neurogranin gene impacts on hippocampus activation during contextual fear conditioning. Neural mechanism of a sex-specific risk- variant for posttraumatic ...
Neural mechanisms of cued and contextual Pavlovian fear conditioning
SFB 636
Pohlack ST, Winkelmann T, Zidda F, Nees F, Grimm O, Rosero M, Cacciaglia R, Ridder S, Flor H Institute of Neuropsychology and Clinical Psychology, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
Hippocampal but not amygdalar volume affects contextual fear conditioning in humans Fig. 1. Three-dimensional rendering of left and right hippocampus of one participant and within the respective brain. Note that different colors indicate substructures of the hippocampus: Red, hippocampal head; light blue, hippocampal body; dark blue, hippocampal tail. Fig. 2. Skin conductance responses (SCRs) for the two groups during context conditioning; hab, habituation phase; acq1, early acquisition phase; acq2, late acquisition phase; ext, extinction phase. # indicate significant between, * within group ttests with p < .05.
Dissociable roles for hippocampal and amygdalar volume in human fear conditioning
Brain morphology correlates of interindividual differences in fear acquisition and extinction learning A)
B) Fig. 4. Tract-based spatial statistics (TBSS) showing the effect of extinction SCR corrected for sex, anxiety (STAI) and acquisition SCR. Voxels in which fractional anisotropy (FA) was significantly lower in participants with higher extinction SCR are shown in yellow-red (FWE cluster correction (pCS-) in the ROI separate for left (red) and right (green) hippocampus during late acquisition.
• Pohlack ST, Nees F, Liebscher C, Cacciaglia R, Diener SJ, Ridder S, Woermann FG, Flor H (2011). Hippocampal but not amygdalar volume affects contextual fear conditioning in humans Hum Brain Mapp. 33(2):478-88. • Pohlack ST, Nees F, Ruttorf M, Witt SH, Nieratschker V, Rietschel M, Flor H (2011). Risk variant for schizophrenia in the neurogranin gene impacts on hippocampus activation during contextual fear conditioning. Mol Psychiatry.16(11):1072-3.
Fear extinction associated with white matter alterations in healthy humans
Brain activation during fear conditioning in humans depends on genetic variations related to functioning of the hypothalamic-pituitaryadrenal axis: first evidence from two independent subsamples
Fig. 5. Exploratory tract visualization: Tracts passing from left hippocampal cingulum (seed) though uncinate fasciculus (waypoint mask) to prefrontal cortex. Color coding gives number of participants which show such a tract.
Neural mechanism of a sex-specific riskvariant for posttraumatic stress disorder in the PAC1 receptor Discovery sample (N = 39)
Replication sample (N = 24) Fig. 9. Relationship between PAC1-R (type I receptor of the pituitary adenylate cyclase activating polypeptide) and hippocampal activation in female participants. A) Discovery study: Significantly decreased hippocampal activation during late acquisition of contextual fear in carriers of the rs2267735 risk allele (CC) compared with heterozygotes and GG-carriers for the CS+ > CScontrast. The peak-voxel at x = -20, y = -37, z = 2, k = 20; t = 4.06, p = .038 is FWE-corrected for the region of interest (ROI). Note that colors indicate t-scores B) Discovery study: Effect sizes (CS+ > CS-) (error-bars indicate s.e.m.). C) Replication study: The peak-voxel at x = -18, y = -41, z = 4, k = 36; t = 4.92, p < .001 is FWE corrected for a 6mm sphere around the peakvoxel from the discovery study. D) Replication study: Effect sizes (CS+ > CS-).
A risk variant for alcoholism in the NMDA receptor affects amygdala-activity during fear conditioning in humans
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Fig. 12. Reduced amygdala activation during fear acquisition in rs2072450 homozygous C-allele carriers (CC-group, N = 76), compared to A-allele carriers (CA/AA-group, N = 38). A) CS+ > CS− contrast is FWE-corrected for the amygdala. B) Weighted-mean scores in the ROI for the right and left amygdala. Bars indicate standard error of the mean.
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Fig. 11. A) Increased differential activity in the left amygdala in the first half of the acquisition as a function of NR3C1 genotype (for sample 1, N=60; for sample 2, N=52). B) Genotype-dependent differential activation of the prefrontal cortex during extinction learning involving CRHR1 and NR3C1 genotypes (for sample 1, N=59; for sample 2, N=52). All values are means, with 95% confidence intervals (CIs) represented by vertical bars. * p CS− contrast is FWEcorrected for the insula. B) Weighted-mean scores in the ROI for the left and right insula during late fear acquisition.
• Cacciaglia R, Nees F, Pohlack ST, Ruttorf M, Winkelmann T, Witt SH, Nieratschker V, Rietschel M, Flor H (2013). A risk variant for alcoholism in the NMDA receptor affects amygdala activity during fear conditioning in humans. Biol Psychol. 94(1):74-81.
Supported by the Deutsche Forschungsgemeinschaft (SFB 636/C1)
