White matter correlates of contextual pavlovian fear extinction and the role of anxiety in healthy humans.

Pavlovian contextual fear extinction is viewed as an important mechanism for behavioral adaptation in everyday life, including challenging situations of stress and anxiety. It has frequently been shown to relate to the function of brain areas like the hippocampus and medial prefrontal cortex (mPFC), while the role of structural properties, like white matter tracts in these regions, has been less studied. We employed diffusion tensor imaging to determine structural white matter connectivity (cingulum and uncinate fasciculus) correlates of contextual pavlovian fear extinction indicators measured through functional magnetic resonance imaging, skin conductance responses (SCRs) and self-reports of valence, arousal and contingency in 93 healthy individuals.

Trauma exposure relates to heightened stress, altered amygdala morphology and deficient extinction learning: Implications for psychopathology.

Stress exposure causes a structural reorganization in neurons of the amygdala. In particular, animal models have repeatedly shown that both acute and chronic stress induce neuronal hypertrophy and volumetric increase in the lateral and basolateral nuclei of amygdala. These effects are visible on the behavioral level, where stress enhances anxiety behaviors and provokes greater fear learning.

Brain morphology correlates of interindividual differences in conditioned fear acquisition and extinction learning.

The neural circuits underlying fear learning have been intensively investigated in pavlovian fear conditioning paradigms across species. These studies established a predominant role for the amygdala in fear acquisition, while the ventromedial prefrontal cortex (vmPFC) has been shown to be important in the extinction of conditioned fear. However, studies on morphological correlates of fear learning could not consistently confirm an association with these structures.

Neural Mechanism of a Sex-Specific Risk Variant for Posttraumatic Stress Disorder in the Type I Receptor of the Pituitary Adenylate Cyclase Activating Polypeptide.

Background: Posttraumatic stress disorder (PTSD) is a frequent anxiety disorder with higher prevalence rates in female patients than in male patients (2.5:1). Association with a single nucleotide polymorphism (rs2267735) in the gene ADCYAP1R1 encoding the type I receptor (PAC1-R) of the pituitary adenylate cyclase activating polypeptide has been reported with PTSD in female patients.

Dissociable roles for hippocampal and amygdalar volume in human fear conditioning.

Fear conditioning is a basic learning process which involves the association of a formerly neutral conditioned stimulus (CS) with a biologically relevant aversive unconditioned stimulus (US). Previous studies conducted in brain-lesioned patients have shown that while the acquisition of autonomic fear responses requires an intact amygdala, a spared hippocampus is necessary for the development of the CS-US contingency awareness. Although these data have been supported by studies using functional neuroimaging techniques in healthy people, attempts to extend these findings to the morphological aspects of amygdala and hippocampus are missing.

Functional MRI studies of the hippocampus.

Developments in tasks and imaging techniques applied over the last decades have yielded substantial support for the hypothesized role of the hippocampus in mnemonic processes. Human imaging research has now moved on to disentangle the contributions of the different hippocampal subregions and adjacent cortices, so as to bridge the gap between rodent and human data. Besides the importance of such studies for basic research, the investigation of hippocampal (dys)function has clinical relevance for diseases ranging from neurological disorders such as Alzheimer's disease or epilepsy to mental disorders such as schizophrenia or anxiety disorders.

A risk variant for alcoholism in the NMDA receptor affects amygdala activity during fear conditioning in humans.

People at high risk for alcoholism show deficits in aversive learning, as indicated by impaired electrodermal responses during fear conditioning, a basic form of associative learning that depends on the amygdala. A positive family history of alcohol dependence has also been related to decreased amygdala responses during emotional processing. In the present study we report reduced amygdala activity during the acquisition of conditioned fear in healthy carriers of a risk variant for alcoholism (rs2072450) in the NR2A subunit-containing N-methyl-d-aspartate (NMDA)-receptor.

Bigger is better! Hippocampal volume and declarative memory performance in healthy young men.

The importance of the hippocampus for declarative memory processes is firmly established. Nevertheless, the issue of a correlation between declarative memory performance and hippocampal volume in healthy subjects still remains controversial. The aim of the present study was to investigate this relationship in more detail.

Activation of the ventral striatum during aversive contextual conditioning in humans.

The goal of this study was to investigate the function of the ventral striatum and brain regions involved in anxiety and learning during aversive contextual conditioning. Functional magnetic resonance imaging was used to assess the hemodynamic brain response of 118 healthy volunteers during a differential fear conditioning paradigm. Concurrently obtained skin conductance responses and self-reports indicated successful context conditioning.

Hippocampal but not amygdalar volume affects contextual fear conditioning in humans.

Both animal and human studies have identified a critical role of the hippocampus in contextual fear conditioning. In humans mainly functional magnetic resonance imaging has been used. To extend these findings to volumetric properties, 58 healthy participants underwent structural magnetic resonance imaging and participated in a differential fear conditioning paradigm with contextual stimuli.