Human studies
Electroencephalographic Activity at Baseline Predicts Alleviation of Symptoms following dTMS Treatment in ADHD
Attention deficit hyperactivity disorder (ADHD) is strongly associated with impaired right prefrontal cortex (rPFC) activity. Here we evaluated whether multiple sessions of repetitive transcranial magnetic stimulation (rTMS) of this region affect clinical symptoms in adults suffering from ADHD, and characterized electrophysiological alterations induced by this local intervention.
in our study, 43 adults with ADHD were randomized to receive either Real, Active Control (AC), or Sham treatment. All groups underwent three weeks of daily high frequency (18 Hz) rTMS treatment directed to the rPFC and refrained from administrating psychostimulants during the study. Treatment related alternations were evaluated using validated questionnaires, computerized cognitive battery and both spontaneous and TMS-induced electroencephalography (EEG).
Treatment resulted in significant improvement of ADHD symptoms in the Real group, but not in the control groups. Furthermore, based on EEG recorded within the first treatment session we established a novel, theoretically apposite, prognostic biomarker which highly predicted the magnitude of the clinical outcome. This EEG biomarker is composed of the Alpha and Low-gamma frequency bands power, where the former demonstrates relatively stable activity patterns during stimulation, while the latter is sensitive to TMS pulses.
We concluded that rPFC stimulation using is a safe and effective treatment for alleviation of adults’ ADHD symptoms.The biomarker is suggested to reflect the responsiveness of the cortex to the rTMS intervention, allowing selection of optimal candidates for treatment, and paving the way to future individually tailored treatments for ADHD.
Animal studies
The pervasiveness of electronic media in recent years has brought about dramatic changes in the pattern of exposure of young children to environmental stimuli. Children today are exposed to non-natural, highly salient and rapidly changing audiovisual stimuli, which characterize electronic media, at younger ages and for longer durations than in the past. Although excessive exposure of young children to such stimuli has been correlated with cognitive deficits in adulthood, this relationship cannot be studied prospectively in developing human subjects, raising the need for relevant animal models. Here, we submitted developing, post-weaned rats to daily 1 h sessions of intense olfactory stimulation (IOS), in which we exposed them to 12 highly salient odors that were presented either sequentially (dynamic IOS) or as a mixture (static IOS). We maintained this regimen for five consecutive weeks, i.e., until the rats reached adulthood, and then tested their attentional functions in the 5-choice serial reaction time task. We report that rats exposed to dynamic IOS do not show attentional deficits under baseline task conditions (in fact, their performance was better in the task-acquisition phase), but show a significantly impaired performance when an audio distractor is introduced in the task. In addition, BDNF levels (a proxy of neuronal plasticity) in the dorsal striatum are higher in rats exposed to dynamic IOS than in rats exposed to static IOS. Our data thus provide empirical evidence that a continuous exposure to dynamic, highly salient stimuli has a long-term influence on attentional functions in adulthood, and that this effect may have neurochemical correlates in the dorsal striatum.
Generating a model for attention deficits in rats. Left: experimental paradigm. Right: a rat in the 5-Choice Serial Reaction Time Task.