The influence of transcranial direct current stimulation to the trigeminal nerve on attention and arousal.

One mechanism by which transcranial direct current stimulation (tDCS) has been proposed to improve attention is by transcutaneous stimulation of cranial nerves, thereby activating the locus coeruleus (LC). Specifically, placement of the electrodes over the frontal bone and mastoid is thought to facilitate current flow across the face as a path of least resistance. The face is innervated by the trigeminal nerve, and the trigeminal nerve is interconnected with the LC. In this study, we tested whether stimulating the trigeminal nerve impacts indices of LC activity and performance on a sustained attention task. We replicated previous research that shows deterioration in task performance, increases in the rate of task-unrelated thoughts, and reduced pupil responses due to time on task irrespective of tDCS condition (sham, anodal, and cathodal stimulation). Importantly, tDCS did not influence pupil dynamics (pretrial or stimulus-evoked), self-reported attention state, nor task performance in active versus sham stimulation conditions. The findings reported here are consistent with theories about arousal centered on a hypothesized link between LC activity indexed by pupil size, task performance, and self-reported attention state but fail to support hypotheses that tDCS over the trigeminal nerve influences indices of LC function.

Midbrain-Hippocampus Structural Connectivity Selectively Predicts Motivated Memory Encoding.

Motivation is a powerful driver of learning and memory. Functional MRI studies show that interactions among the dopaminergic midbrain substantia nigra/ventral tegmental area (SN/VTA), hippocampus, and nucleus accumbens (NAc) are critical for motivated memory encoding. However, it is not known whether these effects are transient and purely functional, or whether individual differences in the structure of this circuit underlie motivated memory encoding. To quantify individual differences in structure, diffusion-weighted MRI and probabilistic tractography were used to quantify SN/VTA-striatum and SN/VTA-hippocampus pathways associated with motivated memory encoding in humans. Male and female participants completed a motivated source memory paradigm. During encoding, words were randomly assigned to one of three conditions, reward ($1.00), control ($0.00), or punishment (-$1.00). During retrieval, participants were asked to retrieve item and source information of the previously studied words and were rewarded or penalized according to their performance. Source memory for words assigned to both reward and punishment conditions was greater than those for control words, but there were no differences in item memory based on value. Anatomically, probabilistic tractography results revealed a heterogeneous, topological arrangement of the SN/VTA. Tract density measures of SN/VTA-hippocampus pathways were positively correlated with individual differences in reward-and-punishment-modulated memory performance, whereas density of SN/VTA-striatum pathways showed no association. This novel finding suggests that pathways emerging from the human SV/VTA are anatomically separable and functionally heterogeneous. Individual differences in structural connectivity of the dopaminergic hippocampus-VTA loop are selectively associated with motivated memory encoding.SIGNIFICANCE STATEMENT Functional MRI studies show that interactions among the SN/VTA, hippocampus, and NAc are critical for motivated memory encoding. This has led to competing theories that posit either SN/VTA-NAc reward prediction errors or SN/VTA-hippocampus signals underlie motivated memory encoding. Additionally, it is not known whether these effects are transient and purely functional or whether individual differences in the structure of these circuits underlie motivated memory encoding. Using diffusion-weighted MRI and probabilistic tractography, we show that tract density measures of SN/VTA-hippocampus pathways are positively correlated with motivated memory performance, whereas density of SN/VTA-striatum pathways show no association. This finding suggests that anatomic individual differences of the dopaminergic hippocampus-VTA loop are selectively associated with motivated memory encoding.

Neural correlates underlying the effect of reward value on recognition memory.

The prioritized encoding and retrieval of valuable information is an essential aspect of human memory. We used electroencephalography (EEG) to determine which of two hypothesized processes underlies the influence of reward value on episodic memory. One hypothesis is that value engages prefrontal executive control processes, so that valuable stimuli engage an elaborative rehearsal strategy that benefits memory. A second hypothesis is that value acts through the reward-related midbrain dopamine system to modulate synaptic plasticity in hippocampal and cortical efferents, thereby benefiting memory encoding. We used a value-directed recognition memory (VDR) paradigm in which participants encoded words assigned different point values and aimed to maximize the point value of subsequently recognized words. Subjective states of recollection (i.e., "remember") and familiarity (i.e., "know") were assessed at retrieval. Words assigned higher values at study were recognized more effectively than words assigned lower values, due to increased "remember" responses but no difference in "know" responses. Greater value was also associated with larger amplitudes of an EEG component at retrieval that indexes recollection (parietal old/new component), but had no relationship with a component that indexes familiarity (FN400 component). During encoding, we assessed a late frontal positivity (frontal slow wave, FSW) that has been related to elaborative rehearsal strategies and an early parietal component (P3) thought to index dopamine driven attention allocation. Our findings indicate that the effect of value on recognition memory is primarily driven by the dopamine-driven reward valuation system (P3) with no discernible effect on rehearsal processes (FSW).

Victory is its own reward: oxytocin increases costly competitive behavior in schizophrenia.

BACKGROUND: Aberrant sensitivity to social reward may be an important contributor to abnormal social behavior that is a core feature of schizophrenia. The neuropeptide oxytocin impacts the salience of social information across species, but its effect on social reward in schizophrenia is unknown. METHODS: We used a competitive economic game and computational modeling to examine behavioral dynamics and oxytocin effects on sensitivity to social reward among 39 men with schizophrenia and 54 matched healthy controls. In a randomized, double-blind study, participants received one dose of oxytocin (40 IU) or placebo and completed a 35-trial Auction Game that quantifies preferences for monetary v. social reward. We analyzed bidding behavior using multilevel linear mixed models and reinforcement learning models. RESULTS: Bidding was motivated by preferences for both monetary and social reward in both groups, but bidding dynamics differed: patients initially overbid less compared to controls, and across trials, controls decreased their bids while patients did not. Oxytocin administration was associated with sustained overbidding across trials, particularly in patients. This drug effect was driven by a stronger preference for winning the auction, regardless of monetary consequences. Learning rate and response variability did not differ between groups or drug condition, suggesting that differences in bidding derive primarily from differences in the subjective value of social rewards. CONCLUSIONS: Our findings suggest that schizophrenia is associated with diminished motivation for social reward that may be increased by oxytocin administration.

On the Neural and Mechanistic Bases of Self-Control.

Intertemporal choice requires a dynamic interaction between valuation and deliberation processes. While evidence identifying candidate brain areas for each of these processes is well established, the precise mechanistic role carried out by each brain region is still debated. In this article, we present a computational model that clarifies the unique contribution of frontoparietal cortex regions to intertemporal decision making. The model we develop samples reward and delay information stochastically on a moment-by-moment basis. As preference for the choice alternatives evolves, dynamic inhibitory processes are executed by way of asymmetric lateral inhibition. We find that it is these lateral inhibition processes that best explain the contribution of frontoparietal regions to intertemporal decision making exhibited in our data.

Beyond Reward Prediction Errors: Human Striatum Updates Rule Values During Learning.

Humans naturally group the world into coherent categories defined by membership rules. Rules can be learned implicitly by building stimulus-response associations using reinforcement learning or by using explicit reasoning. We tested if the striatum, in which activation reliably scales with reward prediction error, would track prediction errors in a task that required explicit rule generation. Using functional magnetic resonance imaging during a categorization task, we show that striatal responses to feedback scale with a "surprise" signal derived from a Bayesian rule-learning model and are inconsistent with RL prediction error. We also find that striatum and caudal inferior frontal sulcus (cIFS) are involved in updating the likelihood of discriminative rules. We conclude that the striatum, in cooperation with the cIFS, is involved in updating the values assigned to categorization rules when people learn using explicit reasoning.

Learning concepts when instances never repeat.

Three experiments explored the learning of categories where the training instances either repeated in each training block or appeared only once during the entire learning phase, followed by a classification transfer (Experiment 1) or a recognition transfer test (Experiments 2 and 3). Subjects received training instances from either two (Experiment 2) or three categories (Experiments 1-3) for either 15 or 20 training blocks. The results showed substantial learning in each experiment, with the notable result that learning was not slowed in the non-repeating condition in any of the three experiments. Furthermore, subsequent transfer was marginally better in the non-repeating condition. The recognition results showed that subjects in the repeat condition had substantial memory for the training instances, whereas subjects in the non-repeat condition had no measurable memory for the training instances, as measured either by hit and false-alarm rates or by signal detectability measures. These outcomes are consistent with prototype models of category learning, at least when patterns never repeat in learning, and place severe constraints on exemplar views that posit transfer mechanisms to stored individual traces. A formal model, which incorporates changing similarity relationships during learning, was shown to explain the major results.

Adolescent impatience decreases with increased frontostriatal connectivity.

Adolescence is a developmental period associated with an increase in impulsivity. Impulsivity is a multidimensional construct, and in this study we focus on one of the underlying components: impatience. Impatience can result from (i) disregard of future outcomes and/or (ii) oversensitivity to immediate rewards, but it is not known which of these evaluative processes underlie developmental changes. To distinguish between these two causes, we investigated developmental changes in the structural and functional connectivity of different frontostriatal tracts. We report that adolescents were more impatient on an intertemporal choice task and reported less future orientation, but not more present hedonism, than young adults. Developmental increases in structural connectivity strength in the right dorsolateral prefrontal tract were related to increased negative functional coupling with the striatum and an age-related decrease in discount rates. Our results suggest that mainly increased control, and the integration of future-oriented thought, drives the reduction in impatience across adolescence.

Mere Exposure: Preference Change for Novel Drinks Reflected in Human Ventral Tegmental Area.

Preferences for novel stimuli tend to develop slowly over many exposures. Psychological accounts of this effect suggest that it depends on changes in the brain's valuation system. Participants consumed a novel fluid daily for 10 days and underwent fMRI on the first and last days. We hypothesized that changes in activation in areas associated with the dopamine system would accompany changes in preference. The change in activation in the ventral tegmental area (VTA) between sessions scaled with preference change. Furthermore, a network comprising the sensory thalamus, posterior insula, and ventrolateral striatum showed differential connectivity with the VTA that correlated with individual changes in preference. Our results suggest that the VTA is centrally involved in both assigning value to sensory stimuli and influencing downstream regions to translate these value signals into subjective preference. These results have important implications for models of dopaminergic function and behavioral addiction.

More Is Meaningful: The Magnitude Effect in Intertemporal Choice Depends on Self-Control.

Impulsivity is a variable behavioral trait that depends on numerous factors. For example, increasing the absolute magnitude of available choice options promotes farsighted decisions. We argue that this magnitude effect arises in part from differential exertion of self-control as the perceived importance of the choice increases. First, we demonstrated that frontal executive-control areas were more engaged for more difficult decisions and that this effect was enhanced for high-magnitude rewards. Second, we showed that increased hunger, which is associated with lower self-control, reduced the magnitude effect. Third, we tested an intervention designed to increase self-control and showed that it reduced the magnitude effect. Taken together, our findings challenge existing theories about the magnitude effect and suggest that visceral and cognitive factors affecting choice may do so by influencing self-control.

Behavioral and neural correlates of increased self-control in the absence of increased willpower.

People often exert willpower to choose a more valuable delayed reward over a less valuable immediate reward, but using willpower is taxing and frequently fails. In this research, we demonstrate the ability to enhance self-control (i.e., forgoing smaller immediate rewards in favor of larger delayed rewards) without exerting additional willpower. Using behavioral and neuroimaging data, we show that a reframing of rewards (i) reduced the subjective value of smaller immediate rewards relative to larger delayed rewards, (ii) increased the likelihood of choosing the larger delayed rewards when choosing between two real monetary rewards, (iii) reduced the brain reward responses to immediate rewards in the dorsal and ventral striatum, and (iv) reduced brain activity in the dorsolateral prefrontal cortex (a correlate of willpower) when participants chose the same larger later rewards across the two choice frames. We conclude that reframing can promote self-control while avoiding the need for additional willpower expenditure.

Distinct midbrain and habenula pathways are involved in processing aversive events in humans.

Emerging evidence implicates the midbrain dopamine system and its interactions with the lateral habenula in processing aversive information and learning to avoid negative outcomes. We examined neural responses to unexpected, aversive events using methods specialized for imaging the midbrain and habenula in humans. Robust activation to aversive relative to neutral events was observed in the habenula and two regions within the ventral midbrain: one located within the ventral tegmental area (VTA) and the other in the substantia nigra (SN). Aversive processing increased functional connectivity between the VTA and the habenula, putamen, and medial prefrontal cortex, whereas the SN exhibited a different pattern of functional connectivity. Our findings provide evidence for a network comprising the VTA and SN, the habenula, and mesocorticolimbic structures that supports processing aversive events in humans.

The effect of cognitive challenge on delay discounting.

Recent findings suggest that the dorsolateral prefrontal cortex (DLPFC), a region consistently associated with impulse control, is vulnerable to transient suppression of its activity and attendant functions by excessive stress and/or cognitive demand. Using functional magnetic resonance imaging, we show that a capacity-exceeding cognitive challenge induced decreased DLPFC activity and correlated increases in the preference for immediately available rewards. Consistent with growing evidence of a link between working memory capacity and delay discounting, the effect was inversely proportional to baseline performance on a working memory task. Subjects who performed well on the working memory task had unchanged, or even decreased, delay discounting rates, suggesting that working memory ability may protect cognitive control from cognitive challenge.

Why more is better: Simultaneous modeling of EEG, fMRI, and behavioral data.

The need to test a growing number of theories in cognitive science has led to increased interest in inferential methods that integrate multiple data modalities. In this manuscript, we show how a method for integrating three data modalities within a single framework provides (1) more detailed descriptions of cognitive processes and (2) more accurate predictions of unobserved data than less integrative methods. Specifically, we show how combining either EEG and fMRI with a behavioral model can perform substantially better than a behavioral-data-only model in both generative and predictive modeling analyses. We then show how a trivariate model - a model including EEG, fMRI, and behavioral data - outperforms bivariate models in both generative and predictive modeling analyses. Together, these results suggest that within an appropriate modeling framework, more data can be used to better constrain cognitive theory, and to generate more accurate predictions for behavioral and neural data.

High-definition tDCS alters impulsivity in a baseline-dependent manner.

In intertemporal choice (ITC), people discount future rewards in proportion to the time delay until reward receipt. Despite recent non-invasive brain stimulation studies suggesting a general causal link between dorsolateral prefrontal cortex (dlPFC) activity and ITC impulsivity, results regarding the functional specificity of dlPFC are mixed. We used high-definition transcranial direct current stimulation (HD-tDCS) to map changes in causal impulsivity through bi-directional modulation of left and right dlPFC during ITC. Model-free and model-based analyses demonstrated that anodal and cathodal stimulation of left dlPFC, but not right dlPFC, decreased and increased impulsivity, respectively. Critically, an individual differences analysis revealed that modulation of impulsivity was contingent on participants' baseline impulsivity. Overall, our results might reconcile the discrepancies in the existing literature and suggest a baseline-dependent role for left dlPFC during ITC.

Connectivity strength of dissociable striatal tracts predict individual differences in temporal discounting.

Large individual differences exist in the ability to delay gratification for the sake of satisfying longer-term goals. These individual differences are commonly assayed by studying intertemporal preferences, as revealed by choices between immediate and delayed rewards. In the brain, reward-based and goal-oriented decisions are believed to rely on the striatum and its interactions with other cortical and subcortical networks. However, it remains unknown which specific cortical-striatal tracts are involved in intertemporal decision making. We use connectivity analyses in both structural and functional MRI to further our understanding of the relationship between distinct corticostriatal networks and intertemporal preferences in humans. Our results revealed distinct striatal pathways that are differentially related to delay discounting. Structural and functional connectivity between striatum and lateral prefrontal cortex was associated with increased patience, whereas connectivity between subcortical areas and striatum was associated with increased impulsivity. These findings provide novel insights into how the anatomy and functioning of striatal circuits mediate individual differences in intertemporal choice.

The neural basis of value accumulation in intertemporal choice.

Making intertemporal choices (choosing between rewards available at different points in time) requires determining and comparing the subjective values of available rewards. Several studies have found converging evidence identifying the neural systems that encode subjective value in intertemporal choice. However, the neural mechanisms responsible for the process that produces intertemporal decisions on the basis of subjective values have not been investigated. Using model-based and connectivity analyses of functional magnetic resonance imaging data, we investigated the neural mechanisms underlying the value-accumulation process by which subjective value guides intertemporal decisions. Our results show that the dorsomedial frontal cortex, bilateral posterior parietal cortex, and bilateral lateral prefrontal cortex are all involved in the accumulation of subjective value for the purpose of action selection. Our findings establish a mechanistic framework for understanding frontoparietal contributions to intertemporal choice and suggest that value-accumulation processes in the frontoparietal cortex may be a general mechanism for value-based choice.

Neural correlates of reinforcement learning and social preferences in competitive bidding.

In competitive social environments, people often deviate from what rational choice theory prescribes, resulting in losses or suboptimal monetary gains. We investigate how competition affects learning and decision-making in a common value auction task. During the experiment, groups of five human participants were simultaneously scanned using MRI while playing the auction task. We first demonstrate that bidding is well characterized by reinforcement learning with biased reward representations dependent on social preferences. Indicative of reinforcement learning, we found that estimated trial-by-trial prediction errors correlated with activity in the striatum and ventromedial prefrontal cortex. Additionally, we found that individual differences in social preferences were related to activity in the temporal-parietal junction and anterior insula. Connectivity analyses suggest that monetary and social value signals are integrated in the ventromedial prefrontal cortex and striatum. Based on these results, we argue for a novel mechanistic account for the integration of reinforcement history and social preferences in competitive decision-making.

Dissociating motivation from reward in human striatal activity.

Neural activity in the striatum has consistently been shown to scale with the value of anticipated rewards. As a result, it is common across a number of neuroscientific subdiscliplines to associate activation in the striatum with anticipation of a rewarding outcome or a positive emotional state. However, most studies have failed to dissociate expected value from the motivation associated with seeking a reward. Although motivation generally scales positively with increases in potential reward, there are circumstances in which this linkage does not apply. The current study dissociates value-related activation from that induced by motivation alone by employing a task in which motivation increased as anticipated reward decreased. This design reverses the typical relationship between motivation and reward, allowing us to differentially investigate fMRI BOLD responses that scale with each. We report that activity scaled differently with value and motivation across the striatum. Specifically, responses in the caudate and putamen increased with motivation, whereas nucleus accumbens activity increased with expected reward. Consistent with this, self-report ratings indicated a positive association between caudate and putamen activity and arousal, whereas activity in the nucleus accumbens was more associated with liking. We conclude that there exist regional limits on inferring reward expectation from striatal activation.