Self-regulation therapy increases frontal gray matter in children with fetal alcohol spectrum disorder: evaluation by voxel-based morphometry

Debra W Soh, Jovanka Skocic, Kelly Nash, Sara Stevens, Gary R Turner, Joanne Rovet, Debra W Soh, Jovanka Skocic, Kelly Nash, Sara Stevens, Gary R Turner, Joanne Rovet

Abstract

Children with fetal alcohol spectrum disorder show executive function (EF) deficits, particularly in self-regulation skills, and abnormalities in brain regions critical for these skills. None of the validated EF interventions for these children has been evaluated with regards to impacts on brain structure. Twenty-nine children with FASD were assigned to either an immediate-treatment (TX) or delayed-treatment control (DTC) group (DTC). Nineteen typically developing children served as healthy controls (CT). All received a structural MRI scan and baseline neuropsychological testing, following which the TX group underwent 12 weekly 1.5-h sessions of the Alert Program for Self-Regulation(®). After treatment or a period of ~14 weeks, all received a repeat scan and post-intervention testing. Whole-brain and region-of-interest analyses using voxel-based morphometry evaluated group differences and changes over time in gray matter (GM). Exploratory analyses revealed significant group changes: (1) At baseline, combined TX and DTC groups demonstrated global GM reductions compared with the CT group. (2) Region-of-interest analysis using a frontal mask, comparing post-intervention to pre-intervention results, showed significantly increased GM in the left middle frontal gyrus (BA10), right frontal pole (BA11), and right anterior cingulate (BA32) in the TX group. Similar results were not found in the DTC or CT groups. (3) At post-intervention, both TX and CT groups showed larger GM volumes than the DTC group in the left superior frontal gyrus (BA9), which was smaller in the FASD group at baseline. These results suggested that Alert led to improvements in post-intervention testing of self-regulation skills and typical brain development in treated children.

Keywords: Alert therapy; FASD; VBM; executive functioning; neuroplasticity; self-regulation of emotions.

Figures

Figure 1
Figure 1
CONSORT flow diagram of progress through enrolment, pretest, posttest, and data analysis for FASD and CT groups.
Figure 2
Figure 2
Sagittal views of regions showing significant (p <0.001, uncorrected) differences in gray matter volume at baseline for CT vs. FASD (TX and DTC combined): left superior frontal gyrus (BA8) [−37, 17, 60] (left) and left medial frontal gyrus (BA8) [−3, 25, 44] (right).
Figure 3
Figure 3
Sagittal view of regions involving significant within-group increases of gray matter volume at post-intervention. (A) TX group, left middle frontal gyrus (BA10) [−32, 47, 0], p < 0.001, uncorrected; (B) DTC group, right cingulate gyrus (BA24) [19, 4, 30], p < 0.001, uncorrected; (C) CT group, left inferior frontal gyrus (BA9) [−45, 6, 18], p < 0.001, uncorrected.
Figure 4
Figure 4
Sagittal views of regions involving significant differences in gray matter volume at post-intervention. (A) TX vs. DTC group, left superior frontal gyrus (BA9) [−23, 38, 32], p < 0.005, uncorrected; (B) CT vs. TX group, left superior frontal gyrus (BA9) [−2, 58, 27], p < 0.001, uncorrected.

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