Influence of COMT genotype and affective distractors on the processing of self-generated thought.
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ABSTRACT:
SUBMITTER: Kilford EJ
PROVIDER: S-EPMC4305337 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Major depressive disorder (MDD) has been associated with abnormal prefrontal-limbic interactions and altered catecholaminergic neurotransmission. The val158met polymorphism on the catechol-O-methyltransferase (COMT) gene has been shown to influence prefrontal cortex (PFC) activation during both emotional processing and working memory (WM). Although COMT-genotype is not directly associated with MDD, it may affect MDD pathology by altering PFC activation, an endophenotype associated with both COMT and MDD. 125 participants, including healthy controls (HC, n=28) and MDD patients were genotyped for the COMT val158met polymorphism and underwent functional magnetic resonance imaging (fMRI-neuroimaging) during emotion processing (viewing of emotional facial expressions) and a WM task (visuospatial planning). Within HC, we observed a positive correlation between the number of met-alleles and right inferior frontal gyrus activation during emotional processing, whereas within patients the number of met-alleles was not correlated with PFC activation. During WM a negative correlation between the number of met-alleles and middle frontal gyrus activation was present in the total sample. In addition, during emotional processing there was an effect of genotype in a cluster including the amygdala and hippocampus. These results demonstrate that COMT genotype is associated with relevant endophenotypes for MDD. In addition, presence of MDD only interacts with genotype during emotional processing and not working memory.
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Project description:Internal cognition like imagination and prospection require sustained internally directed attention and involve self-generated thought. This fMRI study aimed to disentangle the brain mechanisms associated with attention-specific and task-specific processes during internally directed cognition. The direction of attention was manipulated by either keeping a relevant stimulus visible throughout the task, or by masking it, so that the task had to be performed "in the mind's eye". The level of self-directed thought was additionally varied between a convergent and a divergent thinking task. Internally directed attention was associated with increased activation in the right anterior inferior parietal lobe (aIPL), bilateral lingual gyrus and the cuneus, as well as with extended deactivations of superior parietal and occipital regions representing parts of the dorsal attention network. The right aIPL further showed increased connectivity with occipital regions suggesting an active top-down mechanism for shielding ongoing internal processes from potentially distracting sensory stimulation in terms of perceptual decoupling. Activation of the default network was not related to internally directed attention per se, but rather to a higher level of self-generated thought. The findings hence shed further light on the roles of inferior and superior parietal cortex for internally directed cognition.
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Project description:The interplay between exogenous attention to emotional distractors and the baseline affective state has not been well established yet. The present study aimed to explore this issue through behavioral measures and event-related potentials (ERPs). Participants (N = 30) completed a digit categorization task depicted over negative, positive or neutral distractor background pictures, while they experienced negative, positive and neutral affective states elicited by movie scenes. Behavioral results showed higher error rates and longer reaction times for negative distractors than for neutral and positive ones, irrespective of the current emotional state. Neural indices showed that the participants' affective state modulated N1 amplitudes, irrespective of distractor type, while the emotional charge of distractors modulated N2, irrespective of the emotional state. Importantly, an interaction of state and distractor type was observed in LPP. These results demonstrate that exogenous attention to emotional distractors is independent from modulating effects of the emotional baseline state at early, automatic stages of processing. However, attention to emotional distractors and affective state interact at later latencies.
| S-EPMC5556118 | biostudies-literature
Project description:Self-generated cognitions, such as recalling personal memories or empathizing with others, are ubiquitous and essential for our lives. Such internal mental processing is ascribed to the Default Mode Network, a large network of the human brain, though the underlying neural and cognitive mechanisms remain poorly understood. Here, we tested the hypothesis that our mental experience is mediated by a combination of activities of multiple cognitive processes. Our study included four functional MRI experiments with the same participants and a wide range of cognitive tasks, as well as an analytical approach that afforded the identification of cognitive processes during self-generated cognition. We showed that several cognitive processes functioned simultaneously during self-generated mental activity. The processes had specific and localized neural representations, suggesting that they support different aspects of internal processing. Overall, we demonstrate that internally directed experience may be achieved by pooling over multiple cognitive processes.
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Project description:In a widely cited study, Mattay et al. reported that amphetamine (0.25 mg/kg oral, or 17 mg for a 68 kg individual) impaired behavioral and brain indices of executive functioning, measured using the Wisconsin Card Sorting Task (WCST) and N-Back working memory task, in 6 individuals homozygous for the met allele of the val158met polymorphism in the catechol-O-methyltransferase (COMT) gene, whereas it improved executive functioning in 10 individuals homozygous for the more active val allele. We attempted to replicate their behavioral findings in a larger sample, using similar executive functioning tasks and a broader range of amphetamine doses. Over four sessions, n = 200 healthy normal adults received oral placebo, d-amphetamine 5, 10, and 20 mg (average of 0.07, 0.15 and 0.29 mg/kg), under counterbalanced double-blind conditions and completed WCST and N-back tests of executive functioning. Amphetamine had typical effects on blood pressure and processing speed but did not affect executive functioning. COMT genotype (val158met) was not related to executive functioning under placebo or amphetamine conditions, even when we compared only the homozygous val/val and met/met genotypes at the highest dose of amphetamine (20 mg). Thus, we were not able to replicate the behavioral interaction between COMT and amphetamine seen in Mattay et al. We discuss possible differences between the studies and the implications of our findings for the use of COMT genotyping to predict clinical responses to dopaminergic drugs, and the use of intermediate phenotypes in genetic research.
| S-EPMC3553317 | biostudies-literature
Project description:Self-relevant concepts are major building blocks of spontaneous thought, and their dynamics in a natural stream of thought are likely to reveal one's internal states that are important for mental health. Here, we conducted a functional magnetic resonance imaging experiment (n = 62) to examine brain representations and dynamics of self-generated concepts in the context of spontaneous thought using a newly developed free association-based thought sampling task. The dynamics of conceptual associations were predictive of individual differences in general negative affectivity, replicating across multiple datasets (n = 196). Reflecting on self-generated concepts strongly engaged brain regions linked to autobiographical memory, conceptual processes, emotion, and autonomic regulation, including the medial prefrontal and medial temporal subcortical structures. Multivariate pattern-based predictive modeling revealed that the neural representations of valence became more person-specific as the level of perceived self-relevance increased. Overall, this study sheds light on how self-generated concepts in spontaneous thought construct inner affective states and idiosyncrasies.
| S-EPMC9432827 | biostudies-literature
Project description:BACKGROUND: Although the amygdala is thought to be a crucial brain region for negative affect, neuroimaging studies do not always show enhanced amygdala response to aversive stimuli in patients with anxiety disorders. Serotonin (5-HT)-related genotypes may contribute to interindividual variability in amygdala responsiveness. The short (s) allele of the 5-HT transporter linked polymorphic region (5-HTTLPR) and the T variant of the G-703T polymorphism in the tryptophan hydroxylase-2 (TPH2) gene have previously been associated with amygdala hyperresponsivity to negative faces in healthy controls. We investigated the influence of these polymorphisms on amygdala responsiveness to angry faces in patients with social anxiety disorder (SAD) compared with healthy controls. METHODS: We used positron emission tomography with oxygen 15-labelled water to assess regional cerebral blood flow in 34 patients with SAD and 18 controls who viewed photographs of angry and neutral faces presented in counterbalanced order. We genotyped all participants with respect to the 5-HTTLPR and TPH2 polymorphisms. RESULTS: Patients with SAD and controls had increased left amygdala activation in response to angry compared with neutral faces. Genotype but not diagnosis explained a significant portion of the variance in amygdala responsiveness, the response being more pronounced in carriers of s and/or T alleles. LIMITATIONS: Our analyses were limited owing to the small sample and the fact that we were unable to match participants on genotype before enrollment. In addition, other imaging techniques not used in our study may have revealed additional effects of emotional stimuli. CONCLUSION: Amygdala responsiveness to angry faces was more strongly related to serotonergic polymorphisms than to diagnosis of SAD. Emotion activation studies comparing amygdala excitability in patient and control groups could benefit from taking variation in 5-HT-related genes into account.
| S-EPMC2612081 | biostudies-literature
Project description:The relationship between cognition and a functional polymorphism in the catechol-O-methlytransferase (COMT) gene, val108/158met, is one of debate in the literature. Furthermore, based on the dopaminergic differences associated with the COMT val108/158met genotype, neural differences during cognition may be present, regardless of genotypic differences in cognitive performance. To investigate these issues the current study aimed to 1) examine the effects of COMT genotype using a large sample of healthy individuals (n = 496-1218) and multiple cognitive measures, and using a subset of the sample (n = 22), 2) examine whether COMT genotype effects medial temporal lobe (MTL) and frontal activity during successful relational memory processing, and 3) investigate group differences in functional connectivity associated with successful relational memory processing. Results revealed no significant group difference in cognitive performance between COMT genotypes in any of the 19 cognitive measures. However, in the subset sample, COMT val homozygotes exhibited significantly decreased MTL and increased prefrontal activity during both successful relational encoding and retrieval, and reduced connectivity between these regions compared with met homozygotes. Taken together, the results suggest that although the COMT val108/158met genotype has no effect on cognitive behavioral measures in healthy individuals, it is associated with differences in neural process underlying cognitive output.
| S-EPMC2820704 | biostudies-literature
Project description:OBJECTIVES: Although the Val(158)Met catechol-O-methyltransferase (COMT) gene has been linked with the temperament dimension Novelty Seeking (NS), new insights in this polymorphism might point to a major role for character features as well. Given that individual life experiences may influence Val(158) and Met(158) allele carriers differently it has been suggested that the character trait cooperativeness could be implicated. CASE REPORT: A homogeneous group of eighty right-handed Caucasian healthy female university students were assessed with the TCI and genotyped for the COMT Val(158)Met polymorphism (rs4680). Gene determination showed that eighteen were Val(158) homozygotes, forty-four Val/Met(158) heterozygotes, and eighteen were Met(158) homozygotes. All were within the same age range and never documented to have suffered from any neuropsychiatric illness. Bonferroni corrected non-parametric analyses showed that only for the character scale cooperativeness Val(158) homozygotes displayed significant higher scores when compared to Met(158) homozygotes. No significant differences on cooperativeness scores were found between Val(158) and Val/Met(158) carriers or between Met(158) and Val/Met(158) carriers. No differences were observed for the COMT Val(158)Met polymorphism and the other temperament and character scales. CONCLUSIONS: Our findings support the assumption that the Val(158)Met single nucleotide polymorphism (SNP) influences character traits and not only temperament. Our results add to the notion that Val(158) homozygotes are considered to be helpful and empathic and it suggest that these cooperativeness character traits are related to the dopaminergic system.
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Project description:BACKGROUND:The intense loss processing that characterizes grieving may help people to adapt to the loss. However, empirical studies show that more conscious loss-related thinking and greater reactivity to reminders of the deceased correspond to poorer adaptation. These findings raise the possibility that loss processing that is unconscious rather than conscious and is self-generated rather than reactive may facilitate adaptation. Here, we used machine learning to detect a functional magnetic resonance imaging (fMRI) signature of self-generated unconscious loss processing that we hypothesized to correlate with lower grief severity. METHODS:A total of 29 subjects bereaved within the past 14 months participated. Participants performed a modified Stroop fMRI task using deceased-related words. A machine-learning regression, trained on Stroop fMRI data, learned a neural pattern for deceased-related selective attention (d-SA), the allocation of attention to the deceased. Expression of this pattern was tracked during a subsequent sustained attention fMRI task interspersed with deceased-related thought probes (SART-PROBES). d-SA pattern expression during SART-PROBES blocks without reported thoughts of loss indicated self-generated unconscious loss processing. Grief severity was measured with the Inventory for Complicated Grief. RESULTS:d-SA expression during SART-PROBES blocks without conscious deceased-related thinking correlated negatively with Inventory for Complicated Grief score (r25 = -.711, p < .001, 95% confidence interval = -0.89 to -0.42), accounting for 50% of variance. This relationship remained significant independent of demographic correlates of Inventory for Complicated Grief (B25 = -30, t = -2.64, p = .02, 95% confidence interval = -56.2 to -4.6). Unconscious d-SA pattern expression also correlated with activity in dorsolateral prefrontal cortex and temporal parietal junction during the SART-PROBES (voxel: p < .001, cluster: p < .05). CONCLUSIONS:Self-generated unconscious loss processing correlated with reduced grief severity. This activity, supported by a cognitive social neural architecture, may advance adaptation to the loss.
| S-EPMC6389441 | biostudies-literature