Amelia Versace

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.

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.

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.

Concussion often results in psychological symptoms, including anxiety. Post-concussion anxiety has been well documented, although much of this research has focused on collegiate athletes. The purpose of this study was to compare (1) anxiety symptoms in concussed and healthy controls over time and (2) to explore sex differences in post-concussion anxiety within the context of pubertal development. Participants (N = 126, mean age = 15.1 years old), including concussed ( n = 86) and healthy adolescents ( n = 40), completed the Pubertal Development Scale (PDS) and the Screen for Child Anxiety and Related Disorders (SCARED-C). The concussed groups completed SCARED-C at three visits ( < 10 days, 4 weeks, 3 months). Results of an analysis of covariance (ANCOVA) and multi-variate analysis of covariance (MANCOVA) found concussed adolescents reported higher SCARED-C total, generalized, and panic anxiety scores than healthy controls, after controlling for sex, age, and PDS score (PDSS). A three-way mixed ANCOVA examined the effects of sex, PDSS, time, and their interaction on SCARED-C total score in concussed adolescents while controlling for age. There was a significant three-way interaction between sex, age, and PDSS on SCARED-C total score while controlling for age. Overall, we observed increased anxiety in concussed adolescents, compared with controls, as well as greater post-concussion anxiety reported by females compared with males, including within PDSS groups. Concussion providers should be prepared to receive training to administer well-validated measures of psychopathology and should consider that female adolescents, compared with males, regardless of pubertal development, may be at greater risk for post-concussion anxiety.

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.

Obsessive-compulsive disorder is a psychiatric disorder characterized by intrusive thoughts and repetitive behaviors. There are two prominent features: Harm Avoidance (HA) and Incompleteness (INC). Previous resting-state studies reported abnormally elevated connectivity between prefrontal cortical (PFC) and subcortical regions (thalamus, striatum) in OCD participants. Yet, little is known about the white matter (WM) structural abnormalities in these connections. Using brain parcellation and segmentation, whole brain tractography, and Neurite Orientation Dispersion and Density Imaging (NODDI), we aimed to characterize WM structural abnormalities in OCD vs. healthy controls and determine the extent to which NODDI indices of these connections were associated with subthreshold-threshold HA, INC and overall OCD symptom severity across all participants. Four PFC regions were segmented: ventral medial (vmPFC), ventrolateral (vlPFC), dorsomedial (dmPFC), and dorsolateral (dlPFC). NODDI Neurite Density (NDI) and Orientation Dispersion (ODI) indices of WM structure were extracted from connections between these PFC regions and the thalamus (42 OCD, 44 healthy controls, mean age[SD] = 23.65[4.25]y, 63.9% female) and striatum (38 OCD, 41 healthy controls, mean age[SD] = 23.59[4.27]y, 64.5% female). Multivariate analyses of covariance revealed no between-group differences in these indices. Multivariate regression models revealed that greater NDI in vmPFC-thalamus, greater NDI and ODI in vmPFC-striatum, and greater NDI in dmPFC-thalamus connections were associated with greater INC severity (Q ≤ 0.032). These findings highlight the utility of NODDI in the examination of WM structure in OCD, provide valuable insights into specific WM alterations underlying dimensional INC, and can facilitate the development of customized treatments for OCD individuals with treatment-resistant symptoms.

Understanding the developmental trajectories for recognizing facial expressions is important for a better understanding of development of psychiatric disorders. In this study, we examined the recognition of emotional and neutral facial expressions in 93 typically developing adolescents and adults. The Emotion Intensity Rating task required participants to rate the intensity of emotional expression in happy, neutral, and sad faces on a scale from 1 to 9. A score of ‘5’ had to be assigned to neutral faces, scores between ‘6’ (slightly happy) and ‘9’ (very happy) to happy faces, and scores between ‘4’ (slightly sad) and ‘1’ (very sad) to sad faces. Mixed effects models were used to examine the effects of age and emotion on recognition accuracy, reaction time (RT), and emotional intensity. Participants tended to misjudge neutral faces as sad. Adolescents were less accurate than adults for neutral face recognition. There were significant quadratic effects of age on accuracy (negative quadratic effect) and RT (positive quadratic effect). The most accurate and fastest performance was observed in 25- to 35-year-old subjects. This trajectory may be associated with prefrontal cortex maturation, which provides top–down control over the heightened amygdala response to ambiguity that may be misinterpreted as emotional content.

Background: Understanding the behavioral and neural underpinnings of the post-concussion recovery of working memory function is critically important for improving clinical outcomes and adequately planning return-to-activity decisions. Previous studies provided inconsistent results due to small sample sizes and the use of a mixed population of participants who were at different post-injury time points. We aimed to examine working memory recovery during the first 6 months post-concussion in adolescents. Methods: We used functional magnetic resonance imaging (fMRI) to scan 45 concussed adolescents [CONCs] at baseline (p-values < 0.05). It was also characterized by significant difficulty-related activation increases in the left inferior frontal gyrus (LIFG) and the left orbitofrontal cortex (LOFC) at 6 months vs. baseline. Although the activation differences between one-back and two-back were comparable between HCs and CONCs at 6 months, HCs had more pronounced activation in the LIFG than concussed adolescents. Conclusions: Post-concussion recovery is associated with significant performance improvements in speed and accuracy, as well as the normalization of brain responses in the LIFG and LOFC during the n-back task. The observed patterns of LOFC activation might reflect compensatory strategies to distribute neural processing and reduce neural fatigue post-concussion.

Background Understanding behavioral and neural underpinnings of post-concussion recovery of working memory function is critically important for improving clinical outcomes and adequately planning return-to-activity decisions. Previous studies provided inconsistent results due to small sample sizes and the use of a mixed population of participants who were at different post-injury time points. Methods To better understand behavioral and neural correlates of working memory recover during the first 6 months post-concussion, we used functional magnetic resonance imaging (fMRI) to scan 45 concussed adolescents [CONC] at baseline (Results By the 6-month follow-up, all affected adolescents were asymptomatic and cleared to return-to-activity. Working memory function recovery was reflected by faster and more accurate performance at 6 months vs. baseline (p-valuesConclusion Post-concussion recovery is associated with significant performance improvements in speed and accuracy, as well as normalization of brain responses in the LIFG and LOFC during the n-back task. The observed patterns of LOFC activation might reflect compensatory strategies to distribute neural processing and reduce neural fatigue post-concussion.