Functional Connectivity In Adolescents Research Articles

72. Head and Heart Unite: Exploring the Connection Between Heart Rate Variability and Functional Connectivity in Adolescents

72. Head and Heart Unite: Exploring the Connection Between Heart Rate Variability and Functional Connectivity in Adolescents

Assessing resting-state brain functional connectivity in adolescents and young adults with narcolepsy using functional near-infrared spectroscopy.

This study aimed to elucidate the alterations in the prefrontal cortex's functional connectivity and network topology in narcolepsy patients using functional near-infrared spectroscopy (fNIRS). Twelve narcolepsy-diagnosed patients from Guangxi Zhuang Autonomous Region's People's Hospital Sleep Medicine Department and 11 matched healthy controls underwent resting fNIRS scans. Functional connectivity and graph theory analyses were employed to assess the prefrontal cortex network's properties and their correlation with clinical features. Results indicated increased functional connectivity in these adolescent and young adult patients with narcolepsy, with significant variations in metrics like average degree centrality and node efficiency, particularly in the left middle frontal gyrus. These alterations showed correlations with clinical symptoms, including depression and sleep efficiency. However, the significance of these findings was reduced post False Discovery Rate adjustment, suggesting a larger sample size is needed for validation. In conclusion, the study offers initial observations that alterations in the prefrontal cortex's functional connectivity may potentially act as a neurobiological indicator of narcolepsy, warranting further investigation with a larger cohort to substantiate these findings and understand the underlying mechanisms.

Dynamic functional connectivity in anorexia nervosa: alterations in states of low connectivity and state transitions.

The onset of anorexia nervosa (AN) frequently occurs during adolescence and is associated with preoccupation with body weight and shape and extreme underweight. Altered resting state functional connectivity in the brain has been described in individuals with AN, but only from a static perspective. The current study investigated the temporal dynamics of functional connectivity in adolescents with AN and how it relates to clinical features. 99 female patients acutely ill with AN and 99 pairwise age-matched female healthy control (HC) participants were included in the study. Using resting-state functional MRI data and an established sliding-window analytic approach, we identified dynamic resting-state functional connectivity states and extracted dynamic indices such as dwell time (the duration spent in a state), fraction time (the proportion of the total time occupied by a state), and number of transitions (number of switches) from one state to another, to test for group differences. Individuals with AN had relatively reduced fraction time in a mildly connected state with pronounced connectivity within the default mode network (DMN) and an overall reduced number of transitions between states. These findings revealed by a dynamic, but not static analytic approach might hint towards a more "rigid" connectivity, a phenomenon commonly observed in internalizing mental disorders, and in AN possibly related to a reduction in energetic costs as a result of nutritional deprivation.

Atypical Interpersonal Problem-Solving and Resting-state Functional Connectivity in Adolescents with Maltreatment Experience.

Childhood maltreatment is associated with altered neurocognitive functioning, which is thought to reflect, in part, adaptation to early adverse environmental experiences. However, we continue to lack a precise mechanistic understanding linking atypical neurocognitive processing with social functioning and psychiatric outcomes following early adversity. The present work investigated interpersonal problem-solving, resting-state functional connectivity (rsFC), and mental health symptoms in adolescents with documented maltreatment experience and explored whether altered neural function contributes in part to poorer social functioning. Forty adolescents (aged 12-17) with documented experiences of abuse or neglect and a carefully matched group of 42 non-maltreated peers participated in this study that measured task-based interpersonal problem-solving skills and rsFC. Adolescents with maltreatment experience showed poorer interpersonal problem-solving performance, which partly accounted for their elevated mental health symptoms. Resting-state seed-based analyses revealed that adolescents with maltreatment experience showed a significant increase in rsFC between medial Default Mode Network (DMN) hubs, the medial prefrontal cortex (mPFC), with a posterior cluster, including the posterior cingulate cortex (PCC), precuneus (PCu), retrosplenial cortex (RSC), and lingual gyrus (LG). Moderation analyses revealed that maltreatment-related increased DMN rsFC partly accounted for poorer performance in interpersonal problem-solving. Poorer interpersonal problem-solving, partly accounted for by atypical coupling between DMN medial hubs, was associated with maltreatment exposure. Interventions tailored to enhance interpersonal problem-solving represents a promising avenue to promote resilience and reduce the likelihood of mental health disorder following maltreatment experience.

Impact of prenatal marijuana exposure on adolescent brain structural and functional connectivity and behavioural outcomes.

There has been an increase in the number of women using marijuana whilst pregnant. Previous studies have shown that children with prenatal marijuana exposure have developmental deficits in memory and decreased attentiveness. In this study, we assess whether prenatal marijuana exposure is associated with alterations in brain regional morphometry and functional and structural connectivity in adolescents. We downloaded behavioural scores and subject image files from the Adolescent Brain Cognitive DevelopmentSM Study. A total of 178 anatomical and diffusion magnetic resonance imaging files (88 prenatal marijuana exposure and 90 age- and gender-matched controls) and 152 resting-state functional magnetic resonance imaging files (76 prenatal marijuana exposure and 76 controls) were obtained. Behavioural metrics based on the parent-reported child behavioural checklist were also obtained for each subject. The associations of prenatal marijuana exposure with 17 subscales of the child behavioural checklist were calculated. We assessed differences in brain morphometry based on voxel-based and surface-based morphometry in adolescents with prenatal marijuana exposure versus controls. We also evaluated group differences in structural and functional connectivity in adolescents for region-to-region connectivity and graph theoretical metrics. Interactions of prenatal marijuana exposure and graph networks were assessed for impact on behavioural scores. Multiple comparison correction was performed as appropriate. Adolescents with prenatal marijuana exposure had greater abnormal or borderline child behavioural checklist scores in 9 out of 17 subscales. There were no significant differences in voxel- or surface-based morphometry, structural connectivity or functional connectivity between prenatal marijuana exposure and controls. However, there were significant differences in prenatal marijuana exposure-graph network interactions with respect to behavioural scores. There were three structural prenatal marijuana exposure-graph network interactions and seven functional prenatal marijuana exposure-graph network interactions that were significantly associated with behavioural scores. Whilst this study was not able to confirm anatomical or functional differences between prenatal marijuana exposure and unexposed pre-adolescent children, there were prenatal marijuana exposure-brain structural and functional graph network interactions that were significantly associated with behavioural scores. This suggests that altered brain networks may underlie behavioural outcomes in adolescents with prenatal marijuana exposure. More work needs to be conducted to better understand the prognostic value of brain structural and functional network measures in prenatal marijuana exposure.

4.37 The Relationship Between Serum Brain-Derived Neurotrophic Factor and Hippocampal Resting-State Functional Connectivity in Adolescents With MDD

4.37 The Relationship Between Serum Brain-Derived Neurotrophic Factor and Hippocampal Resting-State Functional Connectivity in Adolescents With MDD

Test-Retest Reliability of Functional Connectivity in Adolescents With Depression

BackgroundThe test-retest reliability of functional magnetic resonance imaging is critical to identifying reproducible biomarkers for psychiatric illness. Recent work has shown how reliability limits the observable effect size of brain-behavior associations, hindering detection of these effects. However, while a fast-growing literature has explored both univariate and multivariate reliability in healthy individuals, relatively few studies have explored reliability in populations with psychiatric illnesses or how this interacts with age. MethodsHere, we investigated functional connectivity reliability over the course of 1 year in a longitudinal cohort of 88 adolescents (age at baseline = 15.63 ± 1.29 years; 64 female) with major depressive disorder (MDD) and without MDD (healthy volunteers [HVs]). We compared a univariate metric, intraclass correlation coefficient, and 2 multivariate metrics, fingerprinting and discriminability. ResultsAdolescents with MDD had marginally higher mean intraclass correlation coefficient (μMDD = 0.34, 95% CI, 0.12–0.54; μHV = 0.27, 95% CI, 0.05–0.52), but both groups had poor average intraclass correlation coefficients (<0.4). Fingerprinting index was greater than chance and did not differ between groups (fingerprinting indexMDD = 0.75; fingerprinting indexHV = 0.91; Poisson tests p < .001). Discriminability indicated high multivariate reliability in both groups (discriminabilityMDD = 0.80; discriminabilityHV = 0.82; permutation tests p < .01). Neither univariate nor multivariate reliability was associated with symptom severity or edge-level effect size of group differences. ConclusionsOverall, we found little evidence for a relationship between depression and reliability of functional connectivity during adolescence. These findings suggest that biomarker identification in depression is not limited due to reliability compared with healthy samples and support the shift toward multivariate analysis for improved power and reliability.

Associations between regular cannabis use and brain resting-state functional connectivity in adolescents and adults.

Cannabis use is highly prevalent in adolescents; however, little is known about its effects on adolescent brain function. Resting-state functional magnetic resonance imaging was used in matched groups of regular cannabis users (N = 70, 35 adolescents: 16-17 years old, 35 adults: 26-29 years old) and non-regular-using controls (N = 70, 35 adolescents/35 adults). Pre-registered analyses examined the connectivity of seven major cortical and sub-cortical brain networks (default mode network, executive control network (ECN), salience network, hippocampal network and three striatal networks) using seed-based analysis methods with cross-sectional comparisons between user groups and age groups. The regular cannabis use group (across both age groups), relative to controls, showed localised increases in connectivity only in the ECN analysis. All networks showed localised connectivity differences based on age group, with the adolescents generally showing weaker connectivity than adults, consistent with the developmental effects. Mean connectivity across entire network regions of interest (ROIs) was also significantly decreased in the ECN in adolescents. However, there were no significant interactions found between age group and user group in any of the seed-based or ROI analyses. There were also no associations found between cannabis use frequency and any of the derived connectivity measures. Regular cannabis use is associated with changes in connectivity of the ECN, which may reflect allostatic or compensatory changes in response to regular cannabis intoxication. However, these associations were not significantly different in adolescents compared to adults.

Altered gray matter volume and functional connectivity in adolescent borderline personality disorder with non-suicidal self-injury behavior.

Non-suicidal self-injury (NSSI) behavior is one of the characteristics of borderline personality disorder (BPD) in adolescents. Prior studies have shown that adolescents with BPD may have a unique pattern of brain alterations. The purpose of this study was to investigate the alterations in brain structure and function including gray matter volume and resting-state functional connectivity in adolescents with BPD, and to assess the association between NSSI behavior and brain changes on neuroimaging in adolescents with BPD. 53 adolescents with BPD aged 12-17years and 39 age-gender matched healthy controls (HCs) were enrolled into this study. Brain magnetic resonance imaging (MRI) was acquired with both 3D-T1 weighted structural imaging and resting-state functional imaging. Voxel-based morphometry (VBM) analysis for gray matter volume and seed-based functional connectivity (FC) analysis were performed for assessing gray matter volume and FC. Clinical assessment for NSSI, mood, and depression was also obtained. Correlative analysis of gray matter alterations with self-injury or mood scales were performed. There were reductions of gray matter volume in the limbic-cortical circuit and default mode network in adolescents with BPD as compared to HCs (FWE P < 0.05, cluster size ≥ 1000). The diminished gray matter volumes in the left putamen and left middle occipital gyrus were negatively correlated with NSSI in adolescents with BPD (r = -0.277 and P = 0.045, r = -0.422 and P = 0.002, respectively). Furthermore, there were alterations of FC in these two regions with diminished gray matter volumes (voxel P < 0.001, cluster P < 0.05, FWE corrected). Our results suggest that diminished gray matter volume of the limbic-cortical circuit and default mode network may be an important neural correlate in adolescent BPD. In addition, the reduced gray matter volume and the altered functional connectivity may be associated with NSSI behavior in adolescents with BPD.

Inter-Network Brain Functional Connectivity in Adolescents Assigned Female at Birth Who Experience Gender Dysphoria.

Gender dysphoria (GD) is characterized by distress due to an incongruence between experienced gender and sex assigned at birth. Brain functional connectivity in adolescents who experience GD may be associated with experienced gender (vs. assigned sex) and/or brain networks implicated in own-body perception. Furthermore, sexual orientation may be related to brain functional organization given commonalities in developmental mechanisms proposed to underpin GD and same-sex attractions. Here, we applied group independent component analysis to resting-state functional magnetic resonance imaging (rs-fMRI) BOLD timeseries data to estimate inter-network (i.e., between independent components) timeseries correlations, representing functional connectivity, in 17 GD adolescents assigned female at birth (AFAB) not receiving gender-affirming hormone therapy, 17 cisgender girls, and 15 cisgender boys (ages 12-17 years). Sexual orientation was represented by degree of androphilia-gynephilia and sexual attractions strength. Multivariate partial least squares analyses found that functional connectivity differed among cisgender boys, cisgender girls, and GD AFAB, with the largest difference between cisgender boys and GD AFAB. Regarding sexual orientation and age, the brain’s intrinsic functional organization of GD AFAB was both similar to and different from cisgender girls, and both differed from cisgender boys. The pattern of group differences and the networks involved aligned with the hypothesis that brain functional organization is different among GD AFAB (vs. cisgender) adolescents, and certain aspects of this organization relate to brain areas implicated in own-body perception and self-referential thinking. Overall, brain functional organization of GD AFAB was generally more similar to that of cisgender girls than cisgender boys.

Gray's Impulsivity Is Differentially Associated With Amygdala-Insula Functional Connectivity in Adolescents, Depending on ADHD Risk Status

AimsAttention-Deficit/Hyperactivity Disorder (ADHD) is associated with alterations in both reinforcement sensitivity and affective processing but the nature of the associations of these characteristics is yet to be examined. We hypothesized that individual differences in the sensitivity of the Behavioral Approach System (BAS) would exhibit differential relations with affective network connectivity – involved in emotional regulation and salience monitoring – in youth at-risk for, relative to youth not at-risk for, ADHD.MethodsAdolescents (n = 125; Mage=16.24 years, SD = 1.09 years; 61.6% boys) were recruited as part of The Budapest Longitudinal Study of ADHD and Externalizing Disorders. Forty-nine were classified as at-risk for ADHD (Mage=16.15 years; SD = 1.21 years; 77.6% boys), defined as exhibiting ≥4 parent-rated symptoms of either domain on the ADHD Rating Scale-5. Participants completed a 10-minute resting-state functional Magnetic Resonance Imaging session, during which they were asked to focus their attention on a fixation cross, as well as various self-report assessments, including the Reinforcement Sensitivity Theory of Personality Questionnaire (RST-PQ).ResultsFunctional Network Connectivity analyses indicated an interaction effect between the RST-PQ BAS impulsivity subscale and at-risk status on functional connectivity between four affective network region-pairs (ps &lt; .05, False Discovery Rate [FDR] corrected) within a cluster based on functional similarity (p = .014, FDR-corrected). Follow-up OLS linear regressions showed higher impulsivity scores predicted stronger functional connectivity between the (1) left amygdala-right insula (F(6, 117) = 3.298, p = .005, adjusted R2=.101), (2) left amygdala-left insula (F(6, 117) = 2.2, p = .048, adjusted R2=.055), (3) right amygdala-right insula (F(6, 117) = 3.833, p = .002, adjusted R2=.121), and (4) right amygdala-left insula (F(6, 117) = 3.064, p = .008, adjusted R2=.092) in at-risk youth, whereas an inverse relationship was apparent in not at-risk youth.There was no main effect of group status on BAS impulsivity scores (t(122)=−1.167, p = .246) or on functional connectivity ((1) t(122) = .383, p = .702; (2) t(122) = .195, p = .846; (3) t(122)=−.107, p = .915; (4) t(122)=−.206, p = .837).ConclusionThe amygdala-insula connection has been shown to be involved in trait impulsivity, however, available ADHD-focused studies targeted emotional functioning. To our knowledge, we are the first to demonstrate that Gray's impulsivity – reflecting trait reward sensitivity – is predictive of amygdala-insula functional connectivity at rest and that this relation differs given ADHD risk. Results have conceptual and practical implications (e.g., early identification) as the role of the amygdala-insula connection in reward sensitivity appears especially relevant for a developmental phase and a diagnostic group linked to increased risk taking.

Longitudinal effects of antidepressant treatment on resting state functional connectivity in adolescents with major depressive disorder

IntroductionAdolescents with major depressive disorder (MDD) often show reduced prefrontal functional connectivity with the subcortical regions than healthy controls (HC) (Tang et al., 2018). However, relatively little is known about longitudinal effects of antidepressant (AD) treatment on resting state functional connectivity (RSFC) in the prefrontal cortex (PFC).ObjectivesThis study aimed to investigate abnormal PFC RSFC in MDD adolescents compared to HC and longitudinal effects of AD on PFC RSFC.Methods This study included 59 adolescents with MDD and 43 HC. MDD adolescents were treated with escitalopram in an 8 week, open-label trial. The treatment outcome was assessed by Children’s Depression Rating Scale (CDRS-R) and patients showing at least a 40% improvement in CDRS-R scores from baseline to week 8 were defined as “responders”. Functional and T1 images collected before and after treatment were processed using AFNI and Freesurfer. Our seed was the lateral PFC (LPFC, BA46). T-tests and repeated measures ANCOVAs, controlling for age and IQ, were conducted to examine abnormal PFC RSFC and longitudinal effects of AD on LPFC RSFC.ResultsRelative to HC, MDD showed increased LPFC RSFC with the posterior middle temporal gyrus (pMTG) and superior frontal cortex (SFG) involved in attentional networks. Responders showed greater changes in LPFC RSFC with the MTG and SFG after AD treatment compared to non-responders and HC (Figure 1).ConclusionsOur finding suggests that reduced LPFC RSFC with the pMTG and SFG reflecting decreased attentional network connectivity may serve as a biomarker to predict AD treatment outcome in adolescents with MDD.DisclosureNo significant relationships.

Effects of Methylphenidate on Somatic Symptoms and Brain Functional Connectivity in Adolescents with Attention Deficit Hyperactivity Disorder: A Pilot Study.

ObjectiveThis study aimed to evaluate whether somatic symptoms in adolescents with attention deficit hyperactivity disorder (ADHD) are associated with a dissociative pattern of functional connectivity (FC) within the default mode network (DMN) and whether methylphenidate administration can improve clinical and somatic symptoms. We also evaluated whether the improvement of somatic symptoms is associated with increased FC within the DMN in response to methylphenidate treatment.MethodsFifteen male adolescents with somatic symptoms of ADHD and 15 male adolescents with ADHD without somatic symptoms were included. At baseline and after 6 months of methylphenidate treatment, all adolescents were asked to complete questionnaires for the Korean version of the Dupaul’s ADHD rating scale, the symptom checklist-90- revised-somatization subscales, the Beck Depression Inventory, and the Beck Anxiety Inventory. Additionally, a resting-state functional magnetic resonance imaging scan was conducted.ResultsMethylphenidate treatment improved clinical and somatic symptoms in adolescents with ADHD. In addition, it increased brain FC within the DMN from the posterior cingulate cortex (posterior DMN) to the middle prefrontal cortex (anterior DMN). The improvement of somatic symptoms was associated with FC within the DMN from the posterior cingulate cortex to the middle prefrontal cortex in ADHD adolescents with somatic symptoms.ConclusionMethylphenidate increased brain FC between the anterior and posterior DMN. The improvement of somatic symptoms in adolescents with ADHD was associated with FC within the DMN. The DMN in adolescents with ADHD seems to be associated with the severity of the clinical and somatic symptoms of ADHD.

Early-Life Critical Windows of Susceptibility to Manganese Exposure and Sex-Specific Changes in Brain Connectivity in Late Adolescence

BackgroundEarly-life environmental exposures during critical windows (CWs) of development can impact life course health. Exposure to neuroactive metals such as manganese (Mn) during prenatal and early postnatal CWs may disrupt typical brain development, leading to persistent behavioral changes. Males and females may be differentially vulnerable to Mn, presenting distinctive CWs to Mn exposure. MethodsWe used magnetic resonance imaging to investigate sex-specific associations between early-life Mn uptake and intrinsic functional connectivity in adolescence. A total of 71 participants (15–23 years old; 53% female) from the Public Health Impact of Manganese Exposure study completed a resting-state functional magnetic resonance imaging scan. We estimated dentine Mn concentrations at prenatal, postnatal, and early childhood periods using laser ablation–inductively coupled plasma–mass spectrometry. We performed seed-based correlation analyses to investigate the moderating effect of sex on the associations between Mn and intrinsic functional connectivity adjusting for age and socioeconomic status. ResultsWe identified significant sex-specific associations between dentine Mn at all time points and intrinsic functional connectivity in brain regions involved in cognitive and motor function: 1) prenatal: dorsal striatum, occipital/frontal lobes, and middle frontal gyrus; 2) postnatal: right putamen and cerebellum; and 3) early childhood: putamen and occipital, frontal, and temporal lobes. Network associations differed depending on exposure timing, suggesting that different brain networks may present distinctive CWs to Mn. ConclusionsThese findings suggest that the developing brain is vulnerable to Mn exposure, with effects lasting through late adolescence, and that females and males are not equally vulnerable to these effects. Future studies should investigate cognitive and motor outcomes related to these associations.

Triple Network Functional Connectivity During Acute Stress in Adolescents and the Influence of Polyvictimization

BackgroundExposure to both chronic and acute stressors can disrupt functional connectivity (FC) of the default mode network (DMN), salience network (SN), and central executive network (CEN), increasing risk for negative health outcomes. During adolescence, these stress-sensitive triple networks undergo critical neuromaturation that is altered by chronic exposure to general forms of trauma or victimization. However, no work has directly examined how acute stress affects triple network FC in adolescents or whether polyvictimization—exposure to multiple categories/subtypes of victimization—influences adolescent triple network neural acute stress response. MethodsThis functional magnetic resonance imaging study examined seed-to-voxel FC of the DMN, SN, and CEN during the Montreal Imaging Stress Task. Complete data from 73 participants aged 9 to 16 years (31 female) are reported. ResultsDuring acute stress, FC was increased between DMN and CEN regions and decreased between the SN and the DMN and CEN. Greater polyvictimization was associated with reduced FC during acute stress exposure between the DMN seed and a cluster containing the left insula of the SN. ConclusionsThese results indicate that acute stress exposure alters FC between the DMN, SN, and CEN in adolescents. In addition, FC changes during stress between the DMN and SN are further moderated by polyvictimization exposure.

Resting-state functional connectivity in adolescents experiencing subclinical and clinical symptoms of depression: a mini-review of recent evidence.

Adolescence is a developmental period associated with major neural reorganization and the onset of many psychological disorders. Depression in particular is prevalent and impairing in adolescents and rates have been rising in recent years. Recent advances in the neurobiology of adolescent depression contribute to a better understanding of functional connectivity among neural networks and represent a promising start for determining biomarkers of depression and potential areas of intervention.

Ventral striatal resting-state functional connectivity in adolescents is associated with earlier onset of binge drinking

BackgroundEarlier engagement in heavy drinking during adolescence is a risk factor for the development of alcohol use disorders later in life. Longitudinal studies in adolescents have linked brain structure and task-evoked function to future alcohol use; however, less is known about how intrinsic network-level interactions relate to future substance use during this developmental period. MethodsIn this prospective longitudinal study, resting-state functional connectivity of the ventral striatum, risky decision making, and sensation seeking were measured in 73 adolescents at baseline. Participants were between the ages of 14 and 15 and had no substantial history of substance use upon study entry. Follow-up interviews were conducted approximately every 3 months to assess the initiation of binge drinking (≥ 5 or ≥ 4 drinks per occasion for males or females, respectively). ResultsAdolescents who began binge drinking sooner exhibited greater connectivity of the ventral striatum to the left precuneus, left angular gyrus, and the left superior frontal gyrus. Greater connectivity of the ventral striatum to the right insula/putamen was associated with longer duration to the onset of binge drinking. Resting-state functional connectivity in these regions was not associated with baseline assessments of risky decision making or sensation seeking. ConclusionsFindings provide novel information about potential risk factors for early initiation of heavy alcohol use. Interventions that target relevant resting-state networks may enhance prevention efforts to decrease adolescent substance use by prolonging onset to heavier levels of alcohol consumption.

Critical windows of metal mixture exposure on functional connectivity in adolescents

BACKGROUND AND AIM: Exposure to neurotoxic metals occurs as a mixture, yet most studies consider single exposures, potentially missing the combined effects of environmental metals. Further, health impacts of mixtures may be missed if studied at a single developmental timepoint. In this study, we investigated associations between early life exposure to a mixture of neurotoxic metals and developmental trajectories of brain networks associated with executive functions (EF) among young adults. We hypothesize that associations between early-life metal mixture exposure and developmental trajectories depend upon the timing of exposure and the developmental stage of the outcome. METHODS: In preliminary analysis of 32 subjects enrolled in the Public Health Impact of Metals Exposure (PHIME) study, we generated prenatal (2nd week of gestation to birth), early postnatal (birth to one year) and childhood (1-6 years of age) concentrations of 5 toxic and nutritive metals including manganese, lead, zinc, copper and chromium in naturally shed deciduous teeth using laser ablation-inductively coupled plasma-mass spectrometry. We acquired resting state functional magnetic resonance imaging scans at ages 16-22 years. We used generalized weighted quantile sum (gWQS) regression to examine associations between metal mixtures at each developmental timepoint and functional connectivity in resting state networks. RESULTS:We observed a significant inverse association between the postnatal metal mixture and connectivity in the attention network, i.e., higher metals associated with reduced connectivity (β = -0.029 [95% CI - 0.046, -0.012]). Mn (29%) and Cu (42%) contributed most to the mixture association, suggesting both that these metals were key components and that Mn does not act alone on the brain but is a key part of a larger mixture. CONCLUSIONS:Our preliminary results suggest that postnatal Mn disrupts the trajectory of development in the neural circuitry supporting EF and that the association may be specific to the timing of exposure. KEYWORDS: Heavy metals, Children's environmental health, Mixtures, Mixtures analysis, Neurodevelopmental outcomes

Prospective study on resting state functional connectivity in adolescents with major depressive disorder after antidepressant treatment

Recent advances in functional magnetic resonance imaging (fMRI) have resulted in many studies on resting-state functional connectivity (rsFC) in depressed patients. Previous studies have shown alterations between multiple brain areas, such as the prefrontal cortex, anterior cingulate cortex, and basal ganglia, but there are very few prospective studies with a longitudinal design on adolescent depression patients. We therefore investigated the change in positive rsFC in a homogeneous drug-naïve adolescent group after 12 weeks of antidepressant treatment. Functional neuroimaging data were collected and analyzed from 32 patients and 27 healthy controls. Based on previous literature, the amygdala, anterior cingulate cortex (ACC), insula, hippocampus, and dorsolateral prefrontal cortex (DLPFC) were selected as seed regions. Seed-to-voxel analyses were performed between pre- and post-treatment states as well as between the patients and controls at baseline. The positive rsFC between the right DLPFC and the left putamen/right frontal operculum were shown to be higher in patients than in the controls. The positive rsFC between the left DLPFC and left putamen/left lingual gyrus was also higher in the patients than in the controls. The positive rsFC between the right dorsal ACC and the left precentral gyrus had reduced after the 12-week antidepressant treatment. Regions involved in the frontolimbic circuit showed changes in the positive rsFC in the depressed adolescents as compared to in the healthy controls. There were also significant changes in the positive rsFC after 12-weeks of antidepressant treatment. The involved regions were associated with emotional regulation, cognitive functioning, impulse control, and visual processing.

White matter integrity and functional connectivity in adolescents with a parental history of substance use disorder

A family history (FH+) of substance use disorder (SUD) increases an adolescent's risk for substance use initiation and progression. Greater impulsivity and reward seeking behavior is known to be associated with such risk. At the neurological level, dysfunction of cortico-striatal and cortico-limbic pathways have been proposed as contributors to the increased SUD risk in adolescents with FH+. In addition, disadvantaged environments have been associated with atypical brain connectivity and higher SUD risk. However, it remains unclear if this increased risk is manifested in structural and functional brain abnormalities prior to regular drug use. To examine this, we employed complementary imaging of structural and functional connectivity of 60 FH+ and 55 FH- minority adolescents, all from families with low socio-economic status. We acquired diffusion tensor-imaging (DTI) and resting state fMRI data across the whole brain. Structural connectivity was examined by measuring fractional anisotropy (FA) using DTI, to indicate integrity of the white matter tracts. Functional connectivity within and between resting state networks was assessed by the correlation of blood-oxygen-level-dependent (BOLD) signal between intra and inter-network nodes. Psychological measures of impulsivity and reward seeking were also obtained with standardized measures, the BIS-11 and the BIS/BAS, and their association with FA and functional connectivity was evaluated. We found no differences in white matter integrity between the groups. Compared to FH-, FH + adolescents showed significantly greater functional connectivity between posterior regions of the Default Mode Network (DMN) and the Fronto-Parietal Network (FPN). While psychological measures of reward seeking behavior did not differ between the FH+ and FH- groups, impulsivity, assessed by the BIS-11, was significantly higher for FH+. However, we did not find significant differences between the FH+ and FH- groups when comparing associations of BIS-11 scores and white matter integrity or functional connectivity measures. The stronger inter-network functional connectivity between the DMN and FPN in FH + adolescents suggests that transmitted risk for SUD may be related to large-scale brain dynamics. The lack of structural differences support the importance of early prevention efforts for FH + adolescents, before initiation of drug use, allowing for healthy brain development.