Biology subjects

Kojovic, N.

Publications and source records attributed to Kojovic, N..

8 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↗

bioRxiv2024

Atypical Audio-Visual Neural Synchrony and Speech Processing in children with Autism Spectrum Disorder

BackgroundChildren with Autism Spectrum Disorders (ASD) often exhibit communication difficulties that may stem from basic auditory temporal integration impairment but also be aggravated by an audio-visual integration deficit, resulting in a lack of interest in face-to-face communication. This study addresses whether speech processing anomalies in young (mean age 3.09-year-old) children with ASD are associated with alterations of audio-visual temporal integration. MethodsWe used high-density electroencephalography (HD-EEG) and eye tracking to record brain activity and gaze patterns in 31 children (6 females) with ASD and 33 typically developing (TD) children (11 females), while they watched cartoon videos. Neural responses to temporal audio-visual stimuli were analyzed using Temporal Response Functions model and phase analyses for audiovisual temporal coordination. ResultsThe reconstructability of speech signals from auditory responses was reduced in children with ASD compared to controls, but despite more restricted gaze patterns in ASD it was similar for visual responses in both groups. Speech reception was most strongly affected when visual speech information was also present, an interference that was not seen in TD children. These differences were associated with a broader phase angle distribution (exceeding pi/2) in the EEG theta range in autistic children, signaling reduced reliability of audio-visual temporal alignment. ConclusionThese findings show that speech processing anomalies in ASD do not stand alone and that they are associated already at a very early development stage with audio-visual imbalance with lousier auditory response encoding and disrupted audio-visual temporal coordination.

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↗

bioRxiv2021

Neural oscillation coupling selectively predicts speech reception in young children with Autism Spectrum Disorder

Communication difficulties in autism spectrum disorder (ASD) involve a speech reception deficit, whose biological causes are not yet identified. This deficit could denote atypical neuronal ensemble activity, as reflected by neural oscillations. Atypical cross-frequency oscillation coupling in particular could disrupt the possibility to jointly track and predict dynamic acoustic stimuli, a dual process that is essential for speech comprehension. Whether such oscillation anomalies can already be found in very young children with ASD, and with what specificity they relate to individual language reception capacity is unknown. In this study, neural activity was collected using EEG in 64 very young children with and without ASD (mean age 3) while they were exposed to naturalistic-continuous speech via an age-appropriate cartoon. EEG power typically associated with phrase-level chunking (delta, 1-3Hz), phonemic encoding (low-gamma, 25-35Hz) and top-down control (beta, 12-20Hz) was markedly reduced in ASD relative to typically developing (TD) children. Speech neural-tracking by delta and theta oscillations was also weaker in ASD than TD children. Critically, children with ASD exhibited slightly atypical theta/gamma coupling (PAC) involving a higher-than-normal gamma frequency, and markedly atypical beta/gamma PAC. Even though many oscillation features were atypical in our sample of 31 very young children with ASD, the beta/gamma coupling anomaly was the single best predictor of individual speech reception difficulties. These findings suggest that early interventions targeting the normalization of low-gamma and low-beta activity, might help young children with ASD to engage more in oral interactions. HighlightsVery young children diagnosed with autism spectrum disorder already present marked alterations of neural oscillatory activity in response to natural speech. The hierarchical processing of phonemic- and syllabic-range information (theta/gamma coupling) is atypical in young ASD children. Speech reception deficit in children with ASD is indexed by abnormal bottom-up (low-gamma) and top-down (low-beta) coordination.

neuroscience↗

bioRxiv2021

Distinct profiles of spatio-temporal brain dynamics along symptoms dimensions in autism

Autism Spectrum Disorders are accompanied by atypical brain activity and impairments in brain connectivity. In particular, dynamic functional connectivity approaches highlighted aberrant brain fluctuations at rest in individuals with autism compared to a group composed of typically developed individuals, matched in age and gender. However, the characterization of these variations remains unclear. Here, we quantified the spatio-temporal network dynamics using two novel dynamic group-based measures, namely system diversity and spatio-temporal diversity. Using the public database ABIDE 1, we explored the differences between individuals with autism and typically developed individuals. Our results show evidence that individuals with autism have atypical connectivity patterns over time characterized by a lower integration of heterogeneous cognitive processes and unstable functional activity, except for the default mode network presenting its own specific dynamic pattern. Within the autism group, we find this pattern of results to be stronger in more severely affected patients with a predominance of symptoms in the social affect domain. However, patients with prominently restricted and repetitive behaviours demonstrate a more conservative profile of brain dynamics characterized by a lower spatio-temporal diversity of the default mode network.

neuroscience↗

bioRxiv2020

Early alterations of large-scale brain networkstemporal dynamics in young children with autism.

Disruption of large-scale brain networks is associated with autism spectrum disorders (ASD). Recently, we found that directed functional connectivity alterations of social brain networks are a core component of atypical brain development at early developmental stages in ASD (Sperdin et al., 2018). Here, we investigated the spatio-temporal dynamics of whole-brain neuronal networks at a subsecond scale in 90 toddlers and preschoolers (47 with ASD) using an EEG microstate approach. Results revealed the presence of five microstate classes that best described the entire dataset (labeled as microstate classes A-E). Microstate class C related to the Default Mode Network (DMN) occurred less in children with ASD. Analysis of brain-behavioural relationships within the ASD group suggested that a compensatory mechanism from microstate C was associated with less severe symptoms and better adaptive skills. These results demonstrate that the temporal properties of some specific EEG microstates are altered in ASD at early developmental stages.

neuroscience↗

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↗

bioRxiv2017

Early alterations of social brain networks in young children with autism

Social impairments are a hallmark of Autism Spectrum Disorders (ASD), but empirical evidence for early brain network alterations in response to social stimuli is scant in ASD. Here, we recorded the gaze patterns and brain activity of toddlers and preschoolers with ASD and their typically developing (TD) peers while they explored dynamic social scenes. Source-space directed functional connectivity analyses revealed the presence of network alterations in the theta frequency band, manifesting as increased driving (hyper-activity) and stronger connections (hyper-connectivity) from key nodes of the social brain associated with autism. Further analyses of brain-behavioural relationships within the ASD group suggested that compensatory mechanisms from dorsomedial frontal, inferior temporal and insular cortical regions were associated with lower clinical impairment and less atypical gaze patterns. Our results provide strong evidence that directed functional connectivity alterations of social brain networks is a core component of atypical brain development at early stages of ASD.

neuroscience↗