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Previously, we observed cortisol induced enhancement of neural fear acquisition in women. Yet, less is known about cortisol effects on neural fear extinction. Via differential fear conditioning, we explored cortisol effects on acquisition and extinction. Twenty contingency aware women taking monophasic oral contraceptives were included; 10 received placebo, 10 cortisol before conditioning. Group differences emerged in anterior cingulate cortex (ACC), hippocampus, and--as trend--in insula and thalamus during acquisition and in hippocampus, thalamus, and--as trend--in amygdala, insula, and ACC during extinction. During acquisition group differences were due to higher responses to the CS+ than to the CS- in the cortisol group. Notably, during extinction, group differences were due to higher responses to the CS- than to the CS+ in this group. Thus, cortisol induced a fear acquisition and extinction specific enhanced neural differentiation.
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In an fMRI study, effects of contingency awareness on conditioned responses were assessed in three groups comprising 118 subjects. A differential fear-conditioning paradigm with visual conditioned stimuli, an electrical unconditioned stimulus and two distractors was applied. The instructed aware group was informed about the contingencies, whereas the distractors prevented contingency detection in the unaware group. The third group (learned aware) was not informed about the contingencies, but learned them despite the distractors. Main effects of contingency awareness on conditioned responses emerged in several brain structures. Post hoc tests revealed differential dorsal anterior cingulate, insula and ventral striatum responses in aware conditioning only, whereas the amygdala was activated independent of contingency awareness. Differential responses of the hippocampus were specifically observed in learned aware subjects, indicating a role in the development of contingency awareness. The orbitofrontal cortex showed varying response patterns: lateral structures showed higher responses in instructed aware than unaware subjects, the opposite was true for medial parts. Conditioned subjective and electrodermal responses emerged only in the two aware groups. These results confirm the independence of conditioned amygdala responses from contingency awareness and indicate specific neural circuits for different aspects of fear acquisition in unaware, learned aware and instructed aware subjects.
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Fear learning is a crucial process in the pathogeneses of psychiatric disorders, which highlights the need to identify specific factors contributing to interindividual variation. We hypothesized variation in the serotonin transporter gene (5-HTTLPR) and stressful life events (SLEs) to be associated with neural correlates of fear conditioning in a sample of healthy male adults (n = 47). Subjects were exposed to a differential fear conditioning paradigm after being preselected regarding 5-HTTLPR genotype and SLEs. Individual differences in brain activity as measured by functional magnetic resonance imaging (fMRI), skin conductance responses and preference ratings were assessed. We report significant variation in neural correlates of fear conditioning as a function of 5-HTTLPR genotype. Specifically, the conditioned stimulus (CS(+)) elicited elevated activity within the fear-network (amygdala, insula, thalamus, occipital cortex) in subjects carrying two copies of the 5-HTTLPR S' allele. Moreover, our results revealed preliminary evidence for a significant gene-by-environment interaction, such as homozygous carriers of the 5-HTTLPR S' allele with a history of SLEs demonstrated elevated reactivity to the CS(+) in the occipital cortex and the insula. Our findings contribute to the current debate on 5-HTTLPR x SLEs interaction by investigating crucial alterations on an intermediate phenotype level which may convey an elevated vulnerability for the development of psychopathology.
Erkunden
Team
- Vaitl (3)
Eintragsart
Sprache
- Englisch (3)
Thema
- Image Processing, Computer-Assisted
- Adolescent (1)
- Adult (3)
- Analysis of Variance (1)
- Association Learning/*physiology (1)
- Awareness/physiology (1)
- Awareness/*physiology (1)
- Brain/blood supply/pathology (1)
- Brain Mapping (2)
- Brain/*physiology (1)
- Cerebral Cortex/*physiology (1)
- Conditioning, Classical/*physiology (2)
- Conditioning, Psychological/*physiology (1)
- DNA Mutational Analysis (1)
- Double-Blind Method (1)
- Electric Stimulation (2)
- Extinction, Psychological/*physiology (1)
- Fear/*physiology (1)
- Fear/*psychology (2)
- Female (3)
- Frontal Lobe/physiology (1)
- Galvanic Skin Response/genetics (1)
- Galvanic Skin Response/*physiology (1)
- Genotype (1)
- Humans (3)
- Hydrocortisone/analysis/*metabolism (1)
- *Individuality (1)
- Learning/physiology (1)
- Life Change Events (1)
- Magnetic Resonance Imaging (3)
- Male (2)
- Occipital Lobe/physiology (1)
- Oxygen/blood (1)
- Photic Stimulation (2)
- Saliva/chemistry (1)
- Serotonin Plasma Membrane Transport Proteins/*genetics (1)
- *Stress, Psychological/genetics/pathology/psychology (1)
- Surveys and Questionnaires (1)
- Young Adult (2)