Resting-state networks in adolescents with 22q11.2 deletion syndrome: Associations with prodromal symptoms and executive functions

Atypical functional connectivity in the maturing brains of 22q11.2 deletion syndrome (22q11DS) may contribute to the expression of early psychotic symptoms commonly reported by these youths. This study's objective was to examine functional connectivity in cerebral networks at rest (Resting-State Networks; RSNs) and their relationship to symptomatic and neuropsychological characteristics putting them at very high risk factor for developing psychosis. Twenty-seven adolescents with 22q11DS and 33 typically developing control adolescents matched for age, gender and handedness underwent an 8-minute resting state functional MRI session. RSNs identification procedure employed Independent Component Analysis (ICA). We tested for potential group differences in functional connectivity within-networks. Then, we examined relationships between network connectivity and symptomatic/neuropsychological characteristics in the 22q11DS group. A total of nine resting-state networks were identified. Between-group differences suggested both increased and decreased functional connectivity in the 22q11DS group, involving the default-mode, sensorimotor, visuo-spatial, and high level visual networks. Finally, atypical connectivity in the default-mode network, specifically within the left superior frontal gyrus region, correlated with prodromal symptom intensity and neuropsychological performances in the 22q11DS group. The results suggest that atypical functional connectivity may sustain both increased vulnerability to psychosis and characteristic cognitive impairments in 22q11DS. (C) 2012 Elsevier B.V. All rights reserved.

Structural and functional connectivity in the default mode network in 22q11.2 deletion syndrome

Maria Carmela Padula, Marie Schaer, Maude Schneider, Dimitri Nestor Alice Van De Ville

Background: The neural endophenotype associated with 22q11.2 deletion syndrome (22q11DS) includes deviant cortical development and alterations in brain connectivity. Resting-state functional magnetic resonance imaging (fMRI) findings also reported disconnectivity within the default mode network (DMN). In this study, we explored the relationship between functional and structural DMN connectivity and their changes with age in patients with 22q11DS in comparison to control participants. Given previous evidence of an association between DMN disconnectivity and the manifestation of psychotic symptoms, we further investigated this relationship in our group of patients with 22q11DS. Methods: T1-weighted, diffusion, and resting-state fMRI scans were acquired from 41 patients with 22q11DS and 43 control participants aged 6 to 28 years. A data-driven approach based on independent component analysis (ICA) was used to identify the DMN and to define regions of interest for the structural and functional connectivity analysis. Prodromal psychotic symptoms were assessed in adolescents and adults using the positive symptom scores of the Structured Interview of Prodromal Syndromes (SIPS). Connectivity measures were compared between groups and correlated with age. Repeating the between-group analysis in three different age bins further assessed the presence of age-related alterations in DMN connectivity. Structural and functional connectivity measures were then correlated with the SIPS scores. Results: A simultaneous reduction of functional and structural connectivity between core medial nodes of the DMN was observed. Furthermore, structural connectivity measures significantly increased with age in the control group but not in patients with 22q11DS, suggesting the presence of an age-related alteration of the DMN structural connections. No correlations were found between the DMN disconnectivity and expression of prodromal symptoms in 22q11DS. Conclusions: These findings indicate the presence of functional and structural DMN disconnectivity in 22q11DS and that patients with 22q11DS fail to develop normal structural connections between medial DMN nodes. This suggests the presence of altered neurodevelopmental trajectories in 22q11DS.

BioMed Central2015

Impact of transient emotions on functional connectivity during subsequent resting state: A wavelet correlation approach

Dimitri Nestor Alice Van De Ville

The functional properties of resting brain activity are poorly understood, but have generally been related to self-monitoring and introspective processes. Here we investigated how emotionally positive and negative information differentially influenced subsequent brain activity at rest. We acquired fMRI data in 15 participants during rest periods following fearful, joyful, and neutral movies. Several brain regions were more active during resting than during movie-watching, including posterior/anterior cingulate cortices (PCC. ACC), bilateral insula and inferior parietal lobules (IPL). Functional connectivity at different frequency bands was also assessed using a wavelet correlation approach and small-world network analysis. Resting activity in ACC and insula as well as their coupling were strongly enhanced by preceding emotions, while coupling between ventral-medial prefrontal cortex and amygdala was selectively reduced. These effects were more pronounced after fearful than joyful movies for higher frequency bands. Moreover, the initial suppression of resting activity in ACC and insula after emotional stimuli was followed by a gradual restoration over time. Emotions did not affect IPL average activity but increased its connectivity with other regions. These findings reveal specific neural circuits recruited during the recovery from emotional arousal and highlight the complex functional dynamics of default mode networks in emotionally salient contexts. (C) 2010 Elsevier Inc. All rights reserved.

Elsevier2011

Recovery of the default mode network after demanding neurofeedback training occurs in spatio-temporally segregated subnetworks

Sven Haller, Rotem Roza Kopel, Dimitri Nestor Alice Van De Ville

The default mode (DM) network is a major large-scale cerebral network that can be identified with functional magnetic resonance imaging (fMRI) during resting state. Most studies consider functional connectivity networks as stationary phenomena. Consequently, the transient behavior of the DM network and its subnetworks is still largely unexplored. Most functional connectivity fMRI studies assess the steady state of resting without any task. To specifically investigate the recovery of the DM network during the transition from activation to rest, we implemented a cognitively demanding real-time fMRI neurofeedback task that targeted down-regulation of the primary auditory cortex. Each of twelve healthy subjects performed 16 block-design fMRI runs (4 runs per day repeated on 4 days) resulting 192 runs in total. The analysis included data-driven independent component analysis (ICA) and high-resolution latency estimation between the four components that corresponded to subnetworks of the DM network. These different subnetworks reemerged after regulation with an average time lag or 3.3 s and a time lag of 4.4 s between the first and fourth components; i.e., the DM recovery first shifts from anterior to posterior, and then gradually focuses on the ventral part of the posterior cingulate cortex, which is known to be implicated in internally directed cognition. In addition, we found less reactivation in the early anterior subnetwork as regulation strength increased, but more reactivation with larger regulation for the late subnetwork that encompassed the ventral PCC. This finding confirms that the level of task engagement influences inversely the subsequent recovery of regions related to attention compared to those related to internally directed cognition. (C) 2012 Elsevier Inc. All rights reserved.