Abnormal Speech Motor Control in Individuals with 16p11.2 Deletions

Abstract

Speech and motor deficits are highly prevalent (>70%) in individuals with the 600 kb BP4-BP5 16p11.2 deletion; however, the mechanisms that drive these deficits are unclear, limiting our ability to target interventions and advance treatment. This study examined fundamental aspects of speech motor control in participants with the 16p11.2 deletion. To assess capacity for control of voice, we examined how accurately and quickly subjects changed the pitch of their voice within a trial to correct for a transient perturbation of the pitch of their auditory feedback. When compared to controls, 16p11.2 deletion carriers show an over-exaggerated pitch compensation response to unpredictable mid-vocalization pitch perturbations. We also examined sensorimotor adaptation of speech by assessing how subjects learned to adapt their sustained productions of formants (speech spectral peak frequencies important for vowel identity), in response to consistent changes in their auditory feedback during vowel production. Deletion carriers show reduced sensorimotor adaptation to sustained vowel identity changes in auditory feedback. These results together suggest that 16p11.2 deletion carriers have fundamental impairments in the basic mechanisms of speech motor control and these impairments may partially explain the deficits in speech and language in these individuals.

Figure 1

Apparatus for Pitch Perturbation Task. The participant phonates the vowel sound “ahh” into a headset microphone for the duration of a visual cue presented for 2.5 seconds. The microphone signal is then digitally processed to randomly shift the pitch of the recorded speech at a variable lag from speech onset up or down by 100 cents in real time creating an effect of altered auditory feedback in the participants headphones.

Figure 2

Apparatus for Formant Adaptation Task. The participant is cued to read the word “bed” aloud into a headset microphone. The digital signal processor then alters the formants (F1 and F2) of the auditory feedback so that participants hear the vowel /ae/ when they produced the vowel /eh/. F1 was raised by 200 Hz and F2 was reduced by −250 Hz during the altered block of 30 trials. Thus, on these trials, when subjects produced the word “bed” they heard the word “bad”.

Figure 3

Average changes in compensation over the course of the vocalization in the Pitch Perturbation Task for participants with 16p11.2 deletions and the control group. The shaded area indicates the onset of auditory feedback perturbation. 16p11.2 deletion carriers demonstrate an exaggerated compensation response relative to the control participants.

Figure 4

Individual participant mean responses to pitch perturbation task. Mean percentage compensation (vertical axis) responses (solid lines) and error bars (shaded lines) are depicted for participants in the 16p11.2 deletion (blue) and control (red) groups across time from perturbation onset in seconds (horizontal axis). The shaded regions represent the standard error of the mean percentage compensation across all trials for every individual.

Figure 5

Mean group adaptation across trials for the baseline and altered feedback conditions in the Formant Adaptation Task. While groups did not differ at baseline, significant group differences were identified in the altered feedback condition, with the deletion carriers showing significantly reduced adaptation.

Figure 6

Mean adaptation responses with error bars across trials grouped into bins of five trials. Significant linear effects of group and group by trial number interaction are illustrated. Following the baseline trials in which feedback was unaltered (trials 1–20), the control group demonstrated a gradual increase in adaptation with increasing number of altered feedback trials (21–50), whereas the 16p11.2 deletion group show a weaker adaptation response.

Figure 7

Individual participant across trial responses to speech adaptation task. Mean percentage adaptation (vertical axis) for groups of five trials (asterisks) are depicted with error bars for participants in the 16p11.2 deletion (blue) and control (red) groups across trials (horizontal axis). The dashed vertical line indicates the onset of altered feedback trials.