Faculty Bibliography

Oxytocin modulates social information processing by altering excitatory-inhibitory balance at the microcircuit level, but how such local modulation gives rise to selective processing at the level of distributed brain systems remains unclear. Here, we investigated the effects of oxytocin on large-scale neurodynamics across cortico-limbic network in the mouse brain using multisite local field potential recordings. Oxytocin selectively enhanced neural responses to infant calls in the auditory cortex (AC) and medial prefrontal cortex (mPFC). These enhancements occurred while baseline activity was reduced, indicating increased signal-to-noise ratio rather than a global increase in excitability. During auditory steady-state responses (ASSRs), oxytocin increased prefrontal phase coherence without altering ASSR power. During rest, oxytocin induced a transient, broadband reduction in spontaneous spectral power across regions. Despite this reduction in activity, analyses of interregional interactions revealed a selective increase in low-theta phase coupling and directional connectivity of AC→mPFC. Session-level analyses showed that stronger bottom-up AC→mPFC coupling was associated with lower prefrontal power, consistent with a gating or disinhibitory network regime favoring sensory-to-prefrontal information transfer. Multivariate analyses showed that oxytocin/saline conditions were reliably discriminable using supervised classification models, with specific contributions from spectral power, phase-locking, and Granger-causal connectivity features. Conversely, unsupervised dimensionality reduction did not identify a distinct low-dimensional manifold separating conditions, although a modest shift in the centroid of neural state space was observed. Together, these results indicate that oxytocin reduces background neural activity while selectively enhancing sensory-prefrontal network interactions, providing a systems-level account linking local inhibitory modulation to selective processing of socially salient infant cues.

Studies have reported conflicting findings regarding the contribution of germline variants or somatic genomic drivers to racial disparities in multiple myeloma (MM). To comprehensively investigate somatic drivers in relation to inherited genetics in MM, we combined newly sequenced whole-genome sequencing data with publicly available datasets (total n = 1,286). Overall, we did not identify germline or somatic genomic differences that explain the different risk of developing MM between patients with genetic similarity to African (AFR) or European (EUR) reference populations. A difference in the detectability and timing of APOBEC-associated and germinal center mutational activity was observed. Integrating epidemiological data and mutational signature-based temporal estimates, we challenge the assumption that individuals in the AFR group develop MM at a younger age. Finally, we demonstrate that, with equal access to efficacious therapies, patients in the AFR and EUR groups have equivalent clinical outcomes.

BACKGROUND:The clinical and economic impact of breast cancer screening varies based on the modality, frequency, and age of the screened population. OBJECTIVE:To characterize changes in use and cost of breast cancer screening for older women. DESIGN/METHODS:Serial cross-sectional study using data from SEER-Medicare, 2009-2019. PARTICIPANTS/METHODS:Women 67 and older enrolled in Medicare fee-for-service. MAIN MEASURES/METHODS:Screening use and cost by age, frequency, and modality. We further categorized screening as cost-effective or cost-ineffective based on published economic analyses rather than guidelines. Cost-effective screening included biennial mammography among women < age 80, while cost-ineffective screening included annual mammography, addition of digital breast tomosynthesis (DBT), screening ultrasound, and any screening among women 80 and older. We estimated total annual spending on screening in Medicare fee-for-service, inflated to 2019 dollars. KEY RESULTS/RESULTS:Our sample included a mean of 229,683 (range 222,400- 244,793) Medicare beneficiaries annually. Biennial screening was stable among women 65-79, at 11.2% (95% CI 11.0-11.4) in 2009 and 11.9% (95% CI 11.7-12.0) in 2019. Annual screening was also stable at 32.5% (95% CI 32.3-32.7) in 2009 and 30.0% (95% CI 29.8-30.2) in 2019. Among women 80 and older, screening (annual or biennial) declined from 19% (95% CI 18.8-19.3) to 12.9% (95% CI 12.7-13.2). Between 2009-2019, use of DBT rose from 0% to 70.3% of screened women. Total spending on cost-effective screening rose from $569 million per year to $735 million per year, a 29% increase. Spending on cost-ineffective screening rose from $548 million to $1.025 billion, an 87% increase. By 2019, spending on cost-ineffective screening accounted for 58% of total spending. CONCLUSIONS:Screening costs for older women have risen, driven by expenditures on technologies that may not be cost-effective. Reducing use of low value screening could result in savings that could be reallocated toward high value screening and follow up testing.

IMPORTANCE/UNASSIGNED:Increasing numbers of children are conceived using infertility treatment; concerns remain about potential effects on child neurodevelopment. OBJECTIVE/UNASSIGNED:To evaluate whether infertility treatment is associated with child neurodevelopment and whether such an association may be attributable to underlying subfecundity. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This cohort study was conducted among mother-child dyads in the National Institutes of Health Environmental Influences on Child Health Outcomes Cohort, with infants conceived between 1998 and 2022. Associations of subfecundity and infertility treatment with neurodevelopmental outcomes were assessed among children ages 2 to 10 years. Data were analyzed from May 14, 2025, to March 31, 2026. EXPOSURE/UNASSIGNED:Subfecundity was defined as prior consultation for, treatment of, or diagnosis of infertility for either partner; at least 2 prior miscarriages; or ever having had unprotected heterosexual intercourse for 12 months without conceiving. Infertility treatment was categorized as in vitro fertilization (IVF) or non-IVF treatment. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Harmonized caregiver responses to the Strengths and Difficulties Questionnaire and the Child Behavior Checklist yielded continuous raw scores for externalizing and internalizing problems. The total raw Social Responsiveness Scale (SRS) score quantified autism-like symptoms. Caregivers reported physician diagnosis of autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD). RESULTS/UNASSIGNED:Among 15 382 mother-infant dyads, there were 14 191 unique maternal participants (mean [SD] age at delivery, 30.9 [5.33] years; 8780 parous participants [57.1%]). ASD and ADHD were diagnosed in 876 offspring (7.6%) and 819 offspring (7.1%), respectively. In generalized linear models, subfecundity was associated with higher externalizing problem and SRS scores among all pregnancies (externalizing problems: b = 0.47 [95% CI, 0.14-0.81]; SRS score: b = 1.08 [95% CI, 0.01-2.14]) and when restricted to natural conceptions (externalizing problems: b = 0.45 [95% CI, 0.07-0.83]; SRS score: b = 1.12 [95% CI, -0.09 to 2.34]). Offspring of parents with subfecundity had higher odds of ASD (overall: odds ratio [OR], 1.27 [95% CI, 1.03-1.57]; natural conceptions: OR, 1.31 [95% CI, 1.04-1.64]). Children conceived via non-IVF treatment had higher odds of ADHD compared with those conceived via natural conception with subfecundity (OR, 1.77 [95% CI, 1.16-2.68]) or without subfecundity (OR, 1.54 [95% CI, 1.05-2.25]). There were no significant associations for IVF treatment. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this large US cohort study, subfecundity was associated with elevated scores for caregiver-reported symptoms of behavioral problems and higher odds of ASD diagnosis, independent of infertility treatment. Non-IVF treatment was associated with ADHD, warranting further research into specific indications for treatment that may increase risk of offspring neurodevelopmental problems.

BACKGROUND/UNASSIGNED:Osteoporosis (OP) is a common comorbidity in patients undergoing total hip arthroplasty (THA) and is a known risk factor for poor postoperative outcomes such as periprosthetic fracture (PPF). The impact of preoperative OP medications in patients with OP undergoing THA remains unclear. This study aimed to compare THA outcomes by OP diagnosis and preoperative bone strengthening medication usage. METHODS/UNASSIGNED:This was a retrospective review of primary elective THAs from June 2011-January 2024. Patients were stratified by OP diagnosis and OP medication usage, then propensity matched in a 1:2:3 ratio by age, sex, body mass index, and comorbidities. The resulting cohorts: (1) OP and medication usage for at least 1 year preoperatively and within 7 years of the procedure (n = 296), (2) OP and no medication usage (n = 592), and (3) no diagnosis of OP and no medication usage (n = 888) were then compared for postoperative outcomes. RESULTS/UNASSIGNED:= .009). Of the 12 revisions due to periprosthetic femoral fracture in cohorts 1 and 2 combined, 11 (91.7%) occurred around an uncemented implant. CONCLUSIONS/UNASSIGNED:Osteoporotic patients on OP medications did not have improved outcomes after THA compared with nonmedicated osteoporotic patients or those without a diagnosis of OP. PPF in osteoporotic patients overwhelmingly occurred around uncemented femoral implants. Surgeons should use caution when operating on osteoporotic patients, regardless of utilization of preoperative medications, and strongly consider using cemented femoral implants to decrease the risk of PPF.

INTRODUCTION/BACKGROUND:The relationship between plasma phosphorylated tau 217 (p-Tau217) and domain-specific cognitive performance across race and ethnic groups remains unclear. METHODS: = 1032). RESULTS:-0.05 to -0.11). Associations were strongest in Non-Hispanic White (NHW), limited in NHB, and domain-specific in Hispanic groups. Matched analyses attenuated effects. DISCUSSION/CONCLUSIONS:Plasma p-Tau217 is associated with domain-specific cognitive performance in clinically unimpaired individuals, but these associations vary across racial and ethnic groups.

RATIONALE/BACKGROUND:Aggression is an innate social behavior prevalent across animal species. However, in modern human society, inter-personal aggression is considered disruptive and detrimental to both families and communities. Clinically, antipsychotics, which primarily target dopamine (DA) receptors, have been widely used to suppress hyper-aggression. However, the mechanisms underlying the effect of the antipsychotics remain incompletely understood. OBJECTIVES/OBJECTIVE:We reviewed key steps in brain DA synthesis and summarized genetic and pharmacological evidence supporting the role of the mesolimbic DA system in aggression. Next, we discussed recent circuit studies that elucidate the DA action in modulating aggression-related brain regions. These lines of evidence collectively suggest that DA acts on different brain regions to facilitate aggression and self-learning, and signals the valence of the fighting experience.