Examining relationships among thin-ideal internalization, eating pathology, and motivational reactions to high- and low-calorie food.

Motivational responses to food stimuli are relevant for eating disorders (EDs). Research examining reactions to food in EDs has been mixed, with some studies reporting enhanced appetitive responses, and others observing defensive responses, to food. Thin-ideal internalization, a socio-cognitive factor implicated in EDs, may relate to these mixed findings, as individuals with eating pathology may experience food as a threat to internalized ideals of thinness, despite its inherently appetitive qualities. In the present study, physiological reflexes measuring defensive (startle blink reflex) and appetitive (postauricular reflex) responding as well as self-report ratings were recorded while 88 women with and without eating pathology viewed images of high- and low-calorie food. Greater global eating pathology, but not thin-ideal internalization, was associated with negative self-report valence ratings and lower craving ratings of high-calorie food. In contrast, greater thin-ideal internalization and eating pathology both related to more positive self-report valence ratings of low-calorie food, with thin-ideal internalization accounting for some of the shared variance between low-calorie food ratings and eating pathology. Overall, thin-ideal internalization may represent a higher-order factor that may contribute to the relationship between conscious reactions to food and disordered eating.

Acquisition and inhibition of conditioned fear is modulated by individual stimulus fear-relevance.

Inhibitory learning is an important factor for decreasing fear expression. We investigated conditioned inhibition of learned fear responses using conditioned excitors and inhibitors differing in fear-relevance in a sample of 48 healthy female students. To study the effect of stimulus fear-relevance, we used the fear potentiated startle paradigm in an AX+/BX- discrimination learning task with fear-relevant (spider) vs. fear-irrelevant (butterfly) pictures as CS+ (A) and CS- (B), respectively. We found that, during acquisition, participants with elevated fear of spiders showed stronger fear potentiated startle to AX+ compared to BX- when the inhibitor (B) was fear-irrelevant (butterfly) using both median split as well as correlational analyses. In contrast, when the excitor (A) was fear-irrelevant (butterfly), fear potentiated startle to AX+ compared to BX- was reduced for participants with higher fear of spiders. Effects of conditioned inhibition were studied in a summation test, where excitor and inhibitor were presented in compound (AB) and compared to the last four excitor trials during prior acquisition. Conditioned inhibition was stronger for participants with a higher fear of spiders, when the butterfly acted as conditioned inhibitor (B). On the other hand, when the spider served as conditioned inhibitor, effects of conditioned inhibition were weaker for participants with higher fear of spiders. Hence, rather than to a general preparedness our data point to a specific impairment in safety learning for individually fear-relevant stimuli.

Social stimuli increase physiological reactivity but not defensive responses.

Emotional reactions are crucial in survival because they provide approach and withdrawal behaviors. However, an unsolved question is whether the social content of the affective stimuli has a specific effect on emotional responses. We studied whether the social content of affective pictures influenced the defensive response and response mobilization. For this purpose, we recorded startle blink reflex (a defensive response) and skin conductance responses (a measure of unspecific physiological reactivity or arousal) in 73 participants while they viewed a series of 81 pictures of varying affective valence and social content. Our results revealed that defense response, as indicated by increases in the magnitude of the startle blink reflex, was mainly dependent on threatening or unpleasant cues, but was unrelated to the social content of the pictures. The social content, however, had an influence on pleasant stimuli, provoking an increase in resource mobilization, as reflected by changes in electrodermal activity. Hence, the social content of the affective stimuli may increase the physiological arousal elicited by pleasant stimuli, and it appears to be unrelated to the defense reactivity provoked by unpleasant stimuli.

Effects of intolerance of uncertainty on subjective and psychophysiological measures during fear acquisition and delayed extinction.

Individuals who score high in self-reported Intolerance of Uncertainty (IU) tend to find uncertainty unacceptable and aversive. In recent years, research has shed light on the role of IU in modulating subjective (i.e. expectancy ratings) and psychophysiological responses (i.e. skin conductance) across different classical fear conditioning procedures. In particular, during immediate extinction higher IU is associated with disrupted safety learning. However, there remain gaps in understanding how IU, in comparison to other negative emotionality traits (STAI-T), impact different types of subjective and psychophysiological measures during different classical fear conditioning procedures. In our exploratory study, we analyzed IU, STAI-T, subjective (i.e. fear ratings) and psychophysiological (i.e. skin conductance, auditory startle blink) data recorded during fear acquisition training and 24 h-delayed extinction training (n = 66). Higher IU, controlled for STAI-T, was: (1) significantly associated with greater fear ratings to the learned fear cue during fear acquisition training, and (2) at trend associated with greater fear ratings to the learned fear versus safe cue during delayed extinction training. Null results were observed for both IU and STAI-T in relation to skin conductance and auditory startle blink during fear acquisition training and delayed extinction training. These results add to and extend our current understanding of the role of IU on subjective and physiological measures during different fear conditioning procedures particularly that of subjective fear ratings during acquisition and delayed extinction training. Implications of these findings and future directions are discussed.

Implicit and explicit motivational responses to high- and low-calorie food in women with disordered eating.

Eating disorders and their symptoms are thought to be associated with altered motivational responding to food. Binge eating may relate to increased reward reactivity, restrictive eating may be associated with increased threat and/or decreased reward reactivity, and the combination of these symptoms within an individual may be linked to motivational conflict to food. Using both implicit (i.e., physiological) and explicit (i.e., self-reported) measures, we tested these hypotheses in 88 women with binge eating only, restrictive eating only, both binge eating and restrictive eating, or no eating pathology. Participants viewed and rated high-calorie food, low-calorie food, and emotional images while startle eye blink and postauricular reflexes were measured. Arousal and craving, but not valence, ratings were significantly greater for high- than low-calorie food. Startle blink reflexes during all food images were significantly lower than during neutral images, whereas only high-calorie foods related to greater postauricular reactivity than neutral images. Eating pathology group did not predict implicit and explicit motivational reactions to food. Exploratory dimensional analyses revealed that rating low-calorie foods as lower on craving predicted endorsement of restrictive eating, while rating low-calorie foods as lower on valence and arousal, and experiencing lower postauricular reactivity to high-calorie foods minus neutral images, predicted greater frequency of restrictive eating episodes. Decreased implicit and explicit appetitive motivation to high- and low-calorie food may relate to the presence and frequency of restrictive eating. Future longitudinal research should investigate whether decreased appetitive responding to food is a risk factor for, versus consequence of, restrictive eating.

Better cognitive efficiency is associated with increased experimental anxiety.

There is increased interest in the development of cognitive training targeting working memory (WM) to alleviate anxiety symptoms, but the effectiveness of such an approach is unclear. Improved understanding of the effect of cognitive training on anxiety may facilitate the development of more effective cognitive training treatment for anxiety disorders. This study uses an experimental approach to examine the interplay of WM and anxiety following WM training. Previous studies show that increased demand on WM reduces concurrent anxiety evoked by threat of shock (induced anxiety). However, improving WM pharmacologically or via exercise prevents this anxiolytic effect. Conceivably, improving WM frees up cognitive resources to process threat information, thereby increasing anxiety. The present study tested the hypothesis that practicing a high load WM (i.e., increased demand) task would improve WM, and thus, free cognitive resources to process threat of shock, resulting in more anxiety (i.e., greater startle) during a subsequent WM task. Participants were randomly assigned to two training groups. The active-training group (N = 20) was trained on a 1- (low load) & 3-back (high load) WM task, whereas the control-training group (N = 20) performed a 0-back WM task. The experimental phase, similar in both groups, consisted of a 1- & 3-back WM task performed during both threat of shock and safety. As predicted, active training improved WM accuracy and increased anxiety during the experimental 3-back WM task. Therefore, improving WM efficiency can increase anxiety, possibly by freeing WM resources to process threat information.

Psychophysiological treatment outcomes: Corticotropin-releasing factor type 1 receptor antagonist increases inhibition of fear-potentiated startle in PTSD patients.

After exposure to a traumatic event, a subset of people develop post-traumatic stress disorder (PTSD). One of the key deficits in PTSD is regulation of fear, and impaired inhibition of fear-potentiated startle (FPS) has been identified as a potential physiological biomarker specific to PTSD. As part of a larger clinical trial, this study investigated the effects of a CRF receptor 1 antagonist, GSK561679, on inhibition of fear-potentiated startle during a conditional discrimination fear-conditioning paradigm, termed AX+/BX-. Prior research using this paradigm has demonstrated deficits in inhibition of conditioned fear in several PTSD populations. The randomized, double-blind, placebo-controlled clinical trial compared fear inhibition between female PTSD participants taking 350 mg/day GSK561679 (n = 47 pre- and 29 post-treatment) and patients taking a placebo pill (n = 52 pre- and 30 post-treatment) daily for 6 weeks. There was no significant difference between the two groups in their acquisition of fear or discrimination between threat and safety cues, and no pre-post-treatment effect on these measures. However, there was a significant effect of treatment on inhibition of FPS during the AB trials in the AX+/BX- transfer test (p < 0.05). While all PTSD participants showed typical impairments in fear inhibition prior to treatment, GSK561679 enhanced fear inhibition post-treatment, independent of clinical effects. The current study suggests that CRF receptor 1 antagonism may have specific effects within neural circuitry mediating fear inhibition responses, but not overall symptom presentation, in PTSD.

Attention allocation to subliminally presented affective faces in high and low social anxiety.

Attention bias to affective stimuli, particularly threatening stimuli, has been well documented, with attention bias to affective faces often reported in populations with social anxiety (SA). However, inconsistencies exist in the literature regarding the direction of the bias, with some studies reporting a bias to attend toward social threat, and others reporting a bias to avoid social threat. This variability in the attention bias literature could be related to fluctuations in how attentional resources are allocated toward social stimuli over time. This study aimed to isolate early processing of affective faces using a backward masking paradigm in participants with high and low levels of subclinical SA. We used prepulse inhibition (PPI) of startle to index the amount of early attention allocated to masked affective faces. There was greater PPI to masked angry faces compared to neutral faces across all participants, suggesting that more attention was allocated to threatening faces. This effect was similar across face genders and participant SA levels. There was also a trend for more attention to be allocated to masked affective faces (angry and happy) compared to neutral faces across all participants. These findings demonstrate that attention bias to subliminal affect, and threat specifically, may not be modulated by subclinical levels of SA at very early stages of attention processing.

Startle during backward evaluative conditioning is not modulated by instructions.

Instructions highlighting that backward conditional stimuli (CSs) stop unconditional stimuli (USs) result in their acquiring valence opposite to that of the US on explicit measures of valence. We assessed whether such instructions would influence startle blink modulation in the same way. Two groups were presented with concurrent forward and backward evaluative conditioning (CS-US-CS) using cartoon aliens as CSs, and pleasant, neutral, and unpleasant sounds as USs. Startle magnitude was measured during conditioning and valence ratings were assessed after conditioning. Participants in the "start-stop" instructions group (n = 41) were instructed to learn whether CSs started or stopped US presentations, while participants in the "observe" instructions group (n = 41) were told to pay attention to the stimuli as they would be asked questions about them after the experiment. In the start-stop instructions group backward CSs paired with positive USs were rated as less pleasant than backward CSs paired with neutral and negative USs (contrast effect), whereas ratings of backward CSs did not differ in the observe instructions group. Startle magnitude was larger during backward CSs paired with positive USs in comparison to CSs paired with neutral or negative USs in both instruction groups. Startle blink modulation was unaffected by instructions, suggesting that startle indexes the emotional state at the time of probe presentation rather than CS valence based on propositional information about the function of the CS.

Interoception, conditioning, and fear: The panic threesome.

The present article aims to illustrate and review evidence on how associative learning involving interoceptive stimuli (interoceptive conditioning) can lead to changes in physiological, emotional, and perceptual outcomes. We first outline a functional perspective on Pavlovian conditioning and provide a general introduction and historical background on interoceptive conditioning as a special instance of Pavlovian conditioning. Next, biological and learning accounts of panic disorder are discussed, followed by an analysis of which stimuli and responses may be most promising to model learning that is relevant to panic disorder. Finally, studies on interoceptive fear conditioning with respiratory stimuli are reviewed and discussed, and future directions are outlined.

Fear-potentiated startle response as an endophenotype: Evaluating metrics and methods for genetic applications.

The modulation of the startle response (SR) by threatening stimuli (fear-potentiated startle; FPS) is a proposed endophenotype for disorders of the fearful-fearlessness spectrum. FPS has failed to show evidence of heritability, raising concerns. However, metrics used to index FPS-and, importantly, other conditional phenotypes that are dependent on a baseline-may not be suitable for the approaches used in genetic epidemiology studies. Here, we evaluated multiple metrics of FPS in a population-based sample of preadolescent twins (N = 569 from 320 twin pairs, Mage = 11.4) who completed a fear-conditioning paradigm with airpuff-elicited SR on two occasions (~1 month apart). We applied univariate and multivariate biometric modeling to estimate the heritability of FPS using several proposed standardization procedures. This was extended with data simulations to evaluate biases in heritability estimates of FPS (and similar metrics) under various scenarios. Consistent with previous studies, results indicated moderate test-retest reliability (r = 0.59) and heritability of the overall SR (h2 = 34%) but poor reliability and virtually no unique genetic influences on FPS when considering a raw or standardized differential score that removes baseline SR. Simulations demonstrated that the use of differential scores introduces bias in heritability estimates relative to jointly analyzing baseline SR and FPS in a multivariate model. However, strong dependency of FPS on baseline levels makes unique genetic influences virtually impossible to detect regardless of methodology. These findings indicate that FPS and other conditional phenotypes may not be well suited to serve as endophenotypes unless such codependency can be disentangled.

Measuring the conditioned response: A comparison of pupillometry, skin conductance, and startle electromyography.

In human fear conditioning studies, different physiological readouts can be used to track conditioned responding during fear learning. Commonly employed readouts such as skin conductance responses (SCR) or startle responses have in recent years been complemented by pupillary readouts, but to date it is unknown how pupillary readouts relate to other measures of the conditioned response. To examine differences and communalities among pupil responses, SCR, and startle responses, we simultaneously recorded pupil diameter, skin conductance, and startle electromyography in 47 healthy subjects during fear acquisition, extinction, and a recall test on 2 consecutive days. The different measures correlated only weakly, displaying most prominent differences in their response patterns during fear acquisition. Whereas SCR and startle responses habituated, pupillary measures did not. Instead, they increased in response to fear conditioned stimuli and most closely followed ratings of unconditioned stimulus (US) expectancy. Moreover, we observed that startle-induced pupil responses showed stimulus discrimination during fear acquisition, suggesting a fear potentiation of the auditory pupil reflex. We conclude that different physiological outcome measures of the conditioned response inform about different cognitive-affective processes during fear learning, with pupil responses being least affected by physiological habituation and most closely following US expectancy.

Vagally mediated heart rate variability and safety learning: Effects of instructions and number of extinction trials.

Extinction of conditioned fear serves as a laboratory model for the mechanism of action underlying exposure treatment with patients suffering from anxiety disorders. Thus, an enhanced understanding of individual differences in extinction learning may help to improve exposure procedures by tailoring treatment plans to the specific needs of the patient. Vagally mediated heart rate variability (vmHRV) is a promising candidate to investigate individual differences in extinction learning because vmHRV is influenced by an inhibitory prefrontal-amygdala network that is similarly implied in extinction learning. Moreover, low levels of vmHRV were previously associated with a higher prevalence of anxiety disorders and a deficit in safety learning. Here, we report on two studies (Study 1: N = 48; Study 2: N = 120) in which we investigated the boundary conditions of the observed association between vmHRV and safety learning as indexed by startle potentiation during instructed or uninstructed extinction training. In Study 1 (conditional discrimination task), we found that low vmHRV levels are associated with higher CS+ potentiation during instructed extinction. In Study 2 (differential cue conditional task), we observed an association between individual vmHRV levels and defensive responding during CS- presentations and, in later instructed extinction trials, during intertrial intervals. These findings indicate an overactive defensive system in individuals with low levels of vmHRV that interferes with their ability to recognize safety and thus is associated with a general perception of unsafety.

Associations between self-report and physiological measures of emotional reactions to food among women with disordered eating.

Individuals with eating disorders have exhibited both positive and negative emotional responses to food when assessed via self-report and psychophysiology. These mixed findings may be explained by a lack of association between self-report and physiological measures, and the degree of association may differ based on core eating disorder symptoms like dietary restriction and binge eating. Women from the community (N = 82) were recruited based on the presence or absence of dietary restriction and binge eating. We examined the startle eyeblink reflex, a physiological measure of defensive motivation, in relation to self-reported valence, arousal, and craving ratings of emotional (positive, neutral, negative) and food (high- and low-calorie) images. Dietary restriction and binge eating were investigated as moderators of self-report/physiology relationships. Replicating extant literature, valence ratings of emotional images were correlated with startle blink reflex magnitude, with more unpleasant ratings related to higher startle eyeblink reflex magnitudes. Increased craving, but not valence, ratings of food images were related to lower startle blink reflex magnitudes. Dietary restriction and binge eating did not moderate the relationship between self-report ratings and startle blink magnitude to food. Our findings suggest that self-reported appetitive motivation towards food relates to a decrease in physiologically measured aversion towards food. Future research should examine the extent to which self-report ratings correlate with physiological indices of positive emotion (e.g., postauricular reflex, zygomaticus major) during the viewing of food images in both patients with eating disorders and healthy controls.

Startle reflex modulation during threat of shock and "threat" of reward.

During threat of shock, the startle reflex is potentiated, suggesting modulation by defensive mobilization. To determine whether startle potentiation is specific to aversive anticipation, startle reflexes were measured in the context of either aversive or appetitive anticipation in a between-subject study. Participants wore a device on the wrist that could deliver electrical shock (n = 49), or vibrotactile stimulation indicating monetary reward (n = 48). Cues signaling "threat" or "safe" periods were presented alone, or accompanied by presentation of affective and neutral pictures on half of the trials. Results indicated that the startle reflex was significantly potentiated when anticipating either shock or reward, compared to safe periods, both when no picture was presented, as well as during picture viewing. The difference between threat and safety in both reflex magnitude and skin conductance changes was larger for those anticipating shock, suggesting that the aversive context was more motivationally engaging. The pattern of reflex modulation as a function of picture valence varied under threat and safety, but was identical in the shock and reward groups, consistent with a hypothesis that anticipation of either aversive or appetitive events prompts heightened perceptual vigilance, potentiating the acoustic startle reflex.

Event-related potentials to threat of predictable and unpredictable shock.

Cognitive affective neuroscience tasks that are straightforward to administer, measure key constructs of interest, and can be used in different lab settings and with multiple psychophysiological methods can lead to a more complete understanding of experimental effects. The no-threat, predictable threat, unpredictable threat (NPU-threat) task assesses constructs of interest to both clinical and basic affective science literatures, is relatively brief to administer, and has been used across labs with a number of different measurements (e.g., startle eyeblink, fMRI, corrugator response, subjective ratings). ERPs provide another means of assessing neurobiological reactivity during the NPU-threat task, but to date such measures have been underutilized. That is, no study has yet evaluated cue-elicited ERPs in the NPU-threat task. Here, cue-elicited ERPs were assessed in 78 participants who completed a version of the NPU-threat task previously shown to reliably moderate startle eyeblink amplitudes. Results showed larger P2 amplitudes for unpredictable versus predictable trials, increased P3s and late positive potentials for threatening versus no-threat trials, as well as larger stimulus preceding negativities for threatening versus no-threat trials (driven primarily by predictable threat cues). In line with prior work, we observed enhanced startle eyeblink for threatening versus no-threat trials and for unpredictable compared to predictable threat interstimulus intervals. In addition, the probe-elicited P3 was suppressed for predictable and unpredictable compared to no-threat trials. Therefore, cue-elicited ERPs, which can be recorded alongside other measures in the NPU-threat task (e.g., startle), may provide useful indices of temporally distinct stages of predictable and unpredictable threat processing.

If or when? Uncertainty's role in anxious anticipation.

Uncertainty is often associated with subjective distress and a potentiated anxiety response. Occurrence uncertainty, or the inability to predict if a threat will occur, has rarely been compared experimentally with temporal uncertainty, or the inability to predict when a threat will occur. The current study aimed to (a) directly compare the anxiogenic effects of anticipating these two types of uncertain threat, as indexed by the eyeblink startle response, and (b) assess the relationship between startle response to occurrence and temporal uncertainty and individual differences in self-reported intolerance of uncertainty and anxiety. The findings indicated that anticipation during occurrence uncertainty elicited a larger startle response than anticipating a certain threat, but anticipation during temporal uncertainty was superior at potentiating startle blink overall. Additional analyses of the effects of order and habituation further highlighted temporal uncertainty's superiority in eliciting greater startle responding. This suggests that, while uncertainty is physiologically anxiety provoking, some level of certainty that the threat will occur enhances the robustness of the physiological anxiety response. However, self-reported anxiety was equivalent for temporal and occurrence uncertainty, suggesting that, while defensive responding may be more affected by temporal uncertainty, people perceive both types of uncertainty as anxiogenic. Individual differences in the intolerance of uncertainty and other anxiety measures were not related to anticipatory startle responsivity during any of the conditions.

Using Event-Related Potentials and Startle to Evaluate Time Course in Anxiety and Depression.

The National Institute of Mental Health's Research Domain Criteria initiative is a research framework designed toward understanding psychopathology as abnormalities of dimensional neurobehavioral constructs rather than in terms of DSM-defined categories. Research Domain Criteria constructs within the negative valence domain are particularly relevant for understanding anxiety and depressive disorders, which are pervasive, debilitating, and characterized by negative processing bias. One important direction for Research Domain Criteria research is investigating processes and parameters related to the time course (or chronometry) of negative valenced constructs. Two reliable methods for assessing chronometry are event-related potentials (ERPs) and startle blink. In this qualitative review, we examine ERP and startle studies of individuals with anxiety or depression or individuals vulnerable to affective disorders. The aim of the review is to highlight how these methods can inform the role of chronometry in the spectrum of anxiety and depression. ERP studies examining different chronometry facets of negative valenced responses have shown that transdiagnostic groups of individuals with internalizing psychopathologies exhibit abnormalities at early stages of processing. Startle reactivity studies have robustly differentiated fear-based disorders (e.g., panic disorder, social phobia) from other anxiety disorders (e.g., generalized anxiety disorder) and have also shown that different internalizing phenotypes exhibit different patterns of habituation. Findings lend support to the value of ERP and startle measures in identifying groups that cut across conventional classification systems. We also highlight methodological issues that can aid in the validity and reproducibility of ERP and startle findings and, ultimately, in the goal of developing more precise models of anxiety and depression.

Escaping aversive exposure.

This research examined human defensive reactivity when exposure to an aversive event could be escaped but not entirely avoided. Prolonged visual cues indicated whether exposure to an upcoming aversive (i.e., disgusting) picture could be terminated after onset (escaped) or not, or that a neutral go signal would appear. Acoustically elicited startle reflexes were measured during each cue interval, as were cardiac and skin conductance activity. Early in the cuing interval, startle reflexes were potentiated during both escape and inescapable exposure trials, compared to the simple motor context. Later in the interval, reflexes remained potentiated for both escapable and inescapable trials, with potentiation further enhanced when aversive exposure could not be escaped compared to when exposure could be escaped. Heart rate deceleration in the cuing interval indicated increased vigilance when preparing any (escape or neutral) action, whereas skin conductance responding indicated enhanced sympathetic action mobilization particularly in an escape context. These data suggest that startle reflexes engaged in an escape context reflect both motor-related response inhibition and aversive potentiation, and they indicate that defensive motivation is engaged whenever aversive exposure is guaranteed, regardless of whether it can be escaped or not.

Heritability of startle reactivity and affect modified startle.

Startle reflex and affect-modified startle reflex are used as indicators of defensive reactivity and emotional processing, respectively. The present study investigated the heritability of both the startle blink reflex and affect modification of this reflex in a community sample of 772 twins ages 14-15years old. Subjects were shown affective picture slides falling in three valence categories: negative, positive and neutral; crossed with two arousal categories: high arousal and low arousal. Some of these slides were accompanied with a loud startling noise. Results suggested sex differences in mean levels of startle reflex as well as in proportions of variance explained by genetic and environmental factors. Females had higher mean startle blink amplitudes for each valence-arousal slide category, indicating greater baseline defensive reactivity compared to males. Startle blink reflex in males was significantly heritable (49%), whereas in females, variance was explained primarily by shared environmental factors (53%) and non-shared environmental factors (41%). Heritability of affect modified startle (AMS) was found to be negligible in both males and females. These results suggest sex differences in the etiology of startle reactivity, while questioning the utility of the startle paradigm for understanding the genetic basis of emotional processing.