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Abstract
Attention deficit hyperactivity disorder (ADHD) is a prevalent disorder with effective pharmacological treatment that benefits most patients. However, about one-third fail to benefit while others search non-pharmacological alternatives, and for those options are scarce. One alternative treatment option is to alter abnormal right prefrontal cortex (rPFC) activity, given that rPFC abnormality has been repeatedly implicated in ADHD neurophathology. Here, we evaluated whether targeting the rPFC with multiple sessions of repetitive transcranial magnetic stimulation (rTMS), which can modulate neuronal excitability, activity, and plasticity in a non-invasive manner, will affect clinical symptoms in adults suffering from ADHD. Concomitantly, we used EEG to characterize electrophysiological alterations induced by treatment and to search for correlation between baseline neuronal activity and clinical response.Forty-three drug free adults with ADHD were randomized to receive either Real, Active Control, or Sham treatment (13 females, age ranging 21-46; n = 15, 14, 14, respectively), and underwent three weeks of daily high-frequency (18 Hz) stimulation sessions. We found that Real treatment was safe and resulted in significant improvement of symptoms (η2p = 0.34; Cohen's d(against Sham) = 0.96; Cohen's d(against AC) = 0.68; p = 0.00085). Furthermore, based on EEG recorded within the first treatment session we established a novel biomarker, composed of the Alpha and Low-gamma power, which highly correlated the magnitude of the clinical outcome (r = 0.92, p = 0.0001).Taken together, the results of this pilot study indicate safety and effectiveness of rTMS directed to the rPFC for treatment of adult ADHD patients. The biomarker is suggested to reflect the responsiveness of the cortex to this rTMS intervention. Following validation of the results in larger samples, this study may represent a step towards a non-pharmacological treatment for adults with ADHD using EEG-based selection of optimal candidates for treatment.
Highlights
Attention Deficit Hyperactivity Disorder (ADHD) is characterized by poor attention, impulsivity, hyperactivity and emotional-motivational dysregulation (Sonuga-Barke, 2005), affecting 7.2% of children and 3.4% of adults worldwide (Fayyad et al, 2007; Thomas et al, 2015)
We found that 3 weeks of daily Real right prefrontal cortex (rPFC) stimulation can induce alleviation of adults’ ADHD symptoms, compared to active control (AC) and Sham stimulation
The clinical results indicate that repetitive transcranial magnetic stimulation (TMS) (rTMS) directed to the rPFC may serve as an alternative treatment to those adults suffering from ADHD and do not benefit, or cannot tolerate the side effects of existing pharmacological treatments (Biederman et al, 2004)
Summary
Attention Deficit Hyperactivity Disorder (ADHD) is characterized by poor attention, impulsivity, hyperactivity and emotional-motivational dysregulation (Sonuga-Barke, 2005), affecting 7.2% of children and 3.4% of adults worldwide (Fayyad et al, 2007; Thomas et al, 2015). Taking together the fact that almost 30% of participants find current pharmacological treatments ineffective or intolerable (Biederman et al, 2004), and the lack of treatment producing long-term effects, alternative medical options are needed. One such alternative is non-invasive brain stimulation using transcranial magnetic stimulation (TMS), which may induce long-term alleviation of symptoms by targeting the underline neuropathology. Multiple sessions of repetitive TMS (rTMS) protocols are investigated as potential treatments for various conditions, and are gradually becoming a viable clinical neuromodulation intervention (Lefaucheur et al, 2014). RTMS directed to the left prefrontal cortex (PFC) has been cleared by the FDA for the treatment of medication-resistant depression (Levkovitz et al, 2015; O'Reardon et al, 2007) and rTMS directed to the medial
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