Neonatal lesions of orbital frontal areas 11/13 in monkeys alter goal-directed behavior but spare fear conditioning and safety signal learning

Abstract Introduction Animal and human studies indicate that fear conditioning disrupts subsequent sleep, including REM sleep (REMS). REMS is thought to be central to fear information processing. We utilized an afternoon nap protocol to examine the effects of fear-potentiated startle (FPS), a variant of fear conditioning, on subsequent sleep integrity and REMS in trauma-exposed participants with varying levels of PTSD. We also examined the effects of changes in sleep integrity and REMS on subsequent retention and extinction of pre-sleep learning. Methods Participants (N=47) participated in 3 nap visits. The first was an adaptation nap. The second and third nap visits were counterbalanced: a stress-condition nap, during which participants underwent FPS procedures prior to a nap and assessment of retention of fear and safety signal learning and fear extinction after the nap, and a control visit during which participants had a nap opportunity without stressful procedures. Canonical correlation analysis assessed the relationship between FPS responses and change in subsequent sleep relative to a control nap, as well as the relationship between change in sleep from control to stress condition and both subsequent fear and safety learning retention, and subsequent extinction. Results Results demonstrated a relationship between fear learning and change in sleep and supported a relationship between safety signal learning and subsequent REMS, as well as differential conditioning and wake after sleep onset. Sleep did not predict measures of fear retention or extinction. PTSD symptoms did not predict fear learning or sleep measures. Conclusion These findings replicate prior work showing a relationship between safety learning and REMS, suggesting that this is a core mechanism through which stress impacts fear processing. Further research is critical to further understand this effect, and to examine how different aspects of fear learning impact different components of sleep. This study also demonstrates that nap studies can be a valuable approach for studying the stress-sleep relationship. Support (if any) VA Career Development Award to Dr. Richards (5IK2CX000871-05)

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Altered top-down and bottom-up processing of fear conditioning in panic disorder with agoraphobia

Psychological Medicine ◽

10.1017/s0033291713000792 ◽

2013 ◽

Vol 44 (2) ◽

pp. 381-394 ◽

Cited By ~ 34

Author(s):

U. Lueken ◽

B. Straube ◽

I. Reinhardt ◽

N. I. Maslowski ◽

H.-U. Wittchen ◽

...

Keyword(s):

Signal Processing ◽

Panic Disorder ◽

Fear Conditioning ◽

Differential Conditioning ◽

Inferior Frontal Gyrus ◽

Brain Structures ◽

Safety Signal ◽

Top Down ◽

Bottom Up ◽

Simple Conditioning

BackgroundAlthough several neurophysiological models have been proposed for panic disorder with agoraphobia (PD/AG), there is limited evidence from functional magnetic resonance imaging (fMRI) studies on key neural networks in PD/AG. Fear conditioning has been proposed to represent a central pathway for the development and maintenance of this disorder; however, its neural substrates remain elusive. The present study aimed to investigate the neural correlates of fear conditioning in PD/AG patients.MethodThe blood oxygen level-dependent (BOLD) response was measured using fMRI during a fear conditioning task. Indicators of differential conditioning, simple conditioning and safety signal processing were investigated in 60 PD/AG patients and 60 matched healthy controls.ResultsDifferential conditioning was associated with enhanced activation of the bilateral dorsal inferior frontal gyrus (IFG) whereas simple conditioning and safety signal processing were related to increased midbrain activation in PD/AG patients versus controls. Anxiety sensitivity was associated positively with the magnitude of midbrain activation.ConclusionsThe results suggest changes in top-down and bottom-up processes during fear conditioning in PD/AG that can be interpreted within a neural framework of defensive reactions mediating threat through distal (forebrain) versus proximal (midbrain) brain structures. Evidence is accumulating that this network plays a key role in the aetiopathogenesis of panic disorder.

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1073 SLEEP, FEAR CONDITIONING, AND SAFETY SIGNAL LEARNING IN VETERANS WITH PTSD

SLEEP ◽

10.1093/sleepj/zsx050.1072 ◽

2017 ◽

Vol 40 (suppl_1) ◽

pp. A400-A400

Author(s):

LD Straus ◽

D Acheson ◽

VB Risbrough ◽

SP Drummond ◽

SB Norman

Keyword(s):

Fear Conditioning ◽

Safety Signal

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Federal Advisory Panel Finds No Safety Signal With Vaccine

Pediatric News ◽

10.1016/s0031-398x(10)70051-5 ◽

2010 ◽

Vol 44 (2) ◽

pp. 16

Author(s):

MIRIAM E. TUCKER

Keyword(s):

Advisory Panel ◽

Safety Signal

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Effects of an Anxiety-Specific Psychometric Factor on Fear Conditioning and Fear Generalization

Zeitschrift für Psychologie ◽

10.1027/2151-2604/a000304 ◽

2017 ◽

Vol 225 (3) ◽

pp. 200-213 ◽

Cited By ~ 1

Author(s):

Christian Baumann ◽

Miriam A. Schiele ◽

Martin J. Herrmann ◽

Tina B. Lonsdorf ◽

Peter Zwanzger ◽

...

Keyword(s):

Risk Factor ◽

Anxiety Disorders ◽

Fear Conditioning ◽

Longitudinal Design ◽

Principal Component ◽

Anxiety And Depression ◽

Specific Factor ◽

High Anxious ◽

Two Factors ◽

Fear Generalization

Abstract. Conditioning and generalization of fear are assumed to play central roles in the pathogenesis of anxiety disorders. Here we investigate the influence of a psychometric anxiety-specific factor on these two processes, thus try to identify a potential risk factor for the development of anxiety disorders. To this end, 126 healthy participants were examined with questionnaires assessing symptoms of anxiety and depression and with a fear conditioning and generalization paradigm. A principal component analysis of the questionnaire data identified two factors representing the constructs anxiety and depression. Variations in fear conditioning and fear generalization were solely associated with the anxiety factor characterized by anxiety sensitivity and agoraphobic cognitions; high-anxious individuals exhibited stronger fear responses (arousal) during conditioning and stronger generalization effects for valence and UCS-expectancy ratings. Thus, the revealed psychometric factor “anxiety” was associated with enhanced fear generalization, an assumed risk factor for anxiety disorders. These results ask for replication with a longitudinal design allowing to examine their predictive validity.

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Challenges of Fear Conditioning Research in the Age of RDoC

Zeitschrift für Psychologie ◽

10.1027/2151-2604/a000303 ◽

2017 ◽

Vol 225 (3) ◽

pp. 189-199 ◽

Cited By ~ 5

Author(s):

Tina B. Lonsdorf ◽

Jan Richter

Keyword(s):

Fear Conditioning ◽

Clinical Diagnosis ◽

Research Domain Criteria ◽

Major Focus ◽

The Future ◽

Definition Of ◽

Methodological Considerations ◽

Research Domain

Abstract. As the criticism of the definition of the phenotype (i.e., clinical diagnosis) represents the major focus of the Research Domain Criteria (RDoC) initiative, it is somewhat surprising that discussions have not yet focused more on specific conceptual and procedural considerations of the suggested RDoC constructs, sub-constructs, and associated paradigms. We argue that we need more precise thinking as well as a conceptual and methodological discussion of RDoC domains and constructs, their interrelationships as well as their experimental operationalization and nomenclature. The present work is intended to start such a debate using fear conditioning as an example. Thereby, we aim to provide thought-provoking impulses on the role of fear conditioning in the age of RDoC as well as conceptual and methodological considerations and suggestions to guide RDoC-based fear conditioning research in the future.

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