Stuttering, induced fluency, and natural fluency: a hierarchical series of activation likelihood estimation meta-analyses

Abstract

Developmental stuttering is a speech disorder most likely due to a heritable form of developmental dysmyelination impairing the function of the speech-motor system. Speech-induced brain-activation patterns in persons who stutter (PWS) are anomalous in various ways; the consistency of these aberrant patterns is a matter of ongoing debate. Here, we present a hierarchical series of coordinate-based meta-analyses addressing this issue. Two tiers of meta-analyses were performed on a 17-paper dataset (202 PWS; 167 fluent controls). Four large-scale (top-tier) meta-analyses were performed, two for each subject group (PWS and controls). These analyses robustly confirmed the regional effects previously postulated as "neural signatures of stuttering" (Brown, Ingham, Ingham, Laird, & Fox, 2005) and extended this designation to additional regions. Two smaller-scale (lower-tier) meta-analyses refined the interpretation of the large-scale analyses: (1) a between-group contrast targeting differences between PWS and controls (stuttering trait); and (2) a within-group contrast (PWS only) of stuttering with induced fluency (stuttering state).

Keywords: ALE; Activation likelihood estimation; Functional neuroimaging; Meta-analysis; Persistent developmental stuttering.

Figure 1. Large-Scale Meta-Analyses, (A) Comprehensive and (B) Refined

The top section (A) shows areas of consistent activation for PDS (red) and controls (blue) in ‘comprehensive’ within-group meta-analyses, with areas of overlap in aqua (Cf. Supplementary Table 2 for xyz locations and anatomical labels). The bottom section (B) shows areas of consistent activation for PDS (red) and controls (blue) in the ‘refined’ “within-group meta-analyses, with areas of overlap in aqua (cf. Supplementary Table 2 for xyz locations and anatomical labels. All activations are overlaid on MNI152 atlas; slice numbers reference MNI152 space.

Figure 2. Targeted Sub-Analyses, (A) Between-Group and (B) Within-Group

The left section (A) slices shows areas of consistent activation in the between-group (PDS vs. Controls) meta-analysis. PDS are shown in red, controls in blue. The laterality plot shows right-lateralized speech production in PDS compared to controls (cf. Supplementary Table 3 for xyz coordinates and anatomical labels). All activations are overlaid on MNI152 atlas; slice numbers reference MNI152 space. The right section (B) slices show areas of consistent activation during dysfluent (red) and fluent (blue) speech in the within-group meta-analysis (cf. Supplementary Table 4 for xyz locations and anatomical labels). Areas that retained significance in the contrast analysis are shown for PDS (orange) and controls (aqua). The laterality plot shows the contrast analysis, with frontal and cerebellar activations during dysfluency (red), and temporo-parietal activations during fluency (blue). Note: contrast analysis results (i.e. orange and aqua) are not shown on laterality plot. All activations are overlaid on MNI152 atlas; slice numbers reference MNI152 space. Abbreviations: Sup=superior; RFO=right frontal operculum; Mid=middle.