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Delavari, F.

Publications and source records attributed to Delavari, F..

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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↗

EEG-derived Brain Connectivity in Theta/Alpha Frequency Bands Increases During Reading of Individual Words

ObjectiveAlthough extensive insights about the neural mechanisms of reading have been gained via magnetic and electrographic imaging, the temporal evolution of the brain network during sight reading remains unclear. We tested whether the temporal dynamics of the brain functional connectivity involved in sight reading can be tracked using high-density scalp EEG recordings. ApproachTwenty-eight healthy subjects were asked to read words in a rapid serial visual presentation task while recording scalp EEG, and phase locking value was used to estimate the functional connectivity between EEG channels in the theta, alpha, beta, and gamma frequency bands. The resultant networks were then tracked through time. Main resultsThe networks graph density gradually increases as the task unfolds, peaks 150-250-ms after the appearance of each word, and returns to resting-state values, while the shortest path length between non-adjacent functional areas decreases as the density increases, thus indicating that a progressive integration between regions can be detected at the scalp level. This pattern was independent of the words type or position in the sentence, occurred in the theta/alpha band but not in beta/gamma range, and peaked earlier in the alpha band compared to the theta band (alpha: 184{+/-}61.48-ms; theta: 237{+/-}65.32-ms, P-value P<0.01). Nodes in occipital and frontal regions had the highest eigenvector centrality throughout the words presentation, and no significant lead-lag relationship between frontal/occipital regions and parietal/temporal regions was found, which indicates a consistent pattern in information flow. In the source space, this pattern was driven by a cluster of nodes linked to sensorimotor processing, memory, and semantic integration, with the most central regions being similar across subjects. SignificanceThese findings indicate that the brain network connectivity can be tracked via scalp EEG as reading unfolds, and EEG-retrieved networks follow highly repetitive patterns lateralized to frontal/occipital areas during reading.

neuroscience↗

Functional organization of the neonatal thalamus across development depicted by functional MRI

The thalamus is a central component of the brain that is involved in a variety of functions, from sensory processing to high-order cognition. Its structure and function in the first weeks of extrauterine life, including its connections to different cortical and subcortical areas, have not yet been widely explored. Here, we used resting state functional magnetic resonance imaging data of 730 newborns from the developing Human Connectome Project to study the functional organization of the thalamus from 37 to 44 post-conceptual weeks. We introduce KNIT: K-means for Nuclei in Infant Thalamus. The framework employs a highly granular vector space of 40 features, each corresponding to functional connectivity to a brain region, using k-means clustering and uncertainty quantification through bootstrapping to delineate thalamic units. Although the different clusters showed common patterns of increased connectivity to the superior temporal gyrus, the parietal, and the frontal cortex, implying an expected decrease in specialization at that age, they also show some specificity. That is, a pulvinar unit was identified, similar to the adult thalamus. Ventrolateral motor and medial salience units were also highlighted. The latter appeared around 41 weeks of age, while the former showed at least from 37 weeks, but had a decrease in volume through age, replaced mostly by a dominant dorsal thalamic unit. We also observed an increase in clustering robustness and in hemispheric bilateral symmetry with age, suggesting more specialized functional units. We also found a burst in global thalamic connectivity around 41 weeks. Finally, we demonstrate the benefits of this method in terms of granularity compared to the more conventional winner-takes-all approach.

neuroscience↗

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↗