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The experience of ethnic, racial, and structural inequalities is increasingly recognized as detrimental to health, and early studies suggest that its experience in pregnant mothers may affect the developing fetus. We characterized discrimination and acculturation experiences in a predominantly Hispanic sample of pregnant adolescent women and assessed their association with functional connectivity in their neonate’s brain. We collected self-report measures of acculturation, discrimination, maternal distress (i.e., perceived stress, childhood trauma, and depressive symptoms), and socioeconomic status in 165 women. Then, we performed a data-driven clustering of acculturation, discrimination, perceived stress, depressive symptoms, trauma, and socioeconomic status variables during pregnancy to determine whether discrimination or acculturation clustered into distinct factors. Discrimination and acculturation styles loaded onto different factors from perceived stress, depressive symptoms, trauma, and socioeconomic status, suggesting that they were distinct from other factors in our sample. We associated these data-driven maternal phenotypes (discrimination and acculturation styles) with measures of resting-state functional MRI connectivity of the infant amygdala (n= 38). Higher maternal report of assimilation was associated with weaker connectivity between their neonate’s amygdala and bilateral fusiform gyrus. Maternal experience of discrimination was associated with weaker connectivity between the amygdala and prefrontal cortex and stronger connectivity between the amygdala and fusiform of their neonate. Cautiously, the results may suggest a similarity to self-contained studies with adults, noting that the experience of discrimination and acculturation may influence amygdala circuitry across generations. Further prospective studies are essential that consider a more diverse population of minoritized individuals and with a comprehensive assessment of ethnic, racial, and structural factors.

AbstractThe deleterious effects of adversity are likely intergenerational, such that one generation’s adverse experiences can affect the next. Epidemiological studies link maternal adversity to offspring depression and anxiety, possibly via transmission mechanisms that influence offspring fronto-limbic connectivity. However, studies have not thoroughly disassociated postnatal exposure effects nor considered the role of offspring sex. We utilized infant neuroimaging to test the hypothesis that maternal childhood maltreatment (CM) would be associated with increased fronto-limbic connectivity in infancy and tested brain-behavior associations in childhood. Ninety-two dyads participated (32 mothers with CM, 60 without; 52 infant females, 40 infant males). Women reported on their experiences of CM and non-sedated sleeping infants underwent MRIs at 2.44 ± 2.74 weeks. Brain volumes were estimated via structural MRI and white matter structural connectivity (fiber counts) via diffusion MRI with probabilistic tractography. A subset of parents (n= 36) reported on children’s behaviors at age 5.17 ± 1.73 years. Males in the maltreatment group demonstrated greater intra-hemispheric fronto-limbic connectivity (b= 0.96, p=0.008, [95%CI 0.25, 1.66]), no differences emerged for females. Fronto-limbic connectivity was related to somatic complaints in childhood only for males (r= 0.673, p= 0.006). Our findings suggest that CM could have intergenerational associations to offspring brain development, yet mechanistic studies are needed.

ABSTRACTThe purpose of this qualitative study was to capture the perspectives of individuals representing an urban, predominantly Latinx community who are underresourced by mental health services about the use of telehealth to deliver mental health treatment. The COVID-19 pandemic required hospital- and community-based mental health programs to pivot to telehealth with alarming speed and very little opportunity to assess the feasibility, acceptability, and disparate impact on unique populations of patients. This study aimed to assess perceived strengths and limitations of telehealth mental health service delivery via qualitative focus group methods. Three focus groups were conducted with 13 youth (aged 8–17) who were being treated at an urban, academic children’s hospital serving a predominantly Latinx community mental health population; two focus groups were conducted with 19 parents of said children; and one focus group was conducted with four mental health providers providing services to this population. A coding schema was designed to capture themes relevant to the following: (1) privacy and confidentiality; (2) perceived limitations of telehealth; (3) comfort with telehealth; (4) therapeutic relationship; (5) perceived strengths of telehealth; (6) perceived safety of telehealth; and (7) advice for providers engaging in telehealth. Findings were illustrative of both perceived strengths and limitations across these domains that can inform optimized telehealth mental health services moving forward.

EVERY SO OFTEN a single observation changes how we perceive the universe. In 1610 Galileo pointed a refracting telescope at the sky to discover moons orbiting Jupiter, a view that [...]

Objective: Disturbances in the basal ganglia portions of cortico-striato-thalamo-cortical circuits likely contribute to the symptoms of attention deficit hyperactivity disorder (ADHD). The authors examined the morphologic features of the basal ganglia nuclei (caudate, putamen, and globus pallidus) in children with ADHD. Method: A total of 104 individuals (combined-type ADHD patients: N=47; healthy comparison subjects: N=57), aged 7 to 18 years, were examined in a cross-sectional case-control study using anatomical magnetic resonance imaging. Conventional volumes and the surface morphology for the basal ganglia were measured. Results: Overall volumes were significantly smaller only in the putamen. Analysis of the morphological surfaces revealed significant inward deformations in each of the three nuclei, localized primarily in portions of these nuclei that are components of limbic, associative, and sensorimotor pathways in the cortico-striato-thalamo-cortical circuits in which these nuclei reside. The more prominent these inward deformations were in the patient group, the more severe the ADHD symptoms. Surface analyses also demonstrated significant outward deformations of all basal ganglia nuclei in the ADHD children treated with stimulants compared with those ADHD youth who were untreated. These stimulant-associated enlargements were in locations similar to the reduced volumes detected in the ADHD group relative to the comparison group. The outward deformations associated with stimulant medications attenuated the statistical effects of the primary group comparisons. Conclusions: These findings potentially represent evidence of anatomical dysregulation in the circuitry of the basal ganglia in children with ADHD and suggest that stimulants may normalize morphological features of the basal ganglia in children with the disorder. doi: 10.1176/appi.ajp.2010.09091259

Objective: The role of the thalamus in the genesis of attention deficit hyperactivity disorder (ADHD) remains poorly understood. The authors used anatomical MRI to examine the morphology of the thalamus in youths with ADHD and healthy comparison youths. Method: The authors examined 46 youths with ADHD and 59 comparison youths 8-18 years of age in a cross-sectional case-control study. Conventional volumes and measures of surface morphology of the thalamus served as the main outcome measures. Results: A mixed-effects model comparing whole thalamic volumes revealed no significant differences between groups. Maps of the thalamic surface revealed significantly smaller regional volumes bilaterally in the pulvinar in youths with ADHD relative to comparison subjects. Post hoc analyses showed that ADHD patients who received stimulants (N=31) had larger conventional thalamic volumes than untreated youths with ADHD, and maps of the thalamic surface showed enlargement over the pulvinar in those receiving stimulants. Smaller regional volumes in the right lateral and left posterior thalamic surfaces were associated with more severe hyperactivity symptoms, whereas larger regional volumes in the right medial thalamic surfaces were associated with more severe symptoms of inattention. Conclusion: These findings demonstrate reduced pulvinar volumes in youths with ADHD and indicate that this same area is relatively enlarged in patients treated with stimulants compared to those untreated. Associations of hyperactivity scores with smaller regional volumes on the lateral thalamic surface and inattention scores with larger regional volumes on the medial thalamic surface suggest the differential involvement of thalamic subcircuits in the pathogenesis of differing ADHD symptoms. (Am J Psychiatry 2010; 167:397-408) doi: 10.1176/appi.ajp.2009.09030398

Objective: The authors sought to study activity in neural circuits that subserve the inhibition of a semi-involuntary motor behavior, eye blinking, in children and adults with Tourette syndrome and in healthy comparison subjects. Method: Functional magnetic resonance imaging was used to scan 120 participants (51 with Tourette syndrome and 69 comparison subjects) as they either blinked normally or successfully inhibited eye blinking. The authors compared the blood-oxygen-level dependent signal during these two conditions across the Tourette and comparison groups. Results: Relative to comparison subjects, patients with Tourette syndrome activated more strongly the frontal cortex and striatum during eye blink inhibition. Activation increased more with age in the dorsolateral and inferolateral prefrontal cortex and caudate nucleus in the Tourette group relative to comparison subjects. In addition, the Tourette group more strongly activated the middle frontal gyrus, dorsal anterior cingulate, and temporal cortices. The severity of tic symptoms in the Tourette group correlated inversely with activation in the putamen and inferolateral prefrontal cortex. Conclusions: Frontostriatal activity is increased in persons with Tourette syndrome during the inhibition of eye blinks. Activation of frontostriatal circuits in this population may help to maintain regulatory control over semi-involuntary behaviors, whether these are tics or eye blinks.

Objective: The authors examined the effect of psychostimulants on brain activity in children and adolescents with ADHD performing the Stroop Color and Word Test. Method: The authors acquired 52 functional MRI scans in 16 youths with ADHD who were known responders to stimulant medication and 20 healthy comparison youths. Participants with ADHD were scanned on and off medication in a counterbalanced design, and comparison subjects were scanned once without medication. Results: Stimulant medication significantly improved suppression of default-mode activity in the ventral anterior cingulate cortex in the ADHD group. When off medication, youths with ADHD were unable to suppress default-mode activity to the same degree as comparison subjects, whereas when on medication, they suppressed this activity to comparison group levels. Greater activation of the lateral prefrontal cortex when off medication predicted a greater reduction in ADHD symptoms when on medication. Granger causality analyses demonstrated that activity in the lateral prefrontal and ventral anterior cingulate cortices mutually influenced one another but that the influence of the ventral anterior cingulate cortex on the lateral prefrontal cortex was significantly reduced in youths with ADHD off medication relative to comparison subjects and increased significantly to normal levels when ADHD youths were on medication. Conclusions: Psychostimulants in youths with ADHD improved suppression of default-mode activity in the ventral anterior cingulate and posterior cingulate cortices, components of a circuit in which activity has been shown to correlate with the degree of mind-wandering during attentional tasks. Stimulants seem to improve symptoms in youths with ADHD by normalizing activity within this circuit and improving its functional interactions with the lateral prefrontal cortex. (Am J Psychiatry 2009; 166:1286-1294)

Objective: Neuroimaging studies of healthy individuals inform us about the normative maturation of the frontostriatal circuits that subserve self-regulatory control processes. Findings from these studies can be used as a reference frame against which to compare the aberrant development of these processes in individuals across a wide range of childhood psychopathologies. Method: The authors reviewed extensive neuroimaging evidence for the presence of abnormalities in frontostriatal circuits in children and adults with Tourette's syndrome and obsessive-compulsive disorder (OCD) as well as a more limited number of imaging studies of adolescents and adults with anorexia nervosa or bulimia nervosa that, together, implicate dysregulation of frontostriatal control systems in the pathogenesis of these eating disorders. Results: The presence of an impaired capacity for self-regulatory control that derives from abnormal development of frontostriatal circuits likely interacts in similar ways with normally occurring somatic sensations and motor urges, intrusive thoughts, sensations of hunger, and preoccupation with body shape and weight to contribute, respectively, to the development of the tics of Tourette's syndrome, the obsessions of OCD, the binge eating behaviors of bulimia, and the self-starvation of anorexia. Conclusions: Analogous brain mechanisms in parallel frontostriatal circuits, or even in differing portions of the same frontostriatal circuit, may underlie the differing behavioral disturbances in these multiple disorders, although further research is needed to confirm this hypothesis.

Objective: Cognitive deficits are prominent in schizophrenia. Patients have an average score one standard deviation below normal on a broad spectrum of cognitive tests. It has been repeatedly noted, however, that 20%-25% of patients differ from this general pattern and score close to normal on neuropsychological testing. This study used brain morphometry to 1) identify brain abnormalities associated with more severe cognitive deficits and 2) help determine whether cognitively relatively intact patients perform better because they have less severe illness or because they have a different illness. Method: Patients were assigned to a neuropsychologically near normal (N=21) subgroup if they scored within 0.5 standard deviation of healthy comparison subjects (N=30) on four tests of attention and verbal and nonverbal working memory, and to a neuropsychologically impaired (N= 54) group if they scored at least 1.0 standard deviation below that of comparison subjects. Subgroup assignments were confirmed with the California Verbal Learning Test and degraded stimulus Continuous Performance Test. Volumes of ventricular compartments, hippocampus, amygdala, thalamus, cerebellum, and regional cortical gray and white matter were dependent variables. Differences among groups were evaluated by using linear mixed-model multivariate analyses with gender, age, and height as covariates. Results: Both neuropsychologically near normal and neuropsychologically impaired patients had markedly smaller gray matter and larger third ventricle volumes than healthy comparison subjects. Only neuropsychologically impaired patients, however, had significantly smaller white matter and larger lateral ventricle volumes than healthy comparison subjects. Conclusions: Although both neuropsychologically impaired and neuropsychologically near normal patients have marked neuropathology in their gray matter, the relative absence of white matter pathology in the neuropsychologically near normal group suggests the possibility of differences in the disease process.

We weigh the presumed benefits of routinely searching all research scans for incidental findings (IFs) against its substantial risks, including false-positive and false-negative findings, and the possibility of triggering unnecessary, [...]

Objective: Disturbances in the maturation of neural systems that mediate self-regulatory processes may contribute to the development of Tourette's syndrome by releasing motor and vocal tics from regulatory control. The purpose of this study was to examine the age correlates of functional activity in neural circuits that subserve self-regulatory control in children and adults with Tourette's syndrome. Method: The participants were 136 children and adults, which included 66 Tourette's syndrome patients and 70 healthy comparison subjects. During performance of the Stroop interference task, the authors compared the functional magnetic resonance imaging (fMRI) bloodoxygen-level dependent response in patients with Tourette's syndrome with that of healthy comparison subjects. General linear modeling of Stroop-related activations was used to compare the differential effects of age and behavioral performance on changes in self-regulatory control between the two diagnostic groups. Results: Although the correlations of age with behavioral performance on the Stroop task were similar between patients with Tourette's syndrome and healthy comparison subjects, the two groups differed significantly in their correlations of age with the magnitude of regional brain activation during the task. Interactions of age with diagnosis were detected in the ventral prefrontal (Brodmann's areas 10 and 24) and posterior cingulate cortices (Brodmann's area 31), and post hoc analyses indicated that subjects with Tourette's syndrome deactivated these regions less with advancing age. Greater activation of bilateral frontostriatal regions (Brodmann's areas 9/46, 45/46; lenticular nucleus; and thalamus) accompanied poorer performance in the patient group, which--in the presence of normal behavioral performance on the Stroop task--suggests that greater activation of the frontostriatal systems helps to maintain task performance in individuals with Tourette's syndrome. Conclusions: Normative developmental correlates of activity in frontostriatal circuits that subserve self-regulatory control are disturbed in persons with Tourette's syndrome. These aberrant developmental correlates are likely a consequence of greater anatomical and functional disturbances in these circuits in adults with Tourette's syndrome, which leads to impaired regulation of tic behaviors. Reduced default-mode processing in ventral prefrontal and posterior cingulate cortices in adults with Tourette's syndrome suggests the presence of greater difficulty in engaging mental processes that become active when freed from the demands of more challenging cognitive tasks. However, individuals with Tourette's syndrome appear to co-opt normal developmental processes in circuits that subserve age-related improvement in self-regulatory control while presumably struggling to maintain adequate task performance.

Objective:A previous small study showed lower serum ferritin levels in subjects with Tourette's syndrome than in healthy subjects. The authors measured peripheral iron indices in a large group of Tourette's syndrome and comparison subjects and explored associations of ferritin levels with regional brain volumes. Method: Ferritin was measured in 107 children and adults (63 Tourette's syndrome, 44 comparison); serum iron was measured in 73 (41 Tourette's syndrome, 32 comparison). Magnetic resonance imaging scans were used to measure volumes of the basal ganglia and cortical gray matter. Results: Ferritin and serum iron were significantly lower in the Tourette's syndrome subjects, although still within the normal range. No association was found between tic severity and either iron index. In the Tourette's syndrome subjects, ferritin did not correlate significantly with caudate volume but did correlate positively with putamen volume. In the comparison subjects, ferritin correlated inversely with caudate volume but did not correlate significantly with putamen volume. Irrespective of diagnosis, ferritin correlated positively with volumes of the sensorimotor, midtemporal, and subgenual cortices. Conclusions: The lower peripheral ferritin and iron levels in persons with Tourette's syndrome are consistent with findings in other movement disorders and suggest that lower iron availability may have a causal role in the pathophysiology of tic disorders. Lower iron stores may contribute to hypoplasia of the caudate and putamen, increasing vulnerability to developing tics or to having more severe tics. Lower iron stores may also contribute to smaller cortical volumes and consequently to reduced inhibitory control of tics.

Objective: The purpose of the study was to examine adaptive, emotional, and family functioning in a well-characterized group of children and adolescents with obsessive-compulsive disorder (OCD) and to evaluate the influence of comorbid attention deficit hyperactivity disorder (ADHD) on the levels of impairment in various functional domains. Method: The study group included 287 children and adolescents (191 boys, 96 girls) ages 7-18 years. Fifty-six subjects had a diagnosis of OCD only, 43 had both OCD and ADHD, 95 had ADHD, and 93 were unaffected comparison children. Best estimate DSM-IV diagnoses were assigned on the basis of structured interviews and clinical ratings. The children's functioning was evaluated with a comprehensive battery of well-established, standardized measures, including the Vineland Adaptive Behavior Scales, parents' ratings of social and family functioning, and children's self-reports of emotional adjustment. Results: The children with OCD only were more impaired than were unaffected comparison subjects in most areas of adaptive functioning and emotional adjustment. Children with OCD plus ADHD had additional difficulties in social functioning, school problems, and self-reported depression. Impairment in daily living skills, reduced number of activities, and self-reported anxiety were uniquely associated with the diagnosis of OCD. Family dysfunction was associated with ADHD but not with OCD. Conclusions: Children and adolescents with OCD are impaired in multiple domains of adaptive and emotional functioning. When comorbid ADHD is present, there is an additional burden on social, school, and family functioning.

Objective: The corpus callosum is the major commissure connecting the cerebral hemispheres. Prior evidence suggests involvement of the corpus callosum in the pathophysiology of Tourette's disorder. The authors assessed corpus callosum size and anatomical connectivity across the cerebral hemispheres in persons with Tourette's disorder. Method: The size of the corpus callosum was determined on the true midsagittal slices of reformatted, high-resolution magnetic resonance imaging scans and compared across groups in a cross-sectional case-control study of 158 subjects with Tourette's disorder and 121 healthy corn parison subjects, ages 5-65 years. Results: In the context of increasing mid-sagittal corpus callosum area from childhood to age 30 years, children with Tourette's disorder had smaller overall corpus callosum size, whereas adults with Tourette's disorder on average had larger corpus callosum size, yielding a prominent interaction of diagnosis with age. Corpus callosum size correlated positively with tic severity. Corpus callosum size also correlated inversely with dorsolateral prefrontal and orbitofrontal cortical volumes in both the subjects with Tourette's disorder and the comparison subjects, but the magnitudes of the correlations were significantly greater in the group with Tourette's disorder The effects of medication and comorbid illnesses had no appreciable influence on the findings. Conclusions: Given prior evidence for the role of prefrontal hypertrophy in the regulation of tic symptoms, the current findings suggest that neural plasticity may contribute to smaller corpus callosum size in persons with Tourette's disorder, which thereby limits neuronal trafficking across the cerebral hemispheres and reduces in put to cortical inhibitory interneurons within the prefrontal cortices. Reduced inhibitory input may in turn enhance prefrontal excitation, thus helping to control tics and possibly contributing to the cortical hyperexcitatibility reported previously in patients with Tourette's disorder.

Objective: Function of the ventromedial prefrontal cortex has been implicated in impulse control. The authors used the Stroop paradigm to test attention and response inhibition during the presentation of congruent and incongruent stimuli in male pathological gamblers and a group of comparison subjects. Method: Event-related functional magnetic resonance imaging was used to examine ventromedial prefrontal cortex function during Stroop performance. Results: In response to infrequent in-congruent stimuli, pathological gamblers demonstrated decreased activity in the left ventromedial prefrontal cortex relative to the comparison subjects. Both groups demonstrated similar activity changes in multiple brain regions, including activation of the dorsal anterior cingulate and dorsolateral frontal cortex. Conclusions: Pathological gamblers share many neural correlates of Stroop task performance with healthy subjects but differ in a brain region previously implicated in disorders characterized by poor impulse control.

Objective: An animal model was used to investigate an autoimmune etiology for some cases of Tourette's syndrome. Method: Sera from 12 patients with Tourette's syndrome with high levels of antineural or antinuclear antibodies were infused bilaterally into the ventrolateral striatum of rats. Sera from 12 additional Tourette's syndrome patients and 12 normal subjects (both groups with low levels of autoantibodies) were infused for comparison. Rates of oral stereotypies were recorded by observers who were blind to the origin of the infused sera. Results: Oral stereotypies significantly increased in the rats infused with sera from the patients with high levels of autoantibodies. Conclusions: The results are consistent with an autoimmune etiology in a subset of cases of Tourette's syndrome.

Objective: Obsessive-compulsive disorder encompasses a broad range of symptoms that represent multiple psychological domains, including perception, cognition, emotion, social relatedness, and diverse motor behaviors. The purpose of these analyses was to evaluate the correlational relationships of the symptoms of obsessive-compulsive disorder. Method: This study examined the 13 a priori categories used to group types of obsessions and compulsions in the Yale-Brown Obsessive Compulsive Scale symptom checklist in two independent groups of patients with obsessive-compulsive disorder (N=208 and N=98). A principal-components factor analysis with a varimax rotation was performed, followed by a series of other exploratory analyses. Results: The two data sets yielded nearly identical results. Four factors - obsessions and checking, symmetry and ordering, cleanliness and washing, and hoarding - emerged in each data set, in total accounting for more than 60% of the variance. Conclusions: Obsessive-compulsive disorder is a multidimensional and etiologically heterogeneous condition. The four symptom dimensions identified in this study are largely congruent with those identified in earlier reports. These factors may be of value in future genetic, neurobiological, and treatment response studies.

Objective: To investigate whether cerebral hyperintensities on [T.sub.2]-weighted magnetic resonance images (MRI) are associated with childhood neuropsychiatric disorders. Method: The authors compared the frequency of cortical and subcortical cerebral hyperintensities in 100 children and adolescents with Tourette's syndrome, obsessive-compulsive disorder (OCD), or attention deficit hyperactivity disorder (ADHD) and 32 healthy comparison subjects. Results: The frequency of cerebral hyperintensities was significantly higher in subjects with Tourette's syndrome, OCD, or ADHD than in healthy comparison subjects; each diagnostic group seemed to contribute to this effect. Among the patient groups, the likelihood of detecting cerebral hyperintensities in the subcortex (primarily the basal ganglia and thalamus) was significantly greater than in the cortex. Conclusions: A childhood diagnosis of Tourette's syndrome, OCD, or ADHD significantly increased the likelihood of detecting cerebral hyperintensities, particularly in the subcortex, supporting the notion that subcortical injury may play a role in the pathophysiology of these conditions.

Objective: This study investigated whether the functional abnormalities in prefrontal systems observed in adult bipolar disorder are manifested in adolescents with this illness. Method: Ten adolescents with bipolar disorder and 10 healthy comparison subjects participated in a color-naming Stroop task during event-related functional magnetic resonance imaging. Results: Signal increases in the left putamen and thalamus were significantly greater in the bipolar disorder group than in the healthy group. Age correlated positively with signal increases in the bilateral rostroventral prefrontal cortex and the striatum in the healthy group but not in the bipolar disorder group. In the bipolar disorder subjects, depressive symptoms correlated positively with signal increases in the ventral striatum. Conclusions: These findings suggest the presence of dysfunction in the subcortical portions of the frontostriatal circuits in adolescents with bipolar disorder. The absence of the prefrontal abnormalities that were observed previously in adults and the absence of the age-related increases in prefrontal activity observed in normal comparison subjects suggest that a developmental disturbance in prefrontal function may emerge in bipolar disorder over the course of adolescence.

Exposure therapy is the treatment of choice for anxiety disorders but requires people to confront feared situations and can be distressing. We tested the hypothesis that exposure without conscious awareness would reduce fear in participants with specific phobia by harnessing the neural circuitry supporting the automatic extinction of fear.

IMPORTANCE: Increasing rates of illicit drug use during pregnancy may be associated with risk for long-term health problems in prenatally exposed children. OBJECTIVE: To identify the associations of prenatal exposure to illicit drugs with organization of the newborn brain. DESIGN, SETTING, AND PARTICIPANTS: For this cohort study, a volunteer sample of 210 illicit drug–using and nonusing mothers and their newborns was enrolled from prenatal clinics and drug abuse treatment programs in New York, New York. Enrollment, scanning, and long-term follow-up occurred from September 2004 through February 2012, and image processing and statistical analyses continued through fall 2018. In addition to 26 participants with incomplete data, a total of 64 mothers were lost to follow-up during pregnancy, and 13 newborns were lost to follow-up at birth because of perinatal complications. EXPOSURES: Newborns were assigned to 1 of 4 primary exposure groups based on the history of most frequent maternal drug use: marijuana, cocaine, methadone maintenance, and/or heroin. Unexposed newborns were controls. MAIN OUTCOMES AND MEASURES: Unsedated magnetic resonance imaging (MRI) of newborn brains was performed shortly after birth. Infant neurodevelopmental outcomes were assessed at age 12 months. MRI modalities included anatomical imaging, diffusion tensor imaging, T2 relaxometry, and magnetic resonance spectroscopic imaging. Infant neurodevelopmental outcomes included Bayley scales of infant development–III and Vineland Adaptive Behavior Scales. Statistical analyses were performed with results represented on the brain images. RESULTS: Of 118 mothers, 42 (35%) were in the control group (mean [SD] age, 25.9 [6.1] years), 29 (25%) were in the cocaine group (mean [SD] age, 29.0 [6.1] years), 29 (25%) were in the marijuana group (mean [SD] age, 24.3 [5.5] years), and 18 (15%) were in the methadone and/or heroin group (mean [SD] age, 30.9 [5.7] years). Not all newborns could be scanned successfully; therefore, usable MRIs were acquired for 118 newborns from predominantly minority groups and with economically disadvantaged mothers. Anatomic abnormalities were detected in similar locations across all 3 drug exposures and included smaller volumes in the dorsal, medial, and ventral surfaces of the frontal lobe and dose-related increases in volumes in the lateral temporal lobe, dorsal parietal lobe, and superior frontal gyrus. Dose-related increases in diffusion tensor measures of tissue organization, decreases in T2 relaxometry times, and increases in spectroscopy metabolite concentrations were similar across exposures. These associations of exposures with brain measures were similar to the associations of newborn age with brain measures. The anatomic and diffusion tensor imaging measures suppressively mediated the associations of prenatal exposure with poorer 12-month infant outcomes. CONCLUSIONS AND RELEVANCE: The findings suggest that prenatal drug exposure is associated with measures of newborn brain tissue in patterns that may indicate that exposures accelerated normal fetal brain maturation, which in turn mediated the associations with poorer 12-month infant outcomes.

Decades of overexploitation have devastated shark populations, leaving considerable doubt as to their ecological status1,2. Yet much of what is known about sharks has been inferred from catch records in industrial fisheries, whereas far less information is available about sharks that live in coastal habitats3. Here we address this knowledge gap using data from more than 15,000 standardized baited remote underwater video stations that were deployed on 371 reefs in 58 nations to estimate the conservation status of reef sharks globally. Our results reveal the profound impact that fishing has had on reef shark populations: we observed no sharks on almost 20% of the surveyed reefs. Reef sharks were almost completely absent from reefs in several nations, and shark depletion was strongly related to socio-economic conditions such as the size and proximity of the nearest market, poor governance and the density of the human population. However, opportunities for the conservation of reef sharks remain: shark sanctuaries, closed areas, catch limits and an absence of gillnets and longlines were associated with a substantially higher relative abundance of reef sharks. These results reveal several policy pathways for the restoration and management of reef shark populations, from direct top-down management of fishing to indirect improvement of governance conditions. Reef shark populations will only have a high chance of recovery by engaging key socio-economic aspects of tropical fisheries.

Prenatal maternal distress—an umbrella concept encompassing multiple negative psychological states including stress, anxiety, and depression—is a substantial prenatal exposure. Consistent across preclinical and human studies, the hippocampus displays alterations due to prenatal distress. Nevertheless, most prenatal distress studies do not focus on multiple dimensions of, have not examined hippocampal functional connectivity in association with, and do not consider observer-based functional outcomes related to distress. We investigated the effects of different dimensions of prenatal distress in pregnant adolescents, a population at high risk for distress, in association with neonatal hippocampal connectivity and infant memory. In pregnant adolescents (n= 42), we collected four measures of distress (perceived stress, depression, pregnancy-specific distress, and 24-h ambulatory salivary cortisol) during the 2nd and 3rd trimesters. Resting-state imaging data were acquired in their infants at 40–44 weeks post-menstrual age. Functional connectivity was measured from hippocampal seeds. Memory abilities were obtained at 4 months using the mobile conjugate reinforcement task. Shared across different dimensions of maternal distress, increased 3rd trimester maternal distress associated with weaker hippocampal–cingulate cortex connectivity and stronger hippocampal–temporal lobe connectivity. Perceived stress inversely correlated while hippocampal–cingulate cortex connectivity positively correlated with infant memory. Increased cortisol—collected during the 2nd, but not the 3rd, trimester—associated with weaker hippocampal–cingulate cortex connectivity and stronger hippocampal–temporal lobe connectivity. Different dimensions of prenatal maternal distress likely contribute shared and unique effects to shaping infant brain and behavior.

Lactation has been widely associated with optimal neurocognitive development, but the underlying mechanism remains unknown. Human milk oligosaccharides (HMOs) are complex sugars that support brain development, but prior studies examining their associations with cognition have yielded inconsistent findings.

Q: What causes the central bar in some spiral galaxies?--Dennis Shingler, Inverness, Florida A: Central bars occur in about two-thirds of spiral galaxies. We think they are regions of many [...]

Antidepressant medications offer an effective treatment for depression, yet nearly 50% of patients either do not respond or have side-effects rendering them unable to continue the course of treatment. Mechanistic studies might help advance the pharmacology of depression by identifying pathways through which treatments exert their effects. Toward this goal, we aimed to identify the effects of antidepressant treatment on neural connectivity, the relationship with symptom improvement, and to test whether these effects were reproducible across two studies.

Despite the importance of coastal ecosystems for the global carbon budgets, knowledge of their carbon storage capacity and the factors driving variability in storage capacity is still limited. Here we provide an estimate on the magnitude and variability of carbon stocks within a widely distributed marine foundation species throughout its distribution area in temperate Northern Hemisphere. We sampled 54 eelgrass (Zostera marina) meadows, spread across eight ocean margins and 36° of latitude, to determine abiotic and biotic factors influencing organic carbon (Corg) stocks in Zostera marinasediments. The Corgstocks (integrated over 25‐cm depth) showed a large variability and ranged from 318 to 26,523 g C/m2with an average of 2,721 g C/m2. The projected Corgstocks obtained by extrapolating over the top 1 m of sediment ranged between 23.1 and 351.7 Mg C/ha, which is in line with estimates for other seagrasses and other blue carbon ecosystems. Most of the variation in Corgstocks was explained by five environmental variables (sediment mud content, dry density and degree of sorting, and salinity and water depth), while plant attributes such as biomass and shoot density were less important to Corgstocks. Carbon isotopic signatures indicated that at most sites <50% of the sediment carbon is derived from seagrass, which is lower than reported previously for seagrass meadows. The high spatial carbon storage variability urges caution in extrapolating carbon storage capacity between geographical areas as well as within and between seagrass species. The Z. marinaCorgstocks varied widely within and across studied regions; majority of this variation was explained by five sediment and environmental variablesThe Z. marinaCorgstocks were comparable to other seagrass species and other blue carbon habitats such as salt marshes and mangrove forestsCarbon isotopic signatures indicated that at most sites, only less than half of the sediment carbon is derived from seagrass, though variation was significant

The article discusses the U.S. National Aeronautics and Space Administration's (NASA's) development of an astronomical space telescope the Large Ultraviolet/Optical/Infrared Surveyor (LUVOIR). An overview of the space observatories that NASA is designing, including the James Webb Space Telescope (JWST), is provided.

IMPORTANCE: Selective serotonin reuptake inhibitor (SSRI) use among pregnant women is increasing, yet the association between prenatal SSRI exposure and fetal neurodevelopment is poorly understood. Animal studies show that perinatal SSRI exposure alters limbic circuitry and produces anxiety and depressive-like behaviors after adolescence, but literature on prenatal SSRI exposure in humans is limited and mixed. OBJECTIVE: To examine associations between prenatal SSRI exposure and brain development using structural and diffusion magnetic resonance imaging (MRI). DESIGN, SETTING, AND PARTICIPANTS: A cohort study conducted at Columbia University Medical Center and New York State Psychiatric Institute included 98 infants: 16 with in utero SSRI exposure, 21 with in utero untreated maternal depression exposure, and 61 healthy controls. Data were collected between January 6, 2011, and October 25, 2016. EXPOSURES: Selective serotonin reuptake inhibitors and untreated maternal depression. MAIN OUTCOMES AND MEASURES: Gray matter volume estimates using structural MRI with voxel-based morphometry and white matter structural connectivity (connectome) using diffusion MRI with probabilistic tractography. RESULTS: The sample included 98 mother (31 [32%] white, 26 [27%] Hispanic/Latina, 26 [27%] black/African American, 15 [15%] other) and infant (46 [47%] boys, 52 [53%] girls) dyads. Mean (SD) age of the infants at the time of the scan was 3.43 (1.50) weeks. Voxel-based morphometry showed significant gray matter volume expansion in the right amygdala (Cohen d = 0.65; 95% CI, 0.06-1.23) and right insula (Cohen d = 0.86; 95% CI, 0.26-1.14) in SSRI-exposed infants compared with both healthy controls and infants exposed to untreated maternal depression (P &lt; .05; whole-brain correction). In connectome-level analysis of white matter structural connectivity, the SSRI group showed a significant increase in connectivity between the right amygdala and the right insula with a large effect size (Cohen d = 0.99; 95% CI, 0.40-1.57) compared with healthy controls and untreated depression (P &lt; .05; whole connectome correction). CONCLUSIONS AND RELEVANCE: Our findings suggest that prenatal SSRI exposure has an association with fetal brain development, particularly in brain regions critical to emotional processing. The study highlights the need for further research on the potential long-term behavioral and psychological outcomes of these neurodevelopmental changes.

Schizophrenia, a neurodevelopmental disorder, involves abnormalities in functional connectivity (FC) across distributed neural networks, which are thought to antedate the emergence of psychosis. In a cohort of adolescents and young adults at clinical high risk (CHR) for psychosis, we applied data-driven approaches to resting-state functional magnetic resonance imaging data in order to systematically characterize FC abnormalities during this period and to determine whether these abnormalities are associated with psychosis risk and severity of psychotic symptoms.

Infection is a major complication of severe trauma and may also be a primary cause of prolonged hospitalization and death among trauma patients. The immune system response of 10 infants and children suffering from severe blunt trauma was studied within 36 hours of arrival in an intensive care unit. Possible immune system suppression was present in the form of defective T-helper cells, which could explain the failure of antigen-specific B-cells to proliferate and produce normal amounts of antibody. Other variables may account for the increased rate of infection in these patients. Open wounds and the placement of catheters, monitors, and tubes in the body provide portals for infection. Blood transfusions may also affect immune function, and many of the drugs and anesthetics used in these patients have immunosuppressive effects.

Research into the pathophysiology of major depressive disorder (MDD) has focused largely on individuals already affected by MDD. Studies have thus been limited in their ability to disentangle effects that arise as a result of MDD from precursors of the disorder. By studying individuals at high familial risk for MDD, we aimed to identify potential biomarkers indexing risk for developing MDD, a critical step toward advancing prevention and early intervention. Using resting-state functional connectivity MRI (rs-fcMRI) and diffusion MRI (tractography), we examined connectivity within the default mode network (DMN) and between the DMN and the central executive network (CEN) in 111 individuals, aged 11–60 years, at high and low familial risk for depression. Study participants were part of a three-generation longitudinal, cohort study of familial depression. Based on rs-fcMRI, individuals at high vs low familial risk for depression showed increased DMN connectivity, as well as decreased DMN-CEN-negative connectivity. These findings remained significant after excluding individuals with a current or lifetime history of depression. Diffusion MRI measures based on tractography supported the findings of decreased DMN-CEN-negative connectivity. Path analyses indicated that decreased DMN-CEN-negative connectivity mediated a relationship between familial risk and a neuropsychological measure of impulsivity. Our findings suggest that DMN and DMN-CEN connectivity differ in those at high vs low risk for depression and thus suggest potential biomarkers for identifying individuals at risk for developing MDD.

Cognitive control, a set of functions that develop throughout adolescence, is important in the pathogenesis of psychotic disorders. Whether cognitive control has a role in conferring vulnerability for the development of psychotic illness is still unknown. The aim of this study was to investigate the neural systems supporting cognitive control in individuals deemed to be potentially prodromal for psychotic illness. We recruited 56 participants at clinical high-risk (CHR) for psychosis based on the Structured Interview for Psychosis-Risk Syndromes (SIPS) and 49 healthy controls. Twelve of the CHR participants eventually developed psychosis. We compared functional magnetic resonance imaging (fMRI) BOLD signal during the performance of the Simon task. We tested for differences between CHR individuals and controls in conflict-related functional activity. In the CHR group when compared with controls, we detected smaller conflict-related activations in several cortical areas, including the Dorsolateral Prefrontal Cortex (DLPFC). Furthermore, conflict-related activations in the DLPFC of those CHR individuals who ultimately developed psychosis (CHR converters) were smaller than in non-converters (CHR non-converters). Higher levels of conflict-related activation were associated with better social and role outcome. Risk for psychosis was associated at the neural level with reduced conflict-related brain activity. This neural phenotype appears correlated within the DLPFC with the development of psychosis and with functional outcome.

Background:Children prenatally exposed to inadequate iron have poorer motor and neurocognitive development. No prior study to our knowledge has assessed the influence of maternal prenatal iron intake on newborn brain tissue organization in full-term infants.Methods:Third trimester daily iron intake was obtained using the Automated Self-Administered 24-h Dietary Recall with n = 40 healthy pregnant adolescents (aged 14–19 y). Cord blood ferritin was collected in a subsample (n = 16). Newborn (mean = 39 gestational weeks at birth; range 37–41) magnetic resonance imaging scans were acquired on a 3.0 Tesla MR Scanner. Diffusion Tensor Imaging (DTI) slices were acquired to measure the directional diffusion of water indexed by fractional anisotropy (FA).Results:Reported iron intake was inversely associated with newborn FA values (P = 0.0001) predominantly in cortical gray matter. FA findings were similar using cord blood ferritin values.Conclusion:Higher maternal prenatal iron intake accentuates, and lower intake attenuates, the normal age-related decline in FA values in gray matter, perhaps representing increasing dendritic arborization and synapse formation with higher iron intake. These DTI results suggest that typical variation in maternal iron outside the scope of standard clinical surveillance exerts subtle effects on infant brain development.

The last two decades have marked tremendous progress in our ability to prevent and intervene early in psychiatric illnesses. The interventions described in this article range from established, empirically-supported treatments to creative interventions early in their development and deployment. Some of these interventions are low-technology programs delivered in social settings (such as schools), and some rely on sophisticated emerging technologies such as neuroimaging. This article reviews 4 preventative interventions: 1) The use of structural brain imaging to identify children at risk for familial depression who are most likely to benefit from preventative cognitive behavioral therapy 2) The Good Behavior Game, a school based program that, when implemented in 1st grade classrooms, cut the incidence of substance use disorders in students in half when those students were 19 years old, 3) The SPARX video game, which has the potential to be an accessible, appealing, and cost-effective treatment for the thousands of teens affected by mild to moderate depressive disorders, and 4) Intensive psychosocial treatments which can reduce the progression of from the ultra high risk state to the first episode psychosis by 50% over 12 months. All of these interventions have tremendous potential to reduce the suffering and disability caused by psychiatric illness to both children and adults.

AbstractObjectives:To assess the feasibility and effectiveness of an innovative curriculum designed to teach communicative receptive and expressive language to non-verbal children with autism through reading and writing.Methods:Randomized, controlled clinical trial of 18 children aged 5–13 years with autistic disorder and functional spoken language limited to single words, holophrases, or over-learned phrases. The treatment group (n = 9; mean age: 7·1 years; three female) received 9–11 months of one-to-one instruction in reading and writing. The control group (n = 9; mean age: 8·6 years; two female) received teaching that matched the literacy curriculum in all features of administration and organization, but taught number recognition, addition, and subtraction. Before and after the intervention, participants were given criterion-referenced tests to assess their skills in the knowledge domains taught in the treatment and control interventions.Results:Five literacy participants and four control participants completed the study. Both groups showed greater improvement on the skills in which they had been trained, compared to the other group: Hotelling’s Trace = 0·66, F(1,7) = 4·63, P = 0·034 (one-tailed),  = 0·40. On the literacy criterion-referenced test, the literacy group showed significant improvement: paired t(4) = 2·40, P = 0·037 (one-tailed); the control group did not (P>0·10).Discussion:Literacy instruction may be a route to language acquisition for some children with autism who have little or no functional spoken language.

Safe upper limits for therapeutic hypernatremia in the treatment of intracranial hypertension have not been well established. We investigated complications associated with hypernatremia in children who were treated with prolonged infusions of hypertonic saline.

Somatoform pain is a highly prevalent, debilitating condition and a tremendous public health problem. Effective treatments for somatoform pain are urgently needed. The etiology of this condition is, however, still unknown. On the basis of a review of recent basic and clinical research, we propose one potential mechanism of symptom formation in somatoform pain and a developmental theory of its pathogenesis. Emerging evidence from animal and human studies in developmental neurobiology, cognitive-affective neuroscience, psychoneuroimmunology, genetics, and epigenetics, as well as that from clinical and treatment studies on somatoform pain, points to the existence of a shared neural system that underlies physical and social pain. Research findings also show that nonoptimal early experiences interact with genetic predispositions to influence the development of this shared system and the ability to regulate it effectively. Interpersonal affect regulation between infant and caregiver is crucial for the optimal development of these brain circuits. The aberrant development of this shared neural system during infancy, childhood, and adolescence may therefore ultimately lead to an increased sensitivity to physical and social pain and to problems with their regulation in adulthood. The authors critically review translational research findings that support this theory and discuss its clinical and research implications. Specifically, the proposed theory and research review suggest that psychotherapeutic andor pharmacological interventions that foster the development of affect regulation capacities in an interpersonal context will also serve to more effectively modulate aberrantly activated neural pain circuits and thus be of particular benefit for the treatment of somatoform pain.

We present a neuropsychoanalytic experimental paradigm for demonstrating psychodynamic conflict. The strategy is threefold: to manipulate awareness of emotional stimuli that activate the psychodynamics of participants diagnosed with a pertinent psychological disorder; to compare their neurobiological vs. experiential responses to those of healthy participants; and to correlate the former patterns of neural activation of the diagnostic sample with attending patterns of behavior that are indicative of conflict. Behavioral experiments based on the paradigm have generated findings that are consistent with a theory of psychodynamic conflict. An ongoing functional magnetic resonance imaging (fMRI) study is comparing the scans of phobic, counterphobic, and healthy participants during exposure to masked and unmasked phobic stimuli. If the predicted patterns of neural activation of the phobic groups correlate with corresponding patterns of behavior, it will link brain and behavior in the demonstration of psychodynamic conflict.

Background: Prenatal alcohol exposure is related to a wide range of neurocognitive effects. Eyeblink conditioning (EBC), which involves temporal pairing of a conditioned with an unconditioned stimulus, has been shown to be a potential biomarker of fetal alcohol exposure. A growing body of evidence suggests that white matter may be a specific target of alcohol teratogenesis, and the neural circuitry underlying EBC is known to involve the cerebellar peduncles. Diffusion tensor imaging (DTI) is a magnetic resonance imaging (MRI) technique that has proven useful for assessing central nervous system white matter integrity. This study used DTI to examine the degree to which the fetal alcohol‐related deficit in EBC may be mediated by structural impairment in the cerebellar peduncles.

B-type natriuretic peptide (BNP) has diagnostic, prognostic, and therapeutic roles in adults with heart failure. BNP levels in children undergoing surgical repair of congenital heart disease (CHD) were characterized broadly, and distinguishable subgroup patterns delineated.

We present the results of extensive multi-frequency monitoring of the radio galaxy 3C 120 between 2002 and 2007 at X-ray (2-10 keV), optical (R and V bands), and radio (14.5 and 37 GHz) wave bands, as well as imaging with the Very Long Baseline Array (VLBA) at 43 GHz. Over the 5 yr of observation, significant dips in the X-ray light curve are followed by ejections of bright superluminal knots in the VLBA images. Consistent with this, the X-ray flux and 37 GHz flux are anti-correlated with X-ray leading the radio variations. Furthermore, the total radiative output of a radio flare is related to the equivalent width of the corresponding X-ray dip. This implies that, in this radio galaxy, the radiative state of accretion disk plus corona system, where the X-rays are produced, has a direct effect on the events in the jet, where the radio emission originates. The X-ray power spectral density of 3C 120 shows a break, with steeper slope at shorter timescale and the break timescale is commensurate with the mass of the central black hole (BH) based on observations of Seyfert galaxies and black hole X-ray binaries (BHXRBs). These findings provide support for the paradigm that BHXRBs and both radio-loud and radio-quiet active galactic nuclei are fundamentally similar systems, with characteristic time and size scales linearly proportional to the mass of the central BH. The X-ray and optical variations are strongly correlated in 3C 120, which implies that the optical emission in this object arises from the same general region as the X-rays, i.e., in the accretion disk-corona system. We numerically model multi-wavelength light curves of 3C 120 from such a system with the optical-UV emission produced in the disk and the X-rays generated by scattering of thermal photons by hot electrons in the corona. From the comparison of the temporal properties of the model light curves to that of the observed variability, we constrain the physical size of the corona and the distances of the emitting regions from the central BH. In addition, we discuss physical scenarios for the disk-jet connection that are consistent with our observations.

Objective: To identify the neural substrate of self-regulatory control in children and adults with Tourette syndrome (TS).Method: We used event-related functional magnetic resonance imaging (fMRI) to study the neural correlates of cognitive self-regulation during the Simon task. Forty-two people from The Tic Disorder Specialty Clinic who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for diagnosis with TS (24 children; 18 adults) were compared with 37 control subjects (19 children; 18 adults). Patients with TS were excluded from participation if they had any Axis I psychiatric disorder other than obsessive–compulsive disorder (OCD) or attention-deficit hyperactivity disorder (ADHD) prior to the onset of TS. Control participants were excluded if they reported a history of tic disorder, OCD, ADHD, or if they met diagnostic criteria for any Axis I disorder at the time of interview.Results: We detected greater overall fMRI activation in adults than in children across both diagnostic groups, primarily in frontal and striatal regions. In both groups we also detected an age-related shift away from more general cortical activation toward a more specific reliance on frontostriatal activity, a developmental correlate that was exaggerated in the TS group despite behavioural performances similar to those of control subjects. Moreover, the severity of tics correlated positively with frontal activations across age groups.Conclusion: Frontostriatal circuits support cognitive and behavioural control. These circuits likely contribute both to optimal performance in this self-regulatory task and to the regulation of the severity of tics. Adults with persistent TS likely possess deficient activity in these circuits, attributable to either a failure of prefrontal plasticity or to disturbances in striatal functioning.

We present high-resolution Hubble Space Telescope images of all 35 active galactic nuclei (AGNs) with optical reverberation-mapping results, which we have modeled to create a nucleus-free image of each AGN host galaxy. From the nucleus-free images, we determine the host-galaxy contribution to ground-based spectroscopic luminosity measurements at 5100 A. After correcting the luminosities of the AGNs for the contribution from starlight, we re-examine the Hb R BLR-L relationship. Our best fit for the relationship gives a power-law slope of 0.52 with a range of 0.45-0.59 allowed by the uncertainties. This is consistent with our previous findings, and thus still consistent with the naive assumption that all AGNs are simply luminosity-scaled versions of each other. We discuss various consistency checks relating to the galaxy modeling and starlight contributions, as well as possible systematic errors in the current set of reverberation measurements from which we determine the form of the R BLR-L relationship.