Spencer K. Lynn, PhD

Gender differences in oxytocin-associated disruption of decision bias during emotion perception

spencer — Wed, 17 Apr 2013 20:07:22 +0000

Oxytocin is associated with differences in the perception of and response to socially mediated information, such as facial expressions. Across studies, however, oxytocin’s effect on emotion perception has been inconsistent. Outside the laboratory, emotion perception involves interpretation of perceptual uncertainty and assessment of behavioral risk. An account of these factors is largely missing from studies of oxytocin’s effect on emotion perception and might explain some inconsistency of results. Of relevance, studies of oxytocin’s effect on learning and decision-making indicate that oxytocin attenuates risk aversion. We used the probability of encountering angry faces and the cost of misidentifying them as not angry to create a risky environment wherein a bias to categorize faces as angry would maximize point earnings. Forty participants (45% women) received 30 IU intranasal oxytocin or placebo before testing. Oxytocin was hypothesized to be associated with insufficient bias, due to an underestimation of the factors creating risk, the encounter rate and cost. Men given oxytocin were less influenced by cost and base rate, exhibiting a less liberal (i.e., worse) response bias, than men given placebo (p<0.037). Oxytocin did not influence women's performance. These results suggest that oxytocin may impair men's ability to adapt to changes in risk and uncertainty when introduced to novel or changing social environments. Oxytocin pharmacotherapy may only be helpful when patients exhibit an overly-liberal threat detection bias. Because oxytocin also influences behavior in non-social realms, oxytocin pharmacotherapy could have unintended consequences (i.e., risk-prone decision-making) while nonetheless normalizing pathological social interaction.

Lynn, S. K.*, Hoge, E. A.*, Fischer, L. E., Barrett, L. F., and Simon, N. M. 2013. Gender differences in oxytocin-associated disruption of decision bias during emotion perception. 20th Annual Meeting of the Cognitive Neuroscience Society, 13-16 April 2013, San Francisco, California.

*These authors contributed equally to the study.

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These data also presented at ACNP 2012.

Oxytocin influences response bias in men but not women in a signal detection emotion perception task

spencer — Mon, 18 Mar 2013 19:59:37 +0000

Background: Accumulating studies document changes in the perception of and response to socially mediated information, such as facial expressions, with administration of oxytocin. Across studies, however, its effects on emotion perception have been inconsistent. Outside the laboratory, affective judgments about another person (e.g., Is that person angry at me?) involve interpretation of perceptual uncertainty (e.g., scowls do not always indicate anger) and assessment of behavioral risk (e.g., the costs of inferring anger when it does not exist differ from the costs of missing anger when it does exist). An account of these decision variables is missing from studies of the effects of oxytocin on emotion perception. To characterize oxytocin’s effects on emotion perception from a decision-making perspective, we utilized a task that combines perceptual uncertainty with behavioral economics in a signal detection framework. We used the probability of encountering angry faces and the cost of misidentifying them as not angry (risk) to create a biased (biased towards reporting anger when not sure) perceptual environment. We measured the effect of oxytocin on perceivers’ ability to achieve optimal bias in this environment. Based on prior data suggesting that oxytocin attenuates risk aversion, we hypothesized that receiving oxytocin would result in insufficient bias, due to under-estimating the probability of encountering angry faces and/or to under-valuing the cost of mistakes relative to placebo. Methods: Forty psychotropic-free healthy control participants (age: M=44.0 ± 10.32 [SD] years, 45% women) participated in a randomized double-blind administration of intranasal oxytocin or placebo prior to computer based tasks at the Center for Anxiety and Traumatic Stress Disorders (CATSD) at Massachusetts General Hospital. All were free of psychiatric disorders, per clinical interview with the Structured Clinical Interview for DSM-IV. Participants were given 30 IU of double-blind intranasal oxytocin (Syntocinon®, Novartis) or placebo (oxytocin: n=22, 9 women; placebo: n=18, 7 women) thirty minutes before the computer tasks. In this signal detection framework, faces that depicted expressions ranging from relaxed to strongly scowling comprised two categories: “angry” (targets) and “not angry” (foils). Uncertainty was implemented by creating distributions of targets and foils which shared exemplars (i.e., the distributions overlapped on the perceptual domain: targets were M = 60 ± 15% (1 SD) scowl intensity, foils were M = 40 ± 15% (1 SD) scowl intensity). Risk was created by earning or losing points for correct vs. incorrect categorization of targets and foils (i.e., categorizing a target as “not angry” cost more points than categorizing a foil as “angry”). Additionally, the base rate of targets was 0.6 (60% of trials were targets). The combination of relatively high missed detection cost and relatively frequent targets dictated a liberal optimal bias: a tendency to categorize faces as angry was required to maximize points earned. Over 230 trials, participants attempted to optimize their categorization of the faces, answering the on-screen prompt “Is this person angry?”. Participants received immediate on-screen feedback (“Yes – that was right” or “No – that was wrong”, points earned for the current trial, and cumulative points earned). Results: Controlling for baseline perceived stress (Perceived Stress Scale) and trait anxiety (State Trait Anxiety Index, Trait Total Score) in this non-psychiatrically ill sample, we found a significant interaction of drug and gender on response bias (ANCOVA, F(1,32)=4.1, p<0.049), without main effects. Men who received oxytocin exhibited a significantly less liberal (less optimal, based on experimental parameters) bias for perception of anger in faces than those who received placebo (follow-up ANCOVA among men, F(1,20)=5.0, p<0.037). In contrast, women's bias was not significantly affected by oxytocin (follow-up ANCOVA among women, F(1,12)=0.6, p>0.4). Discussion: Participants attempted to optimize their judgments about angriness depicted in facial expressions, in the context of experimenter-defined values of target-foil perceptual similarity, payoffs (points earned/lost), and “anger” base rate. Men given oxytocin appeared less able to calibrate their emotion perception to the signal detection parameters that cause bias (payoffs, base rate, or both). As a learning experiment, our results suggest that oxytocin may impair men’s ability to optimally adapt emotion perception (e.g., judgments of angriness from faces) to differences in risk and uncertainty that characterize different social contexts, while there was no effect of oxytocin for women. These data suggest that oxytocin might reduce (normalize) over-estimates of the base rate of threat or reduce (normalize) over-estimates of the magnitude of punishments that otherwise might contribute to excessive social withdrawal or reduced social approach behaviors. We cannot rule out, however, that by reducing the salience of risk, oxytocin treatment in men could potentially promote risk-prone decision-making in domains outside a patient’s core symptomatology. More research is needed to understand the potential role and possible side effects of oxytocin in interventions.

Simon, N. M., Lynn, S. K., Hoge, E. A., Fischer, L. E., and Barrett, L. F. 2012. Oxytocin influences response bias in men but not women in a signal detection emotion perception task. 51st Annual Meeting of the American College of Neuropsychopharacology, December 2-6, 2012, Hollywood Florida.

These data also presented at CNS 2013.

Optimizing Threat Detection Under Signal-Borne Risk

spencer — Thu, 27 Sep 2012 15:16:18 +0000

Principal investigator: Spencer Lynn
Source: US Army Research Institute for the Behavioral and Social Sciences
Contract: W5J9CQ-12-C-0028
Dates: 9/27/12-9/26/15
Amount: $434,499

Emotion perception research has revealed marked variability in people’s abilities to infer the emotional states of others. This variability is a function of (i) the uncertainty and risk in the environment inherent to perception (perceivers cannot be certain about what they are experiencing, and errors of perception may be costly) and (ii) factors internal to individual perceivers (physical and psychological states and traits). Using a novel utility-based signal detection framework, we will examine how individual differences in affective reactivity, executive function, and motivation contribute to this variability in perception and decision-making, under conditions of changing environmental uncertainty and risk.

Affective state influences perception by affecting decision parameters underlying bias and sensitivity

spencer — Thu, 26 Apr 2012 00:20:29 +0000

Studies of the effect of affect on perception often show consistent directional effects of a person’s affective state on perception. Unpleasant emotions have been associated with a “locally focused” style of stimulus evaluation, and positive emotions with a “globally focused” style. Typically, however, studies of affect and perception have not been conducted under the conditions of perceptual uncertainty and behavioral risk inherent to perceptual judgments outside the laboratory. We investigated the influence of perceivers’ experienced affect (valence and arousal) on the utility of social threat perception by combining signal detection theory and behavioral economics. We compared 3 perceptual decision environments that systematically differed with respect to factors that underlie uncertainty and risk: the base rate of threat, the costs of incorrect identification threat, and the perceptual similarity of threats and nonthreats. We found that no single affective state yielded the best performance on the threat perception task across the 3 environments. Unpleasant valence promoted calibration of response bias to base rate and costs, high arousal promoted calibration of perceptual sensitivity to perceptual similarity, and low arousal was associated with an optimal adjustment of bias to sensitivity. However, the strength of these associations was conditional upon the difficulty of attaining optimal bias and high sensitivity, such that the effect of the perceiver’s affective state on perception differed with the cause and/or level of uncertainty and risk.

Lynn, SK, X Zhang, & LF Barrett. 2012. Affective state influences perception by affecting decision parameters underlying bias and sensitivity. Emotion 12(4):726-736.

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The Utility of Threat Detection in Generalized Social Anxiety Disorder

spencer — Thu, 26 Apr 2012 00:19:37 +0000

Principal investigators (multi-PIs): Spencer Lynn, Naomi Simon
Source: National Institute of Mental Health
Award: R01 MH093394-01
Dates: 8/1/11-4/30/16
Amount: $1,954,208

Summary: During social interactions, we look into the face of another person and in the blink of an eye infer that person’s emotional state and their intentions. These perceptions inform decisions about what to do or say next. Generalized Social Anxiety Disorder (GSAD) is characterized by exaggerated concerns about negative evaluation and rejection in social situations. These symptoms have been quantified with signal detection theory (SDT). The application of SDT has led to novel approaches within anxiety research; a primary hypothesis, supported by several studies, has been that the “over-reactive” nature of the anxious state can be characterized as a bias to respond to or remember situations as more threatening than they in fact are. In spite of SDT’s power, its conventional use has been limited to simply quantifying differences in sensitivity, bias, and accuracy among perceivers. Left unanswered are questions of particular relevance to research and treatment: what causes the observed differences in bias and sensitivity? A critical barrier to answering this question is the current understanding of SDT in clinical research, which lacks a framework to predict or explain behavior, or in which to pose experimental questions about how mood and anxiety disorders influence the underlying mechanisms involved in threat perception. To bridge this barrier, we introduce a mathematical model of perceptual decision making that incorporates key insights from behavioral economics-utility and optimality- into a signal detection framework. Our primary objective is to use this novel framework to explain differences in threat perception among individuals with GSAD, anxious controls with generalized anxiety disorder (GAD), and non-psychiatrically-ill participants. Our secondary objective is to assess whether our framework could be used to improve interventions to reduce misperceptions of threat in GSAD. Our model is a unique conceptualization of perception (e.g., optimal detection, subjective miscalibration to underlying environmental parameters that influence overt behavior) that could eventually lead to improvements in cognitive-behavioral therapies by tailoring them to a patient’s individual perceptual decision-making impairment. To achieve our aims, we will recruit 100 individuals with GSAD and 100 individuals each from age- and gender-matched GAD and healthy populations. Participants will complete a suite of perceptual tasks to isolate which of several perceptual decision parameters cause misperceptions of social threat in GSAD. Successful characterization of GSAD along such lines will take the field in new directions by framing social threat perception as a decision made by attempting to optimize detection in the presence ambiguous sensory information and conflicting, risky consequences. As well, the novel theoretical developments represented by our model will broaden SDT’s usefulness deepening the insights it affords into the nature of cognitive processes.

Public Health Relevance: Generalized social anxiety disorder (GSAD) is characterized by frequent, debilitating misperceptions of threat and disapproval in non-threatening social circumstances. This research uses a novel theory and method for characterizing various pathways for disordered threat detection in GSAD. The findings will enable clinicians to build more effective behavioral and cognitive therapies by tailoring therapy to target an individual patient’s particular pathways to perceptual impairments.

Behavioral effects of clozapine: Involvement of trace amine pathways in C. elegans and M. musculus

spencer — Thu, 26 Apr 2012 00:19:00 +0000

Clozapine is an antipsychotic medication with superior efficacy in treatment refractory schizophrenia. The molecular basis of clozapine’s therapeutic profile is not well understood. We studied behavioral effects of clozapine in Caenorhabditis elegans to identify novel pathways that modulate clozapine’s biological effects. Clozapine stimulated egg laying in C. elegans in a dose-dependent manner. This effect was clozapine-specific, as it was not observed with exposure to a typical antipsychotic, haloperidol or an atypical antipsychotic, olanzapine. A candidate gene screen of biogenic amine neurotransmitter systems identified signaling pathways that mediate this clozapine-specific effect on egg laying. Specifically, we found that clozapine-induced increase in egg laying requires tyramine biosynthesis. To test the implications of this finding across species, we explored whether trace amine systems modulate clozapine’s behavioral effects in mammals by studying trace amine-associated receptor 1 (TAAR1) knockout mice. Clozapine increased prepulse inhibition (PPI) in wild-type mice. This increase in PPI was abrogated in TAAR1 knockout mice, implicating TAAR1 in clozapine-induced PPI enhancement. In transfected mammalian cell lines, we found no TAAR activation by antipsychotics, suggesting that modulation of trace amine signaling in mice does not occur directly at the receptor itself. In summary, we report a heretofore- unknown role for trace amine systems in clozapine-mediated effects across two species: C. elegans and mice.

Karmacharya, R.*, S.K. Lynn*, S. Demarco, A. Ortiz, X. Wang, M.Y. Lundy, Z. Xie, B.M. Cohen, G.M. Miller, and E.A. Buttner. 2011. Behavioral effects of clozapine: Involvement of trace amine pathways in C. elegans and M. musculus. Brain Research 1393:91-99.

* These authors contributed equally to the study.

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Decision-Making and Learning: The Peak Shift Behavioral Response

spencer — Thu, 26 Apr 2012 00:18:00 +0000

[Excerpt] Peak shift is taxonomically widespread: exhibited by birds; mammals, including humans; fish; and at least some arthropods. The phenomenon thus appears to reflect uni- versal attributes of generalization, discrimination learning, and choice-making behavior. As such, peak shift is a ‘model’ type of decision making, suitable for comparative study at functional and mechanistic levels. Using peak shift as a tractable example of decision making, a variety of organisms can be studied, with strengths differentially well suited to phylogenetic, behavioral, neural, cellular, or molecular investigations.

In addition to being well suited to study at multiple levels, considerations of peak shift go beyond what is typically investigated in research on decision making. Many models of behavioral economics maximize utility: these models consider variability in (1) the costs and benefits of obtaining resources, and how those payoffs change with body state, and (2) the probability of encountering resources of some quality. Game theoretic approaches additionally account for the effect of others’ responses on the decision maker’s own behavior. However, these models overlook the fact that an animal’s estimates of a resource’s payoff and probability are based on sensory signals emitted by the resource. Outside of the laboratory, signals, such as color or tail length, vary. This variation may exist indepen- dently of any variation in the information encoded by the signals. For example, a signal that indicates a particular food quality (yellow skin on a banana signals ripeness) may vary even if the food quality itself does not (ten bananas of the same ripeness may not share the same yellow color). Typical utility optimization approaches account for variance in resource quality, not variance in the stimuli that signal that quality. Since real world signals are noisy, our understanding of choice behavior will be incomplete with- out accounting for signal variation and uncertainty. As a signal detection issue, peak shift experiments present an opportunity to investigate the role of this signal-borne risk in decision making and its interactions with those aspects of decision making more commonly investigated.

Lynn, S.K. 2010. Decision-making and learning: The peak shift behavioral response. In M. Breed & J. Moore (Eds.), Encyclopedia of Animal Behavior (Vol. 1, pp. 470-475). Oxford: Academic Press.

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Normal thermoregulatory responses to 3-iodothyronamine, trace amines and amphetamine-like psychostimulants in trace amine associated receptor 1 knockout mice

spencer — Thu, 26 Apr 2012 00:17:00 +0000

3-Iodothyronamine (T1AM) is a metabolite of thyroid hor- mone. It is an agonist at trace amine-associated receptor 1 (TAAR1), a recently identified receptor involved in mono- aminergic regulation and a potential novel therapeutic tar- get. Here, T1AM was studied using rhesus monkey TAAR1 and/or human dopamine transporter (DAT) co- transfected cells, and wild-type (WT) and TAAR1 knock- out (KO) mice. The IC50 of T1AM competition for binding of the DAT-specific radio-ligand [3H]CFT was highly similar in DAT cells, WT striatal synaptosomes and KO striatal synaptosomes (0.72–0.81 lM). T1AM inhibition of 10 nM [3H]dopamine uptake (IC50: WT, 1.4 6 0.5 lM; KO, 1.2 6 0.4 lM) or 50 nM [3H]serotonin uptake (IC50: WT, 4.5 6 0.6 lM; KO, 4.7 6 1.1 lM) in WT and KO synaptosomes was also highly similar. Unlike other TAAR1 agonists that are DAT substrates, TAAR1 signaling in response to T1AM was not enhanced in the presence of DAT as determined by CRE-luciferase assay. In vivo, T1AM induced robust hypothermia in WT and KO mice equivalently and dose dependently (maximum change degrees Celsius: 50 mg/ kg at 60 min: WT 26.0 6 0.4, KO 25.6 6 1.0; and 25 mg/kg at 30 min: WT 22.7 6 0.4, KO 23.0 6 0.2). Other TAAR1 agonists including beta–phenylethylamine (b-PEA), MDMA (3,4-methylenedioxymethamphetamine) and meth- amphetamine also induced significant, time-dependent thermoregulatory responses that were alike in WT and KO mice. Therefore, TAAR1 co-expression does not alter T1AM binding to DAT in vitro nor T1AM inhibition of [3H]monoamine uptake ex vivo, and TAAR1 agonist- induced thermoregulatory responses are TAAR1-inde- pendent. Accordingly, TAAR1-directed compounds will likely not affect thermoregulation nor are they likely to be cryogens.

Panas, HN, LJ Lynch, EJ Vallender, Z Xie, G Chen, SK Lynn, TS Scanlan, and GM Miller. 2010. Normal thermoregulatory responses to 3-iodothyronamine, trace amines and amphetamine-like psychostimulants in trace amine associated receptor 1 knockout mice. Journal of Neuroscience Research 88:1962-2969.

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Neurophysiological correlates of comprehending emotional meaning in context

spencer — Thu, 26 Apr 2012 00:16:00 +0000

Although the neurocognitive mechanisms of nonaffective language comprehension have been studied extensively, relatively less is known about how the emotional meaning of language is processed. In this study, electrophysiological responses to affectively positive, negative, and neutral words, presented within nonconstraining, neutral contexts, were evaluated under conditions of explicit evaluation of emotional content (Experiment 1) and passive reading (Experiment 2). In both experiments, a widely distributed Late Positivity was found to be larger to negative than to positive words (a ‘‘negativity bias’’). In addition, in Experiment 2, a small, posterior N400 effect to negative and positive (relative to neutral) words was detected, with no differences found between N400 magnitudes to negative and positive words. Taken together, these results suggest that comprehending the emotional meaning of words following a neutral context requires an initial semantic analysis that is relatively more engaged for emotional than for nonemotional words, whereas a later, more extended, attention-modulated process distinguishes the specific emotional valence (positive vs. negative) of words. Thus, emotional processing networks within the brain appear to exert a continuous influence, evident at several stages, on the construction of the emotional meaning of language.

Holt, D.J., S.K. Lynn, and G.R. Kuperberg. 2009. Neurophysiological correlates of comprehending emotional meaning in context. Journal of Cognitive Neuroscience.

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Attenuated modulation of the N170 ERP by facial expressions in schizophrenia

spencer — Thu, 26 Apr 2012 00:15:29 +0000

In psychiatrically-well subjects the modulation of event related potentials (ERPs) by emotional facial expressions is found in several ERPs from ~100 ms and later. A face-related EPR, the N170, is abnormally reduced in schizophrenia to faces relative to other complex objects and research suggests emotional modulation of N170 may be reduced as well. To further examine facial emotion modulation of N170, subjects detected neutral facial expressions from among five emotional expressions (happy, sad, fearful, angry, and disgusted). Over occipitotemporal sites, psychiatrically-well subjects showed bilateral differences in N170 amplitude among expressions (P=0.014). Schizophrenia subjects failed to show this modulation (P=0.551). Accuracy on the task did not differ between groups, nor did the pattern of errors. However, in patients, greater positive and negative symptom ratings were associated with increased failure to button press to neutral faces, suggesting misattribution of emotion to neutral expressions in the more ill patients. Because the N170 is largely specific to faces, these results suggest that an impairment specific to the visual processing of facial expressions contributes to the well-known behavioral abnormalities in facial emotion tasks in schizophrenia.

Lynn, S.K., and D.F. Salisbury. 2008. Attenuated modulation of the N170 ERP by facial expressions in schizophrenia. Journal of Clinical EEG & Neuroscience 39(2):108-111.

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