Motor Cortex Inhibition in Youth with ASD and Co-Morbid ADHD a Marker for Clinical Executive Functioning

Background:  Individuals with a co-diagnosis of ADHD and co-morbid ASD are reported to have higher rates of hospitalization, medication treatment, and behavioral therapy than ASD alone [1]. In addition, youth with dual diagnosis have therapeutic implications including distinct treatment and neural correlates [2, 3]. Currently, there lack of an objective methodology for the diagnosis and management of ASD+ADHD , especially in regards to pharmacotherapy response. Previously, we have demonstrated that a transcranial magnetic stimulation (TMS) evoked measure, short-interval cortical inhibition (SICI) has been associated with ADHD diagnosis and severity [4]. SICI is a TMS measure of the efficiency of inhibitory interneurons in the primary motor cortex (M1) [5].

Objectives: To measure resting paired pulse TMS evoked cortical inhibition (SICI) and determine the relationship between SICI and executive functioning deficits in youth with ASD and co-morbid ADHD.

Methods: Baseline TMS measures of youth with ASD and co-morbid ADHD currently enrolled in a double-blind placebo controlled randomized control trial examining physiological effects of a single dose methylphenidate was analyzed for association with clinical severity of the Connors-3 Parent Rating Scale rating scale. The modulus of TMS motor evoked potentials by surface electromyography of the dominant hand was used as the primary outcome.

Results:  The dataset included 13 male subjects with ASD with a mean age of 15 (SD 2.8, range 11 to 20). As expected, significant inhibition of MEP modulus was demonstrated with a 3 ms subthreshold paired pulse (M=0.008; SD=0.010) compared to single pulse TMS (M=0.011; SD=0.009) t=3.916, p < 0.001). There was a correlation between SICI and Connor’s total executive functioning score (Figure 1; r=-0.578, n=13, p=0.039). A trending relationship was identified between SICI and the total Connor’s score (r=-0.518, n=13, 0.070).

Conclusions: We identified preliminary data suggesting that a TMS measure of motor cortex inhibition is significantly associated with a well-validated behavioral measure of executive function. As a quantitative physiological marker of motor function that can be obtained quickly, SICI is an ideal candidate which to clarify fundamental mechanisms of cerebral function that underlie impaired behavioral control.

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2. RUPP, Randomized, controlled, crossover trial of methylphenidate in pervasive developmental disorders with hyperactivity. Arch Gen Psychiatry, 2005. 62: p. 1266-1274.

3. Geurts, H., et al., How specific are executive functioning deficits in attention deficit hyperactivity disorder and autism? J Child Psychol Psychiatry, 2004. 45: p. 836 - 54.

4. Gilbert, D.L., et al., Motor cortex inhibition: A marker of ADHD behavior and motor development in children. Neurology, 2011. 76(7): p. 615-621.

5. Kujirai, T., et al., Corticocortical inhibition in human motor cortex. J Physiol, 1993. 471: p. 501-19.