Try a new search

Format these results:

Searched for:



Total Results:


Temporally and anatomically specific contributions of the human amygdala to threat and safety learning

Wen, Zhenfu; Raio, Candace M; Pace-Schott, Edward F; Lazar, Sara W; LeDoux, Joseph E; Phelps, Elizabeth A; Milad, Mohammed R
Neural plasticity in subareas of the rodent amygdala is widely known to be essential for Pavlovian threat conditioning and safety learning. However, less consistent results have been observed in human neuroimaging studies. Here, we identify and test three important factors that may contribute to these discrepancies: the temporal profile of amygdala response in threat conditioning, the anatomical specificity of amygdala responses during threat conditioning and safety learning, and insufficient power to identify these responses. We combined data across multiple studies using a well-validated human threat conditioning paradigm to examine amygdala involvement during threat conditioning and safety learning. In 601 humans, we show that two amygdala subregions tracked the conditioned stimulus with aversive shock during early conditioning while only one demonstrated delayed responding to a stimulus not paired with shock. Our findings identify cross-species similarities in temporal- and anatomical-specific amygdala contributions to threat and safety learning, affirm human amygdala involvement in associative learning and highlight important factors for future associative learning research in humans.
PMID: 35727981
ISSN: 1091-6490
CID: 5262982

Cumulative lifetime stressor exposure assessed by the STRAIN predicts economic ambiguity aversion

Raio, Candace M; B Lu, Benjamin; Grubb, Michael; Shields, Grant S; Slavich, George M; Glimcher, Paul
Uncertainty is inherent in most decisions humans make. Economists distinguish between two types of decision-making under non-certain conditions: those involving risk (i.e., known outcome probabilities) and those that involve ambiguity (i.e., unknown outcome probabilities). Prior research has identified individual differences that explain risk preferences, but little is known about factors associated with ambiguity aversion. Here, we hypothesized that cumulative exposure to major psychosocial stressors over the lifespan might be one factor that predicts individuals' ambiguity aversion. Across two studies (Study 1: n = 58, Mage = 25.7; Study 2: n = 188, Mage = 39.81), we used a comprehensive lifetime stressor exposure inventory (i.e., the Stress and Adversity Inventory for Adults, or STRAIN) and a standard economic approach to quantify risk and ambiguity preferences. Greater lifetime stressor exposure as measured by the STRAIN, particularly in early life, was associated with higher aversion to ambiguity but not risk preferences.
PMID: 35354811
ISSN: 2041-1723
CID: 5201222

Neither Threat of Shock nor Acute Psychosocial Stress Affects Ambiguity Attitudes

Sambrano, Deshawn Chatman; Lormestoire, Arlene; Raio, Candace; Glimcher, Paul; Phelps, Elizabeth A
Decisions under uncertainty can be differentiated into two classes: risky, which has known probabilistic outcomes, and ambiguous, which has unknown probabilistic outcomes. Across a variety of types of decisions, people find ambiguity extremely aversive, subjectively more aversive than risk. It has been shown that the transient sympathetic arousal response to a choice predicts decisions under ambiguity but not risk, and that lifetime stress uniquely predicts attitudes toward ambiguity. Building on these findings, this study explored whether we could bias ambiguity and risk preferences with an arousal or acute stress manipulation that is incidental to the choice in two independent experiments. One experiment induced sympathetic arousal with an anticipatory threat paradigm, and the other manipulated incidental acute stress via a psychosocial stressor. The efficacy of the manipulations was confirmed via pupil dilation and salivary cortisol, respectively. Participants made choices between a guaranteed $5 option and a lottery with either a known (risky) or unknown (ambiguous) probabilistic outcome. Consistent with previous findings, participants were more averse to a given level of ambiguity than to a numerically equal level of risk. However, in contrast to our hypothesis, we found no evidence that transient arousal or acute stress that is incidental to the choice biases ambiguity preferences.
PMID: 35791419
ISSN: 2662-205x
CID: 5280332

Reappraisal-but not Suppression-Tendencies Determine Negativity Bias After Laboratory and Real-World Stress Exposure

Raio, Candace M; Harp, Nicholas R; Brown, Catherine C; Neta, Maital
Higher reactivity to stress exposure is associated with an increased tendency to appraise ambiguous stimuli as negative. However, it remains unknown whether tendencies to use emotion regulation strategies-such as cognitive reappraisal, which involves altering the meaning or relevance of affective stimuli-can shape individual differences regarding how stress affects perceptions of ambiguity. Here, we examined whether increased reappraisal use is one factor that can determine whether stress exposure induces increased negativity bias. In Study 1, healthy participants (n = 43) rated the valence of emotionally ambiguous (surprised) faces before and after an acute stress or control manipulation and reported reappraisal habits. Increased negativity ratings were milder for stressed individuals that reported more habitual reappraisal use. In Study 2 (n = 97), we extended this investigation to real-world perceived stress before and during the COVID-19 pandemic. We found that reappraisal tendency moderates the relationship between perceived stress and increased negativity bias. Collectively, these findings suggest that the propensity to reappraise determines negativity bias when evaluating ambiguity under stress.
PMID: 34704072
ISSN: 2662-205x
CID: 5042432

Quantifying the subjective cost of self-control in humans

Raio, Candace M; Glimcher, Paul W
Since Odysseus committed to resisting the Sirens, mechanisms to limit self-control failure have been a central feature of human behavior. Psychologists have long argued that the use of self-control is an effortful process and, more recently, that its failure arises when the cognitive costs of self-control outweigh its perceived benefits. In a similar way, economists have argued that sophisticated choosers can adopt "precommitment strategies" that tie the hands of their future selves in order to reduce these costs. Yet, we still lack an empirical tool to quantify and demonstrate the cost of self-control. Here, we develop and validate an economic decision-making task to quantify the subjective cost of self-control by determining the monetary cost a person is willing to incur in order to eliminate the need for self-control. We find that humans will pay to avoid having to exert self-control in a way that scales with increasing levels of temptation and that these costs appear to be modulated both by motivational incentives and stress exposure. Our psychophysical approach allows us to index moment-to-moment self-control costs at the within-subject level, validating important theoretical work across multiple disciplines and opening avenues of self-control research in healthy and clinical populations.
PMID: 34446546
ISSN: 1091-6490
CID: 5011182

Heterogeneity in Foraging Decisions Relates to Drug Addiction and is a Marker of Midbrain Dopamine Function [Meeting Abstract]

Raio, C; Constantino, S; Biernacki, K; Bonagura, D; Xue, J; Wengler, K; Horga, G; Konova, A
Background: A prominent feature of addiction is the tendency to exploit a previously rewarding resource despite its diminishing returns. Such behavior is aptly captured in animal foraging models that have recently been extended to humans. Catecholaminergic systems are thought to underlie such behavior, but a precise empirical account of this is lacking in humans.
Method(s): We recruited 21 treatment-seeking individuals with opioid use disorder (OUD) and 21 socio-demographically matched controls. Participants completed a patch foraging task, during which they made sequential decisions between "harvesting" a depleting source of rewards or incurring a travel cost to harvest a replenished resource. We further acquired high-resolution (<0.7mm in-plane) neuromelanin-sensitive MRI scans, which reliably probes long-term dopamine and norepinephrine function, in a subset (n=27) of participants. Our imaging protocol separately localized dopaminergic nuclei (SN/VTA) and the noradrenergic LC, which have been theoretically linked to foraging behavior and are implicated in addiction.
Result(s): Behaviorally, OUD participants over-harvested more than controls and showed insensitivity to travel times (travel time effect: p=0.79). These group differences held when controlling for age, sex and cognitive variables. Over-harvesting scaled with increased years of opioid use (OUD; r=-0.51, p=0.03). Our imaging analysis revealed a dissociation whereby, across participants, over-harvesting was associated with lower neuromelanin signal contrast in dopaminergic nuclei (SN/VTA, rho=0.40, p=0.04), but not in LC (p=0.55).
Conclusion(s): Our findings suggest that individual differences in foraging behavior are related to interindividual variability in dopaminergic-but not noradrenergic-circuit function that informs reward rates in dynamic decision environments and may serve as a marker for maladaptive reward-seeking behavior. Supported By: Busch Biomedical Research Grant Keywords: Addiction, Foraging, Dopamine, Neuromelanin-Sensitive MRI
ISSN: 1873-2402
CID: 4857752

Evidence for a minimal role of stimulus awareness in reversal of threat learning

Homan, Philipp; Lau, H Lee; Levy, Ifat; Raio, Candace M; Bach, Dominik R; Carmel, David; Schiller, Daniela
In an ever-changing environment, survival depends on learning which stimuli represent threat, and also on updating such associations when circumstances shift. It has been claimed that humans can acquire physiological responses to threat-associated stimuli even when they are unaware of them, but the role of awareness in updating threat contingencies remains unknown. This complex process-generating novel responses while suppressing learned ones-relies on distinct neural mechanisms from initial learning, and has only been shown with awareness. Can it occur unconsciously? Here, we present evidence that threat reversal may not require awareness. Participants underwent classical threat conditioning to visual stimuli that were suppressed from awareness. One of two images was paired with an electric shock; halfway through the experiment, contingencies were reversed and the shock was paired with the other image. Despite variations in suppression across participants, we found that physiological responses reflected changes in stimulus-threat pairings independently of stimulus awareness. These findings suggest that unconscious affective processing may be sufficiently flexible to adapt to changing circumstances.
PMID: 33593928
ISSN: 1549-5485
CID: 4787332

Trait impulsivity and acute stress interact to influence choice and decision speed during multi-stage decision-making

Raio, Candace M; Konova, Anna B; Otto, A Ross
Impulsivity and stress exposure are two factors that are associated with changes in reward-related behavior in ways that are relevant to both healthy and maladaptive decision-making. Nonetheless, little empirical work has examined the possible independent and joint effects of these factors upon reward learning. Here, we sought to examine how trait impulsivity and acute stress exposure affect participants' choice behavior and decision speed in a two-stage sequential reinforcement-learning task. We found that more impulsive participants were more likely to repeat second-stage choices after previous reward, irrespective of stress condition. Exposure to stress, on the other hand, was associated with an increased tendency to repeat second-stage choices independent of whether these choices previously led to a reward, and this tendency was exacerbated in more impulsive individuals. Such interaction effects between stress and impulsivity were also found on decision speed. Stress and impulsivity levels interacted to drive faster choices overall (again irrespective of reward) at both task stages, while reward received on the previous trial slowed subsequent first-stage choices, particularly among impulsive individuals under stress. Collectively, our results reveal novel, largely interactive effects of trait impulsivity and stress exposure and suggest that stress may reveal individual differences in decision-making tied to impulsivity that are not readily apparent in the absence of stress.
PMID: 32385327
ISSN: 2045-2322
CID: 4430672

Addendum: Preventing the return of fear in humans using reconsolidation update mechanisms

Schiller, Daniela; Monfils, Marie-H; Raio, Candace M; Johnson, David C; LeDoux, Joseph E; Phelps, Elizabeth A
PMID: 30050064
ISSN: 1476-4687
CID: 3235482

Cortisol responses enhance negative valence perception for ambiguous facial expressions

Brown, Catherine C; Raio, Candace M; Neta, Maital
Stress exposure elicits a prolonged neuroendocrine response, marked by cortisol release, which can influence important forms of affective decision-making. Identifying how stress reactivity shapes subjective biases in decisions about emotional ambiguity (i.e., valence bias) provides insight into the role stress plays in basic affective processing for healthy and clinical populations alike. Here, we sought to examine how stress reactivity affects valence decisions about emotional ambiguity. Given that stress prioritizes automatic emotional processing which, in the context of valence bias, is associated with increased negativity, we tested how individual differences in acute stress responses influence valence bias and how this decision process evolves over time. Participants provided baseline ratings of clear (happy, angry) and ambiguous (surprised) facial expressions, then re-rated similar stimuli after undergoing an acute stress or control manipulation a week later; salivary cortisol was measured throughout to assay stress reactivity. Elevations in cortisol were associated with more negative ratings of surprised faces, and with more direct response trajectories toward negative ratings (i.e., less response competition). These effects were selectively driven by the stress group, evidencing that increased stress reactivity is associated with a stronger negativity bias during ambiguous affective decision-making.
PMID: 29118319
ISSN: 2045-2322
CID: 4787322