Motor skill learning in autism: assessment and treatment of altered patterns of learning.

Principal Investigator: Stewart Mostofsky

Detailed study of motor impairments in autism can provide valuable insights into the neural basis of the disorder and help to guide its treatment. Given the developmental nature of autism, during the initial funding period we initiated a research program focused on examining processes underlying acquisition of motor skills, i.e., motor learning. This course of study led to a critical observation: there is a fundamental difference in how children with autism learn motor skills; they build a stronger than normal association between motor commands and proprioceptive feedback and a weaker than normal association between the same commands and visual feedback. The findings provide a rationale for why children with autism are impaired in their ability to acquire models of action through visually-based imitation, including those necessary to understand and interpret the meaning of others’ social and communicative behavior. This behavioral difference may have its roots in the wiring of the brain: imaging and post-mortem studies have revealed an over-expression of short-range axons, including those connecting primary motor and somatosensory cortices, with increased volume and paradoxically decreased organization of white matter in these regions. Our imaging findings from the initial grant period provide preliminary support for this hypothesis, revealing that motor skill impairment in autism is associated with abnormalities in both structural and functional connectivity. Critical questions remain regarding the clinical relevance and neural basis of the stronger than normal association between motor commands and proprioceptive feedback in autism and whether a change in this bias can be achieved, providing an effective method of treating impaired skill acquisition. Consequently, we propose: to confirm that children with autism show a bias towards proprioceptive-guided motor learning and determine whether this is associated with core social, communicative, and behavioral (including motor) impairments (Aim 1); to use both structural (Aim 2) and functional (Aim 3) MRI methods to examine the neural basis of autism-associated alterations in motor learning; and to determine whether transcranial direct current stimulation (tDCS) can help children with autism develop internal models of behavior that are better at predicting external consequences, as is important for guiding socialization and communication (Aim 4). The proposed studies will establish a foundation for using advanced methods of motor and neuroimaging analysis to examine the brain basis of autism, and, most critically, for designing and testing novel methods of treatment. Details of our specific aims are as follows:

Specific Aim #1: To examine learning of internal models in autism and test for correlations between patterns of motor learning and measures of core social, communicative, and behavioral impairments.

The working hypothesis is that children with autism will demonstrate a pattern of increased reliance on proprioceptive feedback during motor learning and that this pattern will predict core social and motor impairments. To test this hypothesis, the properties of the internal models (i.e., the associations between motor actions and sensory feedback) that children form when learning to use novel tools will be examined using a robotic apparatus that produces force fields on the hand. We will correlate measures of internal model formation with measures of core social, communicative and behavioral features of autism.

Specific Aim #2: To determine, using anatomic MRI (aMRI) and diffusion tensor imaging (DTI), whether anomalous overgrowth of white matter connections localized within primary sensorimotor cortex (SM1) contributes to autism-associated differences in motor skill performance and learning.

The working hypothesis is that for children with autism, increased volume and paradoxically decreased organization (lower fractional anisotropy, FA) of connections within neighboring somatosensory and motor cortices (SM1) will predict impaired motor skill performance and anomalous patterns of motor learning (increased reliance on proprioceptive feedback). To test this hypothesis we will use aMRI and DTI methods to examine volume and FA within SM1, correlating this with measures of motor skill performance and altered patterns of motor learning derived in Aim 1.

Specific Aim #3: To determine, using functional connectivity MRI (fcMRI), whether autism-associated differences in motor skill and learning are associated with differences in functional connectivity.

The working hypothesis is that during a task of motor sequence learning, children with autism will show decreased functional connectivity, as compared to TD controls, between distant cortical and subcortical regions important to motor learning and that this decreased functional connectivity will predict autism-associated impairments in motor skill and anomalous patterns of motor learning derived in Aim 1.

Specific Aim #4: Working toward a treatment, we will determine whether modulation of activity in somatosensory and visual association cortices of children with autism will alter the pattern of motor learning, decreasing reliance on proprioceptive feedback and increasing reliance on visual feedback.

The working hypothesis is that cathodal tDCS over the primary sensorimotor cortex will decrease the association between self-generated motor commands and proprioceptive feedback and that anodal tDCS over the posterior parietal cortex will increase the association between self-generated motor commands and visual feedback. To examine this hypothesis we propose to use tDCS to modulate excitability during motor learning using the task in Aim 1. The findings will help determine whether brain stimulation can alter the way children with autism learn skills, and thereby lead to a potentially important therapeutic approach.

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