Noradrenaline tracks emotional modulation of attention in human amygdala.

The noradrenaline (NA) system is one of the brain's major neuromodulatory systems; it originates in a small midbrain nucleus, the locus coeruleus (LC), and projects widely throughout the brain.1,2 The LC-NA system is believed to regulate arousal and attention3,4 and is a pharmacological target in multiple clinical conditions.5,6,7 Yet our understanding of its role in health and disease has been impeded by a lack of direct recordings in humans. Here, we address this problem by showing that electrochemical estimates of sub-second NA dynamics can be obtained using clinical depth electrodes implanted for epilepsy monitoring. We made these recordings in the amygdala, an evolutionarily ancient structure that supports emotional processing8,9 and receives dense LC-NA projections,10 while patients (n = 3) performed a visual affective oddball task. The task was designed to induce different cognitive states, with the oddball stimuli involving emotionally evocative images,11 which varied in terms of arousal (low versus high) and valence (negative versus positive). Consistent with theory, the NA estimates tracked the emotional modulation of attention, with a stronger oddball response in a high-arousal state. Parallel estimates of pupil dilation, a common behavioral proxy for LC-NA activity,12 supported a hypothesis that pupil-NA coupling changes with cognitive state,13,14 with the pupil and NA estimates being positively correlated for oddball stimuli in a high-arousal but not a low-arousal state. Our study provides proof of concept that neuromodulator monitoring is now possible using depth electrodes in standard clinical use.

Delay discounting in adults with and without chronic pain: Differentiation across commodity and sign.

Delay discounting is a component of reward processing that affects decision-making in various health behavior domains. This study examined the discounting of gains and losses for monetary and pain outcomes among adults with and without chronic pain. Pain severity and pain catastrophizing (PC) were examined as additional moderators. This study assessed the discounting rates of 138 adults with chronic pain and 147 adults without chronic pain using online convenience sampling. Delay discounting was measured using an adjusting amount procedure, which titrates discounting rates based on participants' responses to identify points of indifference. Adults with and without chronic pain discounted losses more than gains and discounted pain outcomes more than monetary outcomes. There were no differences between groups based on chronic pain status or average self-reported pain severity. Post hoc analyses show that, on average, adults with chronic pain and high pain catastrophizing discounted monetary losses less than adults without chronic pain and low pain catastrophizing. This finding suggests that a tendency to defer immediate losses in favor of even larger delayed losses is dependent on high pain catastrophizing in the context of chronic pain. If pain catastrophizing is a more robust predictor of discounting rates than other pain metrics, then catastrophizing may be the construct that predicts risky decision-making. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

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.

Resting-State Functional Connectivity Differences in College Students with and without Food Insecurity.

We used functional magnetic resonance imaging (fMRI) to investigate cross-sectional differences in functional connectivity across cognitive networks at rest among age and sex matched college students with very low food security [food insecurity (FI); n = 20] and with high food security (n = 20). The participants completed the Behavior Rating Inventory of Executive Function-2 (BRIEF-2) and Adverse Childhood Experiences (ACEs) questionnaires. Seven-minute resting-state fMRI scans were collected. Independent Component Analysis assessed group connectivity differences in three large-scale networks: the default-mode network (DMN), the frontoparietal network (FPN), and the salience network (SN). FI was associated with poorer Global BRIEF scores (adjusted ß = 8.36; 95% CI: 2.32, 14.40) and five BRIEF subscales: Inhibit, Initiate, Working Memory, Plan, and Organize (p-values < 0.05). The students with FI had greater functional connectivity between the FPN and left middle temporal gyrus (cluster size p-FWE = 0.029), the SN and precuneus (cluster size p-FWE < 0.001), and the SN and right middle frontal gyrus (cluster size p-FWE = 0.016) compared to the students with high food security. Exploratory correlations revealed that greater connectivity between the SN and right middle frontal gyrus was associated with poorer BRIEF Inhibit scores (p = 0.038), and greater connectivity between the FPN and left middle temporal gyrus was associated with poorer BRIEF Organize scores (p = 0.024) for the students with FI. Greater functional connectivity between the FPN, DMN, and SN at rest may contribute to executive function difficulties for college students with FI.

Limbic and Executive Meso- and Nigrostriatal Tracts Predict Impulsivity Differences in Attention-Deficit/Hyperactivity Disorder.

BACKGROUND: Impulsivity is a defining characteristic of attention-deficit/hyperactivity disorder (ADHD), which has been associated with substance use disorders, higher accident rates, and lower educational and occupational outcomes. The meso- and nigrostriatal pathways of the dopamine system are hypothesized to be functionally heterogeneous, supporting diverse cognitive functions and impairments, including those associated with ADHD. We tested whether human midbrain pathways (where dopaminergic cell bodies originate) between the substantia nigra (SN) and ventral tegmental area (VTA) and the striatum differed between participants with ADHD and typically developing adolescent and young adult participants. We also assessed whether pathway connectivity predicted impulsivity regardless of diagnosis. METHODS: Diffusion tensor imaging data were used to predict impulsivity (parent and self-report ratings, task-based behavioral measures) from participants with ADHD and typically developing adolescent and young adult participants (n = 155; 86 male, 69 female). Using probabilistic tractography, we mapped these pathways and divided the tracts into limbic, executive, and sensorimotor based on frontostriatal connectivity. ADHD and typically developing participants differed on all behavioral measures of impulsivity. We used correlation and machine learning analyses to test for a relationship between tract probabilities and impulsivity regardless of diagnosis. RESULTS: Participants with ADHD had stronger structural connectivity between SN/VTA regions and the limbic striatum, weaker connectivity with the executive striatum, and no significant differences in sensorimotor tracts. Increased tract integrity between the limbic striatal and SN/VTA regions predicted greater impulsivity, while increased integrity between executive striatal and SN/VTA regions predicted reduced impulsivity. CONCLUSIONS: These findings support the theory that functional diversity in the dopamine system is an important consideration for understanding dysfunction in ADHD.

Satiety does not alter the ventral striatum's response to immediate reward in bulimia nervosa.

Individuals with bulimia nervosa (BN) cycle between periods of binge-eating and compensatory behavior and periods of dietary restraint, suggesting extremes of under and overcontrol that may be metabolic-state related. This study examined the influence of hunger and satiety on impulsivity and neural responding during decision-making. Twenty-three women remitted from BN (RBN) and 20 healthy comparison women (CW) performed a delay discounting task after a 16-hr fast and following a standardized meal during functional neuroimaging. A dual-systems approach examined reward valuation (decision trials where the early reward option was available immediately) and cognitive control (all decision trials). Interactions of Group × Visit (Hungry, Fed) for immediate reward revealed that CW had greater activation when hungry versus fed in the ventral striatum and dorsal caudate, whereas RBN had greater response when fed versus hungry in the dorsal caudate. Compared to CW, RBN showed decreased response when hungry within the left dorsal caudate and ventral striatum and increased response when fed in bilateral dorsal caudate. No differences were found within cognitive control regions or with choice behavior. Reward sensitivity is normally increased when hungry and decreased when fed; our findings in CW provide further support of hunger-based reward sensitivity within the striatum. However, RBN showed no differences for hunger and satiety in the ventral striatum and greater activation in the dorsal caudate when fed compared to hungry. This suggests RBN may be less sensitive to reward when hungry but do not devalue reward when satiated, indicating altered metabolic modulation of self-regulatory control. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Neural basis of working memory in ADHD: Load versus complexity.

Working memory (WM) deficits are key in attention deficit hyperactivity disorder (ADHD). Nevertheless, WM is not universally impaired in ADHD. Additionally, the neural basis for WM deficits in ADHD has not been conclusively established, with regions including the prefrontal cortex, cerebellum, and caudate being implicated. These contradictions may be related to conceptualizations of WM capacity, such as load (amount of information) versus operational-complexity (maintenance-recall or manipulation). For instance, relative to neurotypical (NT) individuals, complex WM operations could be impaired in ADHD, while simpler operations are spared. Alternatively, all operations may be impaired at higher loads. Here, we compared the impact of these two components of WM capacity: load and operational-complexity, between ADHD and NT, behaviorally and neurally. We hypothesized that the impact of WM load would be greater in ADHD, and the neural activation would be altered. Participants (age-range 12-23 years; 50 ADHD (18 females); 82 NT (41 females)) recalled three or four objects (load) in forward or backward order (operational-complexity) during functional magnetic resonance imaging scanning. The effects of diagnosis and task were compared on performance and neural engagement. Behaviorally, we found significant interactions between diagnosis and load, and between diagnosis, load, and complexity. Neurally, we found an interaction between diagnosis and load in the right striatum, and between diagnosis and complexity in the right cerebellum and left occipital gyrus. The ADHD group displayed hypo-activation compared to NT group during higher load and greater complexity. This informs mechanisms of functional problems related to WM in adolescents and young adults with ADHD (e.g., academic performance) and remedial interventions (e.g., WM-training).

Reinforcer pathology in cocaine use disorder: Temporal window determines cocaine valuation.

AIMS: The Experimental Medicine Approach offers a unique perspective to determine clinical behavior change by engaging a target underlying the cause of a disorder. The present work engaged a novel target of addiction, Reinforcer Pathology, in two studies to test changes in behavior among individuals with cocaine use disorder. METHODS: In Study 1, n = 44 participants engaged the temporal window with episodic future thinking (EFT), a positive prospection exercise. Changes in temporal view and cocaine valuation were tested using delay discounting and behavioral economic demand, respectively. Additionally, a computational model assessed the relative reliance on the near- and far-sighted systems during EFT. In Study 2, n = 71 engaged the temporal window with a negatively-valenced hurricane scenario to test the opposite effects on window length and cocaine valuation. RESULTS: Results demonstrated systematic and symmetrical engagement of the behavioral target. Study 1 robustly replicated previous work, wherein EFT lengthened the temporal window and decreased cocaine valuation. Moreover, EFT increased the weighting of the modeled far-sighted system, increasing the relative impact of long-term discounting decisions. Study 2 produced opposite outcomes, shortened temporal window and increased cocaine valuation. CONCLUSIONS: This approximately equal and opposite reaction to the manipulations supports reinforcer pathology theory and implicates the temporal window over which rewards are valued as a target to be pushed and pulled to produce clinically meaningful behavior change. Using the Experimental Medicine Approach as a guide, future work should identify new potential interventions to engage reinforcer pathology and use the clinically relevant outcomes as a litmus test for mechanism.

Dimensions of childhood trauma and their direct and indirect links to PTSD, impaired control over drinking, and alcohol-related-problems.

INTRODUCTION: Post-Traumatic Stress Disorder (PTSD) develops after experiencing events that evoke fear, helplessness, or horror. The Hyperarousablity Hypothesis suggests that those with PTSD may drink more to dampen physiological reactivity. We examined the direct and indirect relationships between childhood trauma (e.g., physical-neglect, emotional-abuse, physical-abuse, sexual-abuse) versus an emotionally-supportive-family on PTSD, impaired control over drinking (IC), alcohol-use, and alcohol-related-problems. IC reflects consuming more alcohol than one originally intended. METHODS: We fit a multiple-group SEM to data on 835 participants. Mediational analyses were conducted by using the (K = 20,000) bootstrap technique with confidence intervals. RESULTS: Physical-neglect was directly linked to more IC among both genders. Emotional abuse was also found to be directly linked to more PTSD among both genders. Furthermore, PTSD was directly linked to more impaired control over alcohol use (IC) among both genders. Mediational analyses showed that physical-neglect was indirectly linked to more alcohol-related-problems through increased IC. Having an emotionally supportive family was directly linked to fewer PTSD symptoms among women. For both genders, emotional abuse was indirectly linked to more alcohol-related-problems through more PTSD symptoms, impaired control over alcohol use difficulties, and in turn, more alcohol-use. Sexual abuse was indirectly linked to increased alcohol-related- problems through increased PTSD symptoms and more IC, and in turn, more alcohol-use among men. CONCLUSIONS: Recalled childhood trauma (sexual and emotional abuse) may contribute to PTSD symptoms and dysregulated drinking. In conclusion, our data suggest that reducing PTSD symptoms may assist individuals in regaining control over their drinking.

Individual differences in value-directed remembering.

Capacity limits in cognition require that valuable information be prioritized for encoding and retrieval. Individual differences in prioritized value-directed encoding may derive from differences in the general ability to encode memories, or from differences in how strategies are altered for different stimuli to modulate maintenance in working memory. We collected multiple cognitive ability measures to test whether variation in episodic memory, working memory capacity, or both predict differences in value-directed remembering among a large sample of participants (n = 205). Confirmatory factor analysis and structural equation modeling was used to assess the contributions of episodic and working memory to value sensitivity in value-directed remembering tasks. Episodic memory ability, but not working memory capacity, was predictive of value-directed remembering. These results suggest that the ability to prioritize memory derives principally from episodic memory ability overall, so that greater capacity also permits greater flexibility.

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.

Hippocampal pattern separation supports reinforcement learning.

Animals rely on learned associations to make decisions. Associations can be based on relationships between object features (e.g., the three leaflets of poison ivy leaves) and outcomes (e.g., rash). More often, outcomes are linked to multidimensional states (e.g., poison ivy is green in summer but red in spring). Feature-based reinforcement learning fails when the values of individual features depend on the other features present. One solution is to assign value to multi-featural conjunctive representations. Here, we test if the hippocampus forms separable conjunctive representations that enables the learning of response contingencies for stimuli of the form: AB+, B-, AC-, C+. Pattern analyses on functional MRI data show the hippocampus forms conjunctive representations that are dissociable from feature components and that these representations, along with those of cortex, influence striatal prediction errors. Our results establish a novel role for hippocampal pattern separation and conjunctive representation in reinforcement learning.

Joint modeling of reaction times and choice improves parameter identifiability in reinforcement learning models.

BACKGROUND: Reinforcement learning models provide excellent descriptions of learning in multiple species across a variety of tasks. Many researchers are interested in relating parameters of reinforcement learning models to neural measures, psychological variables or experimental manipulations. We demonstrate that parameter identification is difficult because a range of parameter values provide approximately equal quality fits to data. This identification problem has a large impact on power: we show that a researcher who wants to detect a medium sized correlation (r = .3) with 80% power between a variable and learning rate must collect 60% more subjects than specified by a typical power analysis in order to account for the noise introduced by model fitting. NEW METHOD: We derive a Bayesian optimal model fitting technique that takes advantage of information contained in choices and reaction times to constrain parameter estimates. RESULTS: We show using simulation and empirical data that this method substantially improves the ability to recover learning rates. COMPARISON WITH EXISTING METHODS: We compare this method against the use of Bayesian priors. We show in simulations that the combined use of Bayesian priors and reaction times confers the highest parameter identifiability. However, in real data where the priors may have been misspecified, the use of Bayesian priors interferes with the ability of reaction time data to improve parameter identifiability. CONCLUSIONS: We present a simple technique that takes advantage of readily available data to substantially improve the quality of inferences that can be drawn from parameters of reinforcement learning models.

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.

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.

Causal Evidence for the Dependence of the Magnitude Effect on Dorsolateral Prefrontal Cortex.

Impulsivity refers to the tendency to insufficiently consider alternatives or to overvalue rewards that are available immediately. Impulsivity is a hallmark of human decision making with well documented health and financial ramifications. Numerous contextual changes and framing manipulations powerfully influence impulsivity. One of the most robust such phenomenon is the finding that people are more patient as the values of choice options are increased. This magnitude effect has been related to cognitive control mechanisms in the dorsal lateral prefrontal cortex (dlPFC). We used repetitive transcranial magnetic stimulation (rTMS) to transiently disrupt dlPFC neural activity. This manipulation dramatically reduced the magnitude effect, establishing causal evidence that the magnitude effect depends on dlPFC.

Author Correction: Overcoming Bias: Cognitive Control Reduces Susceptibility to Framing Effects in Evaluating Musical Performance.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Overcoming Bias: Cognitive Control Reduces Susceptibility to Framing Effects in Evaluating Musical Performance.

Prior expectations can bias evaluative judgments of sensory information. We show that information about a performer's status can bias the evaluation of musical stimuli, reflected by differential activity of the ventromedial prefrontal cortex (vmPFC). Moreover, we demonstrate that decreased susceptibility to this confirmation bias is (a) accompanied by the recruitment of and (b) correlated with the white-matter structure of the executive control network, particularly related to the dorsolateral prefrontal cortex (dlPFC). By using long-duration musical stimuli, we were able to track the initial biasing, subsequent perception, and ultimate evaluation of the stimuli, examining the full evolution of these biases over time. Our findings confirm the persistence of confirmation bias effects even when ample opportunity exists to gather information about true stimulus quality, and underline the importance of executive control in reducing bias.