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

Padula MC, Schaer M, Scariati E, Schneider M, Van De Ville D, Debbané M, Eliez S - J Neurodev Disord (2015)

Bottom Line: Connectivity measures were compared between groups and correlated with age.A simultaneous reduction of functional and structural connectivity between core medial nodes of the DMN was observed.No correlations were found between the DMN disconnectivity and expression of prodromal symptoms in 22q11DS.

View Article: PubMed Central - PubMed

Affiliation: Office Médico-Pédagogique, Department of Psychiatry, University of Geneva, Rue David-Dufour 1, Case Postale 50, 1211 Genève 8, Switzerland.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

Structural connectivity between the anterior and the posterior node of the DMN (default mode network). DMN clusters were registered in DTI space (a) and used as regions of interest (ROIs) for the probabilistic tractography analysis (b). The connectivity map is represented in red/yellow colors and overlaid onto the fractional anisotropy (FA) map. The lighter the color, the greater the probability to have a connection. Structural connectivity measures (c) were significantly reduced in the 22q11DS population compared with controls (p < 0.05, indicated by *, p < 0.01, indicated by **)
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Fig2: Structural connectivity between the anterior and the posterior node of the DMN (default mode network). DMN clusters were registered in DTI space (a) and used as regions of interest (ROIs) for the probabilistic tractography analysis (b). The connectivity map is represented in red/yellow colors and overlaid onto the fractional anisotropy (FA) map. The lighter the color, the greater the probability to have a connection. Structural connectivity measures (c) were significantly reduced in the 22q11DS population compared with controls (p < 0.05, indicated by *, p < 0.01, indicated by **)

Mentions: Detailed descriptions of the structural connectivity measurements are displayed in Table 2. In the group of patients with 22q11DS, we observed a reduced number of tracts and mean connectivity index between the anterior and posterior medial regions of the DMN and between the anterior node of the DMN and the left IPL (Fig. 2). In order to assess if medication was affecting the results, we repeated the analysis after excluding the patients that were taking any psychotropic medication at the time of the visit. The results of the statistical analysis are reported in the Additional file 1: Table S3. Even with this smaller sample size, the results remained qualitatively the same. The mean FA values for both tracts did not show any significant reduction (p > 0.52) in the 22q11DS population.Table 2


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

Padula MC, Schaer M, Scariati E, Schneider M, Van De Ville D, Debbané M, Eliez S - J Neurodev Disord (2015)

Structural connectivity between the anterior and the posterior node of the DMN (default mode network). DMN clusters were registered in DTI space (a) and used as regions of interest (ROIs) for the probabilistic tractography analysis (b). The connectivity map is represented in red/yellow colors and overlaid onto the fractional anisotropy (FA) map. The lighter the color, the greater the probability to have a connection. Structural connectivity measures (c) were significantly reduced in the 22q11DS population compared with controls (p < 0.05, indicated by *, p < 0.01, indicated by **)
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4522079&req=5

Fig2: Structural connectivity between the anterior and the posterior node of the DMN (default mode network). DMN clusters were registered in DTI space (a) and used as regions of interest (ROIs) for the probabilistic tractography analysis (b). The connectivity map is represented in red/yellow colors and overlaid onto the fractional anisotropy (FA) map. The lighter the color, the greater the probability to have a connection. Structural connectivity measures (c) were significantly reduced in the 22q11DS population compared with controls (p < 0.05, indicated by *, p < 0.01, indicated by **)
Mentions: Detailed descriptions of the structural connectivity measurements are displayed in Table 2. In the group of patients with 22q11DS, we observed a reduced number of tracts and mean connectivity index between the anterior and posterior medial regions of the DMN and between the anterior node of the DMN and the left IPL (Fig. 2). In order to assess if medication was affecting the results, we repeated the analysis after excluding the patients that were taking any psychotropic medication at the time of the visit. The results of the statistical analysis are reported in the Additional file 1: Table S3. Even with this smaller sample size, the results remained qualitatively the same. The mean FA values for both tracts did not show any significant reduction (p > 0.52) in the 22q11DS population.Table 2

Bottom Line: Connectivity measures were compared between groups and correlated with age.A simultaneous reduction of functional and structural connectivity between core medial nodes of the DMN was observed.No correlations were found between the DMN disconnectivity and expression of prodromal symptoms in 22q11DS.

View Article: PubMed Central - PubMed

Affiliation: Office Médico-Pédagogique, Department of Psychiatry, University of Geneva, Rue David-Dufour 1, Case Postale 50, 1211 Genève 8, Switzerland.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus