Biology subjects

Sandini, C.

Publications and source records attributed to Sandini, C..

6 recordsLinked to original sources

bioRxiv2025

Aberrant cerebrovascular reactivity presents as an early biomarker of psychosis susceptibility in patients with 22q11.2DS

The brains ability to regulate blood flow is fundamental to both its function and development. In the context of neurodevelopmental disorders such as schizophrenia, understanding the complex interactions between cerebrovascular health and brain function is crucial for unraveling the pathophysiology of psychosis. This study investigates the developmental trajectory of cerebrovascular reactivity (CVR) in 22q11 deletion syndrome (22q11.2DS) compared to healthy controls, and its association with psychosis susceptibility. Using a longitudinal data-set of resting-state fMRI, we mapped voxel-level CVR across development. We found significant and early CVR impairments in 22q11.2DS, and in particular in those who later developed positive psychotic symptoms (PPS+). These impairments were evident within the anterior cingulate cortex, frontal lobes, and globi pallidi (GB). We propose that the pattern of CVR reduction presenting early during childhood is possibly linked to blood brain barrier impairment. A decrease in CVR during childhood and within the frontal regions and GB was predictive of subsequent development of positive psychotic symptoms (PPS), which often occurs during adolescence in 22q11.2DS patients. These findings suggest that cerebrovascular health is critical for normal brain development, particularly in regions like the striatum, which are vulnerable to vascular damage due to their anatomical features. These results underline the potential of CVR as an early biomarker for psychosis vulnerability, emphasizing the need for targeted interventions to mitigate neurodevelopmental disruptions of cerebrovascular health in 22q11.2DS.

neuroscience↗

bioRxiv2023

Thalamic contributions to psychosis susceptibility: Evidence from co-activation patterns accounting for intra-seed spatial variability (μCAPs)

The temporal variability of the thalamus in functional networks may provide valuable insights into the pathophysiology of schizophrenia. To address the complexity of the role of the thalamic nuclei in psychosis, we introduced micro-co-activation patterns (CAPs) by employing this method on the human genetic model of schizophrenia 22q11.2 deletion syndrome (22q11.2DS). Participants underwent resting-state functional MRI and a data-driven iterative process resulting in the identification of six whole-brain CAPs with specific activity patterns within the thalamus. Unlike conventional methods, CAPs extract dynamic spatial patterns that reveal partially overlapping and non-mutually exclusive functional subparts. Thus, the CAPs method detects finer foci of activity within the initial seed region, retaining valuable and clinically relevant temporal and spatial information. We found that a CAP showing co-activation of the mediodorsal thalamus with brain-wide cortical regions was significantly less frequent in patients with 22q11.2DS, and its occurrence negatively correlated with the severity of positive psychotic symptoms. Additionally, the activity within the auditory-visual cortex and their respective geniculate nuclei were expressed in two different CAPs. One of these auditory-visual CAPs co-activated with salience areas, while the other co-activated with the default mode network (DMN). A significant shift of occurrence from the salience+visuo-auditory-thalamus to the DMN+visuo-auditory-thalamus CAP was observed in patients with 22q11.2DS. Thus, our findings support existing research on the gatekeeping role of the thalamus for sensory information in the pathophysiology of psychosis and revisit the evidence of geniculate nuclei hyperconnectivity with the audio-visual cortex in 22q11.2DS in the context of dynamic functional connectivity as specific hyper-occurrence of these circuits with the task negative brain networks.

neuroscience↗

bioRxiv2023

FRESH™ 3D bioprinted cardiac tissue, a bioengineered platform for in-vitro toxicology and pharmacology

There is critical need for a predictive model of human cardiac physiology in the drug development process for assessment of compound toxicology and pharmacology. In vitro two-dimensional monolayer culture of cardiomyocytes provides biochemical and cellular readouts, and in vivo small and large animal models provide information on systemic cardiovascular response. However, there remains a significant gap in these models due to an incomplete recapitulation of adult human cardiovascular physiology, which results in more difficult safety interpretations. Recent efforts in developing in vitro models from engineered heart tissues have demonstrated potential for bridging this gap using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) in a three-dimensional tissue structure. Here we advance this paradigm by implementing FRESH 3D bioprinting to build human cardiac tissues in a medium throughput, well-plate format with controlled tissue architecture, tailored cellular composition, and native-like physiological function, specifically in its adrenergic agonist drug response. To do this, we combined hiPSC-CMs, endothelial cells and fibroblasts in a cellular bioink and FRESH 3D bioprinted this mixture in the format of a thin tissue strip stabilized on a tissue fixture. Our results confirmed that FRESH 3D bioprinted cardiac tissues could be fabricated directly in a 24-well plate format, were composed of dense and highly aligned hiPSC-CMs at >600 million cells/mL, and within 14 days demonstrated reproducible calcium transients and fast conduction velocity of [~]25 cm/s. Interrogation of these cardiac tissues with the {beta}-adrenergic receptor agonist isoproterenol showed native-like positive chronotropic and inotropic responses, a combination of responses that is not typically observed in 2D monolayer models or standard 3D engineered heart tissue approaches. These results confirm that FRESH 3D bioprinted cardiac tissues represents a novel in vitro platform that enables early in vitro pharmacology and toxicology screening.

bioengineering↗

bioRxiv2020

Unraveling the Developmental Dynamic of Visual Exploration of Social Interactions in Autism

Atypical deployment of social gaze is present early on in toddlers with autism spectrum disorders (ASDs). Yet, studies characterizing the developmental dynamic behind it are scarce. Here we used a data-driven method to delineate the developmental change in visual exploration of social interaction over childhood years in autism. Longitudinal eye-tracking data were acquired as children with ASD and their typically developing (TD) peers freely explored a short cartoon movie. We found divergent moment-to-moment gaze patterns in children with ASD compared to their TD peers. This divergence was particularly evident in sequences that displayed social interactions between characters and even more so in children with lower developmental and functional levels. The basic visual properties of the animated scene did not account for the enhanced divergence. Over childhood years, these differences dramatically increased to become more idiosyncratic. These findings suggest that social attention should be targeted early in clinical treatments.

neuroscience↗

bioRxiv2019

Structural control energy of resting-state functional brain states reveals inefficient brain dynamics in psychosis vulnerability.

How the brains white-matter anatomy constrains brain activity is an open question that might give insights into the mechanisms that underlie mental disorders such as schizophrenia. Chromosome 22q11.2 deletion syndrome (22q11DS) is a neurodevelopmental disorder with an extremely high risk for psychosis providing a test case to study developmental aspects of schizophrenia. In this study, we used principles from network control theory to probe the implications of aberrant structural connectivity for the brains functional dynamics in 22q11DS. We retrieved brain states from resting-state functional magnetic resonance images of 78 patients with 22q11DS and 85 healthy controls. Then, we compared them in terms of persistence control energy; i.e., the control energy that would be required to persist in each of these states based on individual structural connectivity and a dynamic model. Persistence control energy was altered in a broad pattern of brain states including both energetically more demanding and less demanding brain states in 22q11DS. Further, we found a negative relationship between persistence control energy and resting-state activation time, which suggests that the brain reduces energy by spending less time in energetically demanding brain states. In patients with 22q11DS, this behavior was less pronounced, suggesting a dynamic inefficiency of brain function in the disease. In summary, our results provide initial insights into the dynamic implications of altered structural connectivity in 22q11DS, which might improve our understanding of the mechanisms underlying the disease.

neuroscience↗

bioRxiv2019

Large-scale brain network dynamics provide a measure of psychosis and anxiety in 22q11.2 deletion syndrome.

Prodromal positive psychotic symptoms and anxiety are two strong risk factors for schizophrenia in 22q11.2 deletion syndrome (22q11DS). The analysis of large-scale brain network dynamics during rest is promising to investigate aberrant brain function and identify potentially more reliable biomarkers. We retrieved and examined dynamics of large-scale functional brain networks using innovation-driven co-activation patterns (iCAPs) and probed into functional signatures of prodromal psychotic symptoms and anxiety. Patients with 22q11DS had shorter activation in cognitive brain networks and longer activation in emotion processing networks. Functional signatures of prodromal psychotic symptoms confirmed an implication of cingulo-prefrontal salience network activation duration and coupling. Functional signatures of anxiety un-covered an implication of amygdala activation and coupling, indicating differential roles of dorsal and ventral sub-divisions of anterior cingulate and medial prefrontal cortices. These results confirm that the dynamic nature of brain network activation contains essential function to develop clinically relevant imaging markers of psychosis vulnerability.

neuroscience↗