Disturbed transcallosally mediated motor inhibition in children with attention deficit hyperactivity disorder (ADHD)

Abstract

Objective: The aim of this study was to investigate mechanisms of motor-cortical excitability and inhibition which may contribute to motor hyperactivity in children with attention deficit hyperactivity disorder (ADHD).

Methods: Using transcranial magnetic stimulation (TMS), involvement of the motor cortex and the corpus callosum was analysed in 13 children with ADHD and 13 sex- and age-matched controls. Contralateral silent period (cSP) and transcallosally mediated ipsilateral silent period (iSP) were investigated.

Results: Resting motor threshold (RMT), amplitudes of motor evoked potentials (MEP) and cSP were similar in both groups whereas iSP-latencies were significantly longer (p<0.05) and their duration shorter (p<0.01) in the ADHD group. For the ADHD group iSP duration tended to increase and iSP latency to decrease with age (n.s.). Conners-Scores did neither correlate with iSP-latencies and -duration nor with children's age.

Conclusions: The shortened duration of iSP in ADHD children could be explained by an imbalance of inhibitory and excitatory drive on the neuronal network between cortex layer III—the projection site of transcallosal motor-cortical fibers—and layer V, the origin of the pyramidal tract. The longer iSP-latencies might be the result of defective myelination of fast conducting transcallosal fibers in ADHD. iSP may be a useful supplementory diagnostic tool to discriminate between ADHD and normal children.

Introduction

Attention deficit hyperactivity disorder (ADHD) is a frequent neuropsychiatric syndrome in childhood with a prevalance of 3–6% (August et al., 1996, Rohde et al., 1999, Wender et al., 2001). It is characterized by inattentiveness and impulsivity, but the most outstanding symptom of ADHD is motor hyperactivity. Although pathomorphological studies revealed volumetric changes of the caudate nucleus (Castellanos et al., 1994, Filipek et al., 1997, Mataro et al., 1997), the cerebellum (Berquin et al., 1998) and the corpus callosum (CC) (Hynd et al., 1991, Giedd et al., 1994, Steere and Arnsten, 1995), the pathophysiology of ADHD is not well understood. fMRI studies showed that boys suffering from ADHD had longer T2-relaxation times in the putamen bilaterally compared to healthy controls (Teicher et al., 2000). Thus ADHD symptoms may be related to functional abnormalities of the putamen, an anatomical structure considered to be involved in the regulation of motor behaviour. Compatible with this view were PET studies of Lou et al. (1989), demonstrating a decrease of striatal activity as a cardinal feature of ADHD, and of Ernst et al. (1999) showing dysfunctions of dopaminergic nuclei (including caudate nucleus, putamen, frontal cortex, and midbrain (i.e. substantia nigra and ventral tegmentum)). In addition, abnormal low activations of prefrontal systems involved in voluntary regulation of motor control were found (Casey et al., 1997, Rubia et al., 1999). Furthermore event related potentials using oddball and reaction time paradigms in ADHD disclosed inhibitory control deficits as well as impaired orienting to cues (see, for example, Brandeis et al., 1998, van Leeuwen et al., 1998, Pliszka et al., 2000).

Motor hyperactivity in ADHD can be understood either as a result of abnormal facilitation or of defective inhibition of motor programs. Transcranial magnetic cortex stimulation (TMS) is a neurophysiological tool to study non-invasively the motor system in man (Ziemann et al., 1996a, Ziemann et al., 1996b, Ziemann, 2001). Using TMS in ADHD, Moll et al. (1999) found normal central motor latencies as well as unaffected postexcitatory inhibition times (cortical silent period (cSP)). However, they also reported that a sub-threshold conditioning stimulus in a paired pulse paradigm (PPI) produced less inhibition of test stimulus amplitude in ADHD children and in children with a combination of Tic/Tourette and ADHD than in controls (Moll et al., 2000, Moll et al., 2001 indicating a deficit of intracortical motor inhibition in ADHD.

Previous studies have shown that TMS induces not only a response in muscles contralateral to the stimulation, but also a transient inhibition of voluntary tonic muscle activity in ipsilateral hand muscles (Wassermann et al., 1991, Ferbert et al., 1992). This ipsilateral silent period (iSP) is thought to be mediated by transcallosal fibers and inhibitory interneurons affecting the neuronal network between the primary motor cortex layer III contralateral to stimulation—the projection site of transcallosal motor fibers—and cortex layer V, the origin of the pyramidal tract (Meyer et al., 1995, Meyer et al., 1998, Meyer, 1996). Thus iSP is considered to reflect the functional integrity of the transcallosal fibers connecting corresponding motorcortices (Ferbert et al., 1992, Meyer et al., 1995). As a whole, cSP and PPI are considered to be parameters of ipsilaterally TMS-induced intracortical motor inhibition, whereas iSP is used to assess transcallosally mediated motor inhibition between both hemispheres (Ziemann et al., 1996a, Ziemann et al., 1996b).

Since pathomorphological investigations have shown that the volume of the anterior part of the truncus and the rostrum of the CC is decreased in ADHD compared to controls (Hynd et al., 1991, Giedd et al., 1994, Steere and Arnsten, 1995), it is reasonable to assume that disturbances of fiber tracts of CC mediating transcallosal inhibition may contribute to motor hyperactivity. It was the aim of our study to find out if iSP was selectively disturbed in children with ADHD as compared to age- and sex-matched control subjects, and if this were the case, whether iSP could be used as a functional neurophysiological parameter to discriminate ADHD from controls.