Katherine R. Luking

Subgenual cingulate connectivity in children with a history of preschool-depression

The subgenual anterior cingulate cortex (sgACC) presents altered functional connections with other regions of the brain in individuals with depression. However, the developmental nature of this phenomenon remains largely unexplored. Functional connections of the sgACC were examined in 36 school age children, 17 with a history of preschool onset major depressive disorder (PO-MDD). The sgACC exhibited increased connections with cognitive control regions in healthy children and increased connections with thalamic and parietal regions in the PO-MDD group. A significant correlation between dysregulated emotional behavior and connectivity of the sgACC and dorsal medial prefrontal cortex was also found. These findings demonstrate that atypical sgACC functional connections are evident as early as school age in children with a history of PO-MDD and suggest an association with a very early episode of depression.

Reward Processing and Risk for Depression Across Development

Striatal response to reward has been of great interest in the typical development and psychopathology literatures. These parallel lines of inquiry demonstrate that although typically developing adolescents show robust striatal response to reward, adolescents with major depressive disorder (MDD) and those at high risk for MDD show a blunted response to reward. Understanding how these findings intersect is crucial for the development and application of early preventative interventions in at-risk children, ideally before the sharp increase in the rate of MDD onset that occurs in adolescence. Robust findings relating blunted striatal response to reward and MDD risk are reviewed and situated within a normative developmental context. We highlight the need for future studies investigating longitudinal development, specificity to MDD, and roles of potential moderators and mediators.

Kids, candy, brain and behavior: age differences in responses to candy gains and losses.

Highlights • Neural responses to candy loss feedback vary greatly between children and adults.• Children and adults show largely similar neural responses to candy gain feedback.• Striatal responses to candy gains/losses are influenced by age and by task behavior.• Insular responses to loss relate to age, even when controlling for task behavior.

Internal Consistency of Functional Magnetic Resonance Imaging and Electroencephalography Measures of Reward in Late Childhood and Early Adolescence

BACKGROUND Abnormal neural response to reward is increasingly thought to function as a biological correlate of emerging psychopathology during adolescence. However, this view assumes such responses have good psychometric properties-especially internal consistency-an assumption that is rarely tested. METHODS Internal consistency (i.e., spilt-half reliability) was calculated for event-related potentials (ERPs) and Blood Oxygen Level Dependent (BOLD) responses to monetary gain and loss feedback from the same sample of 8-14 year-old females (n=177). Internal consistency for ERPs (i.e. feedback negativity) and BOLD responses within the ventral striatum and medial/lateral prefrontal cortex to gain, loss, difference scores (gain-loss), and residual scores (gain controlling for loss) were compared. Moderation analyses were conducted to investigate whether internal consistency differed by age. RESULTS ERP and BOLD responses to gain and loss feedback showed high internal consistency in all regions (Spearman Brown Coefficients (SB) ≥ 0.70). When considering difference and residual scores, however, responses showed lower internal consistency (SBs ≤ 0.50), with particularly low internal consistency for subtraction-based scores (SB ≤ 0.36). Age was not a significant moderator of split-half relationships, indicating similar internal consistency across late childhood to early adolescence. CONCLUSIONS Within the same subjects, high internal consistency was observed for both ERP and fMRI measures of response to gains and losses, which did not vary as a function of age. Moreover, excellent psychometric properties were evident even within the first half of the experiment. Difference scores were characterized by lower internal consistency, although regression-based approaches outperformed subtraction-based difference scores.

Brain-behavior relationships in the experience and regulation of negative emotion in healthy children: Implications for risk for childhood depression

Structural and functional alterations in a variety of brain regions have been associated with depression and risk for depression across the life span. A majority of these regions are associated with emotion reactivity and/or regulation. However, it is generally unclear what mechanistic role these alterations play in the etiology of depression. A first step toward understanding this is to characterize the relationships between variation in brain structure/function and individual differences in depression severity and related processes, particularly emotion regulation. To this end, the current study examines how brain structure and function predict concurrent and longitudinal measures of depression symptomology and emotion regulation skills in psychiatrically healthy school-age children (N = 60). Specifically, we found that smaller hippocampus volumes and greater responses to sad faces in emotion reactivity regions predict increased depressive symptoms at the time of scan, whereas larger amygdala volumes, smaller insula volumes, and greater responses in emotion reactivity regions predict decreased emotion regulation skills. In addition, larger insula volumes predict improvements in emotion regulation skills even after accounting for emotion regulation at the time of scan. Understanding brain-behavior relationships in psychiatrically healthy samples, especially early in development, will help inform normative developmental trajectories and neural alterations in depression and other affective pathology.

Reduced Hedonic Capacity/Approach Motivation Relates to Blunted Responsivity to Gain and Loss Feedback in Children

Adolescents and adults with major depressive disorder or elevated depressive symptoms show reduced reward responses and tend to show enhanced responses to negative stimuli. However, reward-related behaviors and adaptive responses to negative feedback undergo dramatic changes across puberty. Thus, key questions remain regarding how altered incentive processing relates to depressive and anhedonic symptoms in prepubertal child populations. Twenty-four nonclinical prepubertal children 7–10 years of age (15 male; 16 Caucasian) completed two signal detection tasks that assessed behavioral responsivity to candy gain and loss feedback, respectively. These tasks were based on Pizzagallis probabilistic reward task where asymmetric feedback leads to greater bias toward the more frequently rewarded response in more hedonic or nondepressed adults. We further modified the task to create a version where incorrect responses could result in losses from an original allotment of candy. Children and parents/guardians also completed individual difference questionnaires to assess the childs depressive symptoms, general affect, and hedonic capacity/approach motivation. Regressions indicated a relation between hedonic capacity/approach motivation (child self-report) and response bias in both gain and loss tasks. No significant relations were observed between depressive (child self-report), internalizing (parent report), or externalizing symptoms (parent report) and bias in either the gain or loss task in this small sample. These results suggest that reduced hedonic capacity/approach motivation is associated with blunted responses to both gain and loss feedback in prepubertal children.

Do losses loom larger for children than adults

The large impact of loss of reward on behavior has been well documented in adult populations. However, whether responsiveness to loss relative to gain is similarly elevated in child versus adult populations remains unclear. It is also unclear whether relations between incentive behaviors and self-reported reward/punishment sensitivity are similar within different developmental stages. To investigate these questions, 7- to 10-year-old children (N = 70) and young adults (N = 70) completed the Behavioral Inhibition System/Behavioral Activation System (BIS/BAS) scale, along with 2 probabilistic incentive tasks assessing gain approach and loss avoidance behavior. BIS/BAS subscales were calculated per Pagliaccio et al. (2015), which established an age invariant model of the BIS/BAS. Bias toward responses more frequently followed by gain feedback and away from responses more frequently followed by loss feedback, approach, and avoidance behavior, respectively, were quantified via signal detection statistics. Gain approach behavior did not differ across age groups; however, children exhibited significantly elevated loss avoidance relative to adults. Children also showed greater reductions in accuracy and slower RTs specifically following loss feedback relative to adults. Interestingly, despite age group differences in loss avoidance behavior, relations between self-report measures and approach/avoidance behaviors were similar across age groups. Participants reporting elevated motivation (BAS Drive) showed both elevated gain approach and elevated loss avoidance, with both types of behavior predicting unique variance in BAS Drive. Results highlight the often-neglected developmental and motivational roles of responsiveness to loss of reward.

Orbitofrontal Cortex Activity and Connectivity Predict Future Depression Symptoms in Adolescence

Background Major depressive disorder is a leading cause of disability worldwide; however, little is known about pathological mechanisms involved in its development. Research in adolescent depression has focused on reward sensitivity and striatal mechanisms implementing it. The contribution of loss sensitivity to future depression, as well as the orbitofrontal cortex (OFC) mechanisms critical for processing losses and rewards, remain unexplored. Furthermore, it is unclear whether OFC functioning interacts with familial history in predicting future depression. Methods In this longitudinal study we recorded functional magnetic resonance imaging (fMRI) data while 229 adolescent females with or without parental history of depression completed a monetary gambling task. We examined if OFC blood-oxygen-level-dependent (BOLD) response and functional connectivity during loss and win feedback was associated with depression symptoms concurrently and prospectively (9 months later), and whether this relationship was moderated by parental history of depression. Results Reduced OFC response during loss was associated with higher depression symptoms concurrently and prospectively, even after controlling for concurrent depression, specifically in adolescents with parental history of depression. Similarly, increased OFC-posterior insula connectivity during loss was associated with future depression symptoms but this relationship was not moderated by parental history of depression. Conclusions This study provides the first evidence for loss-related alterations in OFC functioning and its interaction with familial history of depression as possible mechanisms in the development of depression. While the current fMRI literature has mainly focused on reward, the present findings underscore the need to include prefrontal loss processing in existing developmental models of depression.

Robust is not necessarily reliable: From within-subjects fMRI contrasts to between-subjects comparisons

&NA; Advances in cognitive and affective neuroscience come largely from within‐subjects comparisons, in which the functional significance of neural activity is determined by contrasting two or more experimental conditions. Clinical and social neuroscience studies have attempted to leverage between‐subject variability in such condition differences to better understand psychopathology and other individual differences. Shifting from within‐to between‐subjects comparisons requires that measures have adequate internal consistency to function as individual difference variables. This is particularly relevant for difference scores—which have lower reliability. The field has assumed reasonable internal consistency of neural measures based on consistent findings across studies (i.e., if a within‐subject difference in neural activity is robust, then it must be reliable). Using one of the most common fMRI paradigms in the clinical neuroscience literature (i.e., a face‐ and shape‐matching task), in a large sample of adolescents (N = 139) we replicate a robust finding: amygdala activation is greater for faces than shapes. Moreover, we demonstrate that the internal consistency of the amygdala in face and shape blocks was excellent (Spearman‐Brown corrected reliability [SB] > .94). However, the internal consistency of the activation difference between faces and shapes was nearly zero (SB = −.06). This reflected the fact that the amygdala response to faces and shapes was highly correlated (r = .97) across individuals. Increased neural activation to faces versus shapes could not possibly function as an individual difference measure in these data—illustrating how neural activation can be robust within subjects, but unreliable as an individual difference measure. Strong and reproducible condition differences in neural activity are not necessarily well‐suited for individual differences research—and neuroimaging studies should always report the internal consistency of, and correlations between, activations used in individual differences research. HighlightsRobust within‐subject differences are often used as individual difference measures.A robust within‐subject difference may not be internally consistent.Difference scores are problematic when constituent measures are highly correlated.Subtraction‐based measures should report the correlation between the two variables.Internal consistencies should be reported for difference and constituent scores

Dampening, Positive Rumination, and Positive Life Events: Associations with Depressive Symptoms in Children at Risk for Depression

Blunted positive affect is characteristic of depression. Altered positive affect regulation may contribute to this blunting, and two regulation strategies, dampening positive affect and positive rumination, have been implicated in depression. However, the conditions under which these strategies impart risk/protective effects prior to onset of depression are unknown. The current study examined 81 healthy children (age 7–10) at low and high risk for depression on the basis of maternal history of depression and tested how dampening and positive rumination interacted with the experience of recent positive life events to predict depressive symptoms. Children at high and low risk did not differ in their use of dampening or positive rumination. However, elevated use of dampening in the context of many positive life events predicted current depressive symptoms, and specifically anhedonic symptoms, in children at low-risk for depression. These findings held when controlling for negative rumination and negative life events. Positive rumination did not interact with positive life events but was associated with higher depressive symptoms in high-risk children. Results indicate that prior to the onset of depression, positive life events may impart risk when dampening positive affect is utilized in this context, while positive rumination may increase risk for depressive symptoms.