Startle Eyeblink Research Articles

Evidence that Illness-Compatible Cues Are Rewarding in Women Recovered from Anorexia Nervosa: A Study of the Effects of Dopamine Depletion on Eye-Blink Startle Responses.

In anorexia nervosa (AN), motivational salience is attributed to illness-compatible cues (e.g., underweight and active female bodies) and this is hypothesised to involve dopaminergic reward circuitry. We investigated the effects of reducing dopamine (DA) transmission on the motivational processing of AN-compatible cues in women recovered from AN (AN REC, n = 17) and healthy controls (HC, n = 15). This involved the acute phenylalanine and tyrosine depletion (APTD) procedure and a startle eye-blink modulation (SEM) task. In a balanced amino acid state, AN REC showed an increased appetitive response (decreased startle potentiation) to illness-compatible cues (underweight and active female body pictures (relative to neutral and non-active cues, respectively)). The HC had an aversive response (increased startle potentiation) to the same illness-compatible stimuli (relative to neutral cues). Importantly, these effects, which may be taken to resemble symptoms observed in the acute stage of illness and healthy behaviour respectively, were not present when DA was depleted. Thus, AN REC implicitly appraised underweight and exercise cues as more rewarding than did HC and the process may, in part, be DA-dependent. It is proposed that the positive motivational salience attributed to cues of emaciation and physical activity is, in part, mediated by dopaminergic reward processes and this contributes to illness pathology. These observations are consistent with the proposal that, in AN, aberrant reward-based learning contributes to the development of habituation of AN-compatible behaviours.

Modeling startle eyeblink electromyogram to assess fear learning.

Pavlovian fear conditioning is widely used as a laboratory model of associative learning in human and nonhuman species. In this model, an organism is trained to predict an aversive unconditioned stimulus from initially neutral events (conditioned stimuli, CS). In humans, fear memory is typically measured via conditioned autonomic responses or fear‐potentiated startle. For the latter, various analysis approaches have been developed, but a systematic comparison of competing methodologies is lacking. Here, we investigate the suitability of a model‐based approach to startle eyeblink analysis for assessment of fear memory, and compare this to extant analysis strategies. First, we build a psychophysiological model (PsPM) on a generic startle response. Then, we optimize and validate this PsPM on three independent fear‐conditioning data sets. We demonstrate that our model can robustly distinguish aversive (CS+) from nonaversive stimuli (CS‐, i.e., has high predictive validity). Importantly, our model‐based approach captures fear‐potentiated startle during fear retention as well as fear acquisition. Our results establish a PsPM‐based approach to assessment of fear‐potentiated startle, and qualify previous peak‐scoring methods. Our proposed model represents a generic startle response and can potentially be used beyond fear conditioning, for example, to quantify affective startle modulation or prepulse inhibition of the acoustic startle response.

P-02-015 Perception and evaluation of sexually explicit visual stimuli

The aim of the study was to build a database with validated normative ratings of sexually explicit images by collecting subjective evaluations and psychophysiological measures of general arousal while viewing sexually explicit pictures. Additionally, gender and interpersonal differences (body image (dis)satisfaction and sexual functioning) that may affect responding to sexual stimuli were assessed. Participants with predominantly heterosexual orientation were asked to evaluate pictures according to three independent dimensions (valance, arousal and motivation) or to passively watch images displayed on a computer screen in a full view while psychophysiological assessments were conducted (heart rate, skin conductance and startle response). Sexually explicit pictures are expected to receive higher ratings of arousal than pleasant and neutral pictures, and furthermore, more positive ratings and more to approach tendencies than neutral and negative. Smaller startle eye blink responses are predicted to occur to an acoustic stimulus when viewing sexually explicit stimuli compared to neutral stimuli. Additionally, viewing sexually explicit pictures is hypothesized to be associated with an increased skin conductance and initial heart rate deceleration.There was a significant indirect effect of Contextual Body Image level on valance ratings of sexually explicit pictures through sexual functioning level, b = -0.206, 95% CI [-0.404, -0.058]. This represents a medium effect, κ2 = .113, 95% CI [.033, .201]. There was a significant indirect effect of Contextual Body Image level on motivation ratings of sexually explicit pictures through sexual functioning level, b = -0.220, 95% CI [-0.491, -0.066]. This represents a medium effect, κ2 = .103, 95% CI [.031, .215].

The Relationship between Insulin Resistance, Resting EEG Alpha Wave Asymmetry, and Eye Blink Startle Reflex during International Affective Picture System Presentation

According to the CDC, it is estimated that more than one in three U.S. adults have pre‐diabetes. Pre‐diabetes etiology is characterized by insulin resistance (IR), which is a reduced cellular response to insulin and characterized by lower glucose uptake in the brain. IR is also related to deficits in cognitive and affective processing, particularly reactivity to psychological stress. The goal of our analysis was to determine how IR or hyperglycemia predict eye blink startle reflex (EBR) magnitude and amplitude, an objective index of the startle response, in response to positive, negative and neutral pictures using the International Affective Picture System (IAPS). We similarly assessed if IR predicted resting right frontal asymmetry using electroencephalography (EEG), an established biomarker of predisposition toward negative affect. We hypothesized that individuals with higher IR or hyperglycemia would show greater EBR and EEG right frontal asymmetry.The analysis incorporated healthy adults (N=331 participants), aged 36–84 years old, from the University of Wisconsin‐Madison's MIDUS (Midlife in the United States) II longitudinal study. As described in the MIDUS protocol, fasted blood samples were collected during an overnight stay. EBR in response to IAPS visual stimuli paired with acoustic startle was measured by placing two mini electrodes below the eye. Picture duration was 4,000ms. For a given trial, the acoustic startle stimulus occurred for 50ms during one of three phases: 1) The “early” phase at 2,900ms after picture onset while the picture was on the screen to assess reactivity; 2) the “middle” phase at 400ms after picture offset and removal to assess short‐term recovery; and 3) the “late” phase at 1,900ms after picture offset and removal to assess longer‐term recovery.Resting EEG right frontal asymmetry was collected prior to the IAPS presentation.Data was analyzed using SPSS 23.0. Linear mixed models were used to analyze the main effect of log‐transformed homeostasis model assessment of insulin resistance (HOMA‐IR) on EBR, as well as its interaction with IAPS picture valence (positive, neutral, negative). Higher log10 HOMA‐IR predicted greater EBR amplitude during negative versus positive pictures when paired with the startle stimulus (n=290, p<.05, r2=0.127). Resting state EEG at frontal F3/F4 alpha 1 (8–13 Hz) showed that participants with hyperglycemia had more left than right alpha power (−0.0324 +/− 0.026 vs. 0.0126 +/− 0.028) indicating greater right EEG frontal asymmetry. This result is consistent with Jackson et al. (2003) that hyperglycemia individuals are predisposed to negative emotion/affect. In conclusion, higher IR and type 2 diabetes are related to biomarkers of psychological stress reactivity.Support or Funding InformationThis work is directly supported by the National Institute on Aging (AG047282). Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University Southern California. This research was also supported by NIH grants P30 AG010129 and K01 AG030514.

Voluntary emotion regulation in anorexia nervosa: A preliminary emotion-modulated startle investigation

Emotion regulation difficulties are implicated in the development and maintenance of anorexia nervosa (AN). However, research has been limited by an almost exclusive reliance on self-report. This study is the first to use the emotion-modulated startle paradigm (EMSP) to investigate emotional reactivity and voluntary emotion regulation in individuals with AN. Twenty women with AN viewed negative, positive, neutral, and food images and were asked to enhance, suppress, or maintain their emotional responses mid-way through picture presentation. Startle eyeblink magnitudes in response to startle probes administered prior, and subsequent, to regulation instructions indexed emotional reactivity and regulation, respectively. On emotional reactivity trials, startle magnitudes were greater for negative, positive, and food images, compared to neutral images. Participants had difficulty suppressing startle responses to negative and food images, as indicated by non-significant suppress-maintain comparisons. In contrast, startle responses to enhance and suppress cues during presentation of pleasant images were comparable and significantly lower than maintain cues. Findings converge with self-report data to suggest that patients with AN have difficulties with voluntary emotion regulation. The EMSP may be a promising trans-diagnostic method for examining emotion regulation difficulties that underlie risk for eating disorders and other psychiatric conditions.

Affective Modification of the Startle Eyeblink Response During Sexual and Emotional Infidelity Scripts

The sex difference in jealousy has been demonstrated to occur in response to actual experiences with infidelity, continuous measures of jealousy, as well as cross-culturally. However, to date, the evidence for physiological correlates of jealousy has been limited and mixed. As such, the purpose of this study was to explore the sex difference in jealousy using multiple physiological measures of jealousy. In our study, we demonstrate that the sex difference in jealousy occurs using self-report measures of jealousy in addition to occurring with the affective modification of startle response (but not in response to facial electromyography (EMG), skin conductance, or heart rate). As such, this study demonstrates that the sex difference in jealousy is a replicable finding that occurs when using self-report measures of jealousy in addition to manifesting itself in physiological correlates.

Influence of Interoceptive Fear Learning on Visceral Perception.

Interoceptive fear learning and generalization have been hypothesized to play a key role in unexplained abdominal and esophageal pain in patients with functional gastrointestinal disorders. However, there is no experimental evidence demonstrating that fear learning and generalization to visceral sensations can be established in humans and alter visceral perception. In a novel fear learning-generalization paradigm, an innocuous esophageal balloon distension served as conditioned stimulus (CS), and distensions at three different pressure levels around the pain detection threshold were used as generalization stimuli. During fear learning, the CS was paired with a painful electrical stimulus (unconditioned stimulus) in the conditioning group (n = 30), whereas in the control group (n = 30), the unconditioned stimulus was delivered alone. Before and after fear learning, visceral perception thresholds for first sensation, discomfort, and pain and visceral discrimination sensitivity were assessed. Fear learning was established in the conditioning group only (potentiated eye-blink startle to the CS (t(464.06) = 3.17, p = .002), and fear generalization to other stimulus intensities was observed (t(469.12) = 2.97, p = .003; t(464.29) = 4.17, p < .001). The thresholds for first sensation habituated in the control group, whereas it remained constant in the conditioning group (F(1,43) = 9.77, p = .003). These data show that fear learning using visceral stimuli induces fear generalization and influences visceral perception. These findings support the idea that in functional gastrointestinal disorder, fear learning and generalization can foster gastrointestinal-specific anxiety and contribute to visceral hypersensitivity.

Interaction of threat and verbal working memory in adolescents.

Threat induces a state of sustained anxiety that can disrupt cognitive processing, and, reciprocally, cognitive processing can modulate an anxiety response to threat. These effects depend on the level of cognitive engagement, which itself varies as a function of task difficulty. In adults, we recently showed that induced anxiety impaired working memory accuracy at low and medium but not high load. Conversely, increasing the task load reduced the physiological correlates of anxiety (anxiety-potentiated startle). The present work examines such threat-cognition interactions as a function of age. We expected threat to more strongly impact working memory in younger individuals by virtue of putatively restricted cognitive resources and weaker emotion regulation. This was tested by examining the influence of age on the interaction of anxiety and working memory in 25 adolescents (10 to 17 years) and 25 adults (22 to 46 years). Working memory load was manipulated using a verbal n-back task. Anxiety was induced using the threat of an aversive loud scream and measured via eyeblink startle. Findings revealed that, in both age groups, accuracy was lower during threat than safe conditions at low and medium but not high load, and reaction times were faster during threat than safe conditions at high load but did not differ at other loads. Additionally, anxiety-potentiated startle was greater during low and medium than high load. Thus, the interactions of anxiety with working memory appear similar in adolescents and adults. Whether these similarities reflect common neural mechanisms would need to be assessed using functional neuroimaging.

ANSLAB: Integrated multichannel peripheral biosignal processing in psychophysiological science.

Psychophysiological science employs a large variety of signals from the human body that index the activity of the peripheral nervous system. This allows for studying interactions of psychological and physiological processes that are relevant for understanding cognition, emotion, and psychopathology. The multidimensional nature of the data and the interactions between different physiological signals represent a methodological and computational challenge. Analysis software in this domain is often limited in its coverage of the signals from different physiological systems, and therefore only partially addresses these challenges. ANSLAB (short for Autonomic Nervous System Laboratory) is an integrated software suite that supports data visualization, artifact detection, data reduction, automated processing, and statistical analysis for a large range of autonomic, respiratory, and muscular measures. Analysis modules for cardiovascular (e.g., electrocardiogram, heart rate variability, blood pressure wave, pulse wave, and impedance cardiography), electrodermal (skin conductance level and responses), respiratory (respiratory pattern, timing, and volume variables, as well as capnography), and muscular (eye-blink startle, facial and bodily electromyography) systems are complemented by specialized modules (e.g., body temperature and accelerometry, cross-spectral analysis of respiratory and cardiac measures, signal averaging, and statistical analysis) and productivity-enhancing features (batched processing, fully automatized analyses, and data management). ANSLAB also facilitates the analysis of long-term recordings from ambulatory assessment studies. The present article reviews several analysis modules included in ANSLAB and describes how these address some of the current needs and methodological challenges of psychophysiological science.

Affective Modulation of Brain and Autonomic Responses in Patients With Fibromyalgia.

Emotional dysregulation and abnormal processing of affective information are thought to play a significant role for the maintenance of pain in fibromyalgia. The motivational priming hypothesis states that negative emotions could increase pain via activation of the aversive system, thus leading to an affective modulation of defensive reflexes. Nevertheless, little is known about peripheral and central correlates of affective reflex modulation in fibromyalgia. Thirty patients with fibromyalgia and 30 healthy individuals were asked to view three video clips from a self-perspective to induce specific mood states. Video clips consisted of the same virtual walk through different locations of a park under three affective environments (unpleasant, pleasant, and neutral). Startle eyeblink reflex and heart rate response elicited by abrupt startle noises, as well as heart rate variability and electroencephalography (EEG) oscillations were recorded when participants were passively viewing the virtual environments. Patients with fibromyalgia rated all environments as more negative and arousing than did healthy controls (p values < .05). Nevertheless, startle eyeblink reflex and heart rate response were lower in patients with fibromyalgia than in healthy controls when viewing all three environments (p values < .05). Patients with fibromyalgia also displayed lower heart rate variability, as well as higher EEG power (2-22 Hz) during all environments than did healthy controls (p values < .05). Patients with fibromyalgia were characterized by relevant deficits in affective modulation of startle and cardiac responses, heart rate variability, and EEG power spectra in response to sustained induction of affective states. These findings suggest an alteration of emotional and attentional aspects of information processing at subjective, autonomic, and central nervous system levels.

Interoceptive fear learning to mild breathlessness as a laboratory model for unexpected panic attacks.

Fear learning is thought to play an important role in panic disorder. Benign interoceptive sensations can become predictors (conditioned stimuli – CSs) of massive fear when experienced in the context of an initial panic attack (unconditioned stimulus – US). The mere encounter of these CSs on a later moment can induce anxiety and fear, and precipitate a new panic attack. It has been suggested that fear learning to interoceptive cues would result in unpredictable panic. The present study aimed to investigate whether fear learning to an interoceptive CS is possible without declarative knowledge of the CS–US contingency. The CS consisted of mild breathlessness (or: dyspnea), the US was a suffocation experience. During acquisition, the experimental group received six presentations of mild breathlessness immediately followed by suffocation; for the control group both experiences were always separated by an intertrial interval. In the subsequent extinction phase, participants received six unreinforced presentations of the CS. Expectancy of the US was rated continuously and startle eyeblink electromyographic, skin conductance, and respiration were measured. Declarative knowledge of the CS–US relationship was also assessed with a post-experimental questionnaire. At the end of acquisition, both groups displayed the same levels of US expectancy and skin conductance in response to the CS, but the experimental group showed a fear potentiated startle eyeblink and a different respiratory response to the CS compared to the control group. Further analyses on a subgroup of CS–US unaware participants confirmed the presence of startle eyeblink conditioning in the experimental group but not in the control group. Our findings suggest that interoceptive fear learning is not dependent on declarative knowledge of the CS–US relationship. The present interoceptive fear conditioning paradigm may serve as an ecologically valid laboratory model for unexpected panic attacks.

Startle responding in the context of visceral pain

This study aimed to investigate affective modulation of eye blink startle by aversive visceral stimulation. Startle blink EMG responses were measured in 31 healthy participants receiving painful, intermittent balloon distentions in the distal esophagus during 4 blocks (positive, negative, neutral or no pictures), and compared with startles during 3 ‘safe’ blocks without esophageal stimulations (positive, negative or neutral emotional pictures). Women showed enhanced startle during blocks with distentions (as compared with ‘safe’ blocks), both when the balloon was in inflated and deflated states, suggesting that fear and/or expectations may have played a role. Men's startle did not differ between distention and non-distention blocks. In this particular study context affective picture viewing did not further impose any effect on startle eye blink responses. The current results may contribute to a better understanding of emotional reactions to aversive interoceptive stimulation.

Effects of anxiety sensitivity and expectations on the modulation of the startle eyeblink response during a caffeine challenge.

The way in which the tendency to fear somatic arousal sensations (anxiety sensitivity), in interaction with the created expectations regarding arousal induction, might affect defensive responding to a symptom provocation challenge is not yet understood. The present study investigated the effect of anxiety sensitivity on autonomic arousal, startle eyeblink responses, and reported arousal and alertness to expected vs. unexpected caffeine consumption. To create a match/mismatch of expected and experienced arousal, high and low anxiety sensitive participants received caffeine vs. no drug either mixed in coffee (expectation of arousal induction) or in bitter lemon soda (no expectation of arousal induction) on four separate occasions. Autonomic arousal (heart rate, skin conductance level), respiration (end-tidal CO2, minute ventilation), defensive reflex responses (startle eyeblink), and reported arousal and alertness were recorded prior to, immediately and 30 min after beverage ingestion. Caffeine increased ventilation, autonomic arousal, and startle response magnitudes. Both groups showed comparable levels of autonomic and respiratory responses. The startle eyeblink responses were decreased when caffeine-induced arousal occurred unexpectedly, e.g., after administering caffeine in bitter lemon. This effect was more accentuated in high anxiety sensitive persons. Moreover, in high anxiety sensitive persons, the expectation of arousal (coffee consumption) led to higher subjective alertness when administering caffeine and increased arousal even if no drug was consumed. Unexpected symptom provocation leads to increased attention allocation toward feared arousal sensations in high anxiety sensitive persons. This finding broadens our understanding of modulatory mechanisms in defensive responding to bodily symptoms.

Anxiety sensitivity and the anticipation of predictable and unpredictable threat: Evidence from the startle response and event-related potentials

There is growing evidence that heightened sensitivity to unpredictable threat is a core mechanism of dysfunction in anxiety disorders. However, it is unclear whether anxiety sensitivity is also associated with sensitivity to unpredictable threat. In the present study, 131 participants completed the Anxiety Sensitivity Index-3, which includes physical concerns (PC), social concerns (SC), and cognitive concerns (CC) subscales, and a predictable vs. unpredictable threat-of-shock task. Startle eyeblink and ERP responses (N100, P300) to the acoustic startle probes were measured during the task. PC and CC were associated with heightened and attenuated, respectively, startle for the unpredictable (but not predictable) condition. CC were also associated with attenuated probe N100 for the unpredictable condition only, and PC were associated with increased P300 suppression across the predictable and unpredictable conditions. This study provides novel evidence that the different anxiety sensitivity dimensions demonstrate unique relationships with the RDoC domains “acute” and “potential” threat.

The impact of early neglect on defensive and appetitive physiology during the pubertal transition: a study of startle and postauricular reflexes.

This study tested the effect of early neglect on defensive and appetitive physiology during puberty. Emotion-modulated reflexes, eye-blink startle (defensive) and postauricular (appetitive), were measured in 12-to-13-year-old internationally adopted youth (from foster care or from institutional settings) and compared to non-adopted US born controls. Startle Reflex: adopted youth displayed lower overall startle amplitude across all valences and startle potentiation to negative images was negatively related to severity of pre-adoption neglect. Postauricular reflex (PAR): adopted youth showed larger PAR magnitude across all valences. Puberty: adopted youth showed diminished PAR potentiation to positive images and startle potentiation during mid/late puberty versus the opposite pattern in not-adopted. Early neglect was associated with blunted fast defensive reflexes and heightened fast appetitive reflexes. After puberty, early neglected youth showed physiological hyporeactivity to threatening and appetitive stimuli versus heightened reactivity in not adopted youth. Behavioral correlates in this sample and possible neurodevelopmental mechanisms of psychophysiological differences are discussed.

Self-Reported Trait Mindfulness and Affective Reactivity: A Motivational Approach Using Multiple Psychophysiological Measures

As a form of attention, mindfulness is qualitatively receptive and non-reactive, and is thought to facilitate adaptive emotional responding. One suggested mechanism is that mindfulness facilitates disengagement from an affective stimulus and thereby decreases affective reactivity. However, mindfulness has been conceptualized as a state, intervention, and trait. Because evidence is mixed as to whether self-reported trait mindfulness decreases affective reactivity, we used a multi-method approach to study the relationship between individual differences in self-reported trait mindfulness and electrocortical, electrodermal, electromyographic, and self-reported responses to emotional pictures. Specifically, while participants (N = 51) passively viewed pleasant, neutral, and unpleasant IAPS pictures, we recorded high-density (128 channels) electrocortical, electrodermal, and electromyographic data to the pictures as well as to acoustic startle probes presented during the pictures. Afterwards, participants rated their subjective valence and arousal while viewing the pictures again. If trait mindfulness spontaneously reduces general emotional reactivity, then for individuals reporting high rather than low mindfulness, response differences between emotional and neutral pictures would show relatively decreased early posterior negativity (EPN) and late positive potential (LPP) amplitudes, decreased skin conductance responses, and decreased subjective ratings for valence and arousal. High mindfulness would also be associated with decreased emotional modulation of startle eyeblink and P3 amplitudes. Although results showed clear effects of emotion on the dependent measures, in general, mindfulness did not moderate these effects. For most measures, effect sizes were small with rather narrow confidence intervals. These data do not support the hypothesis that individual differences in self-reported trait mindfulness are related to spontaneous emotional responses during picture viewing.

Event-related potentials to acoustic startle probes during the anticipation of predictable and unpredictable threat.

The startle reflex is a robust measure of defense system activation. Startle probes also elicit ERP P300 and N100 responses that capture attentional engagement. The startle probe-elicited P300 and N100 have been primarily examined during affective picture viewing paradigms, and no study has examined these measures in the context of a threat anticipation task or in relation to threat predictability. In the present study, 131 participants completed a no (N), predictable (P), and unpredictable (U) threat-of-shock task, and the startle eye blink reflex, P300, and N100 responses to the startle probe were measured. We also examined several psychometric properties of these psychophysiological measures. Results indicated probe P300 attenuation during the P and U relative to N condition. In contrast, probe N100 enhancement was present only for the U condition. The P300 and N100 decreased (i.e., habituated) at comparable rates across the different threat conditions. The startle reflex also decreased, but only startle during the U (and not P) condition continued to differ from the N condition by the end of the task. Internal consistency of the ERP measures was acceptable and comparable to the startle reflex. Finally, the startle reflex was correlated with the probe N100, but not P300, across threat conditions. This study is one of the first to use startle probe ERPs to demonstrate that a context of potential threat also elicits attentional engagement. Furthermore, this study provides novel evidence that the probe N100 may provide a measure that is uniquely sensitive to unpredictable threat.

Greater general startle reflex is associated with greater anxiety levels: a correlational study on 111 young women.

Startle eyeblink reflex is a valid non-invasive tool for studying attention, emotion and psychiatric disorders. In the absence of any experimental manipulation, the general (or baseline) startle reflex shows a high inter-individual variability, which is often considered task-irrelevant and therefore normalized across participants. Unlike the above view, we hypothesized that greater general startle magnitude is related to participants’ higher anxiety level. 111 healthy young women, after completing the State-Trait Anxiety Inventory (STAI), were randomly administered 10 acoustic white noise probes (50 ms, 100 dBA acoustic level) while integrated EMG from left and right orbicularis oculi was recorded. Results showed that participants with greater state anxiety levels exhibited larger startle reflex magnitude from the left eye (r109 = 0.23, p < 0.05). Furthermore, individuals who perceived the acoustic probe as more aversive reported the largest anxiety scores (r109 = 0.28, p < 0.05) and had the largest eyeblinks, especially in the left eye (r109 = 0.34, p < 0.001). Results suggest that general startle may represent a valid tool for studying the neural excitability underlying anxiety and emotional dysfunction in neurological and mental disorders.

Fear extinction as a model for synaptic plasticity in major depressive disorder.

BackgroundThe neuroplasticity hypothesis of major depressive disorder proposes that a dysfunction of synaptic plasticity represents a basic pathomechanism of the disorder. Animal models of depression indicate enhanced plasticity in a ventral emotional network, comprising the amygdala. Here, we investigated fear extinction learning as a non-invasive probe for amygdala-dependent synaptic plasticity in patients with major depressive disorder and healthy controls.MethodsDifferential fear conditioning was measured in 37 inpatients with severe unipolar depression (International Classification of Diseases, 10th revision, criteria) and 40 healthy controls. The eye-blink startle response, a subcortical output signal that is modulated by local synaptic plasticity in the amygdala in fear acquisition and extinction learning, was recorded as the primary outcome parameter.ResultsAfter robust and similar fear acquisition in both groups, patients with major depressive disorder showed significantly enhanced fear extinction learning in comparison to healthy controls, as indicated by startle responses to conditioned stimuli. The strength of extinction learning was positively correlated with the total illness duration.ConclusionsThe finding of enhanced fear extinction learning in major depressive disorder is consistent with the concept that the disorder is characterized by enhanced synaptic plasticity in the amygdala and the ventral emotional network. Clinically, the observation emphasizes the potential of successful extinction learning, the basis of exposure therapy, in anxiety-related disorders despite the frequent comorbidity of major depressive disorder.

Fear conditioning and extinction in anxious and nonanxious youth and adults: examining a novel developmentally appropriate fear-conditioning task.

Fear conditioning and extinction have been implicated in the pathogenesis of anxiety disorders. However, due to ethical and methodological limitations, few studies have examined these learning processes across development, particularly among anxious individuals. The present study examined differences in fear conditioning and extinction in anxious and nonanxious youth and adults using a novel task designed to be more tolerable for children than existing paradigms. Twenty-two anxious adults, 15 anxious youth, 30 healthy adults, and 17 healthy youth completed two discriminative fear-conditioning tasks. A well-validated task paired a woman's fearful face with a scream as the unconditioned stimulus. The novel task paired a bell with an aversive alarm as the unconditioned stimulus. Self-reported fear, skin conductance response, and fear-potentiated startle eye blink were measured. Both tasks were well tolerated and elicited fear responses with moderate stability. Anxious youth and adults reported overall greater fear than healthy participants during the tasks, although no group differences occurred in discriminative fear conditioning or extinction, as assessed by self-report or physiology. The novel bell-conditioning task is potent in eliciting fear responses but tolerable for pediatric and anxious populations. Our findings are consistent with prior studies that have shown comparable fear learning processes in anxious and nonanxious youth, but dissimilar from studies exhibiting between-group differences in extinction. Given the limited research on fear conditioning in youth, methodological issues and suggestions for future work are discussed.