Forgiveness Mediates the Relationship Between Middle Frontal Gyrus Volume and Clinical Symptoms in Adolescents.

Dispositional forgiveness is positively associated with many facets of wellbeing and has protective implications against depression and anxiety in adolescents. However, little work has been done to examine neurobiological aspects of forgiveness as they relate to clinical symptoms. In order to better understand the neural mechanisms supporting the protective role of forgiveness in adolescents, the current study examined the middle frontal gyrus (MFG), which comprises the majority of the dorsolateral prefrontal cortex (DLPFC) and is associated with cognitive regulation, and its relationship to forgiveness and clinical symptoms in a sample of healthy adolescents. In this cross-sectional study (n = 64), larger MFG volume was significantly associated with higher self-reported dispositional forgiveness scores and lower levels of depressive and anxiety symptoms. Forgiveness mediated the relationship between MFG volume and both depressive and anxiety symptom levels. The mediating role of forgiveness in the relationship between MFG volume and clinical symptoms suggests that one way that cognitive regulation strategies supported by this brain region may improve adolescent mental health is via increasing a capacity for forgiveness. The present study highlights the relevance of forgiveness to neurobiology and their relevance to emotional health in adolescents. Future longitudinal studies should focus on the predictive quality of the relationship between forgiveness, brain volume and clinical symptoms and the effects of forgiveness interventions on these relationships.

Perceived stress and rejection associated with functional network strength during memory retrieval in adolescents.

The brain undergoes substantial structural and functional remodeling during adolescence, including alterations in memory-processing regions influenced by stress. This study evaluated brain activation using functional magnetic resonance imaging (fMRI) during spatial memory performance using a virtual Morris water task (MWT) and examined the associations between default mode network (DMN) activation, task performance, and perceived stress and rejection. Functional magnetic resonance imaging data were acquired at 3 Tesla from 59 (34 female) adolescents (13-14 years). The NIH Emotion Toolbox was used to measure perceived stress and rejection. During the MWT, hippocampus and prefrontal cortex showed greater activation during memory retrieval relative to motor performance. Templates of brain functional networks from the Human Connectome Project study were used to extract individual participants' brain network activation strengths for the retrieval > motor contrast for two sub-networks of the default mode network: medial temporal lobe (MTL-DMN) and dorsomedial prefrontal (dMPFC-DMN). For the MTL-DMN sub-network only, activation was significantly associated with worse MWT performance (p = .008) and greater perceived stress (p = .008) and perceived rejection (p = .002). Further, MWT performance was negatively associated with perceived rejection (p = .007). These findings suggest that perceived stress and rejection are related to engagement of MTL-DMN during spatial memory and that engagement of this network impacts performance. These findings also demonstrate the utility of examining task-related network activation strength to identify the impact of perceived stress and rejection on large-scale brain network functioning during adolescence.

Large-scale brain network activation during emotional inhibitory control: Associations with alcohol misuse in college freshmen.

BACKGROUND: The transition to college is associated with increased risk of alcohol misuse and a consequent increase in negative, alcohol-related social and health impacts. Traits associated with ongoing brain maturation during this period, including impulsivity in emotional contexts, could contribute to risky alcohol use. METHODS: This functional magnetic resonance imaging (fMRI) study examined brain network activation strength during an emotional inhibitory control task (Go-NoGo), which required participants to ignore background images with negative or neutral emotional valence during performance. Participants were 60 college freshmen (aged 18-20 years, 33 women). Survey measures, completed at baseline and one-year follow-up (follow-up n = 52, 29 women), assessed alcohol misuse alcohol use disorders identification test (AUDIT), alcohol/substance use counseling center assessment of psychological symptoms (C-CAPS), and negative consequences of alcohol use young adult alcohol consequences questionnaire (YAACQ). Measures were examined relative to network activation strength, on the Negative NoGo > Neutral NoGo contrast, of four large-scale brain networks implicated in top-down regulation of cognition and attention: right and left lateral frontoparietal networks (rL-FPN; lL-FPN), dorsal attention network (DAN), and salience network (SN). RESULTS: Activation strength of DAN was negatively associated with scores on the AUDIT (p = 0.013) and YAACQ (p = 0.004) at baseline, and with C-CAPS score at baseline and follow-up (p = 0.002; p = 0.005), and positively associated with accuracy on NoGo trials with negative backgrounds (p = 0.014). Activation strength of rL-FPN was positively associated with C-CAPS score at follow-up (p = 0.003). SN activation strength was negatively associated with accuracy on NoGo trials with negative (p < 0.001) and neutral (p = 0.002) backgrounds and with the accuracy difference between negative versus neutral NoGo trials (p = 0.003). CONCLUSION: These findings suggest that less engagement of large-scale brain circuitry that supports top-down attentional control, specifically during negative emotions, is associated with more problematic drinking in emerging adults who attend college. This pattern of network activation may serve as a risk marker for ongoing self-regulation deficits during negative emotion that could increase risk of problematic alcohol use and negative impacts of drinking.

Brain Activation during Memory Retrieval is Associated with Depression Severity in Women.

Major depressive disorder (MDD) is a debilitating disorder that interferes with daily functioning, and that occurs at higher rates in women than in men. Structural and functional alterations in hippocampus and frontal lobe have been reported in MDD, which likely contribute to the multifaceted nature of MDD. One area impacted by MDD is hippocampal-mediated memory, which can be probed using a spatial virtual Morris water task (MWT). Women (n=24) across a spectrum of depression severity underwent functional magnetic resonance imaging (fMRI) during MWT. Depression severity, assessed via Beck Depression Inventory (BDI), was examined relative to brain activation during task performance. Significant brain activation was evident in areas traditionally implicated in spatial memory processing, including right hippocampus and frontal lobe regions, for retrieval > motor contrast. When BDI was included as a regressor, significantly less functional activation was evident in left hippocampus, and other non-frontal, task relevant regions for retrieval > rest contrast. Consistent with previous studies, depression severity was associated with functional alterations observed during spatial memory performance. These findings may contribute to understanding neurobiological underpinnings of depression severity and associated memory impairments, which may have implications for treatment approaches aimed at alleviating effects of depression in women.

Morphometric Biomarkers of Adolescents With Familial Risk for Alcohol Use Disorder.

BACKGROUND: While many adolescents exhibit risky behavior, teenagers with a family history (FH+) of an alcohol use disorder (AUD) are at a heightened risk for earlier initiation of alcohol use, a more rapid escalation in frequency and quantity of alcohol consumption and developing a subsequent AUD in comparison with youth without such family history (FH-). Neuroanatomically, developmentally normative risk-taking behavior parallels an imbalance between more protracted development of the prefrontal cortex (PFC) and earlier development of limbic regions. Magnetic resonance imaging (MRI)-derived volumetric properties were obtained for these structures in FH+ and FH- adolescents. METHODS: Forty-two substance-naïve adolescents (13- to 14-year-olds), stratified into FH+ (N = 19, 13 girls) and FH- (N = 23, 11 girls) age/handedness-matched groups, completed MRI scanning at 3.0T, as well as cognitive and clinical testing. T1 images were processed using FreeSurfer to measure PFC and hippocampi/amygdalae subfields/nuclei volumes. RESULTS: FH+ status was associated with larger hippocampal/amygdala volumes (p < 0.05), relative to FH- adolescents, with right amygdala results appearing to be driven by FH+ boys. Volumetric differences also were positively associated with family history density (p < 0.05) of having an AUD. Larger subfields/nuclei volumes were associated with higher anxiety levels and worse auditory verbal learning performance (p < 0.05). CONCLUSIONS: FH+ risk for AUD is detectable via neuromorphometric characteristics, which precede alcohol use onset and the potential onset of a later AUD, that are associated with emotional and cognitive measures. It is plausible that the development of limbic regions might be altered in FH+ youth, even prior to the onset of alcohol use, which could increase later risk. Thus, targeted preventative measures are warranted that serve to delay the onset of alcohol use in youth, particularly in those who are FH+ for an AUD.

Adolescent Hippocampal and Prefrontal Brain Activation During Performance of the Virtual Morris Water Task.

The frontal cortex undergoes substantial structural and functional changes during adolescence and significant developmental changes also occur in the hippocampus. Both of these regions are notably vulnerable to alcohol and other substance use, which is typically initiated during adolescence. Identifying measures of brain function during adolescence, particularly before initiation of drug or alcohol use, is critical to understanding how such behaviors may affect brain development, especially in these vulnerable brain regions. While there is a substantial developmental literature on adolescent working memory, less is known about spatial memory. Thus, a virtual Morris water task (vMWT) was applied to probe function of the adolescent hippocampus. Multiband blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) data were acquired at 3T during task performance. Participants included 32 healthy, alcohol- and drug-naïve adolescents, 13-14 years old, examined at baseline of a 3-year longitudinal MRI study. Significantly greater BOLD activation was observed in the hippocampus and surrounding areas, and in prefrontal regions involved in executive function, during retrieval relative to motor performance. In contrast, significantly greater BOLD activation was observed in components of the default mode network, including frontal medial cortex, during the motor condition (when task demands were minimal) relative to the retrieval condition. Worse performance (longer path length) during retrieval was associated with greater activation of angular gyrus/supramarginal gyrus, whereas worse performance (longer path length/latency) during motor control was associated with less activation of frontal pole. Furthermore, while latency (time to complete task) was greater in females than in males, there were no sex differences in path length (accuracy), suggesting that females required more time to navigate the virtual environment, but did so as effectively as males. These findings demonstrate that performance of the vMWT elicits hippocampal and prefrontal activation patterns in early adolescence, similar to activation observed during spatial memory retrieval in adults. Given that this task is sensitive to hippocampal function, and that the adolescent hippocampus is notably vulnerable to the effects of alcohol and other substances, data acquired using this task during healthy adolescent development may provide a framework for understanding neurobiological impact of later initiation of use.

College Binge Drinking Associated with Decreased Frontal Activation to Negative Emotional Distractors during Inhibitory Control.

The transition to college is associated with an increase in heavy episodic alcohol use, or binge drinking, during a time when the prefrontal cortex and prefrontal-limbic circuitry continue to mature. Traits associated with this immaturity, including impulsivity in emotional contexts, may contribute to risky and heavy episodic alcohol consumption. The current study used blood oxygen level dependent (BOLD) multiband functional magnetic resonance imaging (fMRI) to assess brain activation during a task that required participants to ignore background images with positive, negative, or neutral emotional valence while performing an inhibitory control task (Go-NoGo). Subjects were 23 college freshmen (seven male, 18-20 years) who engaged in a range of drinking behavior (past 3 months' binge episodes range = 0-19, mean = 4.6, total drinks consumed range = 0-104, mean = 32.0). Brain activation on inhibitory trials (NoGo) was contrasted between negative and neutral conditions and between positive and neutral conditions using non-parametric testing (5000 permutations) and cluster-based thresholding (z = 2.3), p ≤ 0.05 corrected. Results showed that a higher recent incidence of binge drinking was significantly associated with decreased activation of dorsolateral prefrontal cortex (DLPFC), dorsomedial prefrontal cortex (DMPFC), and anterior cingulate cortex (ACC), brain regions strongly implicated in executive functioning, during negative relative to neutral inhibitory trials. No significant associations between binge drinking and brain activation were observed for positive relative to neutral images. While task performance was not significantly associated with binge drinking in this sample, subjects with heavier recent binge drinking showed decreased recruitment of executive control regions under negative versus neutral distractor conditions. These findings suggest that in young adults with heavier recent binge drinking, processing of negative emotional images interferes more with inhibitory control neurocircuitry than in young adults who do not binge drink often. This pattern of altered frontal lobe activation associated with binge drinking may serve as an early marker of risk for future self-regulation deficits that could lead to problematic alcohol use. These findings underscore the importance of understanding the impact of emotion on cognitive control and associated brain functioning in binge drinking behaviors among young adults.