Scaffolding the Attention-Deficit/Hyperactivity Disorder Brain Using Random Noise Stimulation

Abstract

Various methods have been attempted to effectively ameliorate psychiatric and neurological conditions in children and adults. One of the attractive ideas is to develop interventions to create a lasting, rather than only an immediate, effect. Neurostimulation has been shown to yield long-term effect when combined with cognitive training in healthy young adults. We examined whether such approach could benefit children with attention deficit hyperactivity disorder (ADHD), the most common neurodevelopmental disorder in childhood. We used a randomized double-blind active-controlled crossover study of 19 unmedicated children (aged 7-12 years old) with attention deficit hyperactivity disorder, who received either transcranial direct current stimulation or random noise stimulation while completing five-day executive functions training, which includes working memory, cognitive flexibility, and inhibition tasks. Both stimulation protocols have previously shown potential for inducing lasting benefits in adults, while transcranial direct current stimulation was examined in multiple attention deficit hyperactivity disorder studies and has been highlighted as a promising method for treating neuropsychological deficits. For our primary outcome, transcranial random noise stimulation yielded a clinical improvement as indicated by the reduced attention deficit hyperactivity disorder rating scale score from baseline, and in comparison to the changes observed in transcranial direct current stimulation. Moreover, the effect of brain stimulation one week after completion of treatment yielded further improvement, suggesting a neuroplasticity-related effect. Finally, transcranial random noise stimulation improved working memory compared to transcranial direct current stimulation, and a larger transcranial random noise stimulation effect on attention deficit hyperactivity disorder rating scale was predicted for those patients who showed the greatest improvement in working memory. Our results provide a promising direction toward a novel intervention in attention deficit hyperactivity disorder, which is shown to have a lasting effect via the modulating of neuroplasticity, rather than a merely immediate effect as was shown for in previous medical interventions.

How can noise alter neurophysiology in order to improve human behaviour? A combined tRNS and EEG study

“…Given that we matched our participants based on their baseline arithmetic performance and that active tRNS yielded better performance than sham, a likely interpretation is that improvement in performance caused by tRNS reflects greater allocation of attentional resources during the training. Such mechanistic explanation clarify the relative broad improvement seen by tRNS in different tasks, including its effect on learning, where attentional resources play a key role 6 , as well as its potential benefit in attention-deficit/hyperactivity disorder 68 .…”

Impact of chronic transcranial Random-Noise Stimulation (tRNS) on prefrontal cortex excitation-inhibition balance in juvenile mice

“…The present histological results in young mice suggest that tRNS applied at low-density currents is capable of increasing excitability by decreasing GABA levels in a focalized way. These results could be of crucial importance for human tRNS studies suggesting that a decrease in GABA levels could be mediating the behavioral enhancement observed in previous studies (Terney et al, 2008; Fertonani et al, 2011; Cappelletti et al, 2013; Snowball et al, 2013; Pasqualotto, 2016; van der Groen and Wenderoth, 2016; Looi et al, 2017; Brem et al, 2018; Evans et al, 2018; Frank et al, 2018; Brevet-Aeby et al, 2019; Herpich et al, 2019; Berger et al, 2019; Harty & Cohen Kadosh et al, 2019; Sheffield et al, 2020) and that the technique do not produce major histopathological alterations at the density currents used in the study.…”

“…It is surprising that despite the promising results of tRNS in human-based research, in some cases even more than more popular methods such as tDCS and tACS (Fertonani et al, 2011; Brem et al, 2018; Simonsmeier et al, 2018; Berger et al, 2019) its mechanisms are relatively unclear, and are scarce compared to other methods such as tDCS and tACS. In addition, its safety based on animal-based research is lacking.…”

“…In addition, its safety based on animal-based research is lacking. This is a point of potential concern as tRNS is now being used in the case of neurodevelopmental disorders (Looi et al, 2017; Berger et al, 2019). Therefore, the motivation in this study was to mirror a promising protocol of tRNS that was used during a cognitive training in atypical developing children, in order to examine its effects at vGLUT1 and GAD 65-67 that are involved in neuroplasticity and its safety in terms of pathological changes induced by tRNS.…”

The Effect of Transcranial Random Noise Stimulation on Cognitive Training Outcome in Healthy Aging

“…Recent studies have attributed the effect of tRNS on cognitive training (CT) in young adults to modulation of neurophysiological mechanisms that are associated with sustained attention ( 46 ). Indeed, in children with attention deficit/hyperactivity disorder, tRNS with CT over the dorsolateral prefrontal cortices has yielded promising clinical improvement compared to tDCS with CT ( 47 ). Moreover, a recent study in juvenile mice revealed that chronic tRNS over the prefrontal cortex, with similar parameters to what has been used in atypically developing children ( 48 ), reduced GABAergic activity ( 49 ).…”