Alcohol Clin Exp Res

Background:Low levels of response (low LR) to alcohol predict heavy drinking and alcohol problems. Functional magnetic resonance imaging (fMRI) studies of emotion processing have demonstrated low LR individuals exhibit lower activation in task-related brain regions following both placebo and alcohol administration but the studies did not examine functional brain networks that might contribute to the phenomena. The current study expands upon those earlier results by evaluating if functional connectivity differences between the amygdala and other brain regions modulated by emotional face processing are likewise associated with LR. Based on the prior study, we hypothesized that low LR will be related to lower functional connectivity in fronto-amygdalar functional circuits underlying processing of emotional stimuli.Methods:Secondary analyses were conducted on data from a double-blind, placebo controlled, within-subjects, cross-over study in 108 18-to-25-year-old low and high LR sex matched pairs without an alcohol use disorder at baseline. Participants performed modified emotional faces processing tasks after placebo or approximately 0.7 mL/kg of ethanol. Psychophysiological interaction analyses examined functional connectivity between left and right amygdala and related brain circuits using LR-by-alcohol general linear models. The data included 54 sex-matched pairs with 216 fMRI scans comprising alcohol and placebo conditions.Results:Compared with individuals with high LR, low LR subjects demonstrated lower functional connectivity between the amygdala and the frontal lobes, insula, and parietal regions, respectively, while processing angry and happy faces. Interactions showed lower connectivity following alcohol in low LR and higher connectivity in high LR groups.Conclusions:Low LR individuals demonstrated lower functional connectivity both with placebo and in response to a modest ethanol dose. Attenuated connectivity among low LR individuals when processing emotional faces may contribute to an impaired ability to recognize alcohol intoxication in social situations and impaired ability to make appraisals of angry and happy emotions irrespective of consuming alcohol.R01 AA021162/AA/NIAAA NIH HHSUnited States/R21 AA027634/AA/NIAAA NIH HHSUnited States/UO1 DA051077/DA/NIDA NIH HHSUnited States/U01 IP000379/IP/NCIRD CDC HHSUnited States/U01 DA041731/DA/NIDA NIH HHSUnited States/U01 DA051077/DA/NIDA NIH HHSUnited States

Restructuring of amygdala subregion apportion across adolescence

Total amygdala volumes develop in association with sex and puberty, and postmortem studies find neuronal numbers increase in a nuclei specific fashion across development. Thus, amygdala subregions and composition may evolve with age. Our goal was to examine if amygdala subregion absolute volumes and/or relative proportion varies as a function of age, sex, or puberty in a large sample of typically developing adolescents (N = 408, 43 % female, 10–17 years). Utilizing the in vivo CIT168 atlas, we quantified 9 subregions and implemented Generalized Additive Mixed Models to capture potential non-linear associations with age and pubertal status between sexes. Only males showed significant age associations with the basolateral ventral and paralaminar subdivision (BLVPL), central nucleus (CEN), and amygdala transition area (ATA). Again, only males showed relative differences in the proportion of the BLVPL, CEN, ATA, along with lateral (LA) and amygdalostriatal transition area (ASTA), with age. Using a best-fit modeling approach, age, and not puberty, was found to drive these associations. The results suggest that amygdala subregions show unique variations with age in males across adolescence. Future research is warranted to determine if our findings may contribute to sex differences in mental health that emerge across adolescence

Neural connectivity biotypes: associations with internalizing problems throughout adolescence.

BackgroundNeurophysiological patterns may distinguish which youth are at risk for the well-documented increase in internalizing symptoms during adolescence. Adolescents with internalizing problems exhibit altered resting-state functional connectivity (RSFC) of brain regions involved in socio-affective processing. Whether connectivity-based biotypes differentiate adolescents' levels of internalizing problems remains unknown.MethodSixty-eight adolescents (37 females) reported on their internalizing problems at ages 14, 16, and 18 years. A resting-state functional neuroimaging scan was collected at age 16. Time-series data of 15 internalizing-relevant brain regions were entered into the Subgroup-Group Iterative Multi-Model Estimation program to identify subgroups based on RSFC maps. Associations between internalizing problems and connectivity-based biotypes were tested with regression analyses.ResultsTwo connectivity-based biotypes were found: a Diffusely-connected biotype (N = 46), with long-range fronto-parietal paths, and a Hyper-connected biotype (N = 22), with paths between subcortical and medial frontal areas (e.g. affective and default-mode network regions). Higher levels of past (age 14) internalizing problems predicted a greater likelihood of belonging to the Hyper-connected biotype at age 16. The Hyper-connected biotype showed higher levels of concurrent problems (age 16) and future (age 18) internalizing problems.ConclusionsDifferential patterns of RSFC among socio-affective brain regions were predicted by earlier internalizing problems and predicted future internalizing problems in adolescence. Measuring connectivity-based biotypes in adolescence may offer insight into which youth face an elevated risk for internalizing disorders during this critical developmental period

Sex-specific frontal-striatal connectivity differences among adolescents with externalizing disorders

Background: Sex-specific neurobiological underpinnings of impulsivity in youth with externalizing disorders have not been well studied. The only report of functional connectivity (FC) findings in this area demonstrated sex differences in fronto-subcortical connectivity in youth with attention-deficit/hyperactivity disorder (ADHD). Methods: The current study used functional magnetic resonance imaging(fMRI) to examine sex differences in resting-state seed-based FC, self-rated impulsivity, and their interactions in 11-12-year-old boys (n = 43) and girls (n = 43) with externalizing disorders. Generalized linear models controlling for pubertal development were used. Seeds were chosen in the ventral striatum, medial prefrontal cortex, middle frontal gyrus and amygdala. Results: Impulsivity scores were greater in boys than girls (p < 0.05). Boys showed greater positive connectivity within a ventromedial prefrontal-ventral striatal network. In addition, boys demonstrated weaker connectivity than girls within two medial-lateral prefrontal cortical networks. However, only boys showed greater medial-lateral prefrontal connectivity correlated with greater impulsivity. Conclusions: The findings provide evidence supporting sex differences in both ventral striatal-ventromedial prefrontal and medial-lateral prefrontal functional networks in youth with externalizing disorders. These important networks are thought to be implicated in impulse control. Medial-lateral prefrontal connectivity may represent a male-specific biomarker of impulsivity

Insensitive parenting may accelerate the development of the amygdala-medial prefrontal cortex circuit

Development Psychopathology in context: famil

Exploring Age-Related Changes in Resting State Functional Connectivity of the Amygdala: From Young to Middle Adulthood

Functional connectivities of the amygdala support emotional and cognitive processing. Life-span development of resting-state functional connectivities (rsFC) of the amygdala may underlie age-related differences in emotion regulatory mechanisms. To date, age-related changes in amygdala rsFC have been reported through adolescence but not as thoroughly for adulthood. This study investigated age-related differences in amygdala rsFC in 132 young and middle-aged adults (19–55 years). Data processing followed published routines. Overall, amygdala showed positive rsFC with the temporal, sensorimotor and ventromedial prefrontal cortex (vmPFC), insula and lentiform nucleus, and negative rsFC with visual, frontoparietal, and posterior cingulate cortex and caudate head. Amygdala rsFC with the cerebellum was positively correlated with age, and rsFCs with the dorsal medial prefrontal cortex (dmPFC) and somatomotor cortex were negatively correlated with age, at voxel p &lt; 0.001 in combination with cluster p &lt; 0.05 FWE. These age-dependent changes in connectivity appeared to manifest to a greater extent in men than in women, although the sex difference was only evident for the cerebellum in a slope test of age regressions (p = 0.0053). Previous studies showed amygdala interaction with the anterior cingulate cortex (ACC) and vmPFC during emotion regulation. In region of interest analysis, amygdala rsFC with the ACC and vmPFC did not show age-related changes. These findings suggest that intrinsic connectivity of the amygdala evolved from young to middle adulthood in selective brain regions, and may inform future studies of age-related emotion regulation and maladaptive development of the amygdala circuits as an etiological marker of emotional disorders

Sexually divergent development of depression-related brain networks during healthy human adolescence

Sexual differences in human brain development could be relevant to sex differences in the incidence of depression during adolescence. We tested for sex differences in parameters of normative brain network development using fMRI data on N = 298 healthy adolescents, aged 14 to 26 years, each scanned one to three times. Sexually divergent development of functional connectivity was located in the default mode network, limbic cortex, and subcortical nuclei. Females had a more “disruptive” pattern of development, where weak functional connectivity at age 14 became stronger during adolescence. This fMRI-derived map of sexually divergent brain network development was robustly colocated with i prior loci of reward-related brain activation ii a map of functional dysconnectivity in major depressive disorder (MDD), and iii an adult brain gene transcriptional pattern enriched for genes on the X chromosome, neurodevelopmental genes, and risk genes for MDD. We found normative sexual divergence in adolescent development of a cortico-subcortical brain functional network that is relevant to depression

Contextual Influences on Youth Socioemotional and Corticolimbic Development

The formation of adaptive socioemotional skills is a key developmental competency in childhood and such behaviors are supported, in part, by neural function within the corticolimbic system. Multiple features of the social context (e.g., harsh parenting) and individual-level markers of maturation (e.g., pubertal development) are robust predictors of youth socioemotional outcomes, but several gaps in the literature remain. However, more research is needed to investigate the timing and specificity of contextual and maturation effects on youth socioemotional and corticolimbic development, using population-based studies that allow for generalization of the results to a broader population. This three study dissertation integrates research on socioeconomic disadvantage, neural correlates of emotion processing, and internalizing and externalizing behaviors in childhood in service of these goals. Study 1 tests a longitudinal Family Stress Model using prospectively-collected data from a population-based nationwide study of children followed from birth through age 9, with an oversample of disadvantaged families. Study 2 builds on the results of Study 1 by examining the influence of initial levels and changes in harsh parenting across childhood on corticolimbic function during adolescence. Finally, Study 3 evaluates the effects of age and puberty on amygdala-prefrontal connectivity during face processing, using a large cross-sectional population-based sample of twins from Southeast Michigan. The general discussion chapter of this dissertation highlights theoretical and empirical considerations for this research, as well as outlines several future directions.PHDPsychologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/153437/1/arigard_1.pd