Biology subjects

Boen, R.

Publications and source records attributed to Boen, R..

6 recordsLinked to original sources

bioRxiv2026

Symptom Dimension-Specific Neurotransmitter Correlates of Psychopathology and Cognition in Early Psychosis

Extended duration of under-treated psychosis (DUP) is among the strongest predictors of poor outcome, yet diagnostic heterogeneity impedes treatment matching, with approximately 50% of patients failing to respond to first-line antipsychotics. Negative symptoms and cognitive impairment are particularly refractory, lacking effective pharmacological treatments. Identifying neurotransmitter systems associated with specific symptom dimensions could accelerate targeted therapeutic development and reduce DUP. We applied Partial Least Squares correlation (PLSc) to derive whole-brain resting-state functional connectivity (RSFC) and anatomical (cortical thickness and subcortical volume) signatures associated with five psychopathology dimensions (positive symptoms, negative symptoms, general psychopathology, mania, and cognition) in a transdiagnostic sample from the Human Connectome Project-Early Psychosis (HCP-EP; n=124). We tested associations with potential confounds including antipsychotic medication dosage and substance use. Signatures were spatially correlated with 21 Positron Emission Tomography (PET)-derived receptor and transporter maps across 9 neurotransmitter systems using the neuromaps toolbox. Significant RSFC signatures emerged for positive symptoms, negative symptoms, general psychopathology, and cognition, but not mania. The negative symptom RSFC signature correlated with norepinephrine transporter (NET; {rho}=.40, q=.030) and vesicular acetylcholine transporter (VAChT; {rho}=.38, q=.048) distributions. The cognition signature similarly correlated with VAChT ({rho}=.48, q=.025). Anatomical signatures were associated with positive symptoms, general psychopathology, and cognition, but were more susceptible to confounding by medication and substance use. No significant receptor associations were detected for anatomical signatures. These findings implicate cholinergic and noradrenergic systems as molecular targets for negative symptoms and cognitive impairment, supporting prioritization of these systems in pharmacotherapy development in early psychosis.

neuroscience↗

bioRxiv2026

Genetic insights on the mechanisms of human cortical folding

The unique and intricate pattern of human cortical folding is rooted in fetal neurodevelopmental processes and can now be comprehensively quantified by new neuroimaging-derived measures of sulcal complexity. Here, we provide the first genetic maps of human sulcal complexity. Beginning with large effects of rare variants, we survey nine different neurogenetic syndromes (n=615), detecting visible changes in sulcal complexity on a shared axis of sulcal change coupled to the prenatal timing of sulcation. Turning to common genetic variants, we use genome-wide association studies of complexity scores for 40 sulci in the UK Biobank (n[~]29,000) to (i) resolve variable heritability across sulci, (ii) reveal both local and remote shared genetic effects with cortical morphology, and (iii) identify complexity-associated genes and their embedding in brain maps of prenatal gene expression. These reference genetic maps uncover multiple new mechanistic pathways for cortical morphogenesis in health and disease.

neuroscience↗

bioRxiv2025

Convergent and Divergent Cerebellar Alterations in 22q11.2 Copy Number Variants

BackgroundIndividuals with copy number variants (CNVs) at 22q11.2 are at elevated risk for neurodevelopmental and psychiatric disorders, including autism spectrum disorder and intellectual disability. For psychosis, effects diverge, with 22q11.2 deletion (22qDel) conferring one of the highest known risks for schizophrenia, while duplication (22qDup) may be protective. Prior investigations of neurobiological mechanisms in 22q11.2 CNVs have predominantly focused on the cerebrum, whereas the cerebellum--a region increasingly recognized for its contributions to cognitive, affective, and social processes--remains underexplored and represents a promising target for investigation. Although alterations in cerebellar structure have been reported in 22qDel, they remain largely unexplored in 22qDup. This study provides the first characterization of regional cerebellar volumes in 22qDup and the first direct comparison of cerebellar structure across 22q11.2 CNVs, offering a unique opportunity to identify shared and distinct neurobiological mechanisms with implications for understanding cerebellar contributions to brain-behavior relationships in CNV carriers. MethodsWe analyzed 514 longitudinally collected structural Magnetic Resonance Imaging (MRI) scans of 111 individuals with 22qDel, 37 individuals with 22qDup, and 167 typically developing (TD) controls. Total and regional cerebellar volumes were quantified using ACAPULCO, a deep-learning-based parcellation method that segments the cerebellum into 28 subregions. Group differences in cerebellar volumes, as well as their associations with cognition, autism-related traits, and psychosis-risk symptoms, were examined using linear mixed-effects models. False discovery rate (FDR) correction was applied to control for multiple comparisons where appropriate. ResultsIn relation to TD controls, cerebellar volumes were broadly reduced in 22qDel, whereas cerebellar alterations in 22qDup were more modest and variable. Regional analyses revealed both linear (22qDel < TD < 22qDup) and nonlinear (22qDel {approx} 22qDup < TD; 22qDel < 22qDup < TD) gene-dosage patterns, though not all reached significance. Vermis VII was significantly reduced in both CNVs but showed no relationship to behavioral differences. In contrast, reduction of Right Lobule VIIIA was associated with greater social impairment in 22qDup. Unlike TD controls, this region was not associated with IQ in 22qDup, suggesting CNV-specific alterations in cerebellar-behavior relationships. ConclusionThese findings indicate that reciprocal CNVs at the 22q11.2 locus both affect cerebellar structure, yet their functional consequences diverge, suggesting overlapping but distinct pathways to clinical risk. They underscore the cerebellums multifaceted role in neurodevelopment and highlight the need for studies examining broader cognitive and socio-affective domains, as well as cerebellar-cortical connectivity, to clarify links to clinical outcomes.

neuroscience↗

bioRxiv2025

Gene dosage effects of 22q11.2 copy number variants on in-vivo measures of white matter axonal density and dispersion

22q11.2 deletion (22qDel) and duplication (22qDup) carriers have an increased risk of neurodevelopmental disorders and exhibit altered brain structure, including white matter microstructure. However, the underlying cellular architecture and age-related changes contributing to these white matter alterations remain poorly understood. Neurite orientation dispersion and density imaging (NODDI) was used on mixed cross-sectional and longitudinal data to examine group differences and age-related trajectories in measures of axonal density (i.e., intracellular volume fraction; ICVF), axonal orientation (orientation dispersion index; ODI) and free water diffusion (isotropic volume fraction; ISO) in 50 22qDel (n scans = 69, mean age = 20.7, age range = 7.4-51.1, 64.0% female) and 24 22qDup (n scans = 34, mean age = 21.6, age range = 8.3-49.4, 54.2% female) carriers, and 890 controls (n scans = 901, mean age = 21.9, age range = 7.8-51.1, 54.5% female). The results showed widespread gene dosage effects, with higher ICVF in 22qDel and lower ICVF in 22qDup compared to controls, and region-specific effects of the 22qDel and 22qDup on ODI and ISO measures. However, 22qDel and 22qDup carriers did not exhibit altered age-related trajectories relative to controls. Observed differences in ICVF suggest higher white matter axonal density in 22qDel and lower axonal density in 22qDup compared to controls. Conversely, differences in ODI are highly localized, indicating region-specific effects on axonal dispersion in white matter. We do not find evidence for altered developmental trajectories of axonal density or dispersion among 22q11.2 CNV carriers, suggesting stable disruptions to neurodevelopmental events before childhood.

neuroscience↗

bioRxiv2020

Development of attention networks from childhood to young adulthood: A study of performance, intraindividual variability and cortical thickness

Human cognitive development is manifold, with different functions developing at different speeds at different ages. Attention is an important domain of this cognitive development, and involves distinct developmental trajectories in separate functions, including conflict processing, selection of sensory input and alertness. In children, several studies using the Attention Network Test (ANT) have investigated the development of three attentional networks that carry out the functions of executive control, orienting and alerting. There is, however, a lack of studies on the development of these attentional components across adolescence, limiting our understanding of their protracted development. To fill this knowledge gap, we performed a mixed cross-sectional and longitudinal study using mixed methods to examine the development of the attentional components and their intraindividual variability from late childhood to young adulthood (n = 287, n observations = 408, age range = 8.5-26.7 years, mean follow up interval = 4.4 years). The results indicated that executive control stabilized during late adolescence, while orienting and alerting continued to develop into young adulthood. In addition, a continuous development into young adulthood was observed for the intraindividual variability measures of orienting and alerting. In a subsample with available magnetic resonance imaging (MRI) data (n =169, n observations = 281), higher alerting scores were associated with thicker cortices within a right prefrontal cortical region and greater age-related cortical thinning in left rolandic operculum, while higher orienting scores were associated with greater age-related cortical thinning in frontal and parietal regions. Finally, increased consistency of orienting performance was associated with thinner cortex in prefrontal regions and reduced age-related thinning in frontal regions.

neuroscience↗

bioRxiv2020

Inhibitory control and the structural parcellation of the right inferior frontal gyrus

The right inferior frontal gyrus (rIFG) has most strongly, although not exclusively, been associated with response inhibition, not least based on covariations of behavioral performance measures and local grey matter characteristics. However, the white matter microstructure of the rIFG as well as its connectivity has been less in focus, especially when it comes to the consideration of potential subdivisions within this area. The present study reconstructed the structural connections of the three main subregions of the rIFG (i.e. pars opercularis, pars triangularis and pars orbitalis) using diffusion tensor imaging, and further assessed their associations with behavioral measures of inhibitory control. The results revealed a marked heterogeneity of the three subregions with respect to the pattern and extent of their connections, with the pars orbitalis showing the most widespread inter-regional connectivity, while the pars opercularis showed the least amount of connections. When relating behavioral performance measures of a stop signal task to brain structure, the data indicated a differential association of dorsal and ventral opercular connectivity with the go reaction time and the stopping accuracy, respectively.

neuroscience↗