The N100 component, evoked by transcranial magnetic stimulation (TMS) and electroencephalography is associated with the activation of inhibitory cortical circuits and has recently been suggested as a potential marker of inhibition in attention-deficit/hyperactivity disorder (ADHD). The aim of the present ADHD study was to investigate the modulation of the TMS-N100 in go and nogo trials of a response control task considering stages of response preparation, activation, execution and inhibition. Eighteen children with ADHD and 19 typically developing children, aged 10-14 years, were assessed. TMS was delivered over the left motor cortex, the TMS-N100 was measured at electrode P3. The TMS-N100 was determined at rest and at different time points (50 ms before S2; 150, 300 and 500 ms after S2) in a cued go/nogo task (S1-S2 paradigm). Correlations between the TMS-N100 measures, MEP-related TMS measures (e.g., short-interval intracortical inhibition) and performance measures were calculated. At rest, the amplitude of TMS-N100 was not found to be significantly reduced in the ADHD group. During the go/nogo task, children with ADHD showed a smaller increase of TMS-N100 amplitude in go trials and a smaller decrease after inhibiting a response. In go trials, a lower TMS-N100 was associated with a smaller variability of reaction times. A smaller TMS-N100 modulation extends the picture of cortical inhibition deficits in ADHD. Findings suggest a functional involvement of the mechanisms underlying the TMS-N100 at the motor output stage.

Knowledge about the core neural mechanisms of attention-deficit hyperactivity disorder, a pathophysiologically heterogeneous psychiatric disorder starting in childhood, is still limited. Progress may be achieved by combining different methods and levels of investigation. In the present study, we investigated neural mechanisms of motor control in 19 children with attention-deficit hyperactivity disorder (aged 9-14 years) and 21 age-matched typically developing children by relating neural markers of attention and response control (using event-related potentials) and measures of motor excitability/inhibition (evoked by transcranial magnetic stimulation). Thus, an interplay of processes at a subsecond scale could be studied. Using a monetary incentives-based cued Go/No-Go task, parameters that are well-known to be reduced in attention-deficit hyperactivity disorder were analysed: event-related potential components P3 (following cue stimuli; in Go and No-Go trials) and contingent negative variation as well as the transcranial magnetic stimulation-based short-interval intracortical inhibition measured at different latencies in Go and No-Go trials. For patient and control groups, different associations were obtained between performance, event-related potential and transcranial magnetic stimulation measures. In children with attention-deficit hyperactivity disorder, the P3 amplitude in Go trials was not correlated with reaction time measures but with short-interval intracortical inhibition at rest (r=0.56, P=0.01). In No-Go trials, P3 and short-interval intracortical inhibition after inhibiting the response (at 500 ms post-stimulus) were correlated in these children only (r=0.62; P=0.008). A classification rate of 90% was achieved when using short-interval intracortical inhibition (measured shortly before the occurrence of a Go or No-Go stimulus) and the amplitude of the P3 in cue trials as input features in a linear discriminant analysis. Findings indicate deviant neural implementation of motor control in children with attention-deficit hyperactivity disorder reflecting compensatory cognitive mechanisms as a result of a basal motor cortical inhibitory deficit (reduced activation of inhibitory intracortical interneurons). Both deviant inhibitory and attentional processes, which are not related to each other, seem to be characteristic for attention-deficit hyperactivity disorder at the neural level in motor control tasks. The underlying neural mechanisms, which are probably not restricted to the motor cortex and the posterior attention network, may play a key role in the pathophysiology of this child psychiatric disorder. The high classification rate can further be interpreted as a step towards the development of neural markers. In summary, the bimodal neurophysiological concept may contribute to developing an integrative framework for attention-deficit hyperactivity disorder.

Short interval intracortical inhibition (SICI) of motor cortex, measured by transcranial magnetic stimulation (TMS) in a passive (resting) condition, has been suggested as a neurophysiological marker of hyperactivity in attention-deficit/hyperactivity disorder (ADHD). The aim of this study was to determine motor excitability in a go/nogo task at stages of response preparation, activation and suppression in children with ADHD, depending on the level of hyperactivity and impulsivity. Motor evoked potentials were recorded in 29 typically developing children and 43 children with ADHD (subdivided in two groups with higher and lower levels of hyperactivity/impulsivity; H/I-high and H/I-low). In the H/I-high group, SICI was markedly reduced in the resting condition and during response preparation. Though these children were able to increase SICI when inhibiting a response, SICI was still reduced compared to typically developing children. Interestingly, SICI at rest and during response activation were comparable, which may be associated with their hypermotoric behaviour. In the H/I-low group, response activation was accompanied by a pronounced decrease of SICI, indicating reduced motor control in the context of a fast motor response. In summary, different excitability patterns were obtained for the three groups allowing a better understanding of dysfunctional response activation and inhibition processes within the motor cortex in children with ADHD.

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Seizure induction is a rare, but serious adverse effect of the otherwise very safe method of transcranial magnetic stimulation (TMS). There are only very few single case reports concerning seizure in single-pulse TMS. All of these reports describe individuals with neurological disorders or epileptogenic medication. To our knowledge, we are the first to describe a healthy subject who developed symptoms of a seizure after single-pulse TMS during motor threshold estimation. This case report provides evidence that single-pulse TMS may provoke a seizure even in the absence of neurological risk factors. Differential diagnoses of a classic neurological seizure, that is, convulsive syncope and psychogenic seizure, are discussed. Neurogenic seizure after TMS and convulsive syncope are the most probable hypotheses, although clear specification of this singular incident remains impossible. Therefore, to minimize the risk for such rare adverse effects, existing and new suggestions are combined to provide reasonable precautions to be taken before and during TMS application.