Common neural correlates of intertemporal choices and intelligence in adolescents.

Converging behavioral evidence indicates that temporal discounting, measured by intertemporal choice tasks, is inversely related to intelligence. At the neural level, the parieto-frontal network is pivotal for complex, higher-order cognitive processes. Relatedly, underrecruitment of the pFC during a working memory task has been found to be associated with steeper temporal discounting. Furthermore, this network has also been shown to be related to the consistency of intertemporal choices. Here we report an fMRI study that directly investigated the association of neural correlates of intertemporal choice behavior with intelligence in an adolescent sample (n = 206; age 13.7-15.5 years). After identifying brain regions where the BOLD response during intertemporal choice was correlated with individual differences in intelligence, we further tested whether BOLD responses in these areas would mediate the associations between intelligence, the discounting rate, and choice consistency. We found positive correlations between BOLD response in a value-independent decision network (i.e., dorsolateral pFC, precuneus, and occipital areas) and intelligence. Furthermore, BOLD response in a value-dependent decision network (i.e., perigenual ACC, inferior frontal gyrus, ventromedial pFC, ventral striatum) was positively correlated with intelligence. The mediation analysis revealed that BOLD responses in the value-independent network mediated the association between intelligence and choice consistency, whereas BOLD responses in the value-dependent network mediated the association between intelligence and the discounting rate. In summary, our findings provide evidence for common neural correlates of intertemporal choice and intelligence, possibly linked by valuation as well as executive functions.

No differences in ventral striatum responsivity between adolescents with a positive family history of alcoholism and controls.

Individuals with alcohol-dependent parents show an elevated risk of developing alcohol-related problems themselves. Modulations of the mesolimbic reward circuit have been postulated as a pre-existing marker of alcoholism. We tested whether a positive family history of alcoholism is correlated with ventral striatum functionality during a reward task. All participants performed a modified version of the monetary incentive delay task while their brain responses were measured with functional magnetic resonance imaging. We compared 206 healthy adolescents (aged 13-15) who had any first- or second-degree relative with alcoholism to 206 matched controls with no biological relative with alcoholism. Reward anticipation as well as feedback of win recruited the ventral striatum in all participants, but adolescents with a positive family history of alcoholism did not differ from their matched peers. Also we did not find any correlation between family history density and reward anticipation or feedback of win. This finding of no differences did not change when we analyzed a subsample of 77 adolescents with at least one parent with alcohol use disorder and their matched controls. Because this result is in line with another study reporting no differences between children with alcohol-dependent parents and controls at young age, but contrasts with studies of older individuals, one might conclude that at younger age the effect of family history has not yet exerted its influence on the still developing mesolimbic reward circuit.

Prediction of alcohol drinking in adolescents: Personality-traits, behavior, brain responses, and genetic variations in the context of reward sensitivity.

Adolescence is a time that can set the course of alcohol abuse later in life. Sensitivity to reward on multiple levels is a major factor in this development. We examined 736 adolescents from the IMAGEN longitudinal study for alcohol drinking during early (mean age=14.37) and again later (mean age=16.45) adolescence. Conducting structural equation modeling we evaluated the contribution of reward-related personality traits, behavior, brain responses and candidate genes. Personality seems to be most important in explaining alcohol drinking in early adolescence. However, genetic variations in ANKK1 (rs1800497) and HOMER1 (rs7713917) play an equal role in predicting alcohol drinking two years later and are most important in predicting the increase in alcohol consumption. We hypothesize that the initiation of alcohol use may be driven more strongly by personality while the transition to increased alcohol use is more genetically influenced.

Exploring adolescent cognitive control in a combined interference switching task.

Cognitive control enables individuals to flexibly adapt to environmental challenges. In the present functional magnetic resonance imaging (fMRI) study, we investigated 185 adolescents at the age of 14 with a combined response interference switching task measuring behavioral responses (reaction time, RT and error rate, ER) and brain activity during the task. This task comprises two types of conflict which are co-occurring, namely, task switching and stimulus-response incongruence. Data indicated that already in adolescents an overlapping cognitive control network comprising the dorsal anterior cingulate cortex (dACC), dorsolateral prefrontal cortex (DLPFC), pre-supplementary motor area (preSMA) and posterior parietal cortex (PPC) is recruited by conflicts arising from task switching and response incongruence. Furthermore our study revealed higher blood oxygenation level dependent (BOLD) responses elicited by incongruent stimuli in participants with a pronounced incongruence effect, calculated as the RT difference between incongruent and congruent trials. No such correlation was observed for switch costs. Furthermore, increased activation of the default mode network (DMN) was only observed in congruent trials compared to incongruent trials, but not in task repetition relative to task switch trials. These findings suggest that even though the two processes of task switching and response incongruence share a common cognitive control network they might be processed differentially within the cognitive control network. Results are discussed in the context of a novel hypothesis concerning antagonistic relations between the DMN and the cognitive control network.

Interindividual differences in mid-adolescents in error monitoring and post-error adjustment.

A number of studies have concluded that cognitive control is not fully established until late adolescence. The precise differences in brain function between adults and adolescents with respect to cognitive control, however, remain unclear. To address this issue, we conducted a study in which 185 adolescents (mean age (SD) 14.6 (0.3) years) and 28 adults (mean age (SD) 25.2 (6.3) years) performed a single task that included both a stimulus-response (S-R) interference component and a task-switching component. Behavioural responses (i.e. reaction time, RT; error rate, ER) and brain activity during correct, error and post-error trials, detected by functional magnetic resonance imaging (fMRI), were measured. Behaviourally, RT and ER were significantly higher in incongruent than in congruent trials and in switch than in repeat trials. The two groups did not differ in RT during correct trials, but adolescents had a significantly higher ER than adults. In line with similar RTs, brain responses during correct trials did not differ between groups, indicating that adolescents and adults engage the same cognitive control network to successfully overcome S-R interference or task switches. Interestingly, adolescents with stronger brain activation in the bilateral insulae during error trials and in fronto-parietal regions of the cognitive control network during post-error trials did have lower ERs. This indicates that those mid-adolescents who commit fewer errors are better at monitoring their performance, and after detecting errors are more capable of flexibly allocating further cognitive control resources. Although we did not detect a convincing neural correlate of the observed behavioural differences between adolescents and adults, the revealed interindividual differences in adolescents might at least in part be due to brain development.

Amygdala-function perturbations in healthy mid-adolescents with familial liability for depression.

OBJECTIVE: Functional magnetic resonance imaging (fMRI) studies have identified increased amygdala responses to negative stimuli as a risk marker of depression in adults, and as a state marker of depression in adults and adolescents. Hyperreactivity of the amygdala has been linked to negatively biased emotional processing in depression. However, no study has elucidated whether similar amygdala perturbations can be found in healthy mid-adolescents with familial liability for depression. We hypothesized that healthy 14-year-olds with relatives with depression would demonstrate increased amygdala responses to negative stimuli, as compared with their peers with no family history of mental disorders. METHOD: We investigated a community-based sample of 164 typically developing 14-year-olds without record of past or current mental disorders. Of these individuals, 28 fulfilled criteria for family history of depression, and 136 served as controls. Groups did not differ with regard to cognitive ability, depressive symptomatology, and anxiety. During fMRI they performed a perceptual discrimination task in which visual target and distractor stimuli varied systematically with regard to emotional valence. RESULTS: Both a hypothesis-driven region-of-interest analysis and a whole-brain analysis of variance revealed that negative distractors elicited greater amygdala activation in adolescents with a family history of depression compared to controls. Amygdala responses also differed during the processing of negative target stimuli, but effects were reversed. CONCLUSION: Our study demonstrates that familial liability for depression is associated with correlates of negatively biased emotional processing in healthy adolescents. Amygdala perturbations during the processing of negative stimuli might reflect an early and subtle risk marker for depression.

A Genome-Wide Association Study Suggests Novel Loci Associated with a Schizophrenia-Related Brain-Based Phenotype.

Patients with schizophrenia and their siblings typically show subtle changes of brain structures, such as a reduction of hippocampal volume. Hippocampal volume is heritable, may explain a variety of cognitive symptoms of schizophrenia and is thus considered an intermediate phenotype for this mental illness. The aim of our analyses was to identify single-nucleotide polymorphisms (SNP) related to hippocampal volume without making prior assumptions about possible candidate genes. In this study, we combined genetics, imaging and neuropsychological data obtained from the Mind Clinical Imaging Consortium study of schizophrenia (n = 328). A total of 743,591 SNPs were tested for association with hippocampal volume in a genome-wide association study. Gene expression profiles of human hippocampal tissue were investigated for gene regions of significantly associated SNPs. None of the genetic markers reached genome-wide significance. However, six highly correlated SNPs (rs4808611, rs35686037, rs12982178, rs1042178, rs10406920, rs8170) on chromosome 19p13.11, located within or in close proximity to the genes NR2F6, USHBP1, and BABAM1, as well as four SNPs in three other genomic regions (chromosome 1, 2 and 10) had p-values between 6.75×10(-6) and 8.3×10(-7). Using existing data of a very recently published GWAS of hippocampal volume and additional data of a multicentre study in a large cohort of adolescents of European ancestry, we found supporting evidence for our results. Furthermore, allelic differences in rs4808611 and rs8170 were highly associated with differential mRNA expression in the cis-acting region. Associations with memory functioning indicate a possible functional importance of the identified risk variants. Our findings provide new insights into the genetic architecture of a brain structure closely linked to schizophrenia. In silico replication, mRNA expression and cognitive data provide additional support for the relevance of our findings. Identification of causal variants and their functional effects may unveil yet unknown players in the neurodevelopment and the pathogenesis of neuropsychiatric disorders.

Altered reward processing in adolescents with prenatal exposure to maternal cigarette smoking.

IMPORTANCE: Higher rates of substance use and dependence have been observed in the offspring of mothers who smoked during pregnancy. Animal studies indicate that prenatal exposure to nicotine alters the development of brain areas related to reward processing, which might be a risk factor for substance use and addiction later in life. However, no study has examined the effect of maternal smoking on the offspring's brain response during reward processing. OBJECTIVE: To determine whether adolescents with prenatal exposure to maternal cigarette smoking differ from their nonexposed peers in the response of the ventral striatum to the anticipation or the receipt of a reward. DESIGN: An observational case-control study. SETTING: Data were obtained from the IMAGEN Study, a European multicenter study of impulsivity, reinforcement sensitivity, and emotional reactivity in adolescents. The IMAGEN sample consists of 2078 healthy adolescents (age range, 13-15 years) recruited from March 1, 2008, through December 31, 2011, in local schools. PARTICIPANTS: We assessed an IMAGEN subsample of 177 adolescents with prenatal exposure to maternal cigarette smoking and 177 nonexposed peers (age range, 13-15 years) matched by sex, maternal educational level, and imaging site. MAIN OUTCOME AND MEASURE: Response to reward in the ventral striatum measured with functional magnetic resonance imaging. RESULTS: In prenatally exposed adolescents, we observed a weaker response in the ventral striatum during reward anticipation (left side, F = 14.98 [P < .001]; right side, F = 15.95 [P < .001]) compared with their nonexposed peers. No differences were found regarding the responsivity of the ventral striatum to the receipt of a reward (left side, F = 0.21 [P = .65]; right side, F = 0.47 [P = .49]). CONCLUSIONS: The weaker responsivity of the ventral striatum to reward anticipation in prenatally exposed adolescents may represent a risk factor for substance use and development of addiction later in life. This result highlights the need for education and preventive measures to reduce smoking during pregnancy. Future analyses should assess whether prenatally exposed adolescents develop an increased risk for substance use and addiction and which role the reported neuronal differences during reward anticipation plays in this development.

Reward processing and intertemporal decision making in adults and adolescents: the role of impulsivity and decision consistency.

Several studies report differences between adults and adolescents in reward processing and impulsivity. Consistently, adolescents are more impulsive in their decision making, as measured by intertemporal choice tasks. Since impulsivity affects an individual's perception and neural processing of rewards, it is unclear whether previously reported differences in brain activation between adults and adolescents are primarily due to maturation of the brain reward system or differences in impulsivity (i.e. discounting behaviour). To disentangle this, we analysed data from 235 adolescents and 29 adults who performed an intertemporal choice task in which monetary rewards were adapted to individual impulsivity. Using functional magnetic resonance imaging (fMRI), we measured brain activity and assessed impulsivity and consistency of choices at the behavioural level. Although adolescents discounted delayed rewards more steeply than adults, when controlling for impulsivity, neural processing of reward value did not differ between groups. However, more impulsive subjects showed a lower brain response to delayed rewards, independent of age. Concerning decision making, adolescents exhibited a lower consistency of choices and less brain activity in the parietal network than adults. We conclude that processing of the value of prospective delayed rewards is more sensitive to discounting behaviour than to chronological age. Lower consistency of intertemporal choices might indicate ongoing maturation of parietal brain areas in adolescents.