13 research outputs found
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Dissociable Genetic Contributions to Error Processing: A Multimodal Neuroimaging Study
Background: Neuroimaging studies reliably identify two markers of error commission: the error-related negativity (ERN), an event-related potential, and functional MRI activation of the dorsal anterior cingulate cortex (dACC). While theorized to reflect the same neural process, recent evidence suggests that the ERN arises from the posterior cingulate cortex not the dACC. Here, we tested the hypothesis that these two error markers also have different genetic mediation. Methods: We measured both error markers in a sample of 92 comprised of healthy individuals and those with diagnoses of schizophrenia, obsessive-compulsive disorder or autism spectrum disorder. Participants performed the same task during functional MRI and simultaneously acquired magnetoencephalography and electroencephalography. We examined the mediation of the error markers by two single nucleotide polymorphisms: dopamine D4 receptor (DRD4) C-521T (rs1800955), which has been associated with the ERN and methylenetetrahydrofolate reductase (MTHFR) C677T (rs1801133), which has been associated with error-related dACC activation. We then compared the effects of each polymorphism on the two error markers modeled as a bivariate response. Results: We replicated our previous report of a posterior cingulate source of the ERN in healthy participants in the schizophrenia and obsessive-compulsive disorder groups. The effect of genotype on error markers did not differ significantly by diagnostic group. DRD4 C-521T allele load had a significant linear effect on ERN amplitude, but not on dACC activation, and this difference was significant. MTHFR C677T allele load had a significant linear effect on dACC activation but not ERN amplitude, but the difference in effects on the two error markers was not significant. Conclusions: DRD4 C-521T, but not MTHFR C677T, had a significant differential effect on two canonical error markers. Together with the anatomical dissociation between the ERN and error-related dACC activation, these findings suggest that these error markers have different neural and genetic mediation
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Variation in the oxytocin receptor gene (OXTR) is associated with differences in moral judgment
Moral judgments are produced through the coordinated interaction of multiple neural systems, each of which relies on a characteristic set of neurotransmitters. Genes that produce or regulate these neurotransmitters may have distinctive influences on moral judgment. Two studies examined potential genetic influences on moral judgment using dilemmas that reliably elicit competing automatic and controlled responses, generated by dissociable neural systems. Study 1 (N = 228) examined 49 common variants (SNPs) within 10 candidate genes and identified a nominal association between a polymorphism (rs237889) of the oxytocin receptor gene (OXTR) and variation in deontological vs utilitarian moral judgment (that is, judgments favoring individual rights vs the greater good). An association was likewise observed for rs1042615 of the arginine vasopressin receptor gene (AVPR1A). Study 2 (N = 322) aimed to replicate these findings using the aforementioned dilemmas as well as a new set of structurally similar medical dilemmas. Study 2 failed to replicate the association with AVPR1A, but replicated the OXTR finding using both the original and new dilemmas. Together, these findings suggest that moral judgment is influenced by variation in the oxytocin receptor gene and, more generally, that single genetic polymorphisms can have a detectable effect on complex decision processes
Outcome measures divided by diagnosis.
1<p>Collapsed across fMRI and EEG sessions. Note that participants with fewer than 10 usable error trials per modality were excluded from the study.</p
Genetic dissociation between error-related dACC activation and the ERN.
<p>Both error markers are shown in standardized units as a function of risk allele load (677T for <i>MTHFR C677T</i>, -521C for <i>DRD4 C-521T</i>). Error bars represent within subject confidence intervals <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0101784#pone.0101784-Loftus1" target="_blank">[75]</a> for each allele combination.</p
Genetic modulation of error-related dACC activation.
<p>A: <i>MTHFR C677T</i>. B: <i>DRD4 C-521T</i>. Statistical maps show regressions of activation in the error vs. correct contrast on allele load. Blue colors represent a negative correlation, i.e., stronger activation associated with more 677T (A) or -521C (B) alleles. The gray masks cover subcortical regions in which activity is displaced in a surface rendering.</p
fMRI and EEG error markers.
<p>A. Error-related dACC activation. Statistical maps of activation at 6 s in the contrast of error vs. correct are displayed on the inflated medial cortical surfaces. The dACC ROI is outlined in black. Warm colors indicate stronger activation on errors. The gray masks cover subcortical regions in which activity is displaced in a surface rendering. Line graphs show hemodynamic response functions for correct and error trials in the vertices with maximal error-related activation in the dACC. B. The ERN. The left panel shows grand average waveforms for correct (black) and error (red) trials, time locked to the onset of the saccade. The right panel shows the difference waveform, obtained by subtracting the correct waveform from the error waveform. The thin lines on either side of the waveforms represent the standard error of the mean at each time point.</p
Breakdown of study sample by allele load for each SNP.
<p>Allele load (0,1,2) refers to the number of risk alleles: <i>677T</i> for <i>MTHFR C677T</i> and <i>521C</i> for <i>DRD4 C-521T.</i></p
Genetic modulation of the ERN.
<p>A: <i>MTHFR</i> C677T. B: <i>DRD4 C-</i>521T. Correct and error trial waveforms are shown for every allele combination of each polymorphism. The error-correct difference waveforms for each allele combination is shown on the right column. The thin lines on either side of the waveforms represent the standard error of the mean at each time point.</p
Results of the bivariate analyses testing the differential effects of each SNP on error markers.
<p>The primary analysis included the entire sample, allele load, and no covariate for diagnosis.</p><p>*significant at p≤.05.</p
Antisaccade paradigm.
<p>Schematic and timeline of the three conditions: easy, hard, and fake-hard. Each trial lasted 4 s and began with an instructional cue (300 ms), either a blue or yellow “X” that indicated whether the trial was hard or easy. The mapping of cue color to trial type was counterbalanced across participants. The cue was horizontally flanked by two white squares of 0.4° width that marked the potential locations of stimulus appearance, 10° left and right of center. The squares remained visible for the duration of each run. At 300 ms, the instructional cue was replaced by a white fixation ring of 1.3° diameter at the center of the screen. At 1800 ms, the fixation ring disappeared (200 ms gap). At 2000 ms, the fixation ring reappeared at one of the two stimulus locations, right or left with equal probability. This was the imperative stimulus to which the participant responded by making a saccade in the opposite direction. The ring remained in the peripheral location for 1000 ms and then returned to the center, where participants were instructed to return their gaze for 1000 ms before the start of the next trial. Fixation epochs were simply a continuation of this fixation display. Hard trials were distinguished by a 3 db increase in luminance of the peripheral squares starting during the gap. Except for the hard cue, fake-hard trials were identical to easy trials.</p