Faculty Bibliography

The field of adult neuroimaging relies on well-established principles in research design, imaging sequences, processing pipelines, as well as safety and data collection protocols. The field of infant magnetic resonance imaging, by comparison, is a young field with tremendous scientific potential but continuously evolving standards. The present article aims to initiate a constructive dialog between researchers who grapple with the challenges and inherent limitations of a nascent field and reviewers who evaluate their work. We address 20 questions that researchers commonly receive from research ethics boards, grant, and manuscript reviewers related to infant neuroimaging data collection, safety protocols, study planning, imaging sequences, decisions related to software and hardware, and data processing and sharing, while acknowledging both the accomplishments of the field and areas of much needed future advancements. This article reflects the cumulative knowledge of experts in the FIT'NG community and can act as a resource for both researchers and reviewers alike seeking a deeper understanding of the standards and tradeoffs involved in infant neuroimaging.

Intrahippocampal kainic acid (IHKA) has been widely implemented to simulate temporal lobe epilepsy (TLE), but evidence of robust seizures is usually limited. To resolve this problem, we slightly modified previous methods and show robust seizures are common and frequent in both male and female mice. We employed continuous wideband video-EEG monitoring from 4 recording sites to best demonstrate the seizures. We found many more convulsive seizures than most studies have reported. Mortality was low. Analysis of convulsive seizures at 2-4 and 10-12 wks post-IHKA showed a robust frequency (2-4 per day on average) and duration (typically 20-30 s) at each time. Comparison of the two timepoints showed that seizure burden became more severe in approximately 50% of the animals. We show that almost all convulsive seizures could be characterized as either low-voltage fast or hypersynchronous onset seizures, which has not been reported in a mouse model of epilepsy and is important because these seizure types are found in humans. In addition, we report that high frequency oscillations (>250 Hz) occur, resembling findings from IHKA in rats and TLE patients. Pathology in the hippocampus at the site of IHKA injection was similar to mesial temporal lobe sclerosis and reduced contralaterally. In summary, our methods produce a model of TLE in mice with robust convulsive seizures, and there is variable progression. HFOs are robust also, and seizures have onset patterns and pathology like human TLE. SIGNIFICANCE: Although the IHKA model has been widely used in mice for epilepsy research, there is variation in outcomes, with many studies showing few robust seizures long-term, especially convulsive seizures. We present an implementation of the IHKA model with frequent convulsive seizures that are robust, meaning they are >10 s and associated with complex high frequency rhythmic activity recorded from 2 hippocampal and 2 cortical sites. Seizure onset patterns usually matched the low-voltage fast and hypersynchronous seizures in TLE. Importantly, there is low mortality, and both sexes can be used. We believe our results will advance the ability to use the IHKA model of TLE in mice. The results also have important implications for our understanding of HFOs, progression, and other topics of broad interest to the epilepsy research community. Finally, the results have implications for preclinical drug screening because seizure frequency increased in approximately half of the mice after a 6 wk. interval, suggesting that the typical 2 wk. period for monitoring seizure frequency is insufficient.

OBJECTIVE:This study aimed to characterize suicide risk screening results for youth in pediatric ambulatory subspecialty clinics. METHOD/METHODS:The Ask Suicide-Screening Questions was administered to patients ages 9-24 years in 12 subspecialty clinics to assess suicide risk, determined by suicide ideation/behavior. The SAMSHA-HRSA standard framework for integrated health was used to categorize each clinic's level of behavioral health integration. RESULTS:6365 patients completed 7440 suicide risk screens; 6.2% of patients screened positive at their initial screen and 4.1% at subsequent annual screens. There was no dose-response pattern between increasing level of integration and decreasing likelihood of a positive suicide screen. Youth identifying as gender expansive were 3.1 times (95% CI [2.0, 4.9]) more likely to screen positive as compared to cisgender youth, adjusted for age, gender, race/ethnicity, screen type, year, and clinic integration level. CONCLUSION/CONCLUSIONS:Results surrounding disparities in suicide risk based on gender identity underscore the importance of further investigating how to optimally identify and manage high-risk, often understudied youth at suicide risk.

The impact of COVID-19-related stress on perinatal women is of heightened public health concern given the established intergenerational impact of maternal stress-exposure on infants and fetuses. There is urgent need to characterize the coping styles associated with adverse psychosocial outcomes in perinatal women during the COVID-19 pandemic to help mitigate the potential for lasting sequelae on both mothers and infants. This study uses a data-driven approach to identify the patterns of behavioral coping strategies that associate with maternal psychosocial distress during the COVID-19 pandemic in a large multicenter sample of pregnant women (N = 2876) and postpartum women (N = 1536). Data was collected from 9 states across the United States from March to October 2020. Women reported behaviors they were engaging in to manage pandemic-related stress, symptoms of depression, anxiety and global psychological distress, as well as changes in energy levels, sleep quality and stress levels. Using latent profile analysis, we identified four behavioral phenotypes of coping strategies. Critically, phenotypes with high levels of passive coping strategies (increased screen time, social media, and intake of comfort foods) were associated with elevated symptoms of depression, anxiety, and global psychological distress, as well as worsening stress and energy levels, relative to other coping phenotypes. In contrast, phenotypes with high levels of active coping strategies (social support, and self-care) were associated with greater resiliency relative to other phenotypes. The identification of these widespread coping phenotypes reveals novel behavioral patterns associated with risk and resiliency to pandemic-related stress in perinatal women. These findings may contribute to early identification of women at risk for poor long-term outcomes and indicate malleable targets for interventions aimed at mitigating lasting sequelae on women and children during the COVID-19 pandemic.

Prenatal nutrition may significantly impact brain aging. Results from the Dutch Famine Birth Cohort indicated that prenatal undernutrition is negatively associated with cognition, brain volumes, perfusion and structural brain aging in late life, predominantly in men. This study investigates the association between prenatal undernutrition and late-life functional brain network connectivity. In an exploratory resting-state functional magnetic resonance imaging study of 112 participants from the Dutch Famine Birth Cohort, we investigated whether the within- and between-network functional connectivity of the default mode network, salience network and central executive network differ at age 68 in men (N = 49) and women (N = 63) either exposed or unexposed to undernutrition in early gestation. Additionally, we explored sex-specific effects. Compared to unexposed participants, exposed participants revealed multiple clusters of different functional connectivity within and between the three networks studied. Sex-specific analyses suggested a pattern of network desegregation fitting with brain aging in men and a more diffuse pattern of group differences in women. This study demonstrates that associations between prenatal undernutrition and brain network functional connectivity extend late into life.

Irritability, characterized by anger in response to frustration, is normative in childhood. While children typically show a decline in irritability from toddlerhood to school age, elevated irritability throughout childhood may predict later psychopathology. The current study (n = 78) examined associations between trajectories of irritability in early childhood (ages 2-7) and irritability in adolescence (age 12) and tested whether these associations are moderated by parenting behaviors. Results indicate that negative emotion socialization moderated trajectories of irritability - relative to children with low stable irritability, children who exhibited high stable irritability in early childhood and who had parents that exhibited greater negative emotion socialization behaviors had higher irritability in adolescence. Further, negative parental control behavior moderated trajectories of irritability - relative to children with low stable irritability, children who had high decreasing irritability in early childhood and who had parents who exhibited greater negative control behaviors had higher irritability in adolescence. In contrast, positive emotion socialization and control behaviors did not moderate the relations between early childhood irritability and later irritability in adolescence. These results suggest that both irritability in early childhood and negative parenting behaviors may jointly influence irritability in adolescence. The current study underscores the significance of negative parenting behaviors and could inform treatment.

BACKGROUND:Attention-deficit/hyperactivity disorder (ADHD) has been associated with reduced resting state connectivity in the core subsystem of the default mode network (DMN; medial prefrontal cortex - posterior cingulate cortex). However, the neuropsychological consequences of this hypoconnectivity remain to be determined. Building on recent theoretical models of DMN function, we tested the association between DMN hypo-connectivity and three neuropsychological processes previously implicated in ADHD: (i) excessive task-unrelated spontaneous thought (i.e., mind-wandering); (ii) sub-optimal decision-making due to exaggerated temporal discounting; and (iii) delay aversion - a heightened emotional response to the imposition or experience of delay. METHODS:Twenty male adolescents with a clinical diagnosis of ADHD and 18 typically developing adolescents (all aged 11-16 years) underwent a resting-state fMRI scan to assess DMN connectivity. An experimental paradigm was used to assess temporal discounting and self-report questionnaires were used to measure mind wandering and delay aversion. RESULTS:ADHD was significantly associated with DMN hypo-connectivity specifically in the core subsystem, elevated levels of mind-wandering, delay aversion, and temporal discounting. Mediation analysis suggested that DMN hypoconnectivity mediated the link between ADHD and delay aversion. CONCLUSION/CONCLUSIONS:The results provide initial evidence that disturbances in the DMN may impair ability to regulate delay-related negative affect in adolescents with ADHD.

BACKGROUND:Hikikomori is a form of severe social withdrawal that is particularly prevalent in Japan. Social media posts offer insight into public perceptions of mental health conditions and may also inform strategies to identify, engage, and support hard-to-reach patient populations such as individuals affected by hikikomori. OBJECTIVE:In this study, we seek to identify the types of content on Twitter related to hikikomori in the Japanese language and to assess Twitter users' engagement with that content. METHODS:We conducted a mixed methods analysis of a random sample of 4940 Japanese tweets from February to August 2018 using a hashtag (#hikikomori). Qualitative content analysis included examination of the text of each tweet, development of a codebook, and categorization of tweets into relevant codes. For quantitative analysis (n=4859 tweets), we used bivariate and multivariate logistic regression models, adjusted for multiple comparisons, and estimated the predicted probabilities of tweets receiving engagement (likes or retweets). RESULTS:Our content analysis identified 9 codes relevant to tweets about hikikomori: personal anecdotes, social support, marketing, advice, stigma, educational opportunities, refuge (ibasho), employment opportunities, and medicine and science. Tweets about personal anecdotes were the most common (present in 2747/4859, 56.53% of the tweets), followed by social support (902/4859, 18.56%) and marketing (624/4859, 12.84%). In the adjusted models, tweets coded as stigma had a lower predicted probability of likes (-33 percentage points, 95% CI -42 to -23 percentage points; P<.001) and retweets (-11 percentage points, 95% CI -18 to -4 percentage points; P<.001), personal anecdotes had a lower predicted probability of retweets (-8 percentage points, 95% CI -14 to -3 percentage points; P=.002), marketing had a lower predicted probability of likes (-13 percentage points, 95% CI -21 to -6 percentage points; P<.001), and social support had a higher predicted probability of retweets (+15 percentage points, 95% CI 6-24 percentage points; P=.001), compared with all tweets without each of these codes. CONCLUSIONS:Japanese tweets about hikikomori reflect a unique array of topics, many of which have not been identified in prior research and vary in their likelihood of receiving engagement. Tweets often contain personal stories of hikikomori, suggesting the potential to identify individuals with hikikomori through Twitter.

Across species and ages, planning multi-step actions is a hallmark of intelligence and critical for survival. Traditionally, researchers adopt a "top-down" approach to action planning by focusing on the ability to create an internal representation of the world that guides the next step in a multi-step action. However, a top-down approach does not inform on underlying mechanisms, so researchers can only speculate about how and why improvements in planning occur. The current study takes a "bottom-up" approach by testing developmental changes in the real-time, moment-to-moment interplay among perceptual, neural, and motor components of action planning using simultaneous video, motion-tracking, head-mounted eye tracking, and electroencephalography (EEG). Preschoolers (n = 32) and adults (n = 22) grasped a hammer with their dominant hand to pound a peg when the hammer handle pointed in different directions. When the handle pointed toward their non-dominant hand, younger children ("nonadaptive planners") used a habitual overhand grip that interfered with wielding the hammer, whereas adults and older children ("adaptive planners") used an adaptive underhand grip. Adaptive and nonadaptive children differed in when and where they directed their gaze to obtain visual information, neural activation of the motor system before reaching, and straightness of their reach trajectories. Nonadaptive children immediately used a habitual overhand grip before gathering visual information, leaving insufficient time to form a plan before acting. Our novel bottom-up approach transcends mere speculation by providing converging evidence that the development of action planning depends on a real-time "tug of war" between habits and information gathering and processing.

Infant and toddler MRI enables unprecedented insight into the developing brain. However, consensus about optimal data collection practices is lacking, which slows growth of the field and impedes replication efforts. The goal of this study was to collect systematic data across a large number of infant/toddler research laboratories to better understand preferred practices. Survey data addressed MRI acquisition strategies, scan success rates, visit preparations, scanning protocols, accommodations for families, study design, and policies regarding incidental findings. Respondents had on average 8 years' experience in early life neuroimaging and represented more than fifty research laboratories. Areas of consensus across labs included higher success rates among newborns compared to older infants or toddlers, high rates of data loss across age groups, endorsement of multiple layers of hearing protection, and age-specific scan preparation and participant accommodation. Researchers remain divided on decisions in longitudinal study design and practices regarding incidental findings. This study summarizes practices honed over years of work by a large collection of scientists, which may serve as an important resource for those new to the field. The ability to reference data about best practices facilitates future harmonization, data sharing, and reproducibility, all of which advance this important frontier in developmental science.