Influence of COMT genotype and affective distractors on the processing of self-generated thought

The catechol-O-methyltransferase (COMT) enzyme is a major determinant of prefrontal dopamine levels. The Val¹⁵⁸Met polymorphism affects COMT enzymatic activity and has been associated with variation in executive function and affective processing. This study investigated the effect of COMT genotype on the flexible modulation of the balance between processing self-generated and processing stimulus-oriented information, in the presence or absence of affective distractors. Analyses included 124 healthy adult participants, who were also assessed on standard working memory (WM) tasks. Relative to Val carriers, Met homozygotes made fewer errors when selecting and manipulating self-generated thoughts. This effect was partly accounted for by an association between COMT genotype and visuospatial WM performance. We also observed a complex interaction between the influence of affective distractors, COMT genotype and sex on task accuracy: male, but not female, participants showed a sensitivity to the affective distractors that was dependent on COMT genotype. This was not accounted for by WM performance. This study provides novel evidence of the role of dopaminergic genetic variation on the ability to select and manipulate self-generated thoughts. The results also suggest sexually dimorphic effects of COMT genotype on the influence of affective distractors on executive function.     

Working memory brain activity and capacity link MAOA polymorphism to aggressive behavior during development

A developmental increase in working memory capacity is an important part of cognitive development, and low working memory (WM) capacity is a risk factor for developing psychopathology. Brain activity represents a promising endophenotype for linking genes to behavior and for improving our understanding of the neurobiology of WM development. We investigated gene–brain–behavior relationships by focusing on 18 single-nucleotide polymorphisms (SNPs) located in six dopaminergic candidate genes (COMT, SLC6A3/DAT1, DBH, DRD4, DRD5, MAOA). Visuospatial WM (VSWM) brain activity, measured with functional magnetic resonance imaging, and VSWM capacity were assessed in a longitudinal study of typically developing children and adolescents. Behavioral problems were evaluated using the Child Behavior Checklist (CBCL). One SNP (rs6609257), located ∼6.6 kb downstream of the monoamine oxidase A gene (MAOA) on human chromosome X, significantly affected brain activity in a network of frontal, parietal and occipital regions. Increased activity in this network, but not in caudate nucleus or anterior prefrontal regions, was correlated with VSWM capacity, which in turn predicted externalizing (aggressive/oppositional) symptoms, with higher WM capacity associated with fewer externalizing symptoms. There were no direct significant correlations between rs6609257 and behavioral symptoms. These results suggest a mediating role of WM brain activity and capacity in linking the MAOA gene to aggressive behavior during development.     

Neural correlates of task and source switching: Similar or different?

Controlling everyday behaviour relies on the ability to configure appropriate task sets and guide attention towards information relevant to the current context and goals. Here, we ask whether these two aspects of cognitive control have different neural bases. Electrical brain activity was recorded while sixteen adults performed two discrimination tasks. The tasks were performed on either a visual input (letter on the screen) or self-generated information (letter generated internally by continuing the alphabetical sequence). In different blocks, volunteers either switched between (i) the two tasks, (ii) the two sources of information, or (iii) tasks and source of information. Event-related potentials differed significantly between switch and no-switch trials from an early point in time, encompassing at least three distinct effects. Crucially, although these effects showed quantitative differences across switch types, no qualitative differences were observed. Thus, at least under the current circumstances, switching between different tasks and between perceptually derived or self-generated sources of information rely on similar neural correlates until at least 900 ms after the onset of a switch event.     

Distinct regions of medial rostral prefrontal cortex supporting social and nonsocial functions

While some recent neuroimaging studies have implicated medialrostral prefrontal cortex (MPFC) in ‘mentalizing’and self-reflection, others have implicated this region in attentiontowards perceptual vs self-generated information. In order toreconcile these seemingly contradictory findings, we used fMRIto investigate MPFC activity related to these two functionsin a factorial design. Participants performed two separate tasks,each of which alternated between ‘stimulus-oriented phases’(SO), where participants attended to task-relevant perceptualinformation, and ‘stimulus-independent phases’ (SI),where participants performed the same tasks in the absence ofsuch information. In half of the blocks (‘mentalizingcondition’), participants were instructed that they wereperforming these tasks in collaboration with an experimenter;in other blocks (‘non-mentalizing condition’), participantswere instructed that the experimenter was not involved. In fact,the tasks were identical in these conditions. Neuroimaging datarevealed adjacent but clearly distinct regions of activationwithin MPFC related to (i) mentalizing vs non-mentalizing conditions(relatively caudal/superior) and (ii) SO vs SI attention (relativelyrostral/inferior). These results generalized from one task tothe other, suggesting a new axis of functional organizationwithin MPFC.     

Developmental influences on the neural bases of responses to social rejection: implications of social neuroscience for education

Relational aggression such as social rejection is common within school peer groups. Converging evidence suggests that adolescent females are particularly sensitive to social rejection. We used a novel fMRI adaptation of the Cyberball social rejection paradigm to investigate the neural response to social rejection in 19 mid-adolescent (aged 14-16) and 16 adult female participants. Across all participants, social exclusion (relative to inclusion) elicited a response in bilateral medial prefrontal cortex (mPFC) extending into ventral and subgenual anterior cingulate cortex and medial orbitofrontal cortex; and the left ventrolateral PFC (vlPFC); regions that have been associated in previous studies with social evaluation, negative affective processing, and affect regulation respectively. However, the exclusion-related response in right vlPFC, a region associated in previous studies with the regulation of rejection-related distress, was attenuated in adolescents. Within mPFC, greater activation during exclusion vs. inclusion was associated with greater self-reported susceptibility to peer influence in adolescents but not in adults. This suggests that the brain's response to experimentally-induced social rejection relates to adolescent behaviour in real-world social interactions. We speculate about the potential implications of these findings for educational settings. In particular, functional development of affective circuitry during adolescence may influence social interaction within the school peer group.     

Developmental changes in effective connectivity associated with relational reasoning

Rostrolateral prefrontal cortex (RLPFC) is part of a frontoparietal network of regions involved in relational reasoning, the mental process of working with relationships between multiple mental representations. RLPFC has shown functional and structural changes with age, with increasing specificity of left RLPFC activation for relational integration during development. Here, we used dynamic causal modeling (DCM) to investigate changes in effective connectivity during a relational reasoning task through the transition from adolescence into adulthood. We examined fMRI data of 37 healthy female participants (11–30 years old) performing a relational reasoning paradigm. Comparing relational integration to the manipulation of single relations revealed activation in five regions: the RLPFC, anterior insula, dorsolateral PFC, inferior parietal lobe, and medial superior frontal gyrus. We used a new exhaustive search approach and identified a full DCM model, which included all reciprocal connections between the five clusters in the left hemisphere, as the optimal model. In line with previous resting state fMRI results, we showed distinct developmental effects on the strength of long‐range frontoparietal versus frontoinsular short‐range fixed connections. The modulatory connections associated with relational integration increased with age. Gray matter volume in left RLPFC, which decreased with age, partly accounted for changes in fixed PFC connectivity. Finally, improvements in relational integration performance were associated with greater modulatory and weaker fixed PFC connectivity. This pattern provides further evidence of increasing specificity of left PFC function for relational integration compared to the manipulation of single relations, and demonstrates an association between effective connectivity and performance during development. Hum Brain Mapp 35:3262–3276, 2014. © 2013 Wiley Periodicals, Inc.     

Development of rostral prefrontal cortex and cognitive and behavioural disorders

Information on the development and functions of rostral prefrontal cortex (PFC), or Brodmann area 10, has been gathered from different fields, from anatomical development to functional neuroimaging in adults, and put forward in relation to three particular cognitive and behavioural disorders. Rostral PFC is larger and has a lower cell density in humans than in other primates. It also has a large number of dendritic spines per cell and numerous connections to the supramodal cortex. These characteristics suggest that rostral PFC is likely to support processes of integration or coordination of inputs that are particularly developed in humans. The development of rostral PFC is prolonged, with decreases in grey matter and synaptic density continuing into adolescence. Functions attributed to rostral PFC, such as prospective memory, seem similarly to follow a prolonged development until adulthood. Neuroimaging studies have generally found a reduced recruitment of rostral PFC, for example in tasks requiring response inhibition, in adults compared with children or adolescents, which is consistent with maturation of grey matter. The examples of autism, attention-deficit-hyperactivity disorder, and schizophrenia show that rostral PFC could be affected in several disorders as a result of the susceptibility of its prolonged maturation to developmental abnormalities.     

Dual adaptation to sensory conflicts during whole-body rotations

A dual adaptation paradigm was used in order to study the adaptation to two conditions of conflicting visual and kinesthetic and vestibular information. Adaptation was induced in humans by modifying visual information during whole-body rotations with the help of a virtual reality set-up. Real rotations' amplitudes were factored by a gain of 0.5 or 1.5. The two conditions were associated to a visual context cue. The aim of the experiment was to provide support for either the feedback or the feedforward model of adaptive states switch. Results show that subjects could adapt to the two conditions of conflict during whole-body rotations. However, the two conflict situations have been found to differ both in their motor dynamics and in their susceptibility to adaptation, as it seems that the adaptation is more complete in the condition of gain 1.5, i.e., faster and more precise. Subjects could be divided into two groups according to their ability to use contextual information to switch between adaptive gains. The visual cues were sufficient for some subjects to switch adaptive state, which corresponds to a context-dependent dual adaptation, or feedforward model of switching. Other subjects showed a switch cost maintained across the experiment, corresponding with a stimulus-dependent adaptation, or feedback model of switching. We are suggesting that the process enabling switching between adaptive states depends on subjects' abilities to use contextual cues of certain types, and thus on their "perceptive styles". This could explain the variability of results obtained in the literature.