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

Friday, May 12, 2017: 5:00 PM-6:30 PM
Golden Gate Ballroom (Marriott Marquis Hotel)
L. N. Mooney1, D. L. Gilbert2, M. P. Hong1, J. L. Guilfoyle1, S. W. Wu3, C. A. Erickson4, L. K. Wink4 and E. Pedapati5, (1)Psychiatry, Cincinnati Childrens Hospital, Cincinnati, OH, (2)Neurology, Cincinnati Childrens Hospital, Cincinnati, OH, (3)Cincinnati Childrens Hospital, Cincinnati, OH, (4)Cincinnati Children's Hospital Medical Center, Cincinnati, OH, (5)INSAR Cincinnati Children's Hospital Medical Center, Cincinnati, OH
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.

1. Frazier, J.A., et al., Should the diagnosis of Attention-Deficit/ Hyperactivity disorder be considered in children with Pervasive Developmental Disorder? Journal of Attention Disorders, 2001. 4(4): p. 203-211.

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.