Maren Struve

Adolescent impulsivity phenotypes characterized by distinct brain networks

The impulsive behavior that is often characteristic of adolescence may reflect underlying neurodevelopmental processes. Moreover, impulsivity is a multi-dimensional construct, and it is plausible that distinct brain networks contribute to its different cognitive, clinical and behavioral aspects. As these networks have not yet been described, we identified distinct cortical and subcortical networks underlying successful inhibitions and inhibition failures in a large sample (n = 1,896) of 14-year-old adolescents. Different networks were associated with drug use (n = 1,593) and attention-deficit hyperactivity disorder symptoms (n = 342). Hypofunctioning of a specific orbitofrontal cortical network was associated with likelihood of initiating drug use in early adolescence. Right inferior frontal activity was related to the speed of the inhibition process (n = 826) and use of illegal substances and associated with genetic variation in a norepinephrine transporter gene (n = 819). Our results indicate that both neural endophenotypes and genetic variation give rise to the various manifestations of impulsive behavior.

Lower Ventral Striatal Activation During Reward Anticipation in Adolescent Smokers

OBJECTIVE Adolescents are particularly vulnerable to addiction, and in the case of smoking, this often leads to long-lasting nicotine dependence. The authors investigated a possible neural mechanism underlying this vulnerability. METHOD Functional MRI was performed during reward anticipation in 43 adolescent smokers and 43 subjects matched on age, gender, and IQ. The authors also assessed group differences in novelty seeking, impulsivity, and reward delay discounting. RESULTS In relation to the comparison subjects, the adolescent smokers showed greater reward delay discounting and higher scores for novelty seeking. Neural responses in the ventral striatum during reward anticipation were significantly lower in the smokers than in the comparison subjects, and in the smokers this response was correlated with smoking frequency. Notably, the lower response to reward anticipation in the ventral striatum was also observed in smokers (N=14) who had smoked on fewer than 10 occasions. CONCLUSIONS The present findings suggest that a lower response to reward anticipation in the ventral striatum may be a vulnerability factor for the development of early nicotine use.

Risk Taking and the Adolescent Reward System: A Potential Common Link to Substance Abuse

OBJECTIVE Increased risk-taking behavior has been associated with addiction, a disorder also linked to abnormalities in reward processing. Specifically, an attenuated response of reward-related areas (e.g., the ventral striatum) to nondrug reward cues has been reported in addiction. One unanswered question is whether risk-taking preference is associated with striatal reward processing in the absence of substance abuse. METHOD Functional and structural MRI was performed in 266 healthy young adolescents and in 31 adolescents reporting potentially problematic substance use. Activation during reward anticipation (using the monetary incentive delay task) and to gray matter density were measured. Risk-taking bias was assessed by the Cambridge Gamble Task. RESULTS With increasing risk-taking bias, the ventral striatum showed decreased activation bilaterally during reward anticipation. Voxel-based morphometry showed that greater risk-taking bias was also associated with and partially mediated by lower gray matter density in the same structure. The decreased activation was also observed when participants with virtually any substance use were excluded. The group with potentially problematic substance use showed greater risk taking as well as lower striatal activation relative to matched comparison subjects from the main sample. CONCLUSIONS Risk taking and functional and structural properties of the reward system in adolescents are strongly linked prior to a possible onset of substance abuse, emphasizing their potential role in the predisposition to drug abuse.

Determinants of Early Alcohol Use In Healthy Adolescents: The Differential Contribution of Neuroimaging and Psychological Factors

Individual variation in reward sensitivity may have an important role in early substance use and subsequent development of substance abuse. This may be especially important during adolescence, a transition period marked by approach behavior and a propensity toward risk taking, novelty seeking and alteration of the social landscape. However, little is known about the relative contribution of personality, behavior, and brain responses for prediction of alcohol use in adolescents. In this study, we applied factor analyses and structural equation modeling to reward-related brain responses assessed by functional magnetic resonance imaging during a monetary incentive delay task. In addition, novelty seeking, sensation seeking, impulsivity, extraversion, and behavioral measures of risk taking were entered as predictors of early onset of drinking in a sample of 14-year-old healthy adolescents (N=324). Reward-associated behavior, personality, and brain responses all contributed to alcohol intake with personality explaining a higher proportion of the variance than behavior and brain responses. When only the ventral striatum was used, a small non-significant contribution to the prediction of early alcohol use was found. These data suggest that the role of reward-related brain activation may be more important in addiction than initiation of early drinking, where personality traits and reward-related behaviors were more significant. With up to 26% of explained variance, the interrelation of reward-related personality traits, behavior, and neural response patterns may convey risk for later alcohol abuse in adolescence, and thus may be identified as a vulnerability factor for the development of substance use disorders.

Enhancement of steady‐state auditory evoked magnetic fields in tinnitus

The steady‐state auditory evoked magnetic field and the Pbm, the magnetic counterpart of the second frontocentrally positive middle latency component of the transitory auditory evoked potential, were measured in ten tinnitus patients using a 122‐channel gradiometer system. The patients had varying degrees of hearing loss. In all patients, the tinnitus frequency was located above the frequency of the audiometric edge, i.e. the location on the frequency axis above which hearing loss increases more rapidly. Stimuli were amplitude‐modulated sinusoids with carrier frequencies at the tinnitus frequency, the audiometric edge, two frequencies below the audiometric edge, and two frequencies between the audiometric edge and the tinnitus frequency. Below the audiometric edge, the root‐mean‐square field amplitude of the steady‐state response computed across the whole head as well as the contralateral and the ipsilateral dipole moment decreased as a function of carrier frequency. With carrier frequency above the audiometric edge, the steady‐state response increased again. The amplitudes of the transitory Pbm component were patterned in a qualitatively similar way, but without the differences being significant. For the steady‐state response, both whole‐head root‐mean‐square field amplitude and the dipole moment of the sources at the tinnitus frequency showed significant positive correlations with subjective ratings of tinnitus intensity and intrusiveness. These correlations remained significant when the influence of hearing loss was partialled out. The observed steady‐state response amplitude pattern likely reflects an enhanced state of excitability of the frequency region in primary auditory cortex above the audiometric edge. The relationship of tinnitus to auditory cortex hyperexcitability and its independence of hearing loss is discussed with reference to loss of surround inhibition in and map reorganization of primary auditory cortex.

The Brain's Response to Reward Anticipation and Depression in Adolescence: Dimensionality, Specificity, and Longitudinal Predictions in a Community-Based Sample.

OBJECTIVE The authors examined whether alterations in the brains reward network operate as a mechanism across the spectrum of risk for depression. They then tested whether these alterations are specific to anhedonia as compared with low mood and whether they are predictive of depressive outcomes. METHOD Functional MRI was used to collect blood-oxygen-level-dependent (BOLD) responses to anticipation of reward in the monetary incentive task in 1,576 adolescents in a community-based sample. Adolescents with current subthreshold depression and clinical depression were compared with matched healthy subjects. In addition, BOLD responses were compared across adolescents with anhedonia, low mood, or both symptoms, cross-sectionally and longitudinally. RESULTS Activity in the ventral striatum was reduced in participants with subthreshold and clinical depression relative to healthy comparison subjects. Low ventral striatum activation predicted transition to subthreshold or clinical depression in previously healthy adolescents at 2-year follow-up. Brain responses during reward anticipation decreased in a graded manner between healthy adolescents, adolescents with current or future subthreshold depression, and adolescents with current or future clinical depression. Low ventral striatum activity was associated with anhedonia but not low mood; however, the combined presence of both symptoms showed the strongest reductions in the ventral striatum in all analyses. CONCLUSIONS The findings suggest that reduced striatal activation operates as a mechanism across the risk spectrum for depression. It is associated with anhedonia in healthy adolescents and is a behavioral indicator of positive valence systems, consistent with predictions based on the Research Domain Criteria.

Boys do it the right way: sex-dependent amygdala lateralization during face processing in adolescents.

Previous studies have observed a sex-dependent lateralization of amygdala activation related to emotional memory. Specifically, it was shown that the activity of the right amygdala correlates significantly stronger with memory for images judged as arousing in men than in women, and that there is a significantly stronger relationship in women than in men between activity of the left amygdala and memory for arousing images. Using a large sample of 235 male adolescents and 235 females matched for age and handedness, we investigated the sex-specific lateralization of amygdala activation during an emotional face perception fMRI task. Performing a formal sex by hemisphere analysis, we observed in males a significantly stronger right amygdala activation as compared to females. Our results indicate that adolescents display a sex-dependent lateralization of amygdala activation that is also present in basic processes of emotional perception. This finding suggests a sex-dependent development of human emotion processing and may further implicate possible etiological pathways for mental disorders most frequent in adolescent males (i.e., conduct disorder).

Neural and Cognitive Correlates of the Common and Specific Variance Across Externalizing Problems in Young Adolescence

Longitudinal and family-based research suggests that conduct disorder, substance misuse, and ADHD involve both unique forms of dysfunction as well as more specific dysfunctions unique to each condition. Using direct measures of brain function, this study also found evidence in both unique and disorder-specific perturbations.

FTO, obesity and the adolescent brain

Genetic variations in fat mass- and obesity (FTO)-associated gene, a well-replicated gene locus of obesity, appear to be associated also with reduced regional brain volumes in elderly. Here, we examined whether FTO is associated with total brain volume in adolescence, thus exploring possible developmental effects of FTO. We studied a population-based sample of 598 adolescents recruited from the French Canadian founder population in whom we measured brain volume by magnetic resonance imaging. Total fat mass was assessed with bioimpedance and body mass index was determined with anthropometry. Genotype-phenotype associations were tested with Merlin under an additive model. We found that the G allele of FTO (rs9930333) was associated with higher total body fat [TBF (P = 0.002) and lower brain volume (P = 0.005)]. The same allele was also associated with higher lean body mass (P = 0.03) and no difference in height (P = 0.99). Principal component analysis identified a shared inverse variance between the brain volume and TBF, which was associated with FTO at P = 5.5 × 10(-6). These results were replicated in two independent samples of 413 and 718 adolescents, and in a meta-analysis of all three samples (n = 1729 adolescents), FTO was associated with this shared inverse variance at P = 1.3 × 10(-9). Co-expression networks analysis supported the possibility that the underlying FTO effects may occur during embryogenesis. In conclusion, FTO is associated with shared inverse variance between body adiposity and brain volume, suggesting that this gene may exert inverse effects on adipose and brain tissues. Given the completion of the overall brain growth in early childhood, these effects may have their origins during early development.

Effects of stressor controllability on psychophysiological, cognitive and behavioural responses in patients with major depression and dysthymia.

Background The experience of uncontrollability and helplessness in the face of stressful life events is regarded as an important determinant in the development and maintenance of depression. The inability to successfully deal with stressors might be linked to dysfunctional prefrontal functioning. We assessed cognitive, behavioural and physiological effects of stressor uncontrollability in depressed and healthy individuals. In addition, relationships between altered cortical processing and cognitive vulnerability traits of depression were analysed. Method A total of 26 unmedicated depressed patients and 24 matched healthy controls were tested in an expanded forewarned reaction (S1–S2) paradigm. In a factorial design, stressor controllability varied across three consecutive conditions: (a) control, (b) loss of control and (c) restitution of control. Throughout the experiment, error rates, ratings of controllability, arousal, emotional valence and helplessness were assessed together with the post-imperative negative variation (PINV) of the electroencephalogram. Results Depressed participants showed an enhanced frontal PINV as an electrophysiological index of altered information processing during both loss of control and restitution of control. They also felt more helpless than controls. Furthermore, frontal PINV magnitudes were associated with habitual rumination in the depressed subsample. Conclusions These findings indicate that depressed patients are more susceptible to stressor uncontrollability than healthy subjects. Moreover, the experience of uncontrollability seems to bias subsequent information processing in a situation where control is objectively re-established. Alterations in prefrontal functioning appear to contribute to this vulnerability and are also linked to trait markers of depression.