Fear and anxiety are normal responses to a threat. However, anxiety is considered abnormal when the response to the threat is excessive or inappropriate. This study will examine changes in the body and brain that occur during unpleasant learning experiences in healthy volunteers with high, moderate, and low levels of anxiety. A high degree of generalized anxiety is a component of many anxiety disorders and is regarded as a marker of vulnerability for these disorders. People with anxiety disorders and individuals with high degrees of anxiety have inappropriate expectations of unpleasant events. This study will investigate the development of expecting unpleasant events in healthy volunteers with varying degrees of anxiety using aversive conditioning models. A later phase of the study will enroll participants with anxiety disorders and compare their responses to those of healthy volunteers. Patients who meet criteria for an anxiety disorder, and healthy volunteers who have no history of psychiatric or major medical illness will be enrolled in this study. Volunteers will come to the NIH Clinical Center three times for outpatient testing....
High-generalized anxiety is a concomitant of many anxiety disorders and is often regarded as a vulnerability marker for these disorders. One characteristic of patients with anxiety disorders and high trait-anxious individuals is inappropriate expectancies of aversive events. The overall aim of the present protocol is to investigate mechanisms that may promote the development of these aversive expectancies using expectancy-based, associative-learning models. During aversive conditioning in which a phasic explicit-cue (e.g., a light) is repeatedly associated with an aversive unconditioned-stimulus (e.g., a shock), the organism develops fear to the explicit cue as well as to the environmental context in which the experiment took place. We have obtained preliminary evidence suggesting that contextual fear represents aspects of aversive states that are central to anxiety disorders. In this protocol, we seek further evidence for the relevance of contextual fear to mood anxiety disorders. One important determinant of contextual fear in both humans and animals is predictability: contextual fear increases when aversive events (e.g., electric shock) are unpredictable, as opposed to when they are predictable. The present protocol will examine the role of predictability of aversive states and of conditioning on threat appraisal in individuals with mood and anxiety disorders. A second aim is to examine the interaction between experimentally-induced anxiety and cognitive processes, more specifically working memory, in mood and anxiety disorders.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
921
During threat, a participant could receive a shock. During safe, a participant could not receive as shock. Participants selected their highest tolerable level of shock.
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States
Change in Percent of Correct Button Presses During Threat Compared to the Safe Condition (AAST)
Subjects participated in go/no go (GNG) task condition during periods of threat of shocks and periods of safety when no shock could be administered. During the GNG stimuli were presented on a monitor. In the GNG task, participants were asked to respond to frequent 'go' stimuli ('=') by pressing the '2' on the keypad of a computer keyboard and to withhold their response to infrequent 'nogo' stimuli ('O'). Stimuli were randomly distributed. A correct go hit was a response recorded during these 2000 ms to a go trial. Similarly, a correct nogo omission was a no response during the same period to a nogo trial. Performance was determined for each condition (threat, safe) and trial type (go, nogo) by dividing the number of correct responses by the total number of each trial type. Improvement in accuracy was measured as a higher percent of correct button presses during threat compared to safety.
Time frame: 2000 ms during trial
Change in Percent of Correct no Button Presses During Threat Compared to the Safe Condition
Subjects participated in go/no go (GNG) task condition during periods of threat of shocks and periods of safety when no shock could be administered. During the GNG stimuli were presented on a monitor. In the GNG task, participants were asked to respond to frequent 'go' stimuli ('=') by pressing the '2' on the keypad of a computer keyboard and to withhold their response to infrequent 'nogo' stimuli ('O'). Stimuli were randomly distributed. A correct go hit was a response recorded during these 2000 ms to a go trial. Similarly, a correct nogo omission was a no response during the same period to a nogo trial. Performance was determined for each condition (threat, safe) and trial type (go, nogo) by dividing the number of correct responses by the total number of each trial type. Improvement in accuracy was measured as a higher percent of correct button presses during threat compared to safety.
Time frame: 2000 ms during trial
Correct-go Reaction Time (RT) - Safe Condition
Correct go responses were go trials followed by button press. Reaction time (RT) is the time it takes to respond to stimuli. Participants RTs were measured while undergoing alternating periods of safety and shock threat conditions i.e. while anticipating unpleasant electric shocks (threat) or no shock (safe). Mean reaction time (RT) was calculated for correct-go to evaluate speed-accuracy trade-off.
Time frame: 2000 ms during trial
Correct-go Reaction Time (RT) - Threat Condition
Correct go responses were go trials followed by button press. Reaction time (RT) is the time it takes to respond to stimuli. Participants RTs were measured while undergoing alternating periods of safety and shock threat conditions i.e. while anticipating unpleasant electric shocks (threat) or no shock (safe). Mean reaction time (RT) was calculated for correct-go to evaluate speed-accuracy trade-off.
Time frame: 2000 ms during trial
Go Correct Hits Followed by Button Press - Safe Condition
Subjects participated in go/no go (GNG) task condition during periods of threat of shocks and periods of safety when no shock could be administered. During the GNG stimuli were presented on a monitor. In the GNG task, participants were asked to respond to frequent 'go' stimuli ('=') by pressing the '2' on the keypad of a computer keyboard and to withhold their response to infrequent 'nogo' stimuli ('O'). Stimuli were randomly distributed. A correct go hit was a response recorded during these 2000 ms to a go trial. Similarly, a correct nogo omission was a no response during the same period to a nogo trial. Performance was determined for each condition (threat, safe) and trial type (go, nogo) by dividing the number of correct response by the total number of each trial type.
Time frame: 2000 ms during trial
Go Correct Hits Followed by Button Press - Threat Condition
Subjects participated in go/no go (GNG) task condition during periods of threat of shocks and periods of safety when no shock could be administered. During the GNG stimuli were presented on a monitor. In the GNG task, participants were asked to respond to frequent (91%) 'go' stimuli ('=') by pressing the '2' on the keypad of a computer keyboard and to withhold their response to infrequent (9%) 'nogo' stimuli ('O'). Stimuli were randomly distributed. A correct go hit was a response recorded during these 2000 ms to a go trial. Similarly, a correct nogo omission was a no response during the same period to a nogo trial. Performance was determined for each condition (threat, safe) and trial type (go, nogo) by dividing the number of correct response by the total number of each trial type.
Time frame: 2000 ms during trial
Nogo Trials Followed by no Button Press - Safe Condition
Subjects participated in go/no go (GNG) task condition during periods of threat of shocks and periods of safety when no shock could be administered. During the GNG stimuli were presented on a monitor. In the GNG task, participants were asked to respond to frequent 'go' stimuli ('=') by pressing the '2' on the keypad of a computer keyboard and to withhold their response to infrequent 'nogo' stimuli ('O'). Stimuli were randomly distributed. A correct go hit was a response recorded during these 2000 ms to a go trial. Similarly, a correct nogo omission was a no response during the same period to a nogo trial. Performance was determined for each condition (threat, safe) and trial type (go, nogo) by dividing the number of correct response by the total number of each trial type.
Time frame: 2000 ms during trial
Nogo Trials Followed by no Button Press - Threat Condition
Subjects participated in go/no go (GNG) task condition during periods of threat of shocks and periods of safety when no shock could be administered. During the GNG stimuli were presented on a monitor. In the GNG task, participants were asked to respond to frequent 'go' stimuli ('=') by pressing the '2' on the keypad of a computer keyboard and to withhold their response to infrequent 'nogo' stimuli ('O'). Stimuli were randomly distributed. A correct go hit was a response recorded during these 2000 ms to a go trial. Similarly, a correct nogo omission was a no response during the same period to a nogo trial. Performance was determined for each condition (threat, safe) and trial type (go, nogo) by dividing the number of correct response by the total number of each trial type.
Time frame: 2000 ms during trial
Stroop Effect on Accuracy During Congruent Task Viewing Positive Images: Safe Condition
Participants watched as six trial types differing by congruence and emotion (negative, neutral, positive) were presented during condition blocks (safe, threat) on a computer screen. Each trial began with a fixation point which was then immediately followed by a picture stimulus, followed by a numerical display, followed by a repeat of the picture stimulus, and followed by a blank screen. During threat, a participant could receive a shock. During safe, a participant could not receive a shock. The effect of accuracy on congruence across negative, positive, and neutral images in threat and safe conditions was assessed by participants accurate identification of facial expression.
Time frame: 11.2 minutes per run for a total of 22.4 minutes
Stroop Effect on Accuracy During Congruent Task Viewing Positive Images: Threat Condition
Participants watched as six trial types differing by congruence and emotion (negative, neutral, positive) were presented during condition blocks (safe, threat) on a computer screen. Each trial began with a fixation point which was then immediately followed by a picture stimulus, followed by a numerical display, followed by a repeat of the picture stimulus, and followed by a blank screen. During threat, a participant could receive a shock. During safe, a participant could not receive a shock. The effect of accuracy on congruence across negative, positive, and neutral images in threat and safe conditions was assessed by participants accurate identification of facial expression.
Time frame: 11.2 minutes per run for a total of 22.4 minutes
Stroop Effect on Accuracy During Congruent Task Viewing Negative Images: Safe Condition
Participants watched as six trial types differing by congruence and emotion (negative, neutral, positive) were presented during condition blocks (safe, threat) on a computer screen. Each trial began with a fixation point which was then immediately followed by a picture stimulus, followed by a numerical display, followed by a repeat of the picture stimulus, and followed by a blank screen. During threat, a participant could receive a shock. During safe, a participant could not receive a shock. The effect of accuracy on congruence across negative, positive, and neutral images in threat and safe conditions was assessed by participants accurate identification of facial expression.
Time frame: 11.2 minutes per run for a total of 22.4 minutes
Stroop Effect on Accuracy During Congruent Task Viewing Negative Images: Threat Condition
Participants watched as six trial types differing by congruence and emotion (negative, neutral, positive) were presented during condition blocks (safe, threat) on a computer screen. Each trial began with a fixation point which was then immediately followed by a picture stimulus, followed by a numerical display, followed by a repeat of the picture stimulus, and followed by a blank screen. During threat, a participant could receive a shock. During safe, a participant could not receive a shock. The effect of accuracy on congruence across negative, positive, and neutral images in threat and safe conditions was assessed by participants accurate identification of facial expression.
Time frame: 11.2 minutes per run for a total of 22.4 minutes
Stroop Effect on Accuracy During Congruent Task Viewing Neutral Images: Safe Condition
Participants watched as six trial types differing by congruence and emotion (negative, neutral, positive) were presented during condition blocks (safe, threat) on a computer screen. Each trial began with a fixation point which was then immediately followed by a picture stimulus, followed by a numerical display, followed by a repeat of the picture stimulus, and followed by a blank screen. During threat, a participant could receive a shock. During safe, a participant could not receive a shock. The effect of accuracy on congruence across negative, positive, and neutral images in threat and safe conditions was assessed by participants accurate identification of facial expression.
Time frame: 11.2 minutes per run for a total of 22.4 minutes
Stroop Effect on Accuracy During Congruent Task Viewing Neutral Images: Threat Condition
Participants watched as six trial types differing by congruence and emotion (negative, neutral, positive) were presented during condition blocks (safe, threat) on a computer screen. Each trial began with a fixation point which was then immediately followed by a picture stimulus, followed by a numerical display, followed by a repeat of the picture stimulus, and followed by a blank screen. During threat, a participant could receive a shock. During safe, a participant could not receive a shock. The effect of accuracy on congruence across negative, positive, and neutral images in threat and safe conditions was assessed by participants accurate identification of facial expression.
Time frame: 11.2 minutes per run for a total of 22.4 minutes
Stroop Effect on Accuracy During Incongruent Task Viewing Positive Images: Safe Condition
Participants watched as six trial types differing by congruence and emotion (negative, neutral, positive) were presented during condition blocks (safe, threat) on a computer screen. Each trial began with a fixation point which was then immediately followed by a picture stimulus, followed by a numerical display, followed by a repeat of the picture stimulus, and followed by a blank screen. During threat, a participant could receive a shock. During safe, a participant could not receive a shock. The effect of accuracy on congruence across negative, positive, and neutral images in threat and safe conditions was assessed by participants accurate identification of facial expression.
Time frame: 11.2 minutes per run for a total of 22.4 minutes
Stroop Effect on Accuracy During Incongruent Task Viewing Positive Images: Threat Condition
Participants watched as six trial types differing by congruence and emotion (negative, neutral, positive) were presented during condition blocks (safe, threat) on a computer screen. Each trial began with a fixation point which was then immediately followed by a picture stimulus, followed by a numerical display, followed by a repeat of the picture stimulus, and followed by a blank screen. During threat, a participant could receive a shock. During safe, a participant could not receive a shock. The effect of accuracy on congruence across negative, positive, and neutral images in threat and safe conditions was assessed by participants accurate identification of facial expression.
Time frame: 11.2 minutes per run for a total of 22.4 minutes
Stroop Effect on Accuracy During Incongruent Task Viewing Negative Images: Safe Condition
Participants watched as six trial types differing by congruence and emotion (negative, neutral, positive) were presented during condition blocks (safe, threat) on a computer screen. Each trial began with a fixation point which was then immediately followed by a picture stimulus, followed by a numerical display, followed by a repeat of the picture stimulus, and followed by a blank screen. During threat, a participant could receive a shock. During safe, a participant could not receive a shock. The effect of accuracy on congruence across negative, positive, and neutral images in threat and safe conditions was assessed by participants accurate identification of facial expression.
Time frame: 11.2 minutes per run for a total of 22.4 minutes
Stroop Effect on Accuracy During Incongruent Task Viewing Negative Images: Threat Condition
Participants watched as six trial types differing by congruence and emotion (negative, neutral, positive) were presented during condition blocks (safe, threat) on a computer screen. Each trial began with a fixation point which was then immediately followed by a picture stimulus, followed by a numerical display, followed by a repeat of the picture stimulus, and followed by a blank screen. During threat, a participant could receive a shock. During safe, a participant could not receive a shock. The effect of accuracy on congruence across negative, positive, and neutral images in threat and safe conditions was assessed by participants accurate identification of facial expression.
Time frame: 11.2 minutes per run for a total of 22.4 minutes
Stroop Effect on Accuracy During Incongruent Task Viewing Neutral Images: Safe Condition
Participants watched as six trial types differing by congruence and emotion (negative, neutral, positive) were presented during condition blocks (safe, threat) on a computer screen. Each trial began with a fixation point which was then immediately followed by a picture stimulus, followed by a numerical display, followed by a repeat of the picture stimulus, and followed by a blank screen. During threat, a participant could receive a shock. During safe, a participant could not receive a shock. The effect of accuracy on congruence across negative, positive, and neutral images in threat and safe conditions was assessed by participants accurate identification of facial expression.
Time frame: 11.2 minutes per run for a total of 22.4 minutes
Stroop Effect on Accuracy During Incongruent Task Viewing Neutral Images: Threat Condition
Participants watched as six trial types differing by congruence and emotion (negative, neutral, positive) were presented during condition blocks (safe, threat) on a computer screen. Each trial began with a fixation point which was then immediately followed by a picture stimulus, followed by a numerical display, followed by a repeat of the picture stimulus, and followed by a blank screen. During threat, a participant could receive a shock. During safe, a participant could not receive a shock. The effect of accuracy on congruence across negative, positive, and neutral images in threat and safe conditions was assessed by participants accurate identification of facial expression.
Time frame: 11.2 minutes per run for a total of 22.4 minutes
Subjective Rating of Difficulty With Attention During Safe Condition
Following tasks completion, participants provided retrospective ratings of: anxiety and attention during safe and threat conditions using an analog scale ranging from 1 (not at all) to 10 (extremely). Participants rated overall subjective difficulty with attention ('How difficult was it to pay attention during threat/safe?') and level of anxiety ('How anxious were you during threat/safe?'). Retrospective ratings of anxiety and difficulty with attention were analyzed with two way Diagnosis x Condition (safe, threat) ANOVA.
Time frame: Assessed immediately after completing the affective Stroop task
Subjective Rating of Difficulty With Attention During Threat Condition
Following tasks completion, participants provided retrospective ratings of: anxiety and attention during safe and threat conditions using an analog scale ranging from 1 (not at all) to 10 (extremely). Participants rated overall subjective difficulty with attention ('How difficult was it to pay attention during threat/safe?') and level of anxiety ('How anxious were you during threat/safe?'). Retrospective ratings of anxiety and difficulty with attention were analyzed with two way Diagnosis x Condition (safe, threat) ANOVA.
Time frame: Assessed immediately after completing the affective Stroop task
Subjective Rating of Level of Anxiety During Safe Condition
Following tasks completion, participants provided retrospective ratings of: anxiety and attention during safe and threat conditions using an analog scale ranging from 1 (not at all) to 10 (extremely). Participants rated overall subjective difficulty with attention ('How difficult was it to pay attention during threat/safe?') and level of anxiety ('How anxious were you during threat/safe?'). Retrospective ratings of anxiety and difficulty with attention were analyzed with two way Diagnosis x Condition (safe, threat) ANOVA.
Time frame: Assessed immediately after completing the affective Stroop task
Subjective Rating of Level of Anxiety During Threat Condition
Following tasks completion, participants provided retrospective ratings of: anxiety and attention during safe and threat conditions using an analog scale ranging from 1 (not at all) to 10 (extremely). Participants rated overall subjective difficulty with attention ('How difficult was it to pay attention during threat/safe?') and level of anxiety ('How anxious were you during threat/safe?'). Retrospective ratings of anxiety and difficulty with attention were analyzed with two way Diagnosis x Condition (safe, threat) ANOVA.
Time frame: Assessed immediately after completing the affective Stroop task
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