Faculty Bibliography

Neuronal oscillations route external and internal information across brain regions. In the olfactory system, the two central nodes-the olfactory bulb (OB) and the piriform cortex (PC)-communicate with each other via neural oscillations to shape the olfactory percept. Communication between these nodes have been well characterized in non-human animals but less is known about their role in the human olfactory system. Using a recently developed and validated EEG-based method to extract signals from the OB and PC sources, we show in healthy human participants that there is a bottom-up information flow from the OB to the PC in the beta and gamma frequency bands, while top-down information from the PC to the OB is facilitated by delta and theta oscillations. Importantly, we demonstrate that there was enough information to decipher odor identity above chance from the low gamma in the OB-PC oscillatory circuit as early as 100 ms after odor onset. These data further our understanding of the critical role of bidirectional information flow in human sensory systems to produce perception. However, future studies are needed to determine what specific odor information is extracted and communicated in the information exchange.

BACKGROUND:Prevention studies for perinatal depression rarely focus on the mother-infant dyad or consider the impact of maternal childhood maltreatment (CM). METHODS:A secondary analysis of two combined randomized controlled trials of Practical Resources for Effective Postpartum Parenting (PREPP) examined the moderating role of CM on the efficacy of preventing perinatal depression and effects on infant behavior at six weeks. RESULTS:32% of 109 pregnant women endorsed CM (CM+). At six weeks postpartum, women who received PREPP compared to enhanced treatment as usual (ETAU) had significant reductions in depression and anxiety based on the observer-rated Hamilton Rating Scale for Depression (HRSD) and Hamilton Rating Scale for Anxiety (HRSA) (mean difference of M=-3.84 (SD= 0.14, p<0.01) and M=- 4.31 (SD= 0.32, p <0.001) respectively). When CM was added to the models, there no longer was a significant PREPP versus ETAU treatment effect on HRSD and HRSA outcomes in CM+ women though effects remained for CM- women. However, CM+ women who received PREPP vs ETAU reported a mean increase in infant daytime sleep of 189.8 min (SE= 50.48, p = 0.001). LIMITATIONS/CONCLUSIONS:Self-report measures of infant behavior were used. CONCLUSIONS:CM+ women versus CM- had limited response to an intervention to prevent perinatal depression yet still reported an increase in infant daytime sleep. This study adds to the growing literature that prevention studies may need to incorporate approaches tailored to fit women with childhood trauma histories while also considering infant functioning as both may be treatment targets relevant to maternal mood.

In a previous study, dasotraline demonstrated efficacy at a dose of 8 mg/day in adults with attention deficit hyperactivity disorder (ADHD). The aim of the current study was to evaluate the efficacy and safety of dasotraline in doses of 4 and 6 mg/day. Adults meeting Diagnostic and Statistical Manual of Mental Disorders, 5th edition criteria for ADHD were randomized to 8 weeks of double-blind, once-daily, fixed-dose treatment with dasotraline 4 mg/day, 6 mg/day, or placebo. The primary efficacy endpoint was changed in the ADHD Rating Scale, Version IV (ADHD RS-IV) total score. Secondary efficacy endpoints included the Clinical Global Impression, Severity (CGI-S) Scale. Least squares mean reduction at week 8 in the ADHD RS-IV HV total score was not significantly greater (vs. placebo) in the dasotraline 4 mg/day group (-15.0 vs. -13.9; n.s.; or in the dasotraline 6 mg/day group (-16.5 vs. -13.9; P = 0.074; Hochberg correction). Treatment with dasotraline 6 mg/day was significant at week 8 (uncorrected) on the ADHD RS-IV total score (P = 0.037) and the CGI-S score (P = 0.011). Treatment with the 4 mg/day dose of dasotraline was NS. Treatment with dasotraline was generally well tolerated. The results provide additional evidence that supports the potential efficacy of dasotraline, in doses of 6 mg/day, in adults with ADHD.

Background: Autism spectrum disorder (ASD) is a highly prevalent developmental disorder. There is notable disparity in occurrence rates between males and females, with males being 4.5 times as likely as their female counterparts to be diagnosed with the disease. A major objective for improving functional outcomes in ASD is to isolate biomarkers for earlier detection; an area as yet unexplored is whether biomarkers of future ASD symptomology may be observable in the fetal brain. Here, we focus on the amygdala, which shows sex-differential patterns of development and has been implicated in the neurobiology of ASD.
Method(s): We obtained resting-state MRI data in 109 healthy human fetuses (24-39 weeks) and Brief Infant Toddler Social Emotional Assessment (BITSEA) and Child Behavior Checklist (CBCL) measures at child age 3. The average number of frames obtained after scrubbing high-motion frames was N=169, or 5.6 minutes of resting state data (TR=2) with mean XYZ motion 0.9mm (SD=0.3). Subject-specific amygdala connectivity maps were computed and tested in a full factorial model, that included sex, age at scan, and ASD outcome.
Result(s): ASD outcomes were associated with increased amygdala connectivity to prefrontal and sensorimotor cortices, decreased connectivity to anterior insula and cerebellum, and sex interactions were observed in inferior prefrontal and striatal regions (p<0.005 and k min=25).
Conclusion(s): These observations raise exciting new ideas about the advent of risk and the ontogeny of early sex differences. Further analyses will be conducted to examine sex-differential risk and postnatal environmental effects within a multifactorial liability model framework. Supported By: NIMH R01 MH110793 NIDA R34 DA050287 NIMH R01 MH122447 NARSAD Foundation Keywords: Fetal, Autism, Resting-State, Sex Differences
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Trait impulsivity is a multifaceted personality characteristic that contributes to maladaptive life outcomes. Although a growing body of neuroimaging studies have investigated the structural correlates of trait impulsivity, the findings remain highly inconsistent and heterogeneous. Herein, we performed a systematic review to depict an integrated delineation of gray matter (GM) substrates of trait impulsivity and a meta-analysis to examine concurrence across previous whole-brain voxel-based morphometry studies. The systematic review summarized the diverse findings in GM morphometry in the past literature, and the quantitative meta-analysis revealed impulsivity-related volumetric GM alterations in prefrontal, temporal, and parietal cortices. In addition, we identified the modulatory effects of age and gender in impulsivity-GM volume associations. The present study advances understanding of brain GM morphometry features underlying trait impulsivity. The findings may have practical implications in the clinical diagnosis of and intervention for impulsivity-related disorders.

Although increasing numbers of children have socially transitioned to live in line with their gender identities, little is known about factors associated with their wellbeing. This study examines the associations between parent-reported family, peer, and school support for a youth's gender identity, as well as an objective measure of state-level support, with parent-reported internalizing symptoms in 265 transgender youth (67.2% transgender girls, 32.8% transgender boys), ages 3-15 years (M = 9.41, SD = 2.62). Parents who reported higher levels of family, peer, and school support for their child's gender identity also reported fewer internalizing symptoms; the objective measure of state-level support was not related to internalizing symptoms. Additionally, peer and school support buffered against the association between gender-related victimization and internalizing symptoms, as reported by parents. This work demonstrates that even among transgender youth with families who supported their transitions, parents see better well-being in their children when they also see more support for the child's gender identity from family, peers, and schools.

The COVID-19 pandemic exacerbates the mental, emotional, and behavioral (MEB) health problems of children and adolescents in the United States (U.S.). A collective and coordinated national economic and social reconstruction effort aimed at shoring up services to promote children's MEB, like the Marshall Plan that helped rebuild Europe post-World War II, has been proposed to buttress against the expected retrenchment. The plan prioritizes children's well-being as a social objective. We propose strategically reconstructing the public safety-net systems serving youth, including early education, maternal and child health, child welfare, corrections, and mental health. That plan called for a concentrated focus on coalition-building and contracting by state mental health systems to establish a foundation for an improved health system. This paper offers a complementary set of suggestions for the four non-mental health systems mentioned above by recommending actionable steps based on scientific evidence to support improved services for children at risk for MEB problems. For each system we describe examples of evidence-informed services, policies or programs that (1) prevent disabilities and promote health, (2) protect and preserve families and neighborhoods, and (3) provide quality care. Prioritizing the promotion of children's MEB health by all state systems can shape U.S. children's health and well-being for generations to come.

Symptoms of attention-deficit/hyperactivity disorder (ADHD) in elementary school-age children are associated with poor relationships with classroom peers, as indicated by poor social preference, low peer support, and peer victimization. Less is known about how friendship patterns relate to ADHD symptoms, or how friendships may buffer risk for negative peer experiences. Participants were 558 children in 34 classrooms (grades K-5). At the beginning (fall) and end (spring) of an academic year, children completed (a) sociometric interviews to index friendship patterns and social preference, and (b) self-report questionnaires about their support and victimization experiences from classmates. In fall, higher teacher-reported ADHD symptoms were associated with children having more classmates with no friendship ties (non-friends) and who the child nominated but did not receive a nomination in return (unreciprocated friends), and with having fewer classmates with mutual friendship ties (reciprocated friends) and who nominated the child but the child did not nominate in return (unchosen friends). Higher fall ADHD symptoms predicted more non-friend classmates, poorer social preference, and more victimization in the spring, after accounting for the same variables in fall. However, having many reciprocated friends (and to a lesser extent, many unchosen friends) in fall buffered against the trajectory between fall ADHD symptoms and poor peer functioning in spring. By contrast, having many unreciprocated friends in fall exacerbated the trajectory between fall ADHD symptoms and poor peer functioning in spring. Thus, elevated ADHD symptoms are associated with poorer friendship patterns, but reciprocated friendship may protect against negative classroom peer experiences over time.

BACKGROUND:Deep transcranial magnetic stimulation (dTMS) with the H7-coil was FDA cleared for obsessive-compulsive disorder (OCD) in August 2018 based on multicenter sham-controlled studies. Here we look at the efficacy of dTMS for OCD in real world practices. METHODS:All dTMS clinics were asked to supply their data on treatment details and outcome measures. The primary outcome measure was response, defined by at least a 30% reduction in the Yale Brown Obsessive Compulsive Scale (YBOCS) score from baseline to endpoint. Secondary outcome measures included first response, defined as the first time the YBOCS score has met response criteria, and at least one-month sustained response. Analyses included response rate at the endpoint (after 29 dTMS sessions), number of sessions and days required to reach first response and sustained response. RESULTS:Twenty-two clinical sites with H7-coils provided data on details of treatment and outcome (YBOCS) measures from a total of 219 patients. One-hundred-sixty-seven patients who had at least one post-baseline YBOCS measure were included in the main analyses. Overall first and sustained response rates were 72.6% and 52.4%, respectively. The response rate was 57.9% in patients who had YBOCS scores after 29 dTMS sessions. First response was achieved in average after 18.5 sessions (SD = 9.4) or 31.6 days (SD = 25.2). Onset of sustained one-month response was achieved in average after 20 sessions (SD = 9.8) or 32.1 days (SD = 20.5). Average YBOCS scores demonstrated continuous reduction with increasing numbers of dTMS sessions. CONCLUSIONS:In real-world clinical practice, the majority of OCD patients benefitted from dTMS, and the onset of improvement usually occurs within 20 sessions. Extending the treatment course beyond 29 sessions results in continued reduction of OCD symptoms, raising the prospect of value for extended treatment protocols in non-responders.