Faculty Bibliography

While prior research has explored the neurobiological mechanisms underlying adolescent school performance, these mechanisms remain poorly understood in college students. Impulsivity has been highlighted as a key factor affecting academic success; however, its influence on the relationship between school performance and brain structure remains underexplored. In this study, we used a sample of college students to investigate which gray matter volume (GMV) in brain regions was associated with grade point average (GPA), and whether impulsivity mediates these relationships. Our findings revealed correlations between GMV in the caudate nucleus (CN) and cerebellum with GPA. Increased CN was correlated with poorer GPA through higher impulsivity, whereas higher cerebellum was associated with better GPA through lower impulsivity. These results indicate that CN and cerebellum play crucial roles in school performance and associated impulsivity. Various interventions targeting impulsivity, such as therapy, counseling, and medication, could improve educational outcomes by addressing the underlying neurobiological factors.

BACKGROUND/UNASSIGNED:Magnetic resonance imaging (MRI) and electroencephalography (EEG) are valuable tools for studying neuroanatomical and electrophysiological features of early brain development. Studies implementing neuroimaging tools in low- and middle-income countries are still rare, and there is limited data on the acceptability of such tools among rural communities. The present study explores the perceptions, feasibility, and acceptability of introducing MRI and EEG for child development research in the rural Amhara region of Ethiopia. METHODS/UNASSIGNED:= 16). A semi-structured interview included four themes: (1) Baseline imaging knowledge, (2) Perceptions of MRI and EEG, (3) Facilitators and barriers to acceptability of MRI and EEG, and (4) Recommendations to improve MRI and EEG uptake. Interviews were conducted in Amharic, the local language. All interviews were transcribed verbatim to Amharic, translated into English, and double-coded. We used thematic analysis to organize data according to predefined and emerging themes. RESULTS/UNASSIGNED:Knowledge of MRI and EEG was limited, and none of the community members had previous experiences with either technology. Broadly, participants responded positively to our introductory videos showing MRI and EEG acquisition and expressed high levels of acceptability. However, participants reported concerns about possible harms related to radiation, electrical shock, and injury from MRI/EEG procedures. Those with lesser education were identified to be less accepting of MRI/EEG. In addition, several mothers expressed that consent from their husbands was necessary for their child's participation in neurodevelopmental research. Potential logistical barriers identified included transportation challenges to the neuroimaging study sites, especially for rural-dwelling families. Creating awareness, using explanatory videos, and engaging community members and clinicians were recommended to facilitate acceptance of EEG and MRI. CONCLUSION/UNASSIGNED:In this formative study, MRI and EEG were viewed as acceptable methods for assessing child neurodevelopment in rural areas of Ethiopia. Community members' and clinicians' views were impacted largely by social, religious, educational, and logistical aspects. Concerns related to MRI radiation, electrical shock, and injuries from EEG can be addressed through awareness creation and education. Engaging community leaders and healthcare providers is key to improving acceptability.

BACKGROUND AND OBJECTIVE/OBJECTIVE:Recent studies highlight an increase in pediatric mental health disorders, amplified by COVID-19. This study examines changes in mental health-related emergency department visits among New York City public school students across the pandemic timeline. METHODS:We employed logistic regression to examine changes in the probability of a student's emergency department visit being mental health-related, and as a secondary outcome, we analyzed the difference in same-day discharge rates between mental health-related visits and other visits. For this analysis, we used the New York City Student Population Health Registry to link public school students' records to emergency department visit data. RESULTS:No significant linear trends were observed in the average monthly probability of a mental health-related visit before March 2020. From March 2020 through June 2021 there was an increase for all groups except male elementary school students. Female middle and high school students experienced the largest increase (0.031 (CI = [0.027, 0.034])) compared to pre-pandemic (0.103 (CI = [0.103, 0.104])). Post-June 2021, all groups experienced a lower probability except for female middle and high school students, who had a 0.009 (CI = [0.007, 0.011]) higher probability than during the pandemic. Compared to the pre-pandemic period and non-mental health-related visits, a 0.043 (CI = [0.029, 0.057]) lower probability of same-day discharge was observed for mental health-related visits during the pandemic period. CONCLUSIONS:The COVID-19 pandemic correlated with a significant increase in mental health-related emergency department visits and longer stays, particularly among female middle and high school students.

INTRODUCTION/BACKGROUND:Underlying causes of Alzheimer's disease (AD) remain unknown, making it imperative to identify molecular mechanisms driving the pathobiology of AD onset and progression. METHODS:Laser capture microdissection was used to isolate layer III pyramidal neurons from post mortem human prefrontal cortex (Brodmann area 9). Single population RNA sequencing was conducted using tissue from subjects with no cognitive impairment (NCI), mild cognitive impairment (MCI), and AD. Differentially expressed genes (DEGs) were compared across groups. RESULTS:DEGs increased from prodromal (MCI vs. NCI) to progression (AD vs. MCI) to frank AD (AD vs. NCI). The majority of DEGs and pathways shared between prodromal and progression exhibited a change in the direction of dysregulation unlike pathways between progression and frank AD. DISCUSSION/CONCLUSIONS:Candidate genes and pathways were identified that demarcate early-stage AD onset from AD progression, providing a roadmap to study cortical cellular vulnerability and key targets for intervention at early stages of AD. HIGHLIGHTS/CONCLUSIONS:Pyramidal neuron differentially expressed genes (DEGs) are directionally divergent between prodromal, progression, and frank Alzheimer's disease (AD). Pyramidal neuron DEGs are directionally convergent between progression and frank AD. Dysfunctional bioenergetic pathways increased dysregulation as the AD spectrum progressed. Immune response pathways were more dysregulated in frank AD than prodromal stages. DEGs, = biological pathways, and interactomes demarcate specific stages across the AD spectrum.

BACKGROUND:fcMRI correlates of autism spectrum disorder (ASD) diagnosis and familial liability were studied in 24-month-olds at high (older affected sibling) and low familial likelihood for ASD. METHODS:fcMRI comparisons of high-familial-likelihood (HL) ASD-positive (HLP, N = 23) and ASD-negative (HLN, N = 91), and low-likelihood ASD-negative (LLN, N = 27) 24-month-olds from the Infant Brain Imaging Study (IBIS) Network were conducted, employing object oriented data analysis (OODA), support vector machine (SVM) classification, and network-level fcMRI enrichment analyses. RESULTS:OODA (alpha = 0.0167, 3 comparisons) revealed differences in HLP and LLN fcMRI matrices (p = 0.012), but none for HLP versus HLN (p = 0.047) nor HLN versus LLN (p = 0.225). SVM distinguished HLP from HLN (accuracy = 99%, PPV = 96%, NPV = 100%), based on connectivity involving many networks. SVM accurately classified (non-training) LLN subjects with 100% accuracy. Enrichment analyses identified a cross-group fcMRI difference in the posterior cingulate default mode network 1 (pcDMN1)- temporal default mode network (tDMN) pair (p = 0.0070). Functional connectivity for implicated connections in these networks was consistently lower in HLP and HLN than in LLN (p = 0.0461 and 0.0004). HLP did not differ from HLN (p = 0.2254). Secondary testing showed HL children with low ASD behaviors still differed from LLN (p = 0.0036). CONCLUSIONS:24-month-old high-familial-likelihood infants show reduced intra-DMN connectivity, a potential neural finding related to familial liability, while widely distributed functional connections correlate with ASD diagnosis.

BACKGROUND:Individuals with attention deficit hyperactivity disorder (ADHD) are at a higher risk of depression and lower quality of life (QoL); however, it is unclear whether disrupted sleep and circadian rhythms mediate this increased risk. OBJECTIVES/OBJECTIVE:We investigated whether disruption of self-reported sleep and circadian factors mediate the associations of ADHD traits with depression symptom severity and QoL. METHODS:1364 participants (mean: 51.86 (SD=0.37) years, 75% women) from a large-scale cross-sectional online survey (Netherlands Sleep Registry) completed a sociodemographic questionnaire, the Adult ADHD Rating Scale, Hospital Anxiety and Depression Scale, Satisfaction With Life Scale (SLS) and Cantril Ladder (CL) (QoL measures), Insomnia Severity Index, Pittsburgh Sleep Quality Index and Munich Chronotype Questionnaire. FINDINGS/RESULTS:Higher ADHD traits were significantly associated with depression symptom severity (p=0.03), lower QoL (p<0.001), insomnia severity (p<0.001), lower sleep quality (p<0.001) and later chronotype (p=0.01). No sleep or circadian factor significantly mediated the association of the severity of symptoms of ADHD and depression (all p>0.1). Conversely, only insomnia severity significantly mediated the association of ADHD traits and QoL (SLS: standardised β=-0.10, 95% CI (-0.12 to -0.04); CL: standardised β=0.103, 95% CI (0.04 to 0.16)). CONCLUSION/CONCLUSIONS:ADHD traits were associated with lower QoL and it was partially mediated by insomnia severity. Future studies targeting insomnia complaints in this population may help mitigate their depression complaints and improve their QoL. CLINICAL IMPLICATIONS/CONCLUSIONS:Our results may help current clinical guidelines that do not typically link sleep/circadian complaints to QoL in ADHD assessment.

Preterm birth can significantly impact cognitive development, particularly executive functions (EF). This study investigated hot (with emotional/motivational aspects) and cool (purely neutral/cognitive) EF trajectories in preterm and full-term children, examining brain-behavior relationships. It included 3508 participants aged 9-10 years (mean age 10.0 years) at baseline from the Adolescent Brain and Cognitive Development (ABCD®) study, evenly split between preterm and full-term births (54.36 % males; 1.05 % Asian American, 10.69 % Black, 15.68 % Hispanic, 61.57 % White, 11.09 % other). Participants were followed for 4 years, completing MRI scans and a cool EF task at baseline and at the 2-year follow-up, as well as hot/cool and hot EF tasks at the 1- and 3-year follow-ups. Linear mixed models showed varying effects of preterm birth across the different EF tasks. Specifically, preterm children showed persistent cool EF deficits and a catch-up pattern for hot EF, while performance on the hot/cool task showed no association with preterm birth. Brain-behavior bivariate latent change score analyses identified distinct bidirectional relationships in specific regions, suggesting altered cognitive-brain maturation interactions in preterm children. These findings highlight the complex nature of EF development following preterm birth: while cool EF deficits persist, hot EF shows catch-up growth in preterm children during early adolescence. This emphasizes the need for tailored interventions and long-term follow-up in this population.

BACKGROUND/OBJECTIVES/OBJECTIVE:Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive malignancies with a challenging prognosis, especially for patients with Neurofibromatosis type 1 (NF1). Their low incidence necessitates comprehensive studies to investigate the survival outcome. METHODS:We conducted a systematic review and meta-analysis, including data from 16 studies and 4265 patients, to explore surgical outcomes and survival rates, focusing on time-related outcomes, including overall survival (OS), progression-free survival (PFS), and recurrence rate. RESULTS:The analysis revealed that the OS rate was 86% [95% CI: 75-97%] at 1 year, decreasing to 60% [95% CI: 45-75%] at 3 years, and further declining to 47% [95% CI: 35-58%] by 5 years. For PFS, the 1-year rate was 61% [95% CI: 25-98%], which remained similar at 62% [95% CI: 35-89%] for 3 and 5 years. In NF1-associated MPNSTs, the 1-year OS was relatively high at 93% [95% CI: 83-100%], but it dropped to 68% [95% CI: 53-84%] at 3 years and further to 50% [95% CI: 31-68%] at 5 years. Additionally, the hazard ratio indicated a 38% lower survival rate in NF1 patients than those with sporadic MPNSTs when data were presented in the same study. Recurrence rates were high, with 56% of patients experiencing a relapse, primarily as local recurrences (70.6%). Mortality was significant, with over 50% of patients dying within an average follow-up period of 33.45 months. CONCLUSIONS:MPNSTs, particularly in NF1 patients, are associated with poor prognosis and high recurrence rates. These results underline the necessity of targeted therapeutic strategies and improved programs for screening, mainly through a multidisciplinary approach to optimize management.

The subgenual anterior cingulate cortex (sgACC) plays a central role in the pathophysiology of major depressive disorder (MDD). Its functional interactive profile with the left dorsal lateral prefrontal cortex (DLPFC) is associated with transcranial magnetic stimulation (TMS) treatment outcomes. Previous research on sgACC functional connectivity (FC) in MDD has yielded inconsistent results, partly due to small sample sizes and limited statistical power. Furthermore, calculating sgACC-FC to target TMS individually is challenging. We used a large multi-site cross-sectional sample (1660 patients with MDD vs. 1341 healthy controls) from Phase II of the Depression Imaging REsearch ConsorTium (DIRECT) to systematically delineate case-control difference maps of sgACC-FC. We explored the potential impact of group-level abnormality profiles on TMS target localization and clinical efficacy. Next, we developed an MDD big data-guided, individualized TMS targeting algorithm to integrate group-level statistical maps with individual-level brain activity to individually localize TMS targets. We found enhanced sgACC-DLPFC FC in patients with MDD compared with healthy controls (HC). These group differences altered the position of the sgACC anti-correlation peak in the left DLPFC. We showed that the magnitude of case-control differences in the sgACC-FC was related to clinical improvement in two independent clinical samples. This targeting algorithm may generate targets demonstrating stronger associations with clinical efficiency than group-level targets. We reliably delineated MDD-related abnormalities of sgACC-FC profiles in a large, independently ascertained sample and demonstrated the potential impact of such case-control differences on FC-guided localization of TMS targets.