Motor cortex inhibition: a marker of ADHD behavior and motor development in children

Abstract

Objective: Attention-deficit/hyperactivity disorder (ADHD) is a childhood-onset behavioral diagnosis in which children often fail to meet age norms in development of motor control, particularly timed repetitive and sequential movements, motor overflow, and balance. The neural substrate of this motor delay may include mechanisms of synaptic inhibition in or adjacent to the motor cortex. The primary objective of this study was to determine whether transcranial magnetic stimulation (TMS)-evoked measures, particularly short interval cortical inhibition (SICI), in motor cortex correlate with the presence and severity of ADHD in childhood as well as with commonly observed delays in motor control.

Methods: In this case-control study, behavioral ratings, motor skills, and motor cortex physiology were evaluated in 49 children with ADHD (mean age 10.6 years, 30 boys) and 49 typically developing children (mean age 10.5 years, 30 boys), all right-handed, aged 8-12 years. Motor skills were evaluated with the Physical and Neurological Examination for Subtle Signs (PANESS) and the Motor Assessment Battery for Children version 2. SICI and other physiologic measures were obtained using TMS in the left motor cortex.

Results: In children with ADHD, mean SICI was reduced by 40% (p < 0.0001) and less SICI correlated with higher ADHD severity (r = -0.52; p = 0.002). Mean PANESS motor development scores were 59% worse in children with ADHD (p < 0.0001). Worse PANESS scores correlated modestly with less SICI (r = -.30; p = 0.01).

Conclusion: Reduced TMS-evoked SICI correlates with ADHD diagnosis and symptom severity and also reflects motor skill development in children.

Figures

Figure 1. Transcranial magnetic stimulation (TMS) data from one typically developing child

Two EMG tracings are shown: one on the left from a single TMS pulse and one on the right from a 3-ms paired pulse, for which the first, conditioning pulse is subthreshold intensity and the second pulse has the same suprathreshold intensity as the single pulse. The motor evoked potential (MEP) amplitudes, which represent a summation of motor cortex system output, are circled. In the dot plot, each point represents the TMS-evoked, peak-to-peak MEP amplitude in mV from a single trial, out of multiple trials in the same child, after tracings with motion artifact have been removed. Trial-to-trial variability is always high, so multiple trials are needed for a good estimate. As shown on the right, amplitudes evoked by the condition/test paired pulses are smaller on average. Short interval cortical inhibition (SICI) for each individual is calculated from the means of the trials under each condition. Thus, SICI equals mean paired/mean single pulse MEP amplitudes. SICI may also be calculated as a percent reduction, e.g., a ratio of 0.58 would be 42% inhibition.

Figure 2. Short interval cortical inhibition (SICI) is significantly reduced in children with attention-deficit/hyperactivity disorder (ADHD) vs typical children

Larger ratios indicate less paired-pulse vs single-pulse inhibition (see figure 1).

Figure 3. Short interval cortical inhibition (SICI) correlates with behavioral ratings in children with attention-deficit/hyperactivity disorder (ADHD)

Higher Conners' Parent Rating Scale–Revised T scores indicate more severe ADHD symptoms, adjusted for age and gender. Higher SICI ratios indicate less inhibition.