronto-striatal white matter decline in poorer action selection performance of older adults.SIGNIFICANCE STATEMENT As a result of enhanced life expectancy, researchers have devoted increasing attention to the study of age-related alterations in cognitive and motor functions. Here we study associations between brain structure and behavior to reveal the impact of central neural white matter changes as a function of normal aging on action selection performance. We demonstrate the critical role of a reduction in prefronto-striatal structural connectivity in accounting for action selection performance deficits in healthy older adults. Preserving this cortico-subcortical pathway may be critical for behavioral flexibility and functional independence in older age.

Control of response interference: caudate nucleus contributes to selective inhibition.

While the role of cortical regions in cognitive control processes is well accepted, the contribution of subcortical structures (e.g., the striatum), especially to the control of response interference, remains controversial. Therefore, the present study aimed to investigate the cortical and particularly subcortical neural mechanisms of response interference control (including selective inhibition). Thirteen healthy young participants underwent event-related functional magnetic resonance imaging while performing a unimanual version of the Simon task. In this task, successful performance required the resolution of stimulus-response conflicts in incongruent trials by selectively inhibiting interfering response tendencies. The behavioral results show an asymmetrical Simon effect that was more pronounced in the contralateral hemifield. Contrasting incongruent trials with congruent trials (i.e., the overall Simon effect) significantly activated clusters in the right anterior cingulate cortex, the right posterior insula, and the caudate nucleus bilaterally. Furthermore, a region of interest analysis based on previous patient studies revealed that activation in the bilateral caudate nucleus significantly co-varied with a parameter of selective inhibition derived from distributional analyses of response times. Our results corroborate the notion that the cognitive control of response interference is supported by a fronto-striatal circuitry, with a functional contribution of the caudate nucleus to the selective inhibition of interfering response tendencies.

Decoding Odor Mixtures in the Dog Brain: An Awake fMRI Study.

In working and practical contexts, dogs rely upon their ability to discriminate a target odor from distracting odors and other sensory stimuli. Using awake functional magnetic resonance imaging (fMRI) in 18 dogs, we examined the neural mechanisms underlying odor discrimination between 2 odors and a mixture of the odors. Neural activation was measured during the presentation of a target odor (A) associated with a food reward, a distractor odor (B) associated with nothing, and a mixture of the two odors (A+B). Changes in neural activation during the presentations of the odor stimuli in individual dogs were measured over time within three regions known to be involved with odor processing: the caudate nucleus, the amygdala, and the olfactory bulbs. Average activation within the amygdala showed that dogs maximally differentiated between odor stimuli based on the stimulus-reward associations by the first run, while activation to the mixture (A+B) was most similar to the no-reward (B) stimulus. To clarify the neural representation of odor mixtures in the dog brain, we used a random forest classifier to compare multilabel (elemental) versus multiclass (configural) models. The multiclass model performed much better than the multilabel (weighted-F1 0.44 vs. 0.14), suggesting the odor mixture was processed configurally. Analysis of the subset of high-performing dogs' brain classification metrics revealed a network of olfactory information-carrying brain regions that included the amygdala, piriform cortex, and posterior cingulate. These results add further evidence for the configural processing of odor mixtures in dogs and suggest a novel way to identify high-performers based on brain classification metrics.

Frontal eye field and caudate neurons make different contributions to reward-biased perceptual decisions.

Many decisions require trade-offs between sensory evidence and internal preferences. Potential neural substrates include the frontal eye field (FEF) and caudate nucleus, but their distinct roles are not understood. Previously we showed that monkeys' decisions on a direction-discrimination task with asymmetric rewards reflected a biased accumulate-to-bound decision process (Fan et al., 2018) that was affected by caudate microstimulation (Doi et al., 2020). Here we compared single-neuron activity in FEF and caudate to each other and to accumulate-to-bound model predictions derived from behavior. Task-dependent neural modulations were similar in both regions. However, choice-selective neurons in FEF, but not caudate, encoded behaviorally derived biases in the accumulation process. Baseline activity in both regions was sensitive to reward context, but this sensitivity was not reliably associated with behavioral biases. These results imply distinct contributions of FEF and caudate neurons to reward-biased decision-making and put experimental constraints on the neural implementation of accumulation-to-bound-like computations.

Spatiotemporal dissociation of fMRI activity in the caudate nucleus underlies human de novo motor skill learning.

Motor skill learning involves a complex process of generating novel movement patterns guided by evaluative feedback, such as a reward. Previous literature has suggested anteroposteriorly separated circuits in the striatum to be implicated in early goal-directed and later automatic stages of motor skill learning, respectively. However, the involvement of these circuits has not been well elucidated in human de novo motor skill learning, which requires learning arbitrary action-outcome associations and value-based action selection. To investigate this issue, we conducted a human functional MRI (fMRI) experiment in which participants learned to control a computer cursor by manipulating their right fingers. We discovered a double dissociation of fMRI activity in the anterior and posterior caudate nucleus, which was associated with performance in the early and late learning stages. Moreover, cognitive and sensorimotor cortico-caudate interactions predicted individual learning performance. Our results suggest parallel cortico-caudate networks operating in different stages of human de novo motor skill learning.