Modulation of Working Memory Using Transcranial Electrical Stimulation: A Direct Comparison Between TACS and TDCS

Transcranial electrical stimulation (TES) has been considered a promising tool for improving working memory (WM) performance. Recent studies have demonstrated modulation of networks underpinning WM processing through application of transcranial alternating current (TACS) as well as direct current (TDCS) stimulation. Differences between study designs have limited direct comparison of the efficacy of these approaches, however. Here we directly compared the effects of theta TACS (6 Hz) and anodal TDCS on WM, applying TACS to the frontal-parietal loop and TDCS to the dorsolateral prefrontal cortex (DLPFC). WM was evaluated using a visual 2-back WM task. A within-subject, crossover design was applied (N = 30) in three separate sessions. TACS, TDCS, and sham stimulation were administered in a counterbalanced order, and the WM task was performed before, during, and after stimulation. Neither reaction times for hits (RT-hit) nor accuracy differed according to stimulation type with this study design. A marked practice effect was noted, however, with improvement in RT-hit irrespective of stimulation type, which peaked at the end of the second session. Pre-stimulation RT-hits in session three returned to the level observed pre-stimulation in session two, irrespective of stimulation type. The participants who received sham stimulation in session one and had therefore improved their performance due to practice alone, had thus reached a plateau by session two, enabling us to pool RT-hits from sessions two and three for these participants. The pooling allowed implementation of a within-subject crossover study design, with a direct comparison of the effects of TACS and TDCS in a subgroup of participants (N = 10), each of whom received both stimulation types, in a counterbalanced order, with pre-stimulation performance the same for both sessions. TACS resulted in a greater improvement in RT-hits than TDCS (F(2,18) = 4.31 p = 0.03). Our findings suggest that future work optimizing the application of TACS has the potential to facilitate WM performance

Unmet Needs in Children With Attention Deficit Hyperactivity Disorder—Can Transcranial Direct Current Stimulation Fill the Gap? Promises and Ethical Challenges

Attention deficit hyperactivity disorder (ADHD) is a disorder most frequently diagnosed in children and adolescents. Although ADHD can be effectively treated with psychostimulants, a significant proportion of patients discontinue treatment because of adverse events or insufficient improvement of symptoms. In addition, cognitive abilities that are frequently impaired in ADHD are not directly targeted by medication. Therefore, additional treatment options, especially to improve cognitive abilities, are needed. Because of its relatively easy application, well-established safety, and low cost, transcranial direct current stimulation (tDCS) is a promising additional treatment option. Further research is needed to establish efficacy and to integrate this treatment into the clinical routine. In particular, limited evidence regarding the use of tDCS in children, lack of clear translational guidelines, and general challenges in conducting research with vulnerable populations pose a number of practical and ethical challenges to tDCS intervention studies. In this paper, we identify and discuss ethical issues related to research on tDCS and its potential therapeutic use for ADHD in children and adolescents. Relevant ethical issues in the tDCS research for pediatric ADHD center on safety, risk/benefit ratio, information and consent, labeling problems, and nonmedical use. Following an analysis of these issues, we developed a list of recommendations that can guide clinicians and researchers in conducting ethically sound research on tDCS in pediatric ADHD

Combined multi-session transcranial alternating current stimulation (tACS) and language skills training improves individual gamma band activity and literacy skills in developmental dyslexia

Developmental dyslexia is a neurodevelopmental disorder characterized by the pathologically diminished ability to successfully acquire reading and writing skills. Altered cortical activation in the auditory cortex, resulting in inaccurate perception of acoustic information, is thought to provide the neurophysiological basis for impaired phonological processing, which in turn is the bottleneck for successful acquisition of reading and writing skills. Recently, transcranial electrical stimulation has been shown to be an effective method for restoring dysfunctional cortical activation patterns in the disabled brain. In particular, repeated application of electrical stimulation appears to improve neural processes and associated behavior. Here, we aimed to restore dysfunctional activation in the auditory cortex using multi-session gamma-tACS and thereby to enhance the positive effects of a literacy skills training in children and adolescents with developmental dyslexia. Using a double-blind and sham-controlled study design, we investigated the effect of multi-session transcranial electrical stimulation delivered concurrently with an auditory training and in combination with a behavioral training of literacy skills in 29 children and adolescents (13 male, 6 female, aged 8-17 years) with developmental dyslexia. Over a 5-week period, participants received 10 training sessions while 40 Hz-tACS (gamma-tACS) at 1mA intensity was administered for 20 minutes over the bilateral auditory cortex. We found that only participants treated with gamma-tACS showed a shift in the peak frequency of auditory gamma oscillations reflecting a more fine-grained perception of time-critical acoustic information. This amelioration was accompanied by improved phonemic processing skills in the gamma-tACS group. Moreover, 4 months after the intervention, only individuals who received gamma-tACS showed significant improvement in their writing skills. Our results demonstrate that multi-session gamma-tACS can enhance the effects of a behavioral intervention and induce long-term improvement of literacy skills in developmental dyslexia by successfully modulating the gamma peak frequency in the auditory cortex

Combined multi-session transcranial alternating current stimulation (tACS) and language skills training improves individual gamma band activity and literacy skills in developmental dyslexia

Developmental dyslexia is characterized by the pathologically diminished ability to acquire reading and spelling skills. Accurate processing of acoustic information at the phonemic scale is crucial for successful sound-to-letter-mapping which, in turn, is elemental in reading and spelling. Altered activation patterns in the auditory cortex are thought to provide the neurophysiological basis for the inaccurate phonemic perception. Recently, transcranial electrical stimulation has been shown to be an effective method to ameliorate cortical activation patterns in the auditory cortex. In a sample of children and adolescents with dyslexia, we investigated the effect of multi-session transcranial alternating current stimulation delivered concurrently with a phonological training and in combination with a behavioral literacy skills training. Over a 5-week period the participants received 10 training sessions while gamma-tACS was administered over bilateral auditory cortex. We found that gamma-tACS shifted the peak frequency of auditory gamma oscillations reflecting a more fine-grained processing of time-critical acoustic information. This amelioration was accompanied by increased phonemic processing skills. Moreover, individuals who received gamma-tACS showed significant improvements in their spelling skills four months after the intervention. Our results demonstrate that multi-session gamma-tACS enhances the effects of a behavioral intervention and induces long-term improvement on literacy skills in dyslexia

Pupil dilation as a marker of dysfunctional arousal regulation during sustained attention in children and adolescents with ADHD

The pupil size is influenced by attention and arousal enabling the use of pupillometry to explore underlying neurobiological and neurochemical processes. Especially pupil dilation is supposed to be an indirect marker of the activity of the locus coeruleus-norepinephrine (LC-NE) system, that significantly contributes to attention and arousal regulation. The impairment of both functions play an important role in attention deficit/hyperactivity disorder (ADHD) but the underlying neuronal processes and their interplay are not yet sufficiently understood. This study investigates changes in pupil size, spontaneous eye blink rate, and performance in a newly developed sustained attention task in children and adolescents with ADHD and healthy controls (N=65). Individuals with ADHD showed impaired performance compared to controls. The tonic pupil diameter decreased during the task in controls but not in the ADHD group. Moreover, spontaneous eye blink rate was significantly increased in ADHD compared to controls. Our main results indicate a tonic hyperactivity of the LC and an insufficient adaptation of arousal to the requirements of the task in ADHD. Thus, changes in pupil diameter might be a particularly sensitive, non-invasive marker of neuronal mechanisms underlying sustained attention functions that can be easily applied in children and adolescents with ADHD

Error-Related Dynamics of Reaction Time and Frontal Midline Theta Activity in Attention Deficit Hyperactivity Disorder (ADHD) During a Subliminal Motor Priming Task

Post-error slowing (PES) is an established performance monitoring readout. Several previous studies have found that PES is reduced in children and adolescents with attention-deficit hyperactivity disorder (ADHD). We analyzed reaction time data, along with electroencephalography (EEG) data, from a response priming experiment in children and adolescents with ADHD (N = 28) and typically developing (TD) controls (N = 15) between 10 and 17 years of age. We report dynamic reaction time changes before and after errors: whereas TD controls readjusted their response speed to their individual average speed after committing an error, this reaction time adjustment appeared to be delayed and decreased in ADHD patients. In the EEG, error trials were accompanied by increased frontal midline theta activity, which was attenuated in ADHD compared to TD. We conclude that PES has a different time course rather than being fully absent in ADHD and discuss relationships with our EEG findings and potential implications for performance monitoring in ADHD

Transcranial electrical stimulation improves phoneme processing in developmental dyslexia

BACKGROUND: About 10% of the western population suffers from a specific disability in the acquisition of reading and writing skills, known as developmental dyslexia (DD). Even though DD starts in childhood it frequently continuous throughout lifetime. Impaired processing of acoustic features at the phonematic scale based on dysfunctional auditory temporal resolution is considered as one core deficit underlying DD. Recently, the efficacy of transcranial electrical stimulation (tES) to modulate auditory temporal resolution and phoneme processing in healthy individuals has been demonstrated. OBJECTIVE: The present work aims to investigate online effects of tES on phoneme processing in individuals with DD. METHOD: Using an established phoneme-categorization task, we assessed the immediate behavioral and electrophysiological effects of transcranial alternating current stimulation (tACS) and transcranial random noise stimulation (tRNS) over bilateral auditory cortex in children and adolescents with DD (study 1) and adults with DD (study 2) on auditory phoneme processing acuity. RESULTS: Our data revealed that tACS improved phoneme categorization in children and adolescents with DD, an effect that was paralleled by an increase in evoked brain response patterns representing low-level sensory processing. In the adult sample we replicated these findings and additionally showed a more pronounced impact of tRNS on phoneme-categorization acuity. CONCLUSION: These results provide compelling evidence for the potential of both tACS and tRNS to increase temporal precision of the auditory system in DD and suggest transcranial electrical stimulation as potential intervention in DD to foster the effect of standard phonology-based training

Emotional memory in ADHD patients with and without comorbid ODD/CD

The present study investigated whether children and adolescents with attention deficit hyperactivity disorder (ADHD) and comorbid oppositional defiant disorder (ODD) or conduct disorder (CD) show a memory bias for negative emotional pictures. Subjects participated in an incidental memory paradigm involving neutral, positive and negative pictures. In ADHD only patients, memory performance was enhanced to the level of healthy control subjects both by positive and negative pictures, whereas in ADHD patients with comorbid ODD/CD, memory performance was only normalized by negative pictures