Increased Cerebello-Prefrontal Connectivity Predicts Poor Executive Function in Congenital Heart Disease.

BACKGROUND: Children and adolescents with congenital heart disease (CHD) are at risk for cognitive impairments, such as executive function deficits and motor delays, which can impact their academic and adaptive functioning as well as their quality of life. We investigated whether alterations in connectivity between the prefrontal and cerebellar brain structures exist between CHD and control cohorts and if these alterations could predict cognitive or motor impairment among youths with CHD. METHODS: 53 participants with CHD and 73 healthy control participants completed multi-modal magnetic resonance imaging (MRI) of the brain, including high-resolution diffusion tensor imaging at 3T. We measured connectivity from masked regions of interest in the cerebellum to the frontal cortex using a probabilistic tractography method. Participants also completed neuropsychological tests of cognitive and motor skills using the NIH Toolbox. RESULTS: In the CHD group, fractional anisotropy (FA) was increased in the cognitive loop connectivity pathways, including from the right cerebellum to the left thalamus (p = 0.0002) and from the left thalamus to the left medial frontal gyrus (MFG) (p = 0.0048) compared with the healthy control group. In contrast, there were no differences between CHD and controls in motor loop connectivity pathways. An increase in FA from the right thalamus to the MFG tract in the cognitive loop (posterior subdivision) predicted (p = 0.03) lower scores on the NIHTB tests, including those of executive functioning. A transient increase in connectivity of the cognitive loop in the adolescent group was observed relative to the child and adult groups. CONCLUSIONS: Our results suggest that selective alteration of cerebellum-cerebral connectivity circuitry within the cognitive loops predicts cognitive dysfunction in CHD youth. Our study suggests a critical period of cerebellar circuitry plasticity in the adolescent period in CHD subjects that drives neurocognitive function. Further replication and validation in other pediatric CHD cohorts is warranted for future work.

Modular architecture and resilience of structural covariance networks in first-episode antipsychotic-naive psychoses.

Structural covariance network (SCN) studies on first-episode antipsychotic-naïve psychosis (FEAP) have examined less granular parcellations on one morphometric feature reporting lower network resilience among other findings. We examined SCNs of volume, cortical thickness, and surface area using the Human Connectome Project atlas-based parcellation (n = 358 regions) from 79 FEAP and 68 controls to comprehensively characterize the networks using a descriptive and perturbational network neuroscience approach. Using graph theoretical methods, we examined network integration, segregation, centrality, community structure, and hub distribution across the small-worldness threshold range and correlated them with psychopathology severity. We used simulated nodal "attacks" (removal of nodes and all their edges) to investigate network resilience, calculated DeltaCon similarity scores, and contrasted the removed nodes to characterize the impact of simulated attacks. Compared to controls, FEAP SCN showed higher betweenness centrality (BC) and lower degree in all three morphometric features and disintegrated with fewer attacks with no change in global efficiency. SCNs showed higher similarity score at the first point of disintegration with ≈ 54% top-ranked BC nodes attacked. FEAP communities consisted of fewer prefrontal, auditory and visual regions. Lower BC, and higher clustering and degree, were associated with greater positive and negative symptom severity. Negative symptoms required twice the changes in these metrics. Globally sparse but locally dense network with more nodes of higher centrality in FEAP could result in higher communication cost compared to controls. FEAP network disintegration with fewer attacks suggests lower resilience without impacting efficiency. Greater network disarray underlying negative symptom severity possibly explains the therapeutic challenge.

Sex differences in decision-making: Identifying multisensory behavioral differences in males and hermaphrodites.

This present study uses C. elegans as a model to investigate how sex differences can influence sensory behavior and decision-making when encountering conflicting cues. We use a multi-sensory behavioral assay to characterize the differences between hermaphrodites and male worms when escaping from a food lawn during exposure to repulsive odors, such as, 2-nonanone. We find that male worms show a delayed food leaving during exposure to 2-nonanone when compared to hermaphrodite worms, and this is observed across multiple repulsive cues (2-nonanone and undiluted benzaldehyde) and multiple food types ( E. coli (OP50) and Comamonas sp ). Overall, this study provides a platform to further investigate how sensory-dependent decision-making behavior differs between sexes.

Structural covariance networks in schizophrenia: A systematic review Part I.

BACKGROUND: Schizophrenia is proposed as a disorder of dysconnectivity. However, examination of complexities of dysconnectivity has been challenging. Structural covariance networks (SCN) provide important insights into the nature of dysconnectivity. This systematic review examines the SCN studies that employed statistical approaches to elucidate covariation of regional morphometric variations. METHODS: A systematic search of literature was conducted for peer-reviewed publications using different keywords and keyword combinations for schizophrenia. Fifty-two studies met the criteria. RESULTS: Early SCN studies began using correlational structure of selected regions. Over the last 3 decades, methodological approaches have grown increasingly sophisticated from examining selected brain regions using correlation tests on small sample sizes to recent approaches that use advanced statistical methods to examine covariance structure of whole-brain parcellations on larger samples. Although the results are not fully consistent across all studies, a pattern of fronto-temporal, fronto-parietal and fronto-thalamic covariation is reported. Attempts to associate SCN alterations with functional connectivity, to differentiate between disease-related and neurodevelopment-related morphometric changes, and to develop "causality-based" models are being reported. Clinical correlation with outcome, psychotic symptoms, neurocognitive and social cognitive performance are also reported. CONCLUSIONS: Application of advanced statistical methods are beginning to provide insights into interesting patterns of regional covariance including correlations with clinical and cognitive data. Although these findings appear similar to morphometric studies, SCNs have the advantage of highlighting topology of these regions and their relationship to the disease and associated variables. Further studies are needed to investigate neurobiological underpinnings of shared covariance, and causal links to clinical domains.

Structural covariance networks in schizophrenia: A systematic review Part II.

BACKGROUND: Examination of structural covariance network (SCN) is gaining prominence among the strategies to delineate dysconnectivity that case-control morphometric comparisons cannot address. Part II of this review extends on the part I of the review that included SCN studies using statistical approaches by examining SCN studies applying graph theoretic approaches to elucidate network properties in schizophrenia. This review also includes SCN studies using graph theoretic or statistical approaches on persons at-risk for schizophrenia. METHODS: A systematic literature search was conducted for peer-reviewed publications using different keywords and keyword combinations for schizophrenia and risk for schizophrenia. Thirteen studies on schizophrenia and five on persons at risk for schizophrenia met the criteria. RESULTS: A variety of findings from over the last 1½ decades showing qualitative and quantitative differences in the global and local structural connectome in schizophrenia are described. These observations include altered hub patterns, disrupted network topology and hierarchical organization of the brain, and impaired connections that may be localized to default mode, executive control, and dorsal attention networks. Some of these connectomic alterations were observed in persons at-risk for schizophrenia before the onset of the illness. CONCLUSIONS: Observed disruptions may reduce network efficiency and capacity to integrate information. Further, global connectomic changes were not schizophrenia-specific but local network changes were. Existing studies have used different atlases for brain parcellation, examined different morphometric features, and patients at different stages of illness making it difficult to conduct meta-analysis. Future studies should harmonize such methodological differences to facilitate meta-analysis and also elucidate causal underpinnings of dysconnectivity.

The Opioid Awareness and Support Team: an innovative example of medical education and community partnership.

The Opioid Awareness and Support Team (OAST) at the Memorial University Faculty of Medicine is a novel student-led initiative designed to supplement medical student learning related to opioid use disorder and the opioids crisis. OAST has focused on grounding educational initiatives related to opioid use disorder in the local community context, working with community partners, and bringing in individuals with lived experience. We present initial findings from an Opioid Education Day that suggest student-led supplemental education for medical students can improve student knowledge surrounding opioid use.

L'équipe d'aide et de sensibilisation aux opioïdes (OAST) est une initiative des étudiants de la faculté de médecine de l'Université Memorial qui apporte un complément à la formation que reçoivent les étudiants sur le trouble lié à l'usage d'opioïdes. L'OAST s'est efforcée d'inscrire les initiatives éducatives liées à la crise des opïodes dans un contexte local en collaboration avec des partenaires communautaires et de faire participer des personnes ayant une expérience de terrain. Nous présentons les résultats préliminaires d'une journée de sensibilisation aux opioïdes qui suggèrent que cette activité éducative menée par les étudiants en médecine peut améliorer les connaissances des apprenants sur la consommation d'opioïdes.