Abnormal GABA Concentration in Brain Motor Areas Are Related with Gross Motor Impairments in Individuals with Autism Spectrum Disorder

Background: Various motor difficulties are commonly observed in individuals with autism spectrum disorder (ASD). Previous studies have demonstrated that impaired motor performance may be explained by a lower concentration of gamma-aminobutyric acid (GABA) in the primary motor area (M1) in individuals with ASD. However, lower GABA concentrations in M1 have been linked to strong neural activity in the corresponding region and strong muscle constriction in neurotypical individuals; thus, it seems paradoxical that many individuals with ASD have motor skill impairments.

Objectives: We investigated the types of motor skill that are associated with GABA levels in brain motor area. Motor skills were evaluated using the clinically accepted Bruininks-Oseretsky Test of motor proficiency, second edition (BOT-2).

Methods: The BOT-2 measures various motor performances which includes both fine and gross motor skills. The fine motor skills assessed include precise bodily control that requires finger and hand movement (1. fine manual control) and bimanual/arm-hand coordination (2. manual coordination). The gross motor skills include sequential and simultaneous bodily coordination (3. body coordination) and strength of trunk, upper and lower body (4. strength and agility). Total score is summation of the scores for four motor skills. GABA concentration in brain motor area were measured using ¹H-magnetic resonance spectroscopy (¹H-MRS). We measured GABA in left M1 and the supplementary motor area (SMA). In addition, we evaluated degree of the autistic traits by the autism spectrum quotient (AQ) score.

Results: Eight individuals with ASD and ten typically developing (TD) controls participated in the experiments. We found that significant negative correlation between GABA concentration in M1 and total score in the BOT-2 (see figure.1), especially for gross motor skills (3. body coordination, 4. strength and agility) in all participants. ASD participants who had a lower concentration of GABA in SMA tended to exhibit lower levels of motor performance (see figure.2) especially for the skills of whole body coordination (3. body coordination). Furthermore, higher GABA levels in M1 were associated with stronger autistic traits evaluated by the AQ score. M1 receives information from higher-order motor related areas and outputs signals to control muscles via the brainstem and spinal cord. We assumed that excessively high GABA concentration in M1 would suppress strong neural activity, resulting weak neural signal to muscle and degraded muscle contraction necessary for gross motions. Reduced GABA in SMA may induce asynchronized neural oscillations across the left and right hemispheres since GABA is required for synchronising neural oscillations. These atypical conditions of GABA concentration in motor related areas were implied to be an underlying basis of other aspects of autism (e.g., difficulties in social communication).

Conclusions: Abnormal GABA levels in M1 and SMA contributes to motor impairments (i.e., gross motor skills and body coordination, respectively) in ASD. The present findings would contribute to the development of objective evaluations for several motor impairments, and accompanied difficulties derived from autistic features.