Identifying neural mechanisms underlying harm avoidance and incompleteness in OCD and other psychiatric disorders is critical for improving diagnostic precision and developing targeted treatments. However, little is known about the neural pathways underlying these symptom dimensions across clinical populations. The goal of this study was to use diffusion MRI to replicate and extend prior findings in OCD to a transdiagnostic sample of healthy controls (HC) and individuals with Obsessive-Compulsive Disorder (OCD), Obsessive-Compulsive Personality Disorder (OCPD), and non-OCD disorders (e.g., anxiety, post-traumatic stress disorder). Connections between prefrontal (dorsomedial, dorsolateral, ventromedial, and ventrolateral) and subcortical regions (thalamus and striatum) were reconstructed using whole brain tractography in 38 HC (mean age [SD] = 30.97 [10.62), 47 OCD (mean age [SD] = 32.34 [12.23]), 21 OCPD (mean age [SD] = 35.67 [14.65]), and 20 Non-OCD (mean age [SD] = 35.90 [14.26]) participants. Fractional anisotropy (FA) was derived for each connection. Harm avoidance and incompleteness symptom dimensions were assessed using the Obsessive-Compulsive Trait Core Dimensions Questionnaire. In a first replication model, including individuals with OCD and HC, higher left (β = 0.29, P = 0.009, Q = 0.048) and right (β = 0.30, P = 0.005, Q = 0.0048) dorsomedial PFC-thalamus FA was associated with higher harm avoidance, with the left connection also associated with higher incompleteness (β = 0.29, P = 0.009, Q = 0.048). In additional models adding in OCPD and non-OCD participants, only associations among left (β = 0.20, P = 0.027, Q = 0.040) and right (β = 0.18, P = 0.035, Q = 0.045) dorsomedial PFC-thalamus FA and harm avoidance remained significant. There were no associations involving PFC-striatum connections. Dorsomedial PFC-thalamus FA was associated with harm avoidance, but less so with incompleteness. Our findings suggest that higher dorsomedial PFC-thalamic FA is associated with higher harm avoidance across diagnostic groups, providing transdiagnostic neural targets for future treatment developments.

MicroRNAs (miRNAs), which are small noncoding RNAs involved in gene regulation that can be measured reliably in saliva, have emerged as promising biomarker candidates for identifying concussion. However, research thus far is limited, and the role of miRNAs in prognosis following concussion in adolescents remains largely unexplored. This case-cohort study investigated whether salivary miRNAs collected within 10 days of injury could identify concussed adolescents from age- and sex-matched, healthy, uninjured controls, and predict symptom burden at 3-weeks post injury. Saliva samples were collected from 58 concussed adolescents (mean age [SD] = 15.4 [1.6] years; 25 females) within 10 days of injury, and 35 age- and sex-matched, healthy, uninjured controls. Using a neurodegenerative panel of 798 miRNAs, we applied feature selection to identify miRNAs that best identified concussed from healthy, uninjured adolescents. Additional analysis investigated whether these miRNAs were able to predict concussion symptom burden 3-weeks post injury. Results indicated that two miRNAs were significantly upregulated in concussed participants: (1) hsa-miR-26a-5p (F = 8.2, p = 0.005, False Discovery Rate [FDR]-corrected p = 0.008) and (2) hsa-miR-4286 (F = 9.6, p = 0.002, FDR-corrected p = 0.008). Higher hsa-miR-4286 levels predicted lower symptom burden at 3-weeks (β = -0.41, p = 0.001, FDR-corrected p = 0.002). The findings indicated that two salivary miRNAs demonstrated promise as clinically feasible biomarkers for identifying concussion in adolescents, one of which, was also useful for prognosis of symptom burden. The observed miRNA alterations may reflect injury-induced changes in neuroinflammatory and repair pathways, but larger, longitudinal studies are needed to validate these candidates and establish their sensitivity and specificity in this population.

Recent studies link microstructural properties of thalamocortical connections to obsessive-compulsive disorder (OCD) symptom dimensions such as harm avoidance and incompleteness. However, the contribution of specific thalamic nuclei remains unclear. The mediodorsal nucleus (MD), implicated in OCD, includes magnocellular (MDMC) and parvocellular (MDPC) subdivisions, thought to support affective and cognitive processes, respectively. Nucleus-specific connectivity profiles may improve neurobiological models of OCD by clarifying symptom-linked neural mechanisms. In a sample of 51 individuals with OCD and 49 controls, we applied whole-brain tractography to identify pathways connecting MD subdivisions (MDMC and MDPC) with four prefrontal cortex (PFC) regions: Ventrolateral, Ventromedial, Dorsolateral, and Dorsomedial. Neurite Orientation Dispersion and Density Imaging (NODDI) was used to quantify neurite density (NDI) and orientation dispersion (ODI). Harm avoidance and incompleteness dimensions were assessed using the Obsessive-Compulsive Trait Core Dimensions Questionnaire. False discovery rate (FDR) correction was applied for multiple comparisons (Q values). Higher ODI (reflecting greater dispersion/complexity) in MD-Ventrolateral PFC connections (Left MDPC-VLPFC: β = 0.35; Right MDPC-VLPFC: β = 0.31; Left MDMC-VLPFC: β = 0.37; Right MDMC-VLPFC: β = 0.30; all P values < 0.029; all Q values < 0.043) was significantly associated with greater incompleteness symptoms in the combined sample. No associations were found with harm avoidance or for other thalamic nuclei (P > 0.05). These findings suggest that incompleteness is associated with the microstructural complexity of connections involving both MD subdivisions, highlighting their joint contribution to this dimension. Additionally, the specific involvement of the Ventrolateral PFC points to a circuit implicated in cognitive-affective control. Together, these results move toward more precise neurobiological models of incompleteness, which may inform future targeted OCD interventions.

Background Clozapine (CLZ) demonstrates superior efficacy for treatment-resistant schizophrenia (TRS), but mechanisms underlying its effects remain unknown. Pathophysiologic links between cortical regions and the basal ganglia (BG) characterize schizophrenia and are implicated in the mechanism of CLZ's action. Here, we examined CLZ's efficacy with diffusion weighted imaging (DWI) to examine microstructural and white matter-related measures within and between cortical and BG regions. Methods Twenty-six participants with TRS and moderate-to-severe psychosis underwent DWI scanning while starting CLZ, and nineteen were re-scanned after twelve weeks of treatment. Symptoms across treatment were measured via the Brief Psychiatric Rating Scale. DWI scans were processed to derive an array of microstructural measures in frontal and BG gray matter parcels and white matter-related measures in corticostriatal tracts. Exploratory analyses linked results with published functional connectivity findings. Results We found significant links between CLZ response and increased mean kurtosis (MK) in the left dorsolateral putamen, left ventral caudate, and left globus pallidus. Additionally, significant relationships between striatal segments of corticostriatal white matter tracts and CLZ response were observed, including increased MK, decreased axial diffusivity, and decreased fractional anisotropy. Exploratory findings linked changes in BG microstructure with published corticostriatal connectivity findings. Conclusion Our results implicate microstructural changes within gray matter regions of BG and white matter changes within the striatum as mechanisms underlying CLZ treatment. These findings further elucidate CLZ's mechanism of action and warrant further analyses that explore pharmacologic effects at the microstructural level.

There are rapid changes in negative and positive emotionality (NE, PE) and emotional regulation (e.g., soothability) during the first year of life. Understanding the neural basis of these changes during maturation can enhance the understanding of the etiology of early psychopathology. Our goal was to determine how measures of white matter (WM) microstructure in tracts connecting key emotion-related neural networks, including the forceps minor (FM), cingulum bundle (CB), and uncinate fasciculus interconnecting the default mode network (DMN), salience network (SN), and central executive network (CEN), can predict developmental change in infant emotionality and emotional regulation. We used Neurite Orientation Dispersion and Density Imaging (NODDI) measures together with conventional diffusion tensor metrics to examine WM tract microstructure and fiber collinearity in the primary sample ( n = 95), and modeled each WM feature with caregiver-reported infant NE, PE, and soothability, with infant and caregiver sociodemographic factors as covariates. In 3-month infants, higher neurite dispersion and lower longitudinal fiber alignment in the FM were associated with a larger increase in NE from 3 to 9 months of age, suggesting that greater integration of the DMN, SN, and CEN leads to a larger subsequent increase in NE; while higher neurite density and dispersion as well as lower WM longitudinal alignment in the left CB were associated with a larger increase in PE, suggesting that greater integration within the CEN leads to increasing PE over time. In addition, higher neurite dispersion and lower WM longitudinal alignment in the left CB were associated with a larger increase in soothability. Associations among diffusion tensor measures and changes in infant emotionality and emotional regulation measures were replicated in an independent test sample ( n = 44). These findings suggest that early infant WM microstructural features support infant emotionality and emotional regulation development and could represent early biomarkers of future emotional and behavioral disorders.

Purpose Sleep is vital for brain development. Animal models have suggested that insufficient sleep affects axons and dendrites (known as neurites). However, the effects of insufficient sleep on neurites during brain development in humans remain understudied. Deriving neurite density index and orientation dispersion index (ODI) in a large sample (N = 1,016; 47.44% girls), we aimed to identify the effects of insufficient sleep on white matter development between late childhood (mean age [standard deviation] = 9.96 [0.62] years) and early adolescence (mean age [standard deviation] = 11.94 [0.64] years). Methods Longitudinal Latent Class Analysis was used to derive longitudinal classes based on sleep duration from the Sleep Disturbance Scale for Children. The Child Behavior Checklist characterized behavioral (internalizing: anxious/depressed, withdrawn/depressed, somatic; externalizing: social, thought, attention, rule-breaking, and aggressive) problems. Regression analyses evaluated the effects of sleep classes on neurite density index, ODI, and standard tensor-based metrics (Fractional Anisotropy) changes over time, the focal or widespread effects along the tracts, and whether these effects were associated with behavioral problems. Results Insufficient (<9 hours; N = 569) and sufficient sleep (>9 hours; N = 447) groups were identified. Insufficient sleep was associated with worsening fiber coherence (greater ODI) in most tracts, including cingulum bundle (F(1,982) = 9.22, p = .002, Q = 0.009), forceps minor (F(1,982) = 5.30, p = .021, Q = 0.026), and superior longitudinal fasciculus (F(1,982) = 7.41, p = .007, Q = 0.015). These effects were focal, particularly in the frontal portions of the tracts. No other metric was affected (p > .050). In addition, greater ODI in the cingulum bundle was associated with more anxious/depressed problems (β = 0.10, p = .012, Q = 0.036). Discussion Our findings suggest that insufficient sleep during this sensitive period affects white matter development, which in turn affects internalizing problems. Our findings support the importance of promoting sufficient sleep during early adolescence.

PURPOSE:Psychological health issues resulting from emotional dysregulation such as anxiety and depression following pediatric concussion are a public health concern, but the underlying mechanisms remain unclear. Puberty opens a window of vulnerability for emotion dysregulation and a link between pediatric concussion and hormonal deficits has been reported. We investigated the association between pubertal hormones and psychological health in children with and without concussion history. METHODS:Participants included children (9-10 years) from the Adolescent Brain Cognitive Development study comprising with and without a reported history of concussion within the previous 2 years. Salivary Dehydroepiandrosterone (DHEA), testosterone and estradiol were used to determine levels of pubertal hormones, and the Child Behavior Checklist scores were used to characterize psychological health issues in late childhood (N = 264; 50% concussion history; 9.99 [0.64]yy; 36% female) and early adolescence (N = 112; 48% concussion history; 12.06 [0.66]yy; 33% female). Analyses of covariance were performed to relate concussion history to hormone levels from late childhood to early adolescence. Additional analyses determined whether hormone levels at late childhood or changes between late childhood and early adolescence mediated the effect of concussion history on psychological health. RESULTS:Children with a concussion history had lower testosterone at late childhood (F = 6.5, p = .012, Q = 0.035) and larger DHEA increases over time (F = 6.0, p = .016, Q = 0.048). Larger DHEA increases partially mediated the association between concussion history and Child Behavior Checklist scores. DISCUSSION:Pediatric concussion may increase vulnerability to psychological health issues in adolescence via pubertal hormones. Longitudinal studies evaluating the impact of pediatric concussion on psychological health and hormones are warranted to clarify this potential vulnerability.

Deficits in emotional reactivity and regulation assessed in infancy, including high levels of negative emotionality (NE), low positive emotionality (PE) and low soothability, can predict future affective and behavioral disorders. White matter (WM) tracts develop rapidly in the first postnatal year, paralleling the development of emotional regulation. During this period, examining the development of white matter microstructure in tracts connecting cortical and/or subcortical regions supporting emotional regulation, including the cingulum bundle (CB), uncinate fasciculus (UF), and forceps minor (FM), can provide neural markers reflecting pathophysiological processes underlying early emotional regulation development. The Neurite Orientation Dispersion and Density Imaging (NODDI) model can be used to estimate with high intercellular specificity microstructural integrity and myelination using the neurite density index (NDI), and dispersion, using the orientation dispersion index (ODI). Examining relationships among changes in WM tract NODDI measures and changes in emotional reactivity and regulation during the first 3-to-9-months of age (n = 39), we showed that larger 3-to-9-month increases in right UF, FM, and left CB ODI were associated with larger decreases or smaller increases in soothability during this period, while a larger increase in right UF NDI was associated with a smaller increase in PE. These findings suggest that in infancy, larger microstructural changes in major WM tracts interconnecting neural networks supporting emotional regulation are associated with disrupted development of PE and soothability. These findings could provide early neural markers of child emotional dysregulation and may have implications for future affective or behavioral trajectories.

Excessive screen time (ST) use has been linked to more depressive and anxiety symptoms, whereas moderate use may confer benefits for psychological health in adolescents. However, its role in psychological health following concussion in adolescents remains unclear. This study examined the effects of ST use on depressive and anxiety symptoms in adolescents following concussion. A total of 102 adolescents comprising 62 (mean [standard deviation (SD)] = 15.2 [1.7] years; 45.2% female) within 10 days of a diagnosed concussion, and 40 age- and sex-matched healthy controls (mean age [SD] = 14.99 [1.62] years; 50% female) participated in the study. Psychological symptoms were assessed using the Children's Depression Rating Scale and the Screen for Child Anxiety Related Emotional Disorders in the first 10 days (V1) and 3 months (V2) postinjury. Recreational ST use was self-reported at V1. K-means clustering classified adolescents with concussion into ST subgroups. Robust regression and false discovery rate correction examined group differences at V1 and V2 postinjury. Three clusters of ST use were identified: low (N = 14; mean [SD] = 1.97 [0.89] h/day), moderate (N = 25; mean [SD] = 5.22 [0.86] h/day), and high (N = 23; mean [SD] = 8.96 [1.42] h/day). At V1, all groups reported higher depressive and anxiety symptoms than controls (p < 0.041). At V2, all symptoms in the moderate-use group returned to control levels; however, the high-use group reported elevated depressive symptoms (F = 12.48, p = 0.001, Q = 0.003), and the low-use group reported elevated anxiety (F = 23.15, p < 0.001, Q < 0.001) compared with controls. Moderate recreational ST use was associated with significant recovery, while low and high ST use were associated with persistent symptoms in adolescents following concussion. Adolescents may benefit from recommendations that support a "Goldilocks" approach to ST use following concussion.

With the widespread adoption of screen-based devices among adolescents, there is growing concern that more screen time could contribute to mental health problems such as depression. It is thus critical to identify potential mediating factors that could help explain this potential risk relationship. Recent evidence indicates that more screen time could impact sleep duration and brain structural connectivity (ie, white matter organization), which are critical for emotional health. Notably, sleep duration is a modifiable behavior that health care providers can easily target. To identify the association between screen time during late childhood and depressive symptoms in early adolescence, and to investigate whether these associations are mediated by sleep duration and white matter organization. This prospective study was conducted from January 2024 to June 2024. Data from the Adolescent Behavior Cognitive Development (ABCD) Study were used to identify clinical and neuroimaging characteristics of participants at late childhood (T1; defined as aged 9-10 years) and early adolescence (T2; defined as age 11-13 years). Children and their parent/caregiver were recruited across 21 US cities. Participants with no past/current psychiatric disorders at T1 were selected for analyses. Initial analyses were conducted in 2024 and finalized in February 2025. Outcomes included screen time assessed using a self-report questionnaire, sleep duration assessed using the Munich Chronotype Questionnaire, and depressive symptoms characterized using the Child Behavior Checklist. Neurite orientation dispersion and density imaging and a tract profile approach were used to characterize the orientation dispersion index of 3 white matter tracts that are known to be implicated with depression: cingulum bundle, forceps minor, and uncinate fasciculus. Analyses included 976 participants (460 children [47.1%] were female, mean [SD] age was 9.9 [0.6] years at T1 and 11.9 [0.6] years at T2). Each additional hour of daily screen time at T1 was associated with a 0.12-point (95% CI, 0.04-0.20; P = .008) increase in Child Behavior Checklist depressive score at T2. Shorter sleep duration and worse cingulum bundle organization (greater orientation dispersion index) at T2 mediated 36.4% (95% CI, 18.2%-63.6%) of the association between more screen time and more depressive symptoms. Results of this study show that more screen time in late childhood was associated with more depressive symptoms, potentially due to shorter sleep and worse white matter organization during early adolescence. These findings emphasize the importance of promoting healthy habits and balancing screen time with adequate sleep.

Human brain organoids are three-dimensional cellular models that mimic architectural features of the developing brain. Generated from human induced pluripotent stem cells (hiPSCs), these offer an unparalleled physiologically relevant in-vitro system for diseases modeling and drug screening. Here we endeavor to establish a foundation for an MRI-based label-free imaging system with high-resolution capabilities for deep-tissue imaging of whole organoids.

BACKGROUND: Human brain organoids are 3-dimensional cellular models that mimic architectural features of a developing brain. Generated from human induced pluripotent stem cells, these organoids offer an unparalleled physiologically relevant in vitro system for disease modeling and drug screening. In the current study, we sought to establish a foundation for a magnetic resonance imaging (MRI)-based, label-free imaging system that offers high-resolution capabilities for deep tissue imaging of whole organoids. METHODS: An 11.7T Bruker/89 mm microimaging system was used to collect high-resolution multishell 3dimensional diffusion images of 2 induced pluripotent stem cell-derived human hippocampal brain organoids. The MRI features identified in the study were interpreted on the basis of similarities with immunofluorescence microscopy. RESULTS: MRI microscopy at #40 mm isotropic resolution provided a 3-dimensional view of organoid microstructure. T2-weighted contrast showed a rosette-like internal structure and a protruding spherical structure that correlated with immunofluorescence staining for the choroid plexus. Diffusion tractography methods can be used to model tissue microstructural features and possibly map neuronal organization. This approach complements traditional immunohistochemistry imaging methods without the need for tissue clearing. CONCLUSIONS: This proof-of-concept study shows, for the first time, the application of high-resolution diffusion MRI microscopy to image 2-mm diameter spherical human brain organoids. Application of ultrahigh-field MRI and diffusion tractography is a powerful modality for whole organoid imaging and has the potential to make a significant impact for probing microstructural changes in brain organoids used to model psychiatric disorders, neurodegenerative diseases, and viral infections of the human brain, as well as for assessing neurotoxicity in drug screening.

Impulsivity is a risk factor for externalizing behaviors, although the unique relationships between specific impulsivity facets and externalizing behavior development are less clear. We used Adolescent Brain Cognitive Development study data (N = 11,874) to examine whether child-reported UPPS-P impulsivity facets (9-10 years old) predicted parent-reported externalizing behaviors from childhood to early adolescence (11-12 years old). Latent growth model results showed that externalizing behaviors decreased over time. Higher negative urgency and lack of premeditation predicted greater externalizing behaviors in both childhood and early adolescence, as well as steeper declines in externalizing behaviors across time. Among the UPPS-P impulsivity facets, negative urgency and lack of premeditation may represent the most prominent indicators of externalizing behavior risk and development, highlighting their importance for targeted interventions.

Although specific risk factors for brain alterations in bipolar disorders (BD) are currently unknown, obesity impacts the brain and is highly prevalent in BD. Gray matter correlates of obesity in BD have been well documented, but we know much less about brain white matter abnormalities in people who have both obesity and BD. We obtained body mass index (BMI) and diffusion tensor imaging derived fractional anisotropy (FA) from 22 white matter tracts in 899 individuals with BD, and 1287 control individuals from 20 cohorts in the ENIGMA-BD working group. In a mega-analysis, we investigated the associations between BMI, diagnosis or medication and FA. Lower FA was associated with both BD and BMI in six white matter tracts, including the corpus callosum and thalamic radiation. Higher BMI or BD were uniquely associated with lower FA in three and six white matter tracts, respectively. People not receiving lithium treatment had a greater negative association between FA and BMI than people treated with lithium in the posterior thalamic radiation and sagittal stratum. In three tracts BMI accounted for 10.5 to 17% of the negative association between the number of medication classes other than lithium and FA. Both overweight/obesity and BD demonstrated lower FA in some of the same regions. People prescribed lithium had a weaker association between BMI and FA than people not on lithium. In contrast, greater weight contributed to the negative associations between medications and FA. Obesity may add to brain alterations in BD and may play a role in effects of medications on the brain.

Objectives: Sleep and internalizing problems escalate during adolescence and can negatively impact long-term health. However, the directionality of this risk-relationship remains poorly understood within a developmental context. The current study aimed to determine the directionality of this relationship in adolescents with no history of psychiatric disorder and whether sex at birth played a role in this relationship. Methods: We used data from the Adolescent Brain Cognitive Development, an ongoing multisite longitudinal US study, that covered four waves (W1:9-11 years; W2:10-12 years; W3:11-13 years; W4:12-14 years). Analyses included 3,128 youth (50.99%girls) with no past or current psychiatric disorders at W1. The Sleep Disturbance Scale for Children and the Child Behavior Checklist were used to measure sleep and internalizing problems. Cross-lagged panel models were used to evaluate the cross-lagged relationships across waves. Results: The sleep-internalizing cross-lagged relationship was unidirectional, with medium-large effect sizes: greater total sleep problems were associated with more severe internalizing problems at later waves (W2 -> W3, coefficient = 0.052, p = .021; W3 -> W4, coefficient = 0.091, p < .001), with problems in initiating and maintaining sleep predicting internalizing problems early on. Girls showed greater sleep-internalizing risk than boys. Conclusions: Sleep-internalizing relationships change across adolescence, becoming significant and more specific from early to mid-adolescence. Sleep interventions delivered in early adolescence, to girls in particular, may have a positive short and long-term impact on internalizing outcomes.

Background: Attention-Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder characterized by inattention and/or impulsivity/hyperactivity. ADHD, especially when persisting into adulthood, often includes emotional dysregulation, such as affect lability; however, the neural correlates of emotionality in adults with heterogenous ADHD symptom persistence remain unclear. Methods: The present study sought to determine shared and distinct functional neuroanatomical profiles of neural circuitry during emotional interference resistance using an Emotional Faces N-Back task while adult participants with persisting (n = 47), desisting (n = 93) or no childhood ADHD symptoms (n = 42) underwent functional magnetic resonance imaging (fMRI) scans. Results: Participants without any lifetime ADHD diagnosis performed significant better (faster and more accurately) than did participants with ADHD diagnoses on trials with high cognitive loads (2-back) that included task-irrelevant emotional distractors, tapping into executive functioning and emotion regulatory processes (EF+/ER+). In participants with persisting ADHD symptoms, more severe emotional symptoms were related to worse task performance. Heightened dorsal and ventral lateral prefrontal cortex (dlPFC, vlPFC) activation was associated with more accurate and faster performance on EF+/ER+ trials, respectively. Reduced activation was associated with greater affect lability in adults with persisting ADHD and dlPFC activation mediated the relationship between affect lability and task accuracy. Conclusions: These findings suggest that alterations in dlPFC function associated with greater interference in cognitive processes from emotion could represent a marker of risk for problems with emotional dysregulation in individuals with persisting ADHD and thus represent a potential therapeutic target for those with greater emotional symptoms of ADHD.

BACKGROUNDHigh levels of infant negative emotionality (NE) and low positive emotionality (PE) predict future emotional and behavioral problems. The prefrontal cortex (PFC) supports emotional regulation, with each PFC subregion specializing in specific emotional processes. Neurite Orientation Dispersion and Density Imaging (NODDI) estimates microstructural integrity and myelination via the neurite density index (NDI) and dispersion via the orientation dispersion index (ODI), with potential to more accurately evaluate microstructural alterations in the developing brain. Yet, no study has used these indices to examine associations between PFC microstructure and concurrent or developing infant emotionality.METHODSWe modeled PFC subregional NDI and ODI at 3 months with caregiver-reported infant NE and PE at 3 months (n=61) and at 9 months (n=50), using multivariable and subsequent bivariate regression models.RESULTSThe most robust statistically-significant findings were positive associations among 3-month rACC ODI and cACC NDI and concurrent NE, and 3-month lOFC ODI and prospective NE; and a negative association between 3-month dlPFC ODI and concurrent PE. Multivariate models also revealed that other PFC subregional microstructure measures, and infant and caregiver sociodemographic and clinical factors, predicted infant 3- and 9-month NE and PE.CONCLUSIONSGreater NDI and ODI, reflecting greater microstructural complexity, in PFC regions supporting salience perception (rACC), decision-making (lOFC), action selection (cACC), and attentional processes (dlPFC) might result in greater integration of these subregions with other neural networks, greater attention to salient negative external cues, thus higher NE and/or lower PE. These findings provide potential infant cortical markers of future psychopathology risk.