Increased event-related theta activity as a psychophysiological marker of comorbidity in children with tics and attention-deficit/hyperactivity disorders

OBJECTIVE The question as to whether coexisting tic disorder (TD) and attention-deficit/hyperactivity disorder (ADHD) in children represent a combination of two independent pathologies, a separate nosologic entity manifested by both tics and hyperactivity or a phenotype subgroup of one of the two major clinical forms has received increasing attention. The aim of the present study was to classify the TD+ADHD comorbidity in the neurocognitive domain and to elucidate the neurophysiological background of TD+ADHD coexistence by analyzing event-related electroencephalographic (EEG) oscillations in the theta (3-7.5 Hz) frequency band. METHODS Event-related potentials were recorded at 10 electrodes in 53 children (9-13 years old) from four groups (healthy controls, TD-only, ADHD-only, and combined TD+ADHD patients), while they performed an auditory selective attention task requiring a button press to a predefined target. Event-related theta oscillations were analyzed by means of time-frequency decomposition (wavelet analysis) in two latency ranges-early (0-200 ms) and late (200-450 ms). The effects of psychopathology factors (TD and ADHD) and task variables (attended channel and stimulus task relevance) on early (ETR) and late (LTR) theta responses were evaluated statistically. Theta response measures were further correlated with psychopathology scores and spontaneous theta EEG activity. RESULTS (1) The ETR was enhanced only in comorbid children and did not differ between the control, TD-only, and ADHD-only groups. (2) The LTR was larger in children with ADHD (ADHD-only and comorbid), but this effect was mediated by the spontaneous theta EEG activity. (3) The ETR was larger to attended stimuli at frontal-central electrodes contralateral to the side of attention, to the target stimulus type at frontal locations, and at the hemisphere contralateral to the side of the response. The functional reactivity and scalp distribution of ETRs were modulated by psychopathological factors. CONCLUSIONS In the neurocognitive domain, the TD+ADHD comorbidity can be identified as a unique nosologic entity. Both the spontaneous theta activity and late event-related theta oscillations appear as neurophysiological markers of the ADHD condition. In children, the early event-related theta oscillations may be associated with representations of relevant target features in working memory. SIGNIFICANCE (1) A new model is proposed according to which TD+ADHD comorbidity can be classified at different levels (from neurobiological to cognitive). (2) The functional significance of stimulus-synchronized theta oscillations in children is described for the first time.

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