Positive reinforcement modulates fronto-limbic systems subserving emotional interference in adolescents.

Fronto-limbic systems play an important role in supporting resistance to emotional distraction to promote goal-directed behavior. Despite evidence that alterations in the functioning of these systems are implicated in developmental trajectories of psychopathology, most studies have been conducted in adults. This study examined the functioning of fronto-limbic systems subserving emotional interference in adolescents and whether differential reinforcement of correct responding can modulate these neural systems in ways that could promote resistance to emotional distraction. Fourteen healthy adolescents (ages 9-15) completed an emotional delayed working memory task during fMRI with emotional distracters (none, neutral, negative) while positive reinforcement (i.e., monetary reward) was provided for correct responses under some conditions. Adolescents showed slightly reduced behavioral performance and greater activation in amygdala and prefrontal cortical regions (ventrolateral, ventromedial, dorsolateral) on correct trials with negative distracters compared to those with no or neutral distracters. Positive reinforcement yielded an overall improvement in accuracy and reaction times and counteracted the effects of negative distracters as evidenced by significant reductions in activation in key fronto-limbic regions. The present findings extend results on emotional interference from adults to adolescents and suggest that positive reinforcement could be used to potentially promote insulation from emotional distraction. A challenge for the future will be to build upon these findings for constructing reinforcement-based attention training programs that could be used to reduce emotional attention biases in anxious youth.

Right superior temporal gyrus volume in adolescents with a history of suicide attempt.

The extent to which observed differences in emotion processing and regulation neural circuitry in adolescents with a history of suicide attempt are paralleled by structural differences is unknown. We measured brain cortical thickness and grey- and white-matter volumes in 100 adolescents: 28 with a history of suicide attempt and major depressive disorder (MDD); 31 with a history of MDD but no suicide attempt; and a healthy control group (n = 41). The first group compared with controls showed reduction in grey-matter volume in the right superior temporal gyrus (BA38), a region important for social emotion processing.

Differential Anterior Cingulate Activity during Response Inhibition in Depressed Adolescents with Bipolar and Unipolar Major Depressive Disorder.

OBJECTIVE: Cognitive control deficits are commonly seen in Depression of Bipolar Disorder (BDd) and Unipolar Major Depressive Disorder (UDd). Because failure to differentiate BDd from UDd has significant clinical consequences we aimed to identify differential patterns of neural activity in BDd versus UDd underlying response inhibition and motor control in adolescents. METHODS: Functional MRI was used to compare 12 BDd adolescents (mean age= 15.5±1.2) with age- and sex-matched ten UDd and ten healthy control (HC) adolescents during the performance of well-validated Go/NoGo task. NoGo response inhibition versus Go motor control blocks was used in whole-brain analysis and results were corrected for multiple comparisons. RESULTS: There were no significant behavioral or neuroimaging findings between adolescents with BDd and UDd. However, both groups relative to HC showed significantly higher left superior temporal and left caudate activity during the NoGo condition. Moreover, left anterior cingulate (ACC) activity relative to HC was significantly higher only in BDd - not UDd - adolescents during the NoGo condition, and left caudate activity was higher only in UDd - not BDd - adolescents during the Go condition. In addition, several neural regions including dorsolateral prefrontal (DLPFC) were positively correlated with increased reaction time in UDd - not BDd - adolescents. CONCLUSIONS: Despite some similarities, neural correlates of depression are different in BDd and UDd relative to HC, and greater recruitment of ACC resources during response inhibition can help distinguish BDd.

OBJECTIF: Les déficits de contrôle cognitif sont souvent observés dans la dépression du trouble bipolaire (dTB) et dans le trouble dépressif majeur unipolaire (dTU). Parce que ne pas différencier entre la dTB et la dTU a des conséquences cliniques significatives, nous avons cherché à identifier les modèles différentiels d'activité neurale dans la dTB comparativement à la dTU en ce qui concerne l'inhibition sous-jacente de la réponse et le contrôle moteur chez les adolescents. MÉTHODES: L'imagerie par résonance magnétique fonctionnelle (IRMf) a servi à comparer 12 adolescents souffrant de dTB (âge moyen = 15,5±1,2) avec 10 adolescents souffrant de dTU appariés selon l'âge et le sexe, et dix adolescents témoins en santé (TS) durant la performance d'une tâche Go/NoGo bien validée. L'inhibition de la réponse à NoGo par opposition aux blocs de contrôle moteur de GO a été utilisée dans une analyse du cerveau en entier et les résultats ont été corrigés pour de multiples comparaisons. RÉSULTATS: Il n'y avait pas de résultats de comportement ou de neuroimagerie significatifs entre les adolescents souffrant de dTB et de dTU. Cependant, les deux groupes comparés aux TS montraient une activité temporale gauche supérieure et caudale gauche significativement plus élevée durant la condition NoGo. En outre, l'activité du cortex cingulaire antérieur (CCA) gauche, en comparaison avec les TS, était significativement supérieure seulement chez les adolescents souffrant de dTB ­ et non de dTU ­ durant la condition NoGo, et l'activité caudale gauche était plus élevée seulement chez les adolescents souffrant de dTU ­ et non de dTB ­ durant la condition NoGo. De plus, plusieurs régions neurales, dont le cortex préfrontal dorsolatéral (CPFDL), étaient positivement corrélées à un temps de réaction accru chez les adolescents souffrant de dTU ­ et non de dTB. CONCLUSIONS: Malgré certaines similitudes, les corrélats neuraux de la dépression sont différents dans la dTB et la dTU comparativement aux TS, et un meilleur recrutement des ressources du CCA durant l'inhibition de la réponse peut contribuer à distinguer la dTB.

Neural correlates of treatment response in depressed bipolar adolescents during emotion processing.

Depressive mood in adolescents with bipolar disorder (BDd) is associated with significant morbidity and mortality, but we have limited information about neural correlates of depression and treatment response in BDd. Ten adolescents with BDd (8 females, mean age = 15.6 ± 0.9) completed two (fearful and happy) face gender labeling fMRI experiments at baseline and after 6-weeks of open treatment. Whole-brain analysis was used at baseline to compare their neural activity with those of 10 age and sex-matched healthy controls (HC). For comparisons of the neural activity at baseline and after treatment of youth with BDd, region of interest analysis for dorsal/ventral prefrontal, anterior cingulate, and amygdala activity, and significant regions identified by wholebrain analysis between BDd and HC were analyzed. There was significant improvement in depression scores (mean percentage change on the Child Depression Rating Scale-Revised 57 % ± 28). Neural activity after treatment was decreased in left occipital cortex in the intense fearful experiment, but increased in left insula, left cerebellum, and right ventrolateral prefrontal cortex in the intense happy experiment. Greater improvement in depression was associated with baseline higher activity in ventral ACC to mild happy faces. Study sample size was relatively small for subgroup analysis and consisted of mainly female adolescents that were predominantly on psychotropic medications during scanning. Our results of reduced negative emotion processing versus increased positive emotion processing after treatment of depression (improvement of cognitive bias to negative and away from positive) are consistent with the improvement of depression according to Beck's cognitive theory.

Preserved hippocampal function during learning in the context of risk in adolescent suicide attempt.

Impairment in decision-making is frequently observed in suicide attempters. Little is known, however, about neural circuitry underlying decision-making in adolescent attempters. Functional magnetic resonance imaging (fMRI) was used to assess decision-making and learning-related neural activity during Iowa Gambling Task (IGT) performance in adolescents with depression and suicide attempt (ATT, n=15), non-attempters with depression (NAT, n=14), and healthy controls (HC, n=13). ATT performed best on the IGT. A three group by two condition (high-risk versus low-risk) by three IGT block (each of 20 cards) whole-brain analysis (p<0.05, corrected) interaction was found in the left hippocampal, frontal and temporal cortical, striatal and thalamic regions. Post-hoc analyses revealed that during low-risk decisions in blocks 2 and 3, NAT, but not ATT, showed greater left hippocampal activation versus HC (p=0.0004, p=0.003); in block 2, during low-risk decisions NAT showed greater left middle temporal gyral activation versus HC (p=0.003); in block 3, during high-risk decisions ATT showed less activation in the right thalamus versus NAT (p=0.001) and during low risk decisions ATT showed greater activation than HC in the left caudate (p=0.002). NAT, but not ATT are differentiated from HC during performance of the IGT. Functional abnormalities in neural circuitry implicated in learning in the context of risk may underlie risk for MDD, but not risk for suicide attempt, in adolescence.

Dissociable patterns of neural activity during response inhibition in depressed adolescents with and without suicidal behavior.

OBJECTIVES: Impaired attentional control and behavioral control are implicated in adult suicidal behavior. Little is known about the functional integrity of neural circuitry supporting these processes in suicidal behavior in adolescence. METHOD: Functional magnetic resonance imaging was used in 15 adolescent suicide attempters with a history of major depressive disorder (ATTs), 15 adolescents with a history of depressive disorder but no suicide attempt (NATs), and 14 healthy controls (HCs) during the performance of a well-validated go-no-go response inhibition and motor control task that measures attentional and behavioral control and has been shown to activate prefrontal, anterior cingulate, and parietal cortical circuitries. Questionnaires assessed symptoms and standardized interviews characterized suicide attempts. RESULTS: A 3 group by 2 condition (go-no-go response inhibition versus go motor control blocks) block-design whole-brain analysis (p < .05, corrected) showed that NATs showed greater activity than ATTs in the right anterior cingulate gyrus (p = .008), and that NATs, but not ATTs, showed significantly greater activity than HCs in the left insula (p = .004) to go-no-go response inhibition blocks. CONCLUSIONS: Although ATTs did not show differential patterns of neural activity from HCs during the go-no-go response inhibition blocks, ATTs and NATs showed differential activation of the right anterior cingulate gyrus during response inhibition. These findings indicate that suicide attempts during adolescence are not associated with abnormal activity in response inhibition neural circuitry. The differential patterns of activity in response inhibition neural circuitry in ATTs and NATs, however, suggest different neural mechanisms for suicide attempt versus major depressive disorder in general in adolescence that should be a focus of further study.