Longitudinal changes of amygdala functional connectivity in adolescents prenatally exposed to cocaine.
ABSTRACT: BACKGROUND:Prenatal cocaine exposure (PCE) is associated with arousal dysregulation, but interactions between exposure and age are rarely investigated directly with longitudinal study designs. Our previous study had examined task-elicited emotional arousal and noted persistently high amygdala activations in the development of adolescents with PCE. However, while externally imposed emotional arousal could be considered a "state" effect depending on specific task stimuli, it is still unclear whether similar developmental alterations extend to intrinsic functional connectivity (FC), reflecting more of a "trait" effect. METHODS:We used a longitudinal design and analyzed resting-state functional magnetic resonance imaging data acquired twice from 25 adolescents with PCE and 16 non-exposed controls. Both groups were each scanned first at the mean age of 14.3 and then again at 16.6 years. Seeding in bilateral amygdalae and comparing the 2nd scan with the 1st, we examined the interaction effect between PCE and age on FCs in the emotional network. RESULTS:Compared with the younger age, we observed a generally decreased FC in the emotional network of the control group at the older age, but these FCs were generally increased at the older age in this same network of the PCE group. Additionally, this interaction effect of exposure by age in the right fusiform was positively correlated with the emotional interference imposed by external task stimuli. CONCLUSIONS:These results provided additional data directly characterizing developmental changes in the emotional network of adolescents with PCE, complementing and extending the notion of a PCE-associated long-term teratogenic effect on arousal regulation.
Project description:Prenatal cocaine exposure (PCE) is associated with long-term and negative effect on arousal regulation. Recent neuroimaging studies have examined brain mechanisms related to arousal dysregulation with cross-sectional experimental designs; but longitudinal changes in the brain, reflecting group differences in neurodevelopment, have never been directly examined. To directly assess the interaction of PCE and neurodevelopment, the present study used a longitudinal design to analyze functional magnetic resonance imaging (fMRI) data collected from 33 adolescents (21 with PCE and 12 non-exposed controls) while they performed the same working memory task with emotional distracters at two points in time. The mean age of participants was 14.3 years at time_1 and 16.7 years at time_2. With confounding factors statistically controlled, the fMRI data revealed significant exposure-by-time interaction in the activations of the amygdala and default mode network (DMN). For the control adolescents, brain activations associated with emotional arousal (amygdala) and cognitive effort (DMN) were both reduced at time_2 as compared to that at time_1. However, these activation reductions were not observed in the PCE group, indicating persistently high levels of emotional arousal and cognitive effort. In addition, correlations between longitudinal changes in the brain and in behavior have shown that adolescents with persistently high emotional arousal were more likely in need of high cognitive effort; and their cognitive performance was more likely to be affected by distractive challenges. The present results complement and extend previous findings from cross-sectional studies with further evidence supporting the view of PCE associated long-term teratogenic effects on arousal regulation.
Project description:Prenatal cocaine exposure (PCE) is associated with attention/arousal dysregulation and possible inefficiencies in some cognitive functions. However, the neurobiological bases of these teratogenic effects have not been well characterized. Because activities in the default mode network (DMN) reflect intrinsic brain functions that are closely associated with arousal regulation and cognition, alterations in the DMN could underlie cognitive effects related to PCE. With resting-state and task activation functional magnetic resonance imaging (fMRI), this study investigated the possible PCE related changes in functional brain connectivity and brain activation in the DMN. In the resting state, the PCE group was found to have stronger functional connectivity in the DMN, as compared to the nonexposed controls. During a working memory task with emotional distracters, the PCE group exhibited less deactivation in the DMN and their fMRI signal was more increased by emotional arousal. These data revealed additional neural effects related to PCE, and consistent with previous findings, indicate that PCE may affect behavior and functioning by increasing baseline arousal and altering the excitatory/inhibitory balancing mechanisms involved in cognitive resource allocation.
Project description:Preclinical research has demonstrated the effects of prenatal cocaine exposure (PCE) on brain regions involved in emotional regulation, motivational control, and addiction vulnerability-eg, the ventral striatum (VS), anterior cingulate (ACC), and prefrontal cortex (PFC). However, little is known about the function of these regions in human adolescents with PCE. Twenty-two adolescents with PCE and 22 age-, gender-, and IQ-matched non-cocaine exposed (NCE) adolescents underwent functional magnetic resonance imaging (fMRI) during exposure to individually personalized neutral/relaxing, stressful, and favorite-food cues. fMRI data were compared using group-level two-tailed t-tests in the BioImage Suite. In comparison with NCE adolescents, PCE adolescents had reduced activity within cortical and subcortical brain regions, including the VS, ACC, and medial and dorslolateral PFC during exposure to favorite-food cues but did not differ in neural responses to stress cues. Subjective food craving was inversely related to dorsolateral PFC activation among PCE adolescents. Among PCE adolescents, subjective anxiety ratings correlated inversely with activations in the orbitofrontal cortex and brainstem during the stress condition and with ACC, dorsolateral PFC, and hippocampus activity during the neutral-relaxing condition. Thus adolescents with PCE display hypoactivation of brain regions involved in appetitive processing, with subjective intensities of craving and anxiety correlating inversely with extent of activation. These findings suggest possible mechanisms by which PCE might predispose to the development of addictions and related disorders, eg, substance-use disorders and binge-eating.
Project description:Endurance physical exercise is accompanied by subjective perceptions of exertion (reported perceived exertion, RPE), emotional valence, and arousal. These constructs have been hypothesized to serve as the basis for the exerciser to make decisions regarding when to stop, how to regulate pace, and whether or not to exercise again. In dual physical-cognitive tasks, the mental (executive) workload generated by the cognitive task has been shown to influence these perceptions, in ways that could also influence exercise-related decisions. In the present work, we intend to replicate and extend previous findings that manipulating the amount of executive load imposed by a mental task, performed concomitantly with a submaximal cycling session, influenced emotional states but not perceived exertion. Participants (experienced triathletes) were asked to perform a submaximal cycling task in two conditions with different executive demands (a two-back version of the n-back task vs. oddball) but equated in external physical load. Results showed that the higher executive load condition elicited more arousal and less positive valence than the lower load condition. However, both conditions did not differ in RPE. This experimental dissociation suggests that perceived exertion and its emotional correlates are not interchangeable, which opens the possibility that they could play different roles in exercise-related decision-making.
Project description:Individual differences in the intensity of feelings of arousal while viewing emotional pictures have been associated with the magnitude of task-evoked blood-oxygen dependent (BOLD) response in the amygdala. Recently, we reported that individual differences in feelings of arousal are associated with task-free (resting state) connectivity within the salience network. There has not yet been an investigation of whether these two types of functional magnetic resonance imaging (MRI) measures are redundant or independent in their relationships to behavior. Here we tested the hypothesis that a combination of task-evoked amygdala activation and task-free amygdala connectivity within the salience network relate to individual differences in feelings of arousal while viewing of negatively potent images. In 25 young adults, results revealed that greater task-evoked amygdala activation and stronger task-free amygdala connectivity within the salience network each contributed independently to feelings of arousal, predicting a total of 45% of its variance. Individuals who had both increased task-evoked amygdala activation and stronger task-free amygdala connectivity within the salience network had the most heightened levels of arousal. Task-evoked amygdala activation and task-free amygdala connectivity within the salience network were not related to each other, suggesting that resting-state and task-evoked dynamic brain imaging measures may provide independent and complementary information about affective experience, and likely other kinds of behaviors as well.
Project description:In this study, we used event-related potentials to examine how different dimensions of emotion-valence and arousal-influence different stages of word processing under different task demands. In two experiments, two groups of participants viewed the same single emotional and neutral words while carrying out different tasks. In both experiments, valence (pleasant, unpleasant, and neutral) was fully crossed with arousal (high and low). We found that the task made a substantial contribution to how valence and arousal modulated the late positive complex (LPC), which is thought to reflect sustained evaluative processing (particularly of emotional stimuli). When participants performed a semantic categorization task in which emotion was not directly relevant to task performance, the LPC showed a larger amplitude for high-arousal than for low-arousal words, but no effect of valence. In contrast, when participants performed an overt valence categorization task, the LPC showed a large effect of valence (with unpleasant words eliciting the largest positivity), but no effect of arousal. These data show not only that valence and arousal act independently to influence word processing, but that their relative contributions to prolonged evaluative neural processes are strongly influenced by the situational demands (and by individual differences, as revealed in a subsequent analysis of subjective judgments).
Project description:This study sought to examine age-related differences in the influences of social (neutral, emotional faces) and non-social/non-emotional (shapes) distractor stimuli in children, adolescents, and adults. To assess the degree to which distractor, or task-irrelevant, stimuli of varying social and emotional salience interfere with cognitive performance, children (N = 12; 8-12y), adolescents (N = 17; 13-17y), and adults (N = 17; 18-52y) completed the Emotional Identification and Dynamic Faces (EIDF) task. This task included three types of dynamically-changing distractors: (1) neutral-social (neutral face changing into another face); (2) emotional-social (face changing from 0% emotional to 100% emotional); and (3) non-social/non-emotional (shapes changing from small to large) to index the influence of task-irrelevant social and emotional information on cognition. Results yielded no age-related differences in accuracy but showed an age-related linear reduction in correct reaction times across distractor conditions. An age-related effect in interference was observed, such that children and adults showed slower response times on correct trials with socially-salient distractors; whereas adolescents exhibited faster responses on trials with distractors that included faces rather than shapes. A secondary study goal was to explore individual differences in cognitive interference. Results suggested that regardless of age, low trait anxiety and high effortful control were associated with interference to angry faces. Implications for developmental differences in affective processing, notably the importance of considering the contexts in which purportedly irrelevant social and emotional information might impair, vs. improve cognitive control, are discussed.
Project description:Background:Recent data suggest that both word valence and arousal modulate subsequent cognitive processing. However, whether valence or arousal makes a stronger contribution to cognitive processing is less understood. Methods:The present study performed three experiments that varied the valence (positive or negative) and arousal (high or low) of prime-target word pairs in a lexical decision-priming task. Affective priming was derived from pure valence (Experiment 1), pure arousal (Experiment 2), or a combination of valence and arousal (Experiment 3). Results:By comparing three types of priming effects, we found an effect of valence on affective priming was obvious regardless of whether the relationship of the prime-target varied with valence, arousal, or the combination of valence and arousal. In contrast, an effect of arousal on affective priming only appeared in the condition that based on the arousal relationship of the prime-target pair. Moreover, the valence-driven priming effect, arousal-driven priming effect, and emotional-driven priming effect were modulated by valence type but not by arousal level of word stimuli. Conclusion:The present results revealed a pattern of valence and arousal in semantic networks, indicating that the valence information of emotional words tends to be more stable than arousal information within the semantic system, at least in the present lexical decision-priming task.
Project description:Bipolar I disorder is defined by the occurrence of mania. The presence of mania, coupled with a course of illness characterized by waxing and waning of affective symptoms, suggests that bipolar disorder arises from dysfunction of neural systems that maintain emotional arousal and homeostasis. We used functional magnetic resonance imaging (fMRI) to study manic bipolar subjects as they performed a cognitive task designed to examine the ventrolateral prefrontal emotional arousal network.We used fMRI to study regional brain activation in 40 DSM-IV manic bipolar I patients and 36 healthy subjects while they performed a continuous performance task with emotional and neutral distracters. Event-related region-of-interest analyses were performed to test the primary hypothesis. Voxelwise analyses were also completed.Compared with healthy subjects, the manic subjects exhibited blunted activation to emotional and neutral images, but not targets, across most of the predefined regions of interest. Several additional brain regions identified in the voxelwise analysis also exhibited similar differences between groups, including right parahippocampus, right lingual gyrus, and medial thalamus. In addition to these primary findings, the manic subjects also exhibited increased activation in response to targets in a number of brain regions that were primarily associated with managing affective stimuli. Group differences did not appear to be secondary to medication exposure or other confounds.Bipolar manic subjects exhibit blunted brain fMRI response to emotional cues throughout the ventrolateral prefrontal emotional arousal network. Disruption of this emotional network may contribute to the mood dysregulation of bipolar disorder.
Project description:Emotion processing is believed to dominate over other brain functions during adolescence, including inhibitory control. However, few studies have examined the neural underpinnings of affective states during cognitive control. Here, we characterized the brain in an affective state by cross-sectionally assessing age-related changes in amygdala background connectivity during an affective inhibitory control task. Participants completed an antisaccade (AS) fMRI task while affective auditory stimuli were presented, and a 5-minute resting state scan. Results showed that while adolescents reported similar arousal levels across emotional conditions, adults perceived negative sounds to be more "arousing" and performed better than adolescents in negative trials. Amygdala background connectivity showed age-related increases with brain regions related to attention and executive control, which were not evident during resting state. Together, results suggest that amygdala connectivity within an affective context is fairly low in mid-adolescence but much stronger in adulthood, supporting age-related improvements in inhibitory control within an affective state. These findings suggest limitations during adolescence in differentiating between the arousing effects of various emotions, potentially undermining the ability to optimally engage inhibitory control. Furthermore, the age-related fMRI findings suggest that low amygdala connectivity to brain areas involved in executive control may underlie these limited abilities during adolescence.