Faculty Bibliography

BACKGROUND:Freezing of gait (FOG) is a common gait disorder that often accompanies Parkinson's disease (PD). The current understanding of brain functional organization in FOG was built on the assumption that the functional connectivity (FC) of networks is static, but FC changes dynamically over time. We aimed to characterize the dynamic functional connectivity (DFC) in patients with FOG based on high temporal-resolution functional MRI (fMRI). METHODS:Eighty-seven PD patients, including 29 with FOG and 58 without FOG, and 32 healthy controls underwent resting-state fMRI. Spatial independent component analysis and a sliding-window approach were used to estimate DFC. RESULTS:Four patterns of structured FC 'states' were identified: a frequent and sparsely connected network (State I), a less frequent but highly synchronized network (State IV), and two states with opposite connecting directions between the visual network and the sensorimotor network (positively connected in State II, negatively connected in State III). Compared with the non-FOG group, patients with FOG spent significantly less time in State II and more time in State III. The longer dwell time in State III was correlated with more severe FOG symptoms. The fractional window of State III tended to correlate to visual-spatial and executive dysfunction in FOG. Moreover, fewer transitions between brain states and lower variability in local efficiency were observed in FOG, suggesting a relatively 'rigid' brain. CONCLUSIONS:This study highlights how visuomotor network dynamics are related to the presence and severity of FOG in PD patients, which provides new insights into understanding the pathophysiological mechanisms that underly FOG. © 2025 International Parkinson and Movement Disorder Society.

BACKGROUND:To progress adolescent mental health research beyond our present achievements-a complex account of brain and environmental risk factors without understanding neurobiological embedding in the environment-we need methods to uncover relationships between the developing brain and real-world environmental experiences. METHODS:We investigated associations between brain function, environments, and emotional and behavioral problems using participants from the Adolescent Brain Cognitive Development (ABCD) Study (n = 2401 female). We applied manifold learning, a promising technique for uncovering latent structure from high-dimensional biomedical data such as functional magnetic resonance imaging. Specifically, we developed exogenous PHATE (potential of heat-diffusion for affinity-based trajectory embedding) (E-PHATE) to model brain-environment interactions. We used E-PHATE embeddings of participants' brain activation during emotional and cognitive processing tasks to predict individual differences in cognition and emotional and behavioral problems both cross-sectionally and longitudinally. RESULTS:E-PHATE embeddings of participants' brain activation and environments at baseline showed moderate-to-large associations with total, externalizing, and internalizing problems at baseline, across several subcortical regions and large-scale cortical networks, compared with the zero-to-small effects achieved by voxelwise data or common low-dimensional embedding methods. E-PHATE embeddings of the brain and environment at baseline were also related to emotional and behavioral problems 2 years later. These longitudinal predictions showed a consistent moderate effect in the frontoparietal and attention networks. CONCLUSIONS:The embedding of the adolescent brain in the environment yields enriched insight into emotional and behavioral problems. Using E-PHATE, we demonstrated how the harmonization of cutting-edge computational methods with longstanding developmental theories advances the detection and prediction of adolescent emotional and behavioral problems.

Firesetting behaviors are extremely dangerous not only to the individual but to society as one fire has the potential to destroy property and lead to serious injury or death. Youth firesetting behaviors are often under-assessed in psychiatric care settings intakes due to their relatively low base-rate and only are a part of a practitioner’s conceptualization when these behaviors are part of their presentation to an emergency room. Acute psychiatric care settings are well-equipped to assess and treat many highly dangerous behaviors such as active suicidal and homicidal ideation, as well as non-suicidal self-injury. However, youth firesetting is without a formal and directed plan on how to assess the risk of these behaviors, conceptualize, and intervene effectively. A case study of a 16-year-old multiracial male named “Luis”, who was psychiatrically hospitalized on an adolescent inpatient unit following multiple firesetting behaviors in the community, is used is to show the importance of multiinterdisciplinary collaboration between mental health providers and local fire safety programs. In addition, we will offer several recommendations to providers in the assessment and treatment related to juvenile who fireset

Firesetting behaviors are extremely dangerous not only to the individual but to society as one fire has the potential to destroy property and lead to serious injury or death. Youth firesetting behaviors are often under-assessed in psychiatric care settings intakes due to their relatively low base-rate and only are a part of a practitioner’s conceptualization when these behaviors are part of their presentation to an emergency room. Acute psychiatric care settings are well-equipped to assess and treat many highly dangerous behaviors such as active suicidal and homicidal ideation, as well as non-suicidal self-injury. However, youth firesetting is without a formal and directed plan on how to assess the risk of these behaviors, conceptualize, and intervene effectively. A case study of a 16-year-old multiracial male named “Luis”, who was psychiatrically hospitalized on an adolescent inpatient unit following multiple firesetting behaviors in the community, is used is to show the importance of multiinterdisciplinary collaboration between mental health providers and local fire safety programs. In addition, we will offer several recommendations to providers in the assessment and treatment related to juvenile who fireset

Although numerous studies have examined how child demographic characteristics may impact ratings of attention-deficit/hyperactivity disorder (ADHD) symptoms, there is limited research on how these factors are related to ratings of impairment. This study examined child characteristics (assigned sex, age, race, ethnicity) that may affect parent and teacher ratings of ADHD symptom-related impairments in relationships with family and/or teacher, peer relationships, behavior disruption, academic impairment, homework performance, and self-esteem. The study was conducted using independent U.S. national samples of parents (n = 2,075) and teachers (n = 1,070). Informants rated impairments related to inattention and hyperactivity-impulsivity using the ADHD Rating Scale-5. Rasch analyses were used to examine differential item functioning in relation to child characteristics. Separate analyses were conducted for inattention- and hyperactivity-impulsivity-related impairment for both the parent and teacher samples. For teacher ratings, only two items (behavior disruption, homework impairment) demonstrated differential item functioning with intermediate or large effect sizes (≥ .426 logits) in relation to any child characteristic; whereas for parent ratings, all six items displayed differential item functioning with at least intermediate effect sizes in relation to one or more child characteristics. The findings indicated several areas in which child characteristics may have an impact on ratings of ADHD-related impairment, particularly based on parent ratings, which have potential implications for the diagnostic assessment of ADHD and highlight the need for further research. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

Accumulating evidence from neuroimaging studies has implicated widespread disruptions in brain connectivity in autism spectrum disorder (ASD), with altered connectivity patterns reported as early as infancy. However, it remains unexplored whether functional connectivity differences are evident prior to birth in the brain of fetuses who will later exhibit autistic traits in early childhood. In this study, we leveraged a longitudinal sample of 62 children with both quality-assured fetal brain resting-state MRI data and a parent-report measure of autistic traits at age 3 years. Enrichment analysis was employed to identify network pairs significantly correlated with autistic traits. Specificity analysis was conducted by additionally controlling for other childhood psychopathology. Our results demonstrated significant correlations between autistic traits and functional connectivity in the cingulate-left temporal and right prefrontal-left operculum network pairs in both the primary and specificity analyses. Visual network connectivity with prefrontal and opercular regions was also implicated. These network pairs demonstrated positive associations with autistic traits, indicating that stronger connectivity between these network pairs was associated with higher autistic traits. In contrast, weaker cerebellum-right operculum connectivity was associated with higher autistic traits, uniquely in the specificity analysis. This study provides the first in vivo evidence prospectively linking variation in functional network connectivity in the fetal brain to autistic traits in toddlerhood. These findings extend the current understanding of the prenatal brain origins of ASD and highlight the potential of fetal rs-fMRI as a tool to identify neural signatures related to social-emotional development and ASD likelihood.

BACKGROUND:Recent epidemiological evidence links early-life obesity and metabolic dysregulation to adult psychosis vulnerability, though a causal relationship remains unclear. Establishing causality in highly heritable psychotic disorders requires 1) demonstrating that early-life metabolic factors mediate between genetic vulnerability and psychosis trajectory, 2) dissecting mechanisms leading to early-life obesity in genetically vulnerable individuals, and 3) clarifying downstream neurodevelopmental pathways linking early-life obesity to psychosis symptoms. METHODS:Here we investigated bidirectional pathways linking behavioral, body mass index (BMI), and neurodevelopmental trajectories in a unique longitudinal cohort of 184 individuals at high genetic risk for psychosis, due to 22q11.2 deletion syndrome (22q11DS), and 182 neurotypical control individuals, followed-up since childhood. We combined repeated BMI measurements with clinical/neurocognitive phenotyping and neuroimaging. We investigated the relationship between BMI trajectories with risk of psychosis and tested whether altered cortical or cerebellar development could underlie this association. RESULTS:Childhood behavioral impulsivity predicted early and progressive deviations in BMI trajectories, mediating the effects of 22q11DS vulnerability to early-life obesity. Chronic BMI increases manifesting during childhood predicted the subsequent emergence of psychosis during late adolescence/early adulthood, mediating the effects of behavioral impulsivity. A dose-effect relationship linked duration of increased BMI status to worsening of motor and cognitive disorganization, a key schizophrenia symptom domain, which was mediated by progressive gray matter volume reductions in posterior-inferior cerebellum. CONCLUSIONS:These findings suggest that metabolic dysregulation associated with obesity may link childhood behavioral impulsivity to psychosis vulnerability in 22q11DS by influencing cerebellar maturation. These findings might support preventive interventions targeting early-life metabolic trajectories in individuals at risk of psychosis.

BACKGROUND:Risky sexual behaviours (RSB) and attention deficit hyperactivity disorder (ADHD) are both major concerns among university students. However, their association remains insufficiently understood. This study aimed to evaluate the relationship between ADHD symptoms and a broad range of RSB in university students. METHODS:A total of 13 085 French students enrolled in the i-Share (Internet-based Students' Health Research Enterprise study (mean age: 20.6 years, SD=2.4) completed self-reported questionnaires assessing ADHD symptoms (Adult Self-Report Scale V.1.1), RSB, sociodemographic characteristics and alcohol and cannabis use. Logistic regression models were used to examine the cross-sectional associations between ADHD symptoms and RSB, adjusting for relevant confounders. RESULTS:A high level of ADHD symptoms was observed in 5.3% of students. In multivariate models, ADHD symptoms were associated with a wide range of RSB, including early first sexual intercourse (adjusted OR (aOR) 1.26; 95% CI 1.06 to 1.51), inconsistent condom use in the last 12 months (aOR 1.26; 95% CI 1.05 to 1.51), diagnosis of a sexually transmitted infection in the last 12 months (aOR 1.60; 95% CI 1.16 to 2.22) and having had multiple sexual partners in the last 12 months (adjusted incidence rate ratio 1.20; 95% CI 1.14 to 1.27). Among female students, ADHD symptoms were associated with lower current use of any form of contraception (aOR 0.59; 95% CI 0.48 to 0.71), and higher odds of having ever used emergency contraception (aOR 1.22; 95% CI 1.02 to 1.47), and having ever had an abortion (aOR 1.77; 95% CI 1.21 to 2.58). CONCLUSIONS:University students with a high level of ADHD symptoms are at increased risk of engaging in a wide range of RSB. Targeted preventive strategies may be particularly beneficial for this population.