Microstructural properties within the amygdala and affiliated white matter tracts across adolescence.

The amygdala is a heterogenous set of nuclei with widespread cortical connections that continues to develop postnatally with vital implications for emotional regulation. Using high-resolution anatomical and multi-shell diffusion MRI in conjunction with novel amygdala segmentation, cutting-edge tractography, and Neurite Orientation Dispersion and Density (NODDI) methods, the goal of the current study was to characterize age associations with microstructural properties of amygdala subnuclei and amygdala-related white matter connections across adolescence (N = 61, 26 males; ages of 8-22 years). We found age-related increases in the Neurite Density Index (NDI) in the lateral nucleus (LA), dorsal and intermediate divisions of the basolateral nucleus (BLDI), and ventral division of the basolateral nucleus and paralaminar nucleus (BLVPL). Additionally, there were age-related increases in the NDI of the anterior commissure, ventral amygdalofugal pathway, cingulum, and uncinate fasciculus, with the strongest age associations in the frontal and temporal regions of these white matter tracts. This is the first study to utilize NODDI to show neurite density of basolateral amygdala subnuclei to relate to age across adolescence. Moreover, age-related differences were also notable in white matter microstructural properties along the anterior commissure and ventral amydalofugal tracts, suggesting increased bilateral amygdalae to diencephalon structural connectivity. As these basolateral regions and the ventral amygdalofugal pathways have been involved in associative emotional conditioning, future research is needed to determine if age-related and/or individual differences in the development of these microstructural properties link to socio-emotional functioning and/or risk for psychopathology.

White Matter Microstructural Differences in Youth With Classical Congenital Adrenal Hyperplasia.

CONTEXT: Gray matter morphology in the prefrontal cortex and subcortical regions, including the hippocampus and amygdala, are affected in youth with classical congenital adrenal hyperplasia (CAH). It remains unclear if white matter connecting these aforementioned brain regions is compromised in youth with CAH. OBJECTIVE: To examine brain white matter microstructure in youth with CAH compared to controls. DESIGN: A cross-sectional sample of 23 youths with CAH due to 21-hydroxylase deficiency (12.9 ±â€…3.5 year; 61% female) and 33 healthy controls (13.1 ±â€…2.8 year; 61% female) with 3T multishell diffusion-weighted magnetic resonance brain scans. MAIN OUTCOME MEASURES: Complementary modeling approaches, including diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI), to examine in vivo white matter microstructure in six white matter tracts that innervate the prefrontal and subcortical regions. RESULTS: DTI showed CAH youth had lower fractional anisotropy in both the fornix and stria terminalis and higher mean diffusivity in the fornix compared to controls. NODDI modeling revealed that CAH youth have a significantly higher orientation dispersion index in the stria terminalis compared to controls. White matter microstructural integrity was associated with smaller hippocampal and amygdala volumes in CAH youth. CONCLUSIONS: These patterns of microstructure reflect less restricted water diffusion likely due to less coherency in oriented microstructure. These results suggest that white matter microstructural integrity in the fornix and stria terminalis is compromised and may be an additional related brain phenotype alongside affected hippocampus and amygdala neurocircuitry in individuals with CAH.

The Roles of Physical Activity, Exercise, and Fitness in Promoting Resilience During Adolescence: Effects on Mental Well-Being and Brain Development.

Adolescence is a critical yet vulnerable period for developing behaviors important for mental well-being. The existing literature suggests that physical activity (PA), exercise, and aerobic fitness promote well-being and reduce risk of mental health problems. In this review, we focus on PA, exercise, and fitness as modifiable resilience factors that may help promote self-regulation via strengthening of top-down control of bottom-up processes in the brain, thereby acting as a buffer against mental health problems during this period of vulnerability. First, we briefly review the link between PA, exercise, and aerobic fitness with mental well-being and reduced mental health problems in adolescence. Then we present how impairments in self-regulation, which involves top-down control to modulate bottom-up processes, are common across a wide range of mental health disorders. Finally, we use the extant neuroimaging literature to highlight how neural systems underlying top-down control continue to develop across adolescence, and propose that PA, exercise, and aerobic fitness may facilitate resilience through strengthening individual brain regions as well as large-scale neural circuits to improve emotional and behavioral regulation. Future neuroimaging studies assessing the effects of PA, exercise, and aerobic fitness at various developmental stages in each sex and studies considering the characteristics (e.g., frequency, intensity, type) and social context of PA and exercise are vital to better understand both macro- and microscale mechanisms by which these behaviors and attributes may facilitate mental health resilience during adolescent development.

Prefrontal Cortex and Amygdala Subregion Morphology Are Associated With Obesity and Dietary Self-control in Children and Adolescents.

A prefrontal control system that is less mature than the limbic reward system in adolescence is thought to impede self-regulatory abilities, which could contribute to poor dietary choices and obesity. We, therefore, aimed to examine whether structural morphology of the prefrontal cortex (PFC; involved in cognitive control) and the amygdala (a key brain region for reward-related processing) are associated with dietary decisions and obesity in children and adolescents. Seventy-one individuals between the ages of 8-22 years (17.35 ± 4.76 years, 51% female, 56% were overweight or obese) participated in this study; each participant completed a computer-based food choice task and a T1- and T2-weighted structural brain scans. Two indices of obesity were assessed, including age- and sex-specific body mass index (BMIz) and waist-to-height ratio (WHtR). The behavioral task included rating 60 food stimuli for tastiness, healthiness, and liking. Based on each participant's self-ratings, 100 binary food choices were then made utilizing a computer mouse. Dietary "self-control" was calculated as the proportion of trials where the individual chose the healthier food item (vs. the tastier food item) over the total number of trials. Cortical thickness and amygdala subnuclei volumes were quantified using FreeSurfer 6.0 and CIT168 atlas, respectively. We found that WHtR was negatively associated with the thickness of bilateral superior frontal, left superior temporal, right insula, and right inferior temporal regions (p < 0.05, corrected for multiple comparisons). We also found WHtR to be positively associated with the volume of the central nucleus (CEN) region of the amygdala (p = 0.006), after adjusting for the hemisphere, age, sex, and intracranial volumes. A similar data pattern was observed when BMIz was used. Moreover, we found that across all participants, thinner right superior frontal cortex and larger left CEN volumes predicted lower dietary self-control. These results suggest that differential development of the PFC and amygdala relate to obesity and dietary self-control. Further longitudinal studies are merited to determine causal relationships among altered PFC to amygdala neural circuitry, dietary self-control, and obesity.

Brain Differences in the Prefrontal Cortex, Amygdala, and Hippocampus in Youth with Congenital Adrenal Hyperplasia.

CONTEXT: Classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency results in hormone imbalances present both prenatally and postnatally that may impact the developing brain. OBJECTIVE: To characterize gray matter morphology in the prefrontal cortex and subregion volumes of the amygdala and hippocampus in youth with CAH as compared to controls. DESIGN: A cross-sectional study of 27 CAH youth (16 female; 12.6 ±â€…3.4 years) and 35 typically developing, healthy controls (20 female; 13.0 ±â€…2.8 years) with 3-T magnetic resonance imaging scans. Brain volumes of interest included bilateral prefrontal cortex and 9 amygdala and 6 hippocampal subregions. Between-subject effects of group (CAH vs. control) and sex, and their interaction (group-by-sex) on brain volumes, were studied while controlling for intracranial volume (ICV) and group differences in body mass index and bone age. RESULTS: Congenital adrenal hyperplasia youth had smaller ICV and increased cerebrospinal fluid volume compared to controls. In fully-adjusted models, CAH youth had smaller bilateral superior and caudal middle frontal volumes, and smaller left lateral orbitofrontal volumes compared to controls. Medial temporal lobe analyses revealed that the left hippocampus was smaller in fully-adjusted models. Congenital adrenal hyperplasia youth also had significantly smaller lateral nucleus of the amygdala and hippocampal subiculum and CA1 subregions. CONCLUSIONS: This study replicates previous findings of smaller medial temporal lobe volumes in CAH patients and suggests that the lateral nucleus of the amygdala, as well as subiculum and subfield CA1 of the hippocampus, are particularly affected within the medial temporal lobes in CAH youth.