Faculty Bibliography

The human brain is a highly dynamic system with non-stationary neural activity and rapidly-changing neural interaction. Resting-state dynamic functional connectivity (dFC) has been widely studied during recent years, and the emerging aberrant dFC patterns have been identified as important features of many mental disorders such as schizophrenia (SZ). However, only focusing on the time-varying patterns in FC is not enough, since the local neural activity itself (in contrast to the inter-connectivity) is also found to be highly fluctuating from research using high-temporal-resolution imaging techniques. Exploring the time-varying patterns in brain activity and their relationships with time-varying brain connectivity is important for advancing our understanding of the co-evolutionary property of brain network and the underlying mechanism of brain dynamics. In this study, we introduced a framework for characterizing time-varying brain activity and exploring its associations with time-varying brain connectivity, and applied this framework to a resting-state fMRI dataset including 151 SZ patients and 163 age- and gender matched healthy controls (HCs). In this framework, 48 brain regions were first identified as intrinsic connectivity networks (ICNs) using group independent component analysis (GICA). A sliding window approach was then adopted for the estimation of dynamic amplitude of low-frequency fluctuation (dALFF) and dFC, which were used to measure time-varying brain activity and time-varying brain connectivity respectively. The dALFF was further clustered into six reoccurring states by the k-means clustering method and the group difference in occurrences of dALFF states was explored. Lastly, correlation coefficients between dALFF and dFC were calculated and the group difference in these dALFF-dFC correlations was explored. Our results suggested that 1) ALFF of brain regions was highly fluctuating during the resting-state and such dynamic patterns are altered in SZ, 2) dALFF and dFC were correlated in time and their correlations are altered in SZ. The overall results support and expand prior work on abnormalities of brain activity, static FC (sFC) and dFC in SZ, and provide new evidence on aberrant time-varying brain activity and its associations with brain connectivity in SZ, which might underscore the disrupted brain cognitive functions in this mental disorder.

Non-human primate neuroimaging is a rapidly growing area of research that promises to transform and scale translational and cross-species comparative neuroscience. Unfortunately, the technological and methodological advances of the past two decades have outpaced the accrual of data, which is particularly challenging given the relatively few centers that have the necessary facilities and capabilities. The PRIMatE Data Exchange (PRIME-DE) addresses this challenge by aggregating independently acquired non-human primate magnetic resonance imaging (MRI) datasets and openly sharing them via the International Neuroimaging Data-sharing Initiative (INDI). Here, we present the rationale, design, and procedures for the PRIME-DE consortium, as well as the initial release, consisting of 25 independent data collections aggregated across 22 sites (total = 217 non-human primates). We also outline the unique pitfalls and challenges that should be considered in the analysis of non-human primate MRI datasets, including providing automated quality assessment of the contributed datasets.

OBJECTIVE:/UNASSIGNED:The authors examined the impact of a Web-based shared decision-making application, MyCHOIS-CommonGround, on ongoing outpatient mental health treatment engagement (all users) and antipsychotic medication adherence (users with schizophrenia). METHODS:/UNASSIGNED:An intervention study was conducted by comparing Medicaid-enrolled MyCHOIS-CommonGround users in 12 participating mental health clinics (N=472) with propensity score-matched adults receiving services in nonparticipating clinics (N=944). Medicaid claims were used to assess ongoing treatment engagement and antipsychotic adherence (among individuals with schizophrenia) one year prior to and after entry into the cohort. Multilevel linear models were conducted to estimate the effects of the MyCHOIS-CommonGround program over time. RESULTS:/UNASSIGNED:No differences during the baseline year were found between the MyCHOIS-CommonGround group and the matched control group on demographic, diagnostic, or service use characteristics. At one-year follow-up, engagement in outpatient mental health services was significantly higher for MyCHOIS-CommonGround users than for the control group (months with a service, 8.54±.22 versus 6.95±.15; β=1.40, p<.001). Among individuals with schizophrenia, antipsychotic medication adherence was also higher during the follow-up year among MyCHOIS-CommonGround users compared with the control group (proportion of days covered by medication, .78±.04 versus .69±.03; β=.06, p<.01). CONCLUSIONS:/UNASSIGNED:These findings provide new evidence that shared decision-making tools may promote ongoing mental health treatment engagement for individuals with serious mental illness and improved antipsychotic medication adherence for those with schizophrenia.

Post-traumatic stress disorder (PTSD) is an important and often neglected comorbidity of pregnancy; left untreated, it can lead to serious health complications for the mother and developing fetus. Structured interviews were conducted to identify risk factors of PTSD among culturally diverse women with depressive symptomatology receiving perinatal services at community obstetric/gynecologic clinics. Women abused as adults, with two or more instances of trauma, greater trauma severity, insomnia, and low social support were more likely to present perinatal PTSD symptoms. Perinatal PTSD is prevalent and has the potential for chronicity. It is imperative healthcare providers recognize salient risk factors and integrate culturally sensitive screening, appropriate referral, and treatment services for perinatal PTSD.

Although infants learn and remember, they rapidly forget, a phenomenon known as infantile amnesia. While myriad mechanisms impact this rapid forgetting, the molecular events supporting memory maintenance have yet to be explored. To explore memory mechanisms across development, we used amygdala-dependent odor-shock conditioning and focused on mechanisms important in adult memory, the AMPA receptor subunits GluA1/2 and upstream protein kinases important for trafficking AMPAR, protein kinase M zeta (PKMζ) and iota/lambda (PKCι/λ). We use odor-shock conditioning in infant rats because it is late-developing (postnatal day, PN10) and can be modulated by corticosterone during a sensitive period in early life. Our results show that memory-related molecules did not change in pups too young to learn threat (PN8) but were activated in pups old enough to learn (PN12), with increased PKMζ-PKCι/λ and GluA2 similar to that observed in adult memory, but with an uncharacteristic decrease in GluA1. This molecular signature and behavioral avoidance of the conditioned odor was recapitulated in PN8 pups injected with CORT before conditioning to precociously induce learning. Blocking learning via CORT inhibition in older pups (PN12) blocked the expression of these molecules. PN16 pups showed a more adult-like molecular cascade of increased PKMζ-PKCι/λ and GluA1-2. Finally, at all ages, zeta inhibitory peptide (ZIP) infusions into the amygdala 24 hr after conditioning blocked memory. Together, these results identify unique features of memory processes across early development: AMPAR subunits GluA1/2 and PKC isoform expression are differentially used, which may contribute to mechanisms of early life forgetting.

OBJECTIVE:The majority of children who initially engage in mental health treatment in the United States drop out prematurely, a problem further exacerbated among children living in poverty. This study examined the relationships between sociodemographic characteristics, barriers to treatment use, and session attendance. METHODS:Data were obtained from participants (N=225) in the 4R2S field trial. Barriers were measured using the Kazdin Barriers to Treatment Participation Scale. RESULTS:Barriers endorsed by families attending less treatment primarily aligned with practical rather than perceptual obstacles. Critical events linked to lower attendance included moving too far away from the clinic, a job change, and a child's moving out of the home. CONCLUSIONS:Child mental health programs serving low-income families may consider structural modifications to allow for greater family support as well as flexibility in treatment delivery by leveraging technology. Future research is needed to evaluate barriers to treatment and alternate modalities in relation to service utilization.

OBJECTIVE:Most studies of pediatric bipolar disorder (BP) combine youth who have manic symptoms, but do not meet criteria for BP I/II, into one "not otherwise specified" (NOS) group. Consequently, little is known about how youth with cyclothymic disorder (CycD) differ from youth with BP NOS. The objective of this study was to determine whether youth with a research diagnosis of CycD (RDCyc) differ from youth with operationalized BP NOS. METHOD:Participants from the Course and Outcome of Bipolar Youth study were evaluated to determine whether they met RDCyc criteria. Characteristics of RDCyc youth and BP NOS youth were compared at baseline, and over eight-years follow-up. RESULTS:Of 154 youth (average age 11.96 (3.3), 42% female), 29 met RDCyc criteria. RDCyc youth were younger (p = .04) at baseline. Over follow-up, RDCyc youth were more likely to have a disruptive behavior disorder (p = .01), and were more likely to experience irritability (p = .03), mood reactivity (p = .02), and rejection sensitivity (p = .03). BP NOS youth were more likely to develop hypomania (p = .02), or depression (p = .02), and tended to have mood episodes earlier in the eight-year follow-up period. LIMITATIONS:RDCyc diagnoses were made retrospectively and followed stringent criteria, which may highlight differences that, under typical clinical conditions and more vague criteria, would not be evident. CONCLUSION:There were few differences between RDCyc and BP NOS youth. However, the ways in which the groups diverged could have implications; chronic subsyndromal mood symptoms may portend a severe, but ultimately non-bipolar, course. Longer follow-up is necessary to determine the trajectory and outcomes of CycD symptoms.

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders with multiple biological etiologies and highly variable symptoms. Using a novel analytical framework that integrates cortex-wide MRI markers of vertical (i.e., thickness, tissue contrast) and horizontal (i.e., surface area, geodesic distance) cortical organization, we could show that a large multi-centric cohort of individuals with ASD falls into 3 distinctive anatomical subtypes (ASD-I: cortical thickening, increased surface area, tissue blurring; ASD-II: cortical thinning, decreased distance; ASD-III: increased distance). Bootstrap analysis indicated a high consistency of these biotypes across thousands of simulations, while analysis of behavioral phenotypes and resting-state fMRI showed differential symptom load (i.e., Autism Diagnostic Observation Schedule; ADOS) and instrinsic connectivity anomalies in communication and social-cognition networks. Notably, subtyping improved supervised learning approaches predicting ADOS score in single subjects, with significantly increased performance compared to a subtype-blind approach. The existence of different subtypes may reconcile previous results so far not converging on a consistent pattern of anatomical anomalies in autism, and possibly relate the presence of diverging corticogenic and maturational anomalies. The high accuracy for symptom severity prediction indicates benefits of MRI biotyping for personalized diagnostics and may guide the development of targeted therapeutic strategies.

Please note that following publication of the original article [1], one of the authors has flagged that the abbreviations section lists "BRIC" as "Britain, Russia, India and China".

New York City (NYC) public hospitals recently mandated that all pregnant women be screened for depression, but no funds were allocated for screening or care coordination/treatment, and research suggests that unfunded mandates are not likely to be successful. To address this, we implemented an on-site depression prevention intervention (NYC ROSE) for positive depression screens among pregnant, mostly Black and Hispanic, lower-income women in one public hospital. In this paper, we used Aarons' implementation model to describe the successes and challenges of screening and intervention. Patient tracking sheets and electronic medical records were abstracted. Key informant interviews and an informal focus group were conducted, and staff observations were reviewed; common implementation themes were identified and fit into Aarons' model. We found that a lack of funding and staff training, which led to minimal psychoeducation for patients, were outer context factors that may have made depression screening difficult, screening results unreliable, and NYC ROSE enrollment challenging. Although leadership agreed to implement NYC ROSE, early involvement of all levels of staff and patients would have better informed important inner context factors, like workflow and logistical/practical challenges. There was also a mismatch between the treatment model and the population being served; patients often lived too far away to receive additional services on site, and economic issues were often a higher priority than mental health services. Screening and interventions for perinatal depression are essential for optimal family health, and a detailed, thoughtful and funded approach can help ensure effectiveness of such efforts.