The well-worn route revisited: Striatal and hippocampal system contributions to familiar route navigation.

Classic research has shown a division in the neuroanatomical structures that support flexible (e.g., short-cutting) and habitual (e.g., familiar route following) navigational behavior, with hippocampal-caudate systems associated with the former and putamen systems with the latter. There is, however, disagreement about whether the neural structures involved in navigation process particular forms of spatial information, such as associations between constellations of cues forming a cognitive map, versus single landmark-action associations, or alternatively, perform particular reinforcement learning algorithms that allow the use of different spatial strategies, so-called model-based (flexible) or model-free (habitual) forms of learning. We sought to test these theories by asking participants (N = 24) to navigate within a virtual environment through a previously learned, 9-junction route with distinctive landmarks at each junction while undergoing functional magnetic resonance imaging (fMRI). In a series of probe trials, we distinguished knowledge of individual landmark-action associations along the route versus knowledge of the correct sequence of landmark-action associations, either by having absent landmarks, or "out-of-sequence" landmarks. Under a map-based perspective, sequence knowledge would not require hippocampal systems, because there are no constellations of cues available for cognitive map formation. Within a learning-based model, however, responding based on knowledge of sequence would require hippocampal systems because prior context has to be utilized. We found that hippocampal-caudate systems were more active in probes requiring sequence knowledge, supporting the learning-based model. However, we also found greater putamen activation in probes where navigation based purely on sequence memory could be planned, supporting models of putamen function that emphasize its role in action sequencing.

Neurofeedback Training versus Treatment-as-Usual for Alcohol Dependence: Results of an Early-Phase Randomized Controlled Trial and Neuroimaging Correlates.

INTRODUCTION: Alcohol dependence is one of the most common substance use disorders, and novel treatment options are urgently needed. Neurofeedback training (NFT) based on real-time functional magnetic resonance imaging (rtf-MRI) has emerged as an attractive candidate for add-on treatments in psychiatry, but its use in alcohol dependence has not been formally investigated in a clinical trial. We investigated the use of rtfMRI-based NFT to prevent relapse in alcohol dependence. METHODS: Fifty-two alcohol-dependent patients from the UK who had completed a detoxification program were randomly assigned to a treatment group (receiving rtfMRI NFT in addition to standard care) or the control group (receiving standard care only). At baseline, alcohol consumption was assessed as the primary outcome measure and a variety of psychological, behavioral, and neural parameters as secondary outcome measures to determine feasibility and secondary training effects. Participants in the treatment group underwent 6 NFT sessions over 4 months and were trained to downregulate their brain activation in the salience network in the presence of alcohol stimuli and to upregulate frontal activation in response to pictures related to positive goals. Four, 8, and 12 months after baseline assessment, both groups were followed up with a battery of clinical and psychometric tests. RESULTS: Primary outcome measures showed very low relapse rates for both groups. Analysis of neural secondary outcome measures indicated that the majority of patients modulated the salience system in the desired directions, by decreasing activity in response to alcohol stimuli and increasing activation in response to positive goals. The intervention had a good safety and acceptability profile. CONCLUSION: We demonstrated that rtfMRI-neurofeedback targeting hyperactivity of the salience network in response to alcohol cues is feasible in currently abstinent patients with alcohol dependence.

Evidence of absence: no relationship between behaviourally measured prediction error response and schizotypy.

INTRODUCTION: The predictive processing framework has attracted much interest in the field of schizophrenia research in recent years, with an increasing number of studies also carried out in healthy individuals with nonclinical psychosis-like experiences. The current research adopted a continuum approach to psychosis and aimed to investigate different types of prediction error responses in relation to psychometrically defined schizotypy. METHODS: One hundred and two healthy volunteers underwent a battery of behavioural tasks including (a) a force-matching task, (b) a Kamin blocking task, and (c) a reversal learning task together with three questionnaires measuring domains of schizotypy from different approaches. RESULTS: Neither frequentist nor Bayesian statistical methods supported the notion that alterations in prediction error responses were related to schizotypal traits in any of the three tasks. CONCLUSIONS: These null results suggest that deficits in predictive processing associated with clinical states of psychosis are not always present in healthy individuals with schizotypal traits.

Associations between polygenic risk for schizophrenia and brain function during probabilistic learning in healthy individuals.

A substantial proportion of schizophrenia liability can be explained by additive genetic factors. Risk profile scores (RPS) directly index risk using a summated total of common risk variants weighted by their effect. Previous studies suggest that schizophrenia RPS predict alterations to neural networks that support working memory and verbal fluency. In this study, we apply schizophrenia RPS to fMRI data to elucidate the effects of polygenic risk on functional brain networks during a probabilistic-learning neuroimaging paradigm. The neural networks recruited during this paradigm have previously been shown to be altered to unmedicated schizophrenia patients and relatives of schizophrenia patients, which may reflect genetic susceptibility. We created schizophrenia RPS using summary data from the Psychiatric Genetic Consortium (Schizophrenia Working Group) for 83 healthy individuals and explore associations between schizophrenia RPS and blood oxygen level dependency (BOLD) during periods of choice behavior (switch-stay) and reflection upon choice outcome (reward-punishment). We show that schizophrenia RPS is associated with alterations in the frontal pole (PWHOLE-BRAIN-CORRECTED  = 0.048) and the ventral striatum (PROI-CORRECTED  = 0.036), during choice behavior, but not choice outcome. We suggest that the common risk variants that increase susceptibility to schizophrenia can be associated with alterations in the neural circuitry that support the processing of changing reward contingencies. Hum Brain Mapp 37:491-500, 2016. © 2015 Wiley Periodicals, Inc.

Neural Mechanisms Underlying Visual Short-Term Memory Gain for Temporally Distinct Objects.

Recent research has shown that visual short-term memory (VSTM) can substantially be improved when the to-be-remembered objects are split in 2 half-arrays (i.e., sequenced) or the entire array is shown twice (i.e., repeated), rather than presented simultaneously. Here we investigate the hypothesis that sequencing and repeating displays overcomes attentional "bottlenecks" during simultaneous encoding. Using functional magnetic resonance imaging, we show that sequencing and repeating displays increased brain activation in extrastriate and primary visual areas, relative to simultaneous displays (Study 1). Passively viewing identical stimuli did not increase visual activation (Study 2), ruling out a physical confound. Importantly, areas of the frontoparietal attention network showed increased activation in repetition but not in sequential trials. This dissociation suggests that repeating a display increases attentional control by allowing attention to be reallocated in a second encoding episode. In contrast, sequencing the array poses fewer demands on control, with competition from nonattended objects being reduced by the half-arrays. This idea was corroborated by a third study in which we found optimal VSTM for sequential displays minimizing attentional demands. Importantly these results provide support within the same experimental paradigm for the role of stimulus-driven and top-down attentional control aspects of biased competition theory in setting constraints on VSTM.

On the variability of the McGurk effect: audiovisual integration depends on prestimulus brain states.

The McGurk effect demonstrates the influence of visual cues on auditory perception. Mismatching information from both sensory modalities can fuse to a novel percept that matches neither the auditory nor the visual stimulus. This illusion is reported in 60-80% of trials. We were interested in the impact of ongoing brain oscillations-indexed by fluctuating local excitability and interareal synchronization-on upcoming perception of identical stimuli. The perception of the McGurk effect is preceded by high beta activity in parietal, frontal, and temporal areas. Beta activity is pronounced in the left superior temporal gyrus (lSTG), which is considered as a site of multimodal integration. This area is functionally (de)coupled to distributed frontal and temporal regions in illusion trials. The disposition to fuse multisensory information is enhanced as the lSTG is more strongly coupled to frontoparietal regions. Illusory perception is accompanied by a decrease in poststimulus theta-band activity in the cuneus, precuneus, and left superior frontal gyrus. Event-related activity in the left middle temporal gyrus is pronounced during illusory perception. Thus, the McGurk effect depends on fluctuating brain states suggesting that functional connectedness of left STS at a prestimulus stage is crucial for an audiovisual percept.

Early adolescents show sustained susceptibility to cognitive interference by emotional distractors.

A child's ability to continuously pay attention to a cognitive task is often challenged by distracting events. Distraction is especially detrimental in a learning or classroom environment in which attended information is typically associated with establishing skills and knowledge. Here we report a study examining the effect of emotional distractors on performance in a subsequent visual lexical decision task in 11- to 13-year-old students (n=30). Lexical decisions about neutral verbs and verb-like pseudowords (i.e., targets) were analysed as a function of the preceding distractor type (pleasant, neutral, or unpleasant photos) and the picture-target stimulus-onset asynchrony (SOA; 200 or 600 ms). Across distractor categories, emotionally arousing pictures prolonged decisions about word targets when compared to neutral pictures, irrespective of the SOA. The present results demonstrate that similar to adults, early adolescent students exhibit sustained susceptibility to cognitive interference by irrelevant emotional events.

A Systematic Review of Structural and Functional MRI Studies Investigating Social Networking Site Use.

An understanding of the neurocognitive profile underlying the use of social networking sites (SNSs) can help inform decisions about the classification of problematic SNS use as an addictive disorder and elucidate how/when 'SNS addiction' might develop. The present review aimed to synthesize structural and functional MRI research investigating problematic/compulsive forms of SNS use or regular (non-addicted) SNS use behaviours. We conducted a systematic search for research articles published in English using the Web of Science, PubMed, and Scopus databases up to October 2022. Studies meeting our inclusion criteria were assessed for quality and a narrative synthesis of the results was conducted. Twenty-eight relevant articles were identified comprising structural MRI (n = 9), resting-state fMRI (n = 6) and task-based fMRI studies (n = 13). Current evidence suggests that problematic SNS use might be characterised by (1) reduced volume of the ventral striatum, amygdala, subgenual anterior cingulate cortex, orbitofrontal cortex and posterior insula; (2) increased ventral striatum and precuneus activity in response to SNS cues; (3) abnormal functional connectivity involving the dorsal attention network; (4) inter-hemispheric communication deficits. Regular SNS use behaviours appear to recruit regions involved in the mentalising network, the self-referential cognition network, the salience network, the reward network and the default mode network. Such findings are at least partially consistent with observations from the substance addiction literature and provide some provisional support for the addictive potential of SNSs. Nonetheless, the present review is limited by the small number of eligible studies and large heterogeneity in the methods employed, and so our conclusions should remain tentative. Moreover, there is a lack of longitudinal evidence suggesting SNSs cause neuroadaptations and thus conclusions that problematic SNS use represents a disease process akin to substance use addictions are premature. More well-powered longitudinal research is needed to establish the neural consequences of excessive and problematic SNS use.

Restricting social networking site use for one week produces varied effects on mood but does not increase explicit or implicit desires to use SNSs: Findings from an ecological momentary assessment study.

Recent research on the addictive potential of modern technologies such as the internet, smartphones, or social networking sites (SNSs) has suggested that emotional and motivational changes associated with the sudden discontinuation of engagement with the technology mirror the aversive consequences seen when drug use is ceased abruptly. This has been observed even in moderate users and interpreted as a manifestation of withdrawal, an important marker of physical dependence in substance use disorders. On the other hand, a growing literature emphasises the positive effects of "digital detox" on mental health and well-being. Using a battery of affective and motivational measures, both explicit and implicit, the present study tracked the effects of a week of significantly reduced SNS use in moderate to heavy SNS users (N = 51). Our pre-registered analyses showed that the intervention elicited affective changes neither consistent with a general withdrawal syndrome (i.e., increased negative affect and cravings) nor with a general beneficial effect on well-being: While our data indicated some abstinence-related decreases of negative affect and boredom, they also showed a reduction of positive affect. These changes occurred regardless of problematic/addictive use behaviours. Importantly, restricting SNS use for one week had no effect on implicit measures of SNS use motivation (i.e., approach biases, time distortion and effort expenditure for SNS access) nor did it influence explicit cravings and SNS cue-reactivity. Together our findings suggest that restricting SNS use has nuanced and potentially offsetting effects on well-being. These could arise because use reduction may concurrently remove experiences that trigger negative emotions (e.g., upward social comparisons or Fear of Missing Out) but also those that elicit positive emotions (e.g., social approval). The hypothesised lack of a net effect on well-being would be consistent with our finding that voluntary reduction of SNS use does not mitigate or exacerbate SNS-related urges.

Correction: Wadsley, M.; Ihssen, N. A Systematic Review of Structural and Functional MRI Studies Investigating Social Networking Site Use. Brain Sci. 2023, 13, 787.

During the final proofreading step of this paper [...].

The role of outgroup homogeneity and the neurodynamics of the frontal cortex during beauty comparisons.

The distance effect states that the closer two compared magnitudes (e.g., two numbers, physical attractiveness in two faces), the more difficult the comparison, and the greater the activity of the frontoparietal control network. However, it is unclear whether this network is also recruited to the same extent when we perform ingroup and outgroup beauty comparisons and whether the activation of these networks is tracked by interindividual variation in the perceptions we hold about an outgroup. We recorded brain activity with fMRI, where participants compared the beauty of two women ostensibly either from their ingroup or from an outgroup. Low-distance conditions produced longer response times than the high-distance conditions, and this was found in both the ingroup and outgroup conditions. However, our neuroimaging analyses revealed that the left IFG/anterior insula showed the classic distance effect only during ingroup processing but not during outgroup processing. Notably, interaction-specific activity within the left IFG/anterior insula was related to perceptions of outgroup homogeneity assessed via a questionnaire. This set of findings reveals the dynamic role of the prefrontal cortex and its interplay with perceptions of outgroup homogeneity in shaping ingroup and outgroup decision-making.

Differentiating heavy from light drinkers by neural responses to visual alcohol cues and other motivational stimuli.

The course to alcohol dependence often starts with a preclinical period of heavy drinking. The present article reports functional magnetic resonance imaging data showing that even this pattern of alcohol consumption is associated with maladaptive neural responses to alcohol and other stimuli. When participants were confronted with visual cues related to alcohol, heavy drinkers showed amplified blood oxygen level-dependent signal responses in specific emotional areas (insular cortex) and in parts of the brain's reward circuitry (ventral striatum). This neuronal amplification was not present in light drinkers. Crucially, at the same time heavy drinkers showed reduced responses in frontal areas to pictures related to higher order life goals and in the cingulate cortex to appetitive food stimuli, suggesting that they have difficulty finding alternative, socially desirable goals. Using discriminant function analysis, we demonstrate that the combination of alcohol-related overactivation and underactivation to alternative goals allows heavy and light drinkers to be differentiated with a high degree of precision. Our findings highlight the diagnostic value of functional brain mapping of cue reactivity. Imaging measures may help to identify addictive dispositions in preclinical stages and to clarify the mechanisms that underlie the development and maintenance of alcohol dependence.

The roles of implicit approach motivation and explicit reward in excessive and problematic use of social networking sites.

Despite growing concerns about the addictive potential of social networking sites (SNSs), little is known about the precise neural, cognitive, and emotional processes underpinning compulsive SNS behaviours, such as excessive checking of SNSs. Recent evidence points to the important role of reward in SNS behaviours and one avenue to examine reward processes related to SNSs is the use of behavioural paradigms that allow for the measurement of implicit motivational responses, such as the approach avoidance task (AAT). The AAT has been successfully utilised to capture changes in unconscious reward processes in substance use disorders and other behavioural addictions, with faster approach reactions to addiction-related stimuli reflecting increased wanting/urges to have/consume the reward. In the present study 411 young adults completed an online Visual Approach/Avoidance by the Self Task (VAAST) with social media and control logos as well as other subjective (explicit) measures of reward experience related to SNSs. Our results showed that across participants SNS logos elicited strong approach reactions (compared to control stimuli) and that stronger SNS approach tendencies predicted more frequent SNS checking. Importantly, increased approach motivation was not associated with more problematic use. However, both checking frequency and problematic use were related to alterations of explicit reward processing, including the subjective experience of SNS urges or wanting. We conclude that changes in automatic approach motivation towards SNS stimuli are common in most SNS users, which suggests that implicit imbuement of social media with reward has become pervasive among young adults. Problematic SNS use however may be more reliably indicated by changes in explicit reward processing, such as subjective wanting.

The Predictive Utility of Reward-Based Motives Underlying Excessive and Problematic Social Networking Site Use.

Compulsive seeking of reward is a hallmark feature of drug addiction, but the role of reward is less well understood in behavioural addictions. The present study investigated the predictive utility of ten reward-based motives, which we identified in the literature, in explaining excessive and problematic use of social networking sites (SNSs). These motives were examined in a cross-sectional survey of 411 young adults, revealing that prolonged use and excessive checking were predicted by distinctly different motives. More frequent checking of SNSs was most closely associated with motives related to obtaining social rewards (impression management/social comparisons/fear of missing out) and the desire to find/consume enjoyable content. In contrast, the amount of time an individual spends on SNSs was predicted by the desire to engage in negative social interactions or to fulfil personal needs (self-expression/documentation of life events). Problematic SNS use was best explained by the motivation to obtain social rewards and to a lesser extent by enjoyment and negative social potency (e.g., trolling) motives. Our results highlight the importance of social reward in explaining excessive and problematic SNS use, suggesting that a focus on reducing the desire to obtain social reward (e.g., through likes, social comparisons, continual connection) may be most beneficial in tackling problematic SNS behaviours.

A reward and incentive-sensitization perspective on compulsive use of social networking sites - Wanting but not liking predicts checking frequency and problematic use behavior.

The use of Social Networking Sites (SNSs) has exponentially increased over the past decade, leading to warnings about the addictive potential of this technology. Yet, the idea of SNS addiction remains controversial and more theory-driven research is required to understand the mechanisms of excessive and compulsive SNS use and to facilitate the development of targeted interventions helping affected users. In the present article we propose to utilize a reward-based approach to further our understanding of these behaviors. In particular, we suggest that concepts borrowed from the drug addiction literature that focus on incentive processes (incentive-sensitization and cue reactivity) can explain some SNS behaviors, such as compulsive checking. One elemental finding of the neurobiological drug addiction literature is that repeated exposure to a rewarding substance can render the brain's reward system oversensitive to cues related to the drug. We report preliminary findings from 358 participants showing that cue-elicited urges to use SNSs characterized both excessive and problematic use behaviors. Moreover, desires and urges to use SNSs (wanting responses) could be reliably dissociated from the enjoyment and pleasure (liking responses) associated with SNSs, with the latter being less predictive of the intensity and problematicity of behaviors than the former. Such divergence between motivational and hedonic processes is another hallmark finding in the literature on drug and food rewards. Together our initial findings thus suggest that examining alterations of reward processes holds promise to explain the compulsive use of SNSs and to identify potential avenues to help affected individuals.

Neural coding of human values is underpinned by brain areas representing the core self in the cortical midline region.

The impact of human values on our choices depends on their nature. Self-Transcendence values motivate us to act for the benefit of others and care for the environment. Self-Enhancement values motivate us to act for our benefit. The present study examines differences in the neural processes underlying these two value domains. Extending our previous research, we used fMRI to explore first of all neural correlates of Self-Transcendence vs Self-Enhancement values, with a particular focus on the putative role of the medial prefrontal cortex (MPFC), which has been linked to a self-transcendent mind-set. Additionally, we investigated the neural basis of Openness to Change vs Conservation values. We asked participants to reflect on and rate values as guiding principles in their lives while undergoing fMRI. Mental processing of Self-Transcendence values was associated with higher brain activity in the dorsomedial (BA9, BA8) and ventromedial (BA10) prefrontal cortices, as compared to Self-Enhancement values. The former involved activation and the latter deactivation of those regions. We did not detect differences in brain activation between Openness to Change vs Conservation values. Self-Transcendence values thus shared brain regions with social processes that have previously been linked to a self-transcendent mind-set, and the "core self" representation.

The effects of spatial stability and cue type on spatial learning: Implications for theories of parallel memory systems.

Some theories of spatial learning predict that associative rules apply under only limited circumstances. For example, learning based on a boundary has been claimed to be immune to cue competition effects because boundary information is the basis for the formation of a cognitive map, whilst landmark learning does not involve cognitive mapping. This is referred to as the cue type hypothesis. However, it has also been claimed that cue stability is a prerequisite for the formation of a cognitive map, meaning that whichever cue type was perceived as stable would enter a cognitive map and thus be immune to cue competition, while unstable cues will be subject to cue competition, regardless of cue type. In experiments 1 and 2 we manipulated the stability of boundary and landmark cues when learning the location of two hidden goals. One goal location was constant with respect to the boundary, and the other constant with respect to the landmark cues. For both cue types, the presence of distal orientation cues provided directional information. For half the participants the landmark cues were unstable relative to the boundary and orientation cues, whereas for the remainder of the participants the boundary was unstable relative to landmarks and orientation cues. In a second stage of training, all cues remained stable so that both goal locations could be learned with respect to both landmark and boundary information. According to the cue type hypothesis, boundary information should block learning about landmarks regardless of cue stability. According to the cue stability hypothesis, however, landmarks should block learning about the boundary when the landmarks appear stable relative to the boundary. Regardless of cue type or stability the results showed reciprocal blocking, contrary to both formulations of incidental cognitive mapping. Experiment 3 established that the results of Experiments 1 and 2 could not be explained in terms of difficulty in learning certain locations with respect to different cue types. In a final experiment, following training in which both landmarks and boundary cues signalled two goal locations, a new goal location was established with respect to the landmark cues, before testing with the boundary, which had never been used to define the new goal location. The results of this novel test of the interaction between boundary and landmark cues indicated that new learning with respect to the landmark had a profound effect on navigation with respect to the boundary, counter to the predictions of incidental cognitive mapping of boundaries.

Re-entrant projections modulate visual cortex in affective perception: evidence from Granger causality analysis.

Re-entrant modulation of visual cortex has been suggested as a critical process for enhancing perception of emotionally arousing visual stimuli. This study explores how the time information inherent in large-scale electrocortical measures can be used to examine the functional relationships among the structures involved in emotional perception. Granger causality analysis was conducted on steady-state visual evoked potentials elicited by emotionally arousing pictures flickering at a rate of 10 Hz. This procedure allows one to examine the direction of neural connections. Participants viewed pictures that varied in emotional content, depicting people in neutral contexts, erotica, or interpersonal attack scenes. Results demonstrated increased coupling between visual and cortical areas when viewing emotionally arousing content. Specifically, intraparietal to inferotemporal and precuneus to calcarine connections were stronger for emotionally arousing picture content. Thus, we provide evidence for re-entrant signal flow during emotional perception, which originates from higher tiers and enters lower tiers of visual cortex.

So pretty! The neural correlates of self-other vs familiar-other attractiveness comparisons.

Previous research has demonstrated that comparing two persons activates a frontoparietal network associated with numbers and nonsocial magnitudes. However, it is unclear whether this network is also recruited by comparisons involving the self. Self-reflection engages self-serving motivations (e.g., the maintenance of a positive self-image) and is associated with specific brain structures, such as the medial prefrontal cortex (MPFC), the anterior insula (AI) and the anterior cingulate cortex (ACC). Self-other comparisons may thus rely on distinct neural activity. To clarify this question, we used fMRI and asked female participants to compare their own attractiveness (or the attractiveness of a familiar woman) to pictures of unknown women. Participants were slower for comparisons with targets whose attractiveness was similar to their own (or their familiar other). Yet although this behavioral result resembles the distance effect reported for nonsocial magnitudes, at the brain level, it was linked to the activity of the AI, the ACC and the MPFC. The effect of distance in these regions was stronger for self-other than familiar-other comparisons. We interpret these results in relation to previous literature in social psychology and social neuroscience.

Genetic Variation in the Psychiatric Risk Gene CACNA1C Modulates Reversal Learning Across Species.

Genetic variation in CACNA1C, which encodes the alpha-1 subunit of Cav1.2 L-type voltage-gated calcium channels (VGCCs), has been strongly linked to risk for psychiatric disorders including schizophrenia and bipolar disorder. How genetic variation in CACNA1C contributes to risk for these disorders is however not fully known. Both schizophrenia and bipolar disorder are associated with impairments in reversal learning (RL), which may contribute to symptoms seen in these conditions. We used a translational RL paradigm to investigate whether genetic variation in CACNA1C affects RL in both humans and transgenic rats. Associated changes in gene expression were explored using in situ hybridization and quantitative PCR in rats and the BRAINEAC online human database. Risk-associated genetic variation in CACNA1C in healthy human participants was associated with impairments in RL. Consistent with this finding, rats bearing a heterozygous deletion of Cacna1c were impaired in an analogous touchscreen RL task. We investigated the possible molecular mechanism underlying this impairment and found that Cacna1c +/- rats show decreased expression of Bdnf in prefrontal cortex. Examination of BRAINEAC data showed that human risk-associated genetic variation in CACNA1C is also associated with altered expression of brain-derived neurotrophic factor (BDNF) in the prefrontal cortex in humans. These results indicate that genetic variation in CACNA1C may contribute to risk for schizophrenia and bipolar disorder by impacting behavioral flexibility, potentially through altered regulation of BDNF expression in the prefrontal cortex. Tests of RL may be useful for translational studies and in the development of therapies targeting VGCCs.