Individuals with 16p11.2 syndrome, a disorder caused by a deletion or duplication of a section of chromosome 16, exhibit a broad variety of motor abnormalities, including clumsiness, poor coordination, hypotonia (decreased muscle tone) and tremor, as well as some features of autism. The underlying neurobiological basis for motor impairments in 16p11.2 syndrome has not yet been investigated.

Magnetic resonance spectroscopy (MRS) is a noninvasive neuroimaging technique that estimates the concentration of metabolites and neurotransmitters in vivo. Gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the human brain, can be measured using this technique in combination with spectral editing techniques (such as MEGA-PRESS). Using such an approach, William Gaetz and his colleagues previously observed decreased GABA concentrations in auditory and motor areas, but not in visual areas, in the brains of children with autism¹. The aim of the current study was to extend these findings to investigate whether the neurochemistry of the motor system is atypical in individuals with 16p11.2 syndrome.

In the first part of the study, MRS was used to assess GABA concentrations in the motor cortex of 38 individuals with 16p11.2 syndrome (17 with 16p11.2 deletions and 21 with duplications) and 40 controls.  Children and adults were included in both study groups. Gaetz and his team observed a significant decrease in GABA levels in children with 16p11.2 duplications compared with typically developing children. Children with 16p11.2 deletions did not differ from typically developing children. In addition, no significant differences were observed between the groups in adult participants.

In a second set of experiments, the researchers sought to evaluate if the MRS estimates of GABA levels in the motor cortex correlate with clinical measures of motor impairment. A significant impairment in motor ability — as scored using the Movement-Assessment Battery for Children — was observed in children with 16p11.2 syndrome. Interestingly, children with 16p11.2 deletions displayed more motor impairments than those with 16p11.2 duplications. 16p11.2 deletion individuals who exhibit greater motor impairment also tende to have lower GABA concentrations in the motor cortex, although such a correlation is not statistically significant at this stage.

Gaetz and his colleagues also performed preliminary studies to assess motor cortex function in individuals with 16p11.2 syndrome. A functional neuroimaging technique known as magnetoencephalography (MEG) was used to map brain activity while participants performed a visually cued button-press task. Poor compliance on this task significantly undermined MEG measurements in these children. Further studies are required to address whether motor cortex oscillations are changed in children with 16p11.2 syndrome.