Effects of blue- and red-enriched light on attention and sleep in typically developing adolescents.

Differential effects of blue- and red-enriched light on attention and sleep have been primarily described in adults. In our cross-over study in typically developing adolescents (11-17 years old), we found attention enhancing effects of blue- compared to red-enriched light in the morning (high intensity of ca. 1000 lx, short duration: <1 h) in two of three attention tasks: e.g. better performance in math tests and reduced reaction time variability in a computerized attention test. In our pilot study, actigraphy measures of sleep indicated slight benefits for red- compared to blue-enriched light in the evening: tendencies toward a lower number of phases with movement activity after sleep onset in the complete sample and shorter sleep onset latency in a subgroup with later evening exposure times. These findings point to the relevance of light concepts regarding attention and sleep in typically developing adolescents. Such concepts should be developed and tested further in attention demanding contexts (at school) and for therapeutic purposes in adolescents with impaired attention or impaired circadian rhythms.

Theta/beta neurofeedback in children with ADHD: Feasibility of a short-term setting and plasticity effects.

Neurofeedback (NF) is increasingly used as a therapy for attention-deficit/hyperactivity disorder (ADHD), however behavioral improvements require 20 plus training sessions. More economic evaluation strategies are needed to test methodological optimizations and mechanisms of action. In healthy adults, neuroplastic effects have been demonstrated directly after a single session of NF training. The aim of our study was to test the feasibility of short-term theta/beta NF in children with ADHD and to learn more about the mechanisms underlying this protocol. Children with ADHD conducted two theta/beta NF sessions. In the first half of the sessions, three NF trials (puzzles as feedback animations) were run with pre- and post-reading and picture search tasks. A significant decrease of the theta/beta ratio (TBR), driven by a decrease of theta activity, was found in the NF trials of the second session demonstrating rapid and successful neuroregulation by children with ADHD. For pre-post comparisons, children were split into good vs. poor regulator groups based on the slope of their TBR over the NF trials. For the reading task, significant EEG changes were seen for the theta band from pre- to post-NF depending on individual neuroregulation ability. This neuroplastic effect was not restricted to the feedback electrode Cz, but appeared as a generalized pattern, maximal over midline and right-hemisphere electrodes. Our findings indicate that short-term NF may be a valuable and economical tool to study the neuroplastic mechanisms of targeted NF protocols in clinical disorders, such as theta/beta training in children with ADHD.

Manipulating motor performance and memory through real-time fMRI neurofeedback.

Task performance depends on ongoing brain activity which can be influenced by attention, arousal, or motivation. However, such modulating factors of cognitive efficiency are unspecific, can be difficult to control, and are not suitable to facilitate neural processing in a regionally specific manner. Here, we non-pharmacologically manipulated regionally specific brain activity using technically sophisticated real-time fMRI neurofeedback. This was accomplished by training participants to simultaneously control ongoing brain activity in circumscribed motor and memory-related brain areas, namely the supplementary motor area and the parahippocampal cortex. We found that learned voluntary control over these functionally distinct brain areas caused functionally specific behavioral effects, i.e. shortening of motor reaction times and specific interference with memory encoding. The neurofeedback approach goes beyond improving cognitive efficiency by unspecific psychological factors such as attention, arousal, or motivation. It allows for directly manipulating sustained activity of task-relevant brain regions in order to yield specific behavioral or cognitive effects.

Refining the picture of reduced alerting responses in ADHD - a single-trial analysis of event-related potentials.

In attention-deficit/hyperactivity disorder (ADHD), a reduced phasic alerting response (event-related potential component P3 to cue stimuli) has been reported for different subtypes and task types in a series of studies. In order to get a refined picture of this attentional deficit, which is based on the analysis of averaged event-related potentials, we studied the distribution of single-trial cue-P3 amplitudes and the relation between the cue-P3 and the neural state (EEG spectral analysis) when expecting the stimulus. Brain electrical activity was recorded in children of different ADHD subtypes (combined type, predominantly inattentive) and typically developing children while conducting the attention network test. In children with ADHD of the combined type, smaller cue-P3 amplitudes in the averaged signal were due to a larger portion of single trials with reduced cue-P3 amplitudes whereas maximum amplitudes did not differ from typically developing children. In this ADHD subtype, larger activity in the upper theta/lower alpha range (5.5-10.5Hz) was strongly associated with the range (difference between 0.9 quantile and 0.1 quantile) of the cue-P3 amplitude in single trials (correlation coefficient r=0.77) indicating a suboptimal neural state before stimulus presentation. In children with ADHD of the predominantly inattentive subtype, single-trial P3 amplitudes were comparable at lower quantiles but maximum amplitudes were reduced. This result pattern indicates an intact triggering of the cue-P3 but a reduced capacity of resource allocation for the predominantly inattentive subtype. Though findings are limited by a relative small sample size, the cue-P3 may be considered as a neurophysiological marker of alerting deficits in ADHD reflecting different underlying mechanisms in ADHD subtypes.

EEG spectral analysis of attention in ADHD: implications for neurofeedback training?

OBJECTIVE: In children with attention-deficit/hyperactivity disorder (ADHD), an increased theta/beta ratio in the resting EEG typically serves as a rationale to conduct theta/beta neurofeedback (NF) training. However, this finding is increasingly challenged. As NF may rather target an active than a passive state, we studied the EEG in a condition that requires attention. METHODS: In children with ADHD of the DSM-IV combined type (ADHD-C; N = 15) and of the predominantly inattentive type (ADHD-I; N = 9) and in typically developing children (N = 19), EEG spectral analysis was conducted for segments during the attention network test (ANT) without processing of stimuli and overt behavior. Frontal (F3, Fz, F4), central (C3, Cz, C4) and parietal (P3, Pz, P4) electrodes were included in the statistical analysis. To investigate if EEG spectral parameters are related to performance measures, correlation coefficients were calculated. RESULTS: Particularly in the ADHD-C group, higher theta and alpha activity was found with the most prominent effect in the upper-theta/lower-alpha (5.5-10.5 Hz) range. In the ADHD-I group, a significantly higher theta/beta ratio was observed at single electrodes (F3, Fz) and a tendency for a higher theta/beta ratio when considering all electrodes (large effect size). Higher 5.5-10.5 Hz activity was associated with higher reaction time variability with the effect most prominent in the ADHD-C group. A higher theta/beta ratio was associated with higher reaction times, particularly in the ADHD-I group. CONCLUSIONS: (1) In an attention demanding period, children with ADHD are characterized by an underactivated state in the EEG with subtype-specific differences. (2) The functional relevance of related EEG parameters is indicated by associations with performance (reaction time) measures. (3) Findings provide a rationale for applying NF protocols targeting theta (and alpha) activity and the theta/beta ratio in subgroups of children with ADHD.

Slow cortical potential and theta/beta neurofeedback training in adults: effects on attentional processes and motor system excitability.

Neurofeedback (NF) is being successfully applied, among others, in children with attention deficit/hyperactivity disorder (ADHD) and as a peak performance training in healthy subjects. However, the neuronal mechanisms mediating a successful NF training have not yet been sufficiently uncovered for both theta/beta (T/B), and slow cortical potential (SCP) training, two protocols established in NF in ADHD. In the present, randomized, controlled investigation in adults without a clinical diagnosis (n = 59), the specificity of the effects of these two NF protocols on attentional processes and motor system excitability were to be examined, focusing on the underlying neuronal mechanisms. Neurofeedback training consisted of 10 double sessions, and self-regulation skills were analyzed. Pre- and post-training assessments encompassed performance and event-related potential measures during an attention task, and motor system excitability assessed by transcranial magnetic stimulation. Some NF protocol-specific effects have been obtained. However, due to the limited sample size medium effects did not reach the level of significance. Self-regulation abilities during negativity trials of the SCP training were associated with increased contingent negative variation amplitudes, indicating improved resource allocation during cognitive preparation. Theta/beta training was associated with increased response speed and decreased target-P3 amplitudes after successful theta/beta regulation suggested reduced attentional resources necessary for stimulus evaluation. Motor system excitability effects after theta/beta training paralleled the effects of methylphenidate. Overall, our results are limited by the non-sufficiently acquired self-regulation skills, but some specific effects between good and poor learners could be described. Future studies with larger sample sizes and sufficient acquisition of self-regulation skills are needed to further evaluate the protocol-specific effects on attention and motor system excitability reported.

Neurofeedback in ADHD: further pieces of the puzzle.

Among the different neuromodulation techniques, neurofeedback (NF) is gaining increasing interest in the treatment of children with attention-deficit/hyperactivity disorder (ADHD). In this article, a methodological framework is summarised considering the training as a neuro-behavioural treatment. Randomised controlled trials are selectively reviewed. Results from two smaller-scale studies are presented with the first study comprising a tomographic analysis over the course of a slow cortical potential (SCP) training and a correlational analysis of regulation skills and clinical outcome in children with ADHD. In the second study, ADHD-related behaviour was studied in children with tic disorder who either conducted a SCP training or a theta/low-beta (12-15 Hz) training (single-blind, randomised design). Both studies provide further evidence for the specificity of NF effects in ADHD. Based on these findings, a refined model of the mechanisms contributing to the efficacy of SCP training is developed. Despite a number of open questions concerning core mechanisms, moderators and mediators, NF (theta/beta and SCP) training seems to be on its way to become a valuable and ethically acceptable module in the treatment of children with ADHD.

Differential effects of methylphenidate and atomoxetine on attentional processes in children with ADHD: an event-related potential study using the Attention Network Test.

Methylphenidate (MPH) and atomoxetine (ATX) are effective medications in the treatment of attention deficit/hyperactivity disorder (ADHD). The aim of this study was to investigate differential effects of MPH and ATX on attentional functions at the performance and the neuronal level in children with ADHD. Using the Attention Network Test (ANT), differential effects of both medications on the noradrenergic alerting network and the dopaminergic executive attention network were considered. Nineteen children with ADHD performed the ANT three times while event-related potentials (ERPs) were recorded. The baseline testing was conducted without medication. In two medication blocks of 8 weeks each, medication was individually titrated for each child (cross-over design, balanced order). At the end of the medication blocks the testing was repeated. While both medications comparably reduced ADHD symptomatology, MPH had some advantages over ATX with regard to performance measures on the ANT and the underlying neuronal mechanisms. Compared with ATX, MPH led to a larger reduction in reaction time variability, which was accompanied by an MPH-related increase in the contingent negative variation (CNV) compared to the baseline testing. Contrary to our expectations, specific alerting network effects were not observed with ATX. Due to the chosen study design, it remains unresolved to what extent e.g. shortened reaction times and smaller conflict scores that were observed with both medications reflect practice or medication effects. The differential pattern of MPH vs. ATX effects on attentional functions in children with ADHD may be explained by the dopaminergic effects of MPH within the cortico-striato-thalamo-cortical circuit.

Attentional processes in children with ADHD: an event-related potential study using the attention network test.

A variety of event-related potential (ERP) based studies have shown differences in neuronal processes underlying attention, inhibition and error processing in children with attention-deficit/hyperactivity disorder (ADHD) compared to controls. However, so far there are no studies that have compared children with ADHD and typically developing (TD) children regarding effects in ERP components associated with the attention network test (ANT). The ANT allows to differentiate between three particular aspects of attention: alerting, orienting, conflict. Twenty-five children with ADHD and 19 TD children (comparable with respect to age, sex, and IQ) performed the ANT while ERPs were recorded. Based on DSM-IV, the group of children with ADHD was divided in an inattentive (ADHDin, n=10) and a combined (ADHDcom, n=15) subgroup. On the performance level, the ADHD group showed a significantly higher variability of reaction times. Concerning ERP measures, smaller cue-P3 amplitudes were found in the ADHD group indicating that children with ADHD allocate less attentional resources for cue processing. In addition, the target-P3 in ADHD showed smaller amplitudes. Subgroup analysis revealed reduced cue-P3 amplitudes in both subgroups and reduced target-P3 amplitudes in ADHDin compared to TD children. Except for a higher alerting score in ADHD after correction for cue-P3 group differences, performance data revealed no group differences specific for the three attention networks. No group differences related to the attention networks were observed at the ERP level. Our results suggest that deviant attentional processing in children with ADHD is only partly related to ANT-specific effects. Findings are compatible with the model of a suboptimal energetic state regulation in ADHD. Furthermore, our results suggest that deviant cue processing in ADHD and related differences in task modulations should be accounted for in data analysis.

Neurofeedback in children with ADHD: specific event-related potential findings of a randomized controlled trial.

OBJECTIVE: In a randomized controlled trial, we could demonstrate clinical efficacy of neurofeedback (NF) training for children with ADHD (Gevensleben et al., 2009a). The present investigation aimed at learning more about the neuronal mechanisms of NF training. METHODS: Children with ADHD either completed a NF training or a computerized attention skills training (ratio 3:2). NF training consisted of one block of theta/beta training and one block of slow cortical potential (SCP) training, each comprising 18 training units. At three times (pre-training, between the two training blocks and at post-training), event-related potentials (ERP) were recorded during the Attention Network Test. ERP analysis focused on the P3, reflecting inter alia attentional resources for stimulus evaluation, and the contingent negative variation (CNV), primarily related to cognitive preparation. RESULTS: After NF training, an increase of the CNV in cue trials could be observed, which was specific for the SCP training. A larger pre-training CNV was associated with a larger reduction of ADHD symptomatology for SCP training. CONCLUSIONS: CNV effects reflect neuronal circuits underlying resource allocation during cognitive preparation. These distinct ERP effects are closely related to a successful NF training in children with ADHD. In future studies, neurophysiological recordings could help to optimize and individualize NF training. SIGNIFICANCE: The findings contribute to a better understanding of the mechanisms underlying NF training in children with ADHD.

Seizure in a nonpredisposed individual induced by single-pulse transcranial magnetic stimulation.

Seizure induction is a rare, but serious adverse effect of the otherwise very safe method of transcranial magnetic stimulation (TMS). There are only very few single case reports concerning seizure in single-pulse TMS. All of these reports describe individuals with neurological disorders or epileptogenic medication. To our knowledge, we are the first to describe a healthy subject who developed symptoms of a seizure after single-pulse TMS during motor threshold estimation. This case report provides evidence that single-pulse TMS may provoke a seizure even in the absence of neurological risk factors. Differential diagnoses of a classic neurological seizure, that is, convulsive syncope and psychogenic seizure, are discussed. Neurogenic seizure after TMS and convulsive syncope are the most probable hypotheses, although clear specification of this singular incident remains impossible. Therefore, to minimize the risk for such rare adverse effects, existing and new suggestions are combined to provide reasonable precautions to be taken before and during TMS application.

ERP effects of methylphenidate and working memory load in healthy adults during a serial visual working memory task.

The objective of the study was to investigate neuronal processing during the encoding, retention and retrieval phases of a serial visual working memory task. Particularly, we were interested in how these phases are affected by working memory load and how processing is modulated by methylphenidate. Healthy adults were asked to memorize the order of four, five or six pictures under methylphenidate (20mg) and under placebo while brain electrical activity was recorded. On the performance level, the number of correct responses decreased with increasing working memory load. Concerning brain electrical activity, in the encoding phase P3 amplitudes increased at midline electrodes with increasing memory load while load had no effect in the retention and retrieval phase. Medication neither influenced performance nor the different processing stages significantly. Our data provide evidence that during the encoding phase more attentional resources are allocated in trials with higher load as reflected by larger P3 amplitudes.

Neurofeedback training in children with ADHD: 6-month follow-up of a randomised controlled trial.

Neurofeedback (NF) could help to improve attentional and self-management capabilities in children with attention-deficit/hyperactivity disorder (ADHD). In a randomised controlled trial, NF training was found to be superior to a computerised attention skills training (AST) (Gevensleben et al. in J Child Psychol Psychiatry 50(7):780-789, 2009). In the present paper, treatment effects at 6-month follow-up were studied. 94 children with ADHD, aged 8-12 years, completed either 36 sessions of NF training (n = 59) or a computerised AST (n = 35). Pre-training, post-training and follow-up assessment encompassed several behaviour rating scales (e.g., the German ADHD rating scale, FBB-HKS) completed by parents. Follow-up information was analysed in 61 children (ca. 65%) on a per-protocol basis. 17 children (of 33 dropouts) had started a medication after the end of the training or early in the follow-up period. Improvements in the NF group (n = 38) at follow-up were superior to those of the control group (n = 23) and comparable to the effects at the end of the training. For the FBB-HKS total score (primary outcome measure), a medium effect size of 0.71 was obtained at follow-up. A reduction of at least 25% in the primary outcome measure (responder criterion) was observed in 50% of the children in the NF group. In conclusion, behavioural improvements induced by NF training in children with ADHD were maintained at a 6-month follow-up. Though treatment effects appear to be limited, the results confirm the notion that NF is a clinically efficacious module in the treatment of children with ADHD.

Distinct EEG effects related to neurofeedback training in children with ADHD: a randomized controlled trial.

In a randomized controlled trial, neurofeedback (NF) training was found to be superior to a computerised attention skills training concerning the reduction of ADHD symptomatology (Gevensleben et al., 2009). The aims of this investigation were to assess the impact of different NF protocols (theta/beta training and training of slow cortical potentials, SCPs) on the resting EEG and the association between distinct EEG measures and behavioral improvements. In 72 (of initially 102) children with ADHD, aged 8-12, EEG changes after either a NF training (n=46) or the control training (n=26) could be studied. The combined NF training consisted of one block of theta/beta training and one block of SCP training, each block comprising 18 units of 50 minutes (balanced order). Spontaneous EEG was recorded in a two-minute resting condition before the start of the training, between the two training blocks and after the end of the training. Activity in the different EEG frequency bands was analyzed. In contrast to the control condition, the combined NF training was accompanied by a reduction of theta activity. Protocol-specific EEG changes (theta/beta training: decrease of posterior-midline theta activity; SCP training: increase of central-midline alpha activity) were associated with improvements in the German ADHD rating scale. Related EEG-based predictors were obtained. Thus, differential EEG patterns for theta/beta and SCP training provide further evidence that distinct neuronal mechanisms may contribute to similar behavioral improvements in children with ADHD.

Effects of methylphenidate on motor system excitability in a response inhibition task.

BACKGROUND: Motor system excitability is based on a complex interaction of excitatory and inhibitory processes, which in turn are modulated by internal (e.g., volitional inhibition) and external (e.g., drugs) factors. A well proven tool to investigate motor system excitability in vivo is the transcranial magnetic stimulation (TMS). In this study, we used TMS to investigate the effects of methylphenidate (MPH) on the temporal dynamics of motor system excitability during a go/nogo task. METHODS: Using a double-blind, placebo-controlled, crossover design, 14 healthy adults (8 male, 6 female; aged 20-40 yrs) performed a spatial go/nogo task (S1-S2 paradigm) either under dl-methylphenidate (MPH, 20 mg) or placebo. TMS single and double-pulses (interstimulus interval: 3 ms) were delivered either at 120, 230 or 350 ms after the S2 stimulus (control, go and nogo trials). RESULTS: At the performance level, faster reaction times and a trend towards less impulsivity errors under MPH vs. placebo were observed.In nogo trials, i.e., when a prepared response had to be inhibited, motor evoked potentials (MEPs) had a smaller amplitude at an interval of 230 ms compared to 120 and 350 ms. The short-interval intracortical inhibition (SICI) increased over time.Under MPH, SICI in nogo trials was larger compared to placebo. With the interval between S2 and the TMS-pulse increasing, MEP amplitudes increased under MPH in nogo trials but an early inhibitory effect (at 120 ms) could also be observed. CONCLUSION: Our results show a distinct pattern of excitatory and inhibitory phenomena in a go/nogo task. MPH appears to significantly alter the dynamics of motor system excitability. Our findings suggest that a single dose of 20 mg MPH provides some fine-tuning of the motor system in healthy adults.

Is neurofeedback an efficacious treatment for ADHD? A randomised controlled clinical trial.

BACKGROUND: For children with attention deficit/hyperactivity disorder (ADHD), a reduction of inattention, impulsivity and hyperactivity by neurofeedback (NF) has been reported in several studies. But so far, unspecific training effects have not been adequately controlled for and/or studies do not provide sufficient statistical power. To overcome these methodological shortcomings we evaluated the clinical efficacy of neurofeedback in children with ADHD in a multisite randomised controlled study using a computerised attention skills training as a control condition. METHODS: 102 children with ADHD, aged 8 to 12 years, participated in the study. Children performed either 36 sessions of NF training or a computerised attention skills training within two blocks of about four weeks each (randomised group assignment). The combined NF treatment consisted of one block of theta/beta training and one block of slow cortical potential (SCP) training. Pre-training, intermediate and post-training assessment encompassed several behaviour rating scales (e.g., the German ADHD rating scale, FBB-HKS) completed by parents and teachers. Evaluation ('placebo') scales were applied to control for parental expectations and satisfaction with the treatment. RESULTS: For parent and teacher ratings, improvements in the NF group were superior to those of the control group. For the parent-rated FBB-HKS total score (primary outcome measure), the effect size was .60. Comparable effects were obtained for the two NF protocols (theta/beta training, SCP training). Parental attitude towards the treatment did not differ between NF and control group. CONCLUSIONS: Superiority of the combined NF training indicates clinical efficacy of NF in children with ADHD. Future studies should further address the specificity of effects and how to optimise the benefit of NF as treatment module for ADHD.