Neuroanatomical Predictors of Transcranial Direct Current Stimulation (tDCS)-Induced Modifications in Neurocognitive Task Performance in Typically Developing Individuals.

Transcranial direct current stimulation (tDCS) is a noninvasive neuromodulation technique gaining more attention in neurodevelopmental disorders (NDDs). Due to the phenotypic heterogeneity of NDDs, tDCS is unlikely to be equally effective in all individuals. The present study aimed to establish neuroanatomical markers in typically developing (TD) individuals that may be used for the prediction of individual responses to tDCS. Fifty-seven male and female children received 2 mA anodal and sham tDCS, targeting the left dorsolateral prefrontal cortex (DLPFCleft), right inferior frontal gyrus, and bilateral temporoparietal junction. Response to tDCS was assessed based on task performance differences between anodal and sham tDCS in different neurocognitive tasks (N-back, flanker, Mooney faces detection, attentional emotional recognition task). Measures of cortical thickness (CT) and surface area (SA) were derived from 3 Tesla structural MRI scans. Associations between neuroanatomy and task performance were assessed using general linear models (GLM). Machine learning (ML) algorithms were employed to predict responses to tDCS. Vertex-wise estimates of SA were more closely linked to differences in task performance than measures of CT. Across ML algorithms, highest accuracies were observed for the prediction of N-back task performance differences following stimulation of the DLPFCleft, where 65% of behavioral variance was explained by variability in SA. Lower accuracies were observed for all other tasks and stimulated regions. This suggests that it may be possible to predict individual responses to tDCS for some behavioral measures and target regions. In the future, these models might be extended to predict treatment outcome in individuals with NDDs.

[Parent-Child Treatment in Child and Adolescent Psychiatry: Models and Clinical Implementation Using the Example of a Modular Parent-Child Ward]. / Eltern-Kind-Behandlung in der Kinder- und Jugendpsychiatrie: Modelle und klinische Umsetzung am Beispiel einer bausteinorientierten Eltern-Kind-Station.

The joint treatment of mentally ill children and their parents represents a special treatment concept in child and adolescent psychiatry. A study conducted by the Working Group (BAG) "Early Childhood" shows the current situation of care and possible models of child and adolescent psychiatric parent-child treatment in Germany. Using the parent-child ward of the Child and Adolescent Psychiatry Department in Magdeburg as an example, the combined treatment of mentally ill children and their parents is presented. The treatment approach consists of a three-week diagnostic phase, after which families are discharged again to their home environment followed by a five-week therapy block, for which the families have to be readmitted to the ward. With a focus on the parent-child relationship, the treatment concept - in contrast to regular child psychiatric treatments - is dynamically adapted to the quality of the parent-child interaction and not primarily related to the disorder of the children. First studies indicate the effectiveness of the special treatment setting and illustrate the efficiency of a joint treatment of parents and child, which, however, is associated with increased economic costs. Based on these results, the chances and limitations of parent-child wards are discussed and conclusions for parent-child treatment are drawn.

Orbitofrontal Signaling of Future Reward is Associated with Hyperactivity in Attention-Deficit/Hyperactivity Disorder.

Alterations in motivated behavior are a hallmark of attention-deficit/hyperactivity disorder (ADHD), one of the most common psychiatric disorders in children and adolescents. The orbitofrontal cortex (OFC) plays a key role in controlling goal-directed behavior, but the link between OFC dysfunction and behavioral deficits in ADHD, particularly in adolescence, remains poorly understood. Here we used advanced high-resolution functional magnetic resonance imaging (fMRI) of the human OFC in adolescents with ADHD and typically developing (TD) controls (N = 39, age 12-16, all male except for one female per group) to study reward-related OFC responses and how they relate to behavioral dysfunction in ADHD. During fMRI data acquisition, participants performed a simple decision-making task, allowing us to image expectation-related responses to small and large monetary outcomes. Across all participants, we observed significant signal increases to large versus small expected rewards in the OFC. These responses were significantly enhanced in ADHD relative to TD participants. Moreover, stronger reward-related activity was correlated with individual differences in hyperactive/impulsive symptoms in the ADHD group, whereas high cognitive ability was associated with normalized OFC responses. These results provide evidence for the importance of OFC dysfunctions in the neuropathology of ADHD, highlighting the role of OFC-dependent goal-directed control mechanisms in this disorder.SIGNIFICANCE STATEMENT Attention-deficit/hyperactivity disorder (ADHD) is characterized by alterations in motivated behavior which can be understood as diminished goal-directed control. The orbitofrontal cortex (OFC) plays a key role in controlling goal-directed behavior, but its potential contribution to ADHD symptomatology remains poorly understood. Using high-resolution fMRI, we show that adolescent ADHD patients display enhanced OFC signaling of future rewards and that these increased reward-related responses are correlated with the severity of hyperactivity/impulsivity. These findings suggest that an inability to adequately evaluate future outcomes may translate into maladaptive behavior in ADHD patients. They also challenge the idea that dysfunctions in dopaminergic brain areas are the sole contributor to reward-related symptoms in ADHD and point to a central contribution of goal-directed control circuits in hyperactivity.

Modulation of pre-attentive spectro-temporal feature processing in the human auditory system by HD-tDCS.

The present study examined the functional lateralization of the human auditory cortex (AC) for pre-attentive spectro-temporal feature processing. By using high-definition transcranial direct current stimulation (HD-tDCS), we systematically modulated neuronal activity of the bilateral AC. We assessed the influence of anodal and cathodal HD-tDCS delivered over the left or right AC on auditory mismatch negativity (MMN) in response to temporal as well as spectral deviants in 12 healthy subjects. The results showed that MMN to temporal deviants was significantly enhanced by anodal HD-tDCS applied over the left AC only. Our data indicate a left hemispheric dominance for the pre-attentive processing of low-level temporal information.

Altered salience processing in attention deficit hyperactivity disorder.

Attentional problems in patients with attention deficit hyperactivity disorder (ADHD) have often been linked with deficits in cognitive control. Whether these deficits are associated with increased sensitivity to external salient stimuli remains unclear. To address this issue, we acquired functional brain images (fMRI) in 38 boys with and without ADHD (age: 11-16 years). To differentiate the effects of item novelty, contextual rareness and task relevance, participants performed a visual oddball task including four stimulus categories: a frequent standard picture (62.5%), unique novel pictures (12.5%), one repeated rare picture (12.5%), and a target picture (12.5%) that required a specific motor response. As a main finding, we can show considerable overlap in novelty-related BOLD responses between both groups, but only healthy participants showed neural deactivation in temporal as well as frontal regions in response to novel pictures. Furthermore, only ADHD patients, but not healthy controls, engaged wide parts of the novelty network when processing the rare but familiar picture. Our results provide first evidence that ADHD patients show enhanced neural activity in response to novel but behaviorally irrelevant stimuli as well as reduced habituation to familiar items. These findings suggest an inefficient use of neuronal resources in children with ADHD that could be closely linked to increased distractibility.

Audio-visual synchrony modulates the ventriloquist illusion and its neural/spatial representation in the auditory cortex.

An essential task of our perceptual systems is to bind together the distinctive features of single objects and events into unitary percepts, even when those features are registered in different sensory modalities. In cases where auditory and visual inputs are spatially incongruent, they may still be perceived as belonging to a single event at the location of the visual stimulus - a phenomenon known as the 'ventriloquist illusion'. The present study examined how audio-visual temporal congruence influences the ventriloquist illusion and characterized its neural underpinnings with functional magnetic resonance imaging (fMRI). Behaviorally, the ventriloquist illusion was reduced for asynchronous versus synchronous audio-visual stimuli, in accordance with previous reports. Neural activity patterns associated with the ventriloquist effect were consistently observed in the planum temporale (PT), with a reduction in illusion-related fMRI-signals ipsilateral to visual stimulation for central sounds perceived peripherally and a contralateral increase in illusion-related fMRI-signals for peripheral sounds perceived centrally. Moreover, it was found that separate but adjacent regions within the PT were preferentially activated for ventriloquist illusions produced by synchronous and asynchronous audio-visual stimulation. We conclude that the left-right balance of neural activity in the PT represents the neural code that underlies the ventriloquist illusion, with greater activity in the cerebral hemisphere contralateral to the direction of the perceived shift of sound location.

Task-demands and audio-visual stimulus configurations modulate neural activity in the human thalamus.

Recent electrophysiological studies have reported short latency modulations in cortical regions for multisensory stimuli, thereby suggesting a subcortical, possibly thalamic origin of these modulations. Concurrently, there is an ongoing debate, whether multisensory interplay reflects automatic, bottom-up driven processes or relies on top-down influences. Here, we dissociated the effects of task set and stimulus configurations on BOLD-signals in the human thalamus with event-related functional magnetic resonance imaging (fMRI). We orthogonally manipulated temporal and spatial congruency of audio-visual stimulus configurations, while subjects judged either their temporal or spatial congruency. Voxel-based fMRI results revealed increased fMRI-signals for the temporal versus spatial task in posterior and central thalamus, respectively. A more sensitive region of interest (ROI)-analysis confirmed that the posterior thalamic nuclei showed a preference for the temporal task and central thalamic nuclei for the spatial task. Moreover, the ROI-analysis also revealed enhanced fMRI-signals for spatially incongruent stimuli in the central thalamus. Together, our results demonstrate that both audio-visual stimulus configurations and task-related processing of spatial or temporal stimulus features selectively modulate thalamic processing and thus are in a position to influence cortical processing at an early stage.

Psychological distress in cancer patients with underage children: gender-specific differences.

BACKGROUND: Findings on gender differences in the psychological distress of cancer patients have been inconsistent. The objectives of the current study were to examine whether being a parent differentially modulates anxiety and depression in men and women and to compare whether psychological distress differs in male and female patients with and without children. METHODS: There were 235 patients (77% female, 23% male) with different cancer types included in the group with underage children (age <18 years). The comparison group with no children comprised 85 patients. Psychological distress was assessed via the Hospital Anxiety and Depression Scale within 12 months after first diagnosis or during treatment of metastases. RESULTS: In the patient group with underage children, women tended to report more anxiety than men. The comparison with the patient group without children, however, revealed that men were significantly more affected by anxiety when they had children, whereas in women, anxiety ratings did not differ between the groups. Men tended to report more depressive symptoms, but depression was not differentially associated with parenthood. A binary logistic regression showed that in men with cancer, anxiety, as well as depression, was highly related to unemployment. In women, occurrence of metastases as well as suffering from other cancer types than breast cancer was associated with higher ratings of anxiety. CONCLUSION: Even though our findings need to be supported in future investigations using larger sample sizes, they imply that male cancer patients with underage children are in particular need of psychosocial support.

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.

Stratification of responses to tDCS intervention in a healthy pediatric population based on resting-state EEG profiles.

Transcranial Direct Current Stimulation (tDCS) is a non-invasive neuromodulation technique with a wide variety of clinical and research applications. As increasingly acknowledged, its effectiveness is subject dependent, which may lead to time consuming and cost ineffective treatment development phases. We propose the combination of electroencephalography (EEG) and unsupervised learning for the stratification and prediction of individual responses to tDCS. A randomized, sham-controlled, double-blind crossover study design was conducted within a clinical trial for the development of pediatric treatments based on tDCS. The tDCS stimulation (sham and active) was applied either in the left dorsolateral prefrontal cortex or in the right inferior frontal gyrus. Following the stimulation session, participants performed 3 cognitive tasks to assess the response to the intervention: the Flanker Task, N-Back Task and Continuous Performance Test (CPT). We used data from 56 healthy children and adolescents to implement an unsupervised clustering approach that stratify participants based on their resting-state EEG spectral features before the tDCS intervention. We then applied a correlational analysis to characterize the clusters of EEG profiles in terms of participant's difference in the behavioral outcome (accuracy and response time) of the cognitive tasks when performed after a tDCS-sham or a tDCS-active session. Better behavioral performance following the active tDCS session compared to the sham tDCS session is considered a positive intervention response, whilst the reverse is considered a negative one. Optimal results in terms of validity measures was obtained for 4 clusters. These results show that specific EEG-based digital phenotypes can be associated to particular responses. While one cluster presents neurotypical EEG activity, the remaining clusters present non-typical EEG characteristics, which seem to be associated with a positive response. Findings suggest that unsupervised machine learning can be successfully used to stratify and eventually predict responses of individuals to a tDCS treatment.

Neural Mechanisms Underlying the Effects of Novel Sounds on Task Performance in Children With and Without ADHD.

Distractibility is one of the key features of attention deficit hyperactivity disorder (ADHD) and has been associated with alterations in the neural orienting and alerting networks. Task-irrelevant stimuli are thus expected to have detrimental effects on the performance of patients with ADHD. However, task-irrelevant presentation of novel sounds seems to have the opposite effect and improve subsequent attentional performance particularly in patients with ADHD. Here, we aimed to understand the neural modulations of the attention networks underlying these improvements. Fifty boys (25 with ADHD) participated in a functional magnetic resonance imaging (fMRI) study in which unique (novel) or repeatedly presented (familiar) sounds were placed before a visual flanker task in 2/3 of the trials. We found that presenting any sound improved task performance in all participants, but the underlying neural mechanisms differed for the type of sound. Familiar sounds led to a stronger increase in activity in the left posterior insula in patients with ADHD compared to typically developing peers. Novel sounds led to activations of the fronto-temporoparietal ventral attention network, likewise in ADHD and TD. These changes in signaling by novelty in the right inferior frontal gyrus were directly related to improved response speed showing that neural orienting network activity following novel sounds facilitated subsequent attentional performance. This mechanism of behavioral enhancement by short distractions could potentially be useful for cognitive trainings or homework situations.

Transcutaneous vagus nerve stimulation in patients with attention-deficit/hyperactivity disorder: A viable option?

Individuals with attention-deficit/hyperactivity disorder (ADHD) suffer from a range of cognitive and behavioral problems that severely impair their educational and occupational attainment. ADHD symptoms have been linked to structural and functional changes within and between different brain regions, particularly the prefrontal cortex. At the system level, reduced availability of the neurotransmitters dopamine (DA) and norepinephrine (NE) but also γ-aminobutyric acid (GABA) have been repeatedly demonstrated. Recently, non-invasive brain stimulation (NIBS) techniques have been explored as treatment alternatives to alter dysfunctional activation patterns in specified brain areas or networks. In the current paper, we introduce transcutaneous vagus nerve stimulation (tVNS) as a systemic approach to directly affect NE and GABA neurotransmission. TVNS is a non-drug intervention with low risk and proven efficacy in improving cognitive particularly executive functions. It is easy to apply and therefore well-suited to provide home-based or mobile treatment options allowing a significant increase in treatment intensity and providing easier access to medical care for individuals who are unable to regularly visit a clinician. We describe in detail the underlying mechanisms of tVNS and current fields of application and discuss its potential as an adjuvant treatment for ADHD.

The LC-NE system as a potential target for neuromodulation to ameliorate non-motor symptoms in Parkinson's disease.

Parkinson's disease (PD) is associated with severe motor symptoms but also with several non-motor symptoms (NMS). A substantial reduction of norepinephrine (NE) levels in various brain regions reflecting an extensive loss of innervation from the LC has been assumed as causal for the development of NMS and specifically of attentional impairments in PD. Transcutaneous auricular vagus nerve stimulation (taVNS) is a new, non-invasive neurostimulation method supposed to modulate the LC-NE system in humans. In the current opinion paper, we introduce taVNS as a systemic approach to directly affect NE neurotransmission in healthy as well as clinical populations and discuss its potential as therapeutic option for the treatment of NMS, specifically attentional deficits, in patients with PD. Here, we first describe the LC-NE system and discuss how LC-NE dysfunction might affects cognition in PD before detailing the mode of action of taVNS and proposing its use to modulate cognitive deficits in these patients.

Effects of a five-day HD-tDCS application to the right IFG depend on current intensity: A study in children and adolescents with ADHD.

Impaired executive functions in ADHD are associated with hypoactivity of the right inferior frontal gyrus (IFG). This region was targeted via repetitive applications of anodal, high-definition transcranial direct current simulation (HD-tDCS) on five consecutive days in 33 ADHD patients (10-17years) and in a healthy control group (n=13, only sham). Patients received either sham (n=13) or verum tDCS with 0.5mA (n=9) or 0.25mA (n=11) depending on individual cutaneous sensitivity. During stimulation, participants performed a combined working memory and response inhibition paradigm (n-back/nogo). At baseline, post, and a 4-month follow up, electroencephalography was recorded during this task. Moreover, interference control (flanker task) and spatial working memory (spanboard task) were assessed to explore possible transfer effects. Omission errors and reaction time variability in all tasks served as measures of attention. In the 0.25mA group increased nogo commission errors indicated a detrimental tDCS effect on response inhibition. After the 5-day stimulation, attentional improvements in the 0.5mA group were indicated by reduced omission errors and reaction time variability. Variability improvements were still evident at follow up. In all groups, nogo P3 amplitudes were reduced post-stimulation, but in the 0.5mA group this reduction was smaller than in the 0.25mA group. Results of the current study suggest distinct effects of tDCS with different current intensities demonstrating the importance of a deeper understanding on the impact of stimulation parameters and repeated tDCS applications to develop effective tDCS-based therapy approaches in ADHD.

Transcranial direct-current stimulation and pediatric attention deficit hyperactivity disorder (ADHD)-Findings from an interview ethics study with children, adolescents, and their parents.

INTRODUCTION: Transcranial direct current stimulation (tDCS) is a brain stimulation technique for an alternative or complementary treatment for various neurological disorders, including pediatric ADHD. However, little is known about the experiences of participants undergoing tDCS treatments in clinical trials. Exploration of their views on the matter is an important contribution to the societal debate on ethical issues of tDCS, allowing for a responsible translation into clinical practice and timely identification of potential challenges. METHODS: in-depth interviews study with children with ADHD undertaking tDCS and their parents (n=32). RESULTS: Children reported overall good experiences with the stimulation, although they found participation in the clinical study very tiring and time consuming. Their responses to the actual effects of the stimulation were mixed. Parents were very keen for their children to participate in the study as they saw it as a promising and safe alternative to medication. Even though many of them understood the techniques, they often did not see the link between the (current) lack of side effects and an absence of longitudinal studies. Unlike children, interviewed parents were cautious about using tDCS for non-medical/enhancement purposes. DISCUSSION: There is a need for more transparent information about the state of the art of tDCS, its function and what it actually might be able to offer. It is especially important in order to prevent unrealistic hopes and to make sure that future pediatric patients and their carers are more aware of the potential side-effects and long-term effects of tDCS.

Multichannel anodal tDCS over the left dorsolateral prefrontal cortex in a paediatric population.

Methodological studies investigating transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (lDLPFC) in paediatric populations are limited. Therefore, we investigated in a paediatric population whether stimulation success of multichannel tDCS over the lDLPFC depends on concurrent task performance and individual head anatomy. In a randomised, sham-controlled, double-blind crossover study 22 healthy participants (10-17 years) received 2 mA multichannel anodal tDCS (atDCS) over the lDLPFC with and without a 2-back working memory (WM) task. After stimulation, the 2-back task and a Flanker task were performed. Resting state and task-related EEG were recorded. In 16 participants we calculated the individual electric field (E-field) distribution. Performance and neurophysiological activity in the 2-back task were not affected by atDCS. atDCS reduced reaction times in the Flanker task, independent of whether atDCS had been combined with the 2-back task. Flanker task related beta oscillation increased following stimulation without 2-back task performance. atDCS effects were not correlated with the E-field. We found no effect of multichannel atDCS over the lDLPFC on WM in children/adolescents but a transfer effect on interference control. While this effect on behaviour was independent of concurrent task performance, neurophysiological activity might be more sensitive to cognitive activation during stimulation. However, our results are limited by the small sample size, the lack of an active control group and variations in WM performance.

Economical Assessment of Working Memory and Response Inhibition in ADHD Using a Combined n-back/Nogo Paradigm: An ERP Study.

The development of cognitive interventions in attention-deficit/hyperactivity disorder (ADHD) often requires the assessment of multiple cognitive functions. However, experimental settings consisting of various tasks are particularly strenuous for patients and can thus result in poor data quality. For the economical assessment of working memory and response inhibition, this study aims to validate a combined n-back/nogo paradigm by comparing it to single task versions and to demonstrate its applicability for ADHD research. Twenty-five healthy individuals and 34 ADHD patients between 9 and 16 years participated in this event-related potential (ERP) study. Healthy controls underwent single task versions of a 2-back working memory task and a go/nogo response inhibition task as well as the introduced combined 2-back/nogo task. This combined task demonstrated a comparable ERP structure for working memory and response inhibition aspects as single task versions. Behaviorally, higher working memory performance during the combined paradigm indicated lower task difficulty, while high correlations between combined and single task versions still indicated valid working memory measures. For response inhibition performance, different task versions resulted in similar outcomes. The application of the combined n-back/nogo paradigm in ADHD patients revealed the expected working memory and response inhibition deficits, increased omission errors, reaction times, and standard deviation of reaction time, as well as diminished n-back P3 and nogo P3 amplitudes. We conclude that the combined n-back/nogo task is an effective paradigm for the economical assessment of working memory and response inhibition deficits in ADHD on a behavioral and neurophysiological level.

Comparison between conventional and HD-tDCS of the right inferior frontal gyrus in children and adolescents with ADHD.

OBJECTIVE: To investigate whether the effects of HD-tDCS and conventional tDCS of the right IFG are superior to the effects of sham stimulation for the improvement of working memory performance in ADHD. METHODS: 15 ADHD patients between 10 and 16 years underwent three tDCS sessions in which conventional, HD and sham tDCS of the right IFG were applied. In all sessions a 2-back working memory task was solved and EEG was recorded. Baseline data were assessed from 15 age matched healthy controls. RESULTS: In ADHD patients, increased positive values of P300 and N200 mean amplitudes were found after conventional and HD-tDCS. Thus, both components were more in resemblance to ERPs in healthy controls. Behavioral performance was not generally influenced by tDCS but effects of HD-tDCS depended on individual hyperactive/impulsive symptom load. The rate of responders for HD-tDCS was equivalent to the responder rate for conventional tDCS. CONCLUSIONS: ERP data indicate that HD-tDCS is equally suitable as conventional tDCS for the recruitment of the right IFG in the context of working memory processing. SIGNIFICANCE: HD-tDCS of the right IFG is a promising approach for neuromodulation in ADHD but further research is necessary to develop adaptations that produce reliable behavioral benefits.

Learning in anticipation of reward and punishment: perspectives across the human lifespan.

Learning to act to receive reward and to withhold to avoid punishment has been found to be easier than learning the opposite contingencies in young adults. To what extent this type of behavioral adaptation might develop during childhood and adolescence and differ during aging remains unclear. We therefore tested 247 healthy individuals across the human life span (7-80 years) with an orthogonalized valenced go/no-go learning task. Computational modeling revealed that peak performance in young adults was attributable to greater sensitivity to both reward and punishment. However, in children and adolescents, we observed an increased bias toward action but not reward sensitivity. By contrast, reduced learning in midlife and older adults was accompanied by decreased reward sensitivity and especially punishment sensitivity along with an age-related increase in the Pavlovian bias. These findings reveal distinct motivation-dependent learning capabilities across the human life span, which cannot be probed using conventional go/reward no-go/punishment style paradigms that have important implications in lifelong education.

Exploration of a novel virtual environment improves memory consolidation in ADHD.

Experimental evidence in rodents and humans suggests that long-term memory consolidation can be enhanced by the exploration of a novel environment presented during a vulnerable early phase of consolidation. This memory enhancing effect (behavioral tagging) is caused by dopaminergic and noradrenergic neuromodulation of hippocampal plasticity processes. In translation from animal to human research, we investigated whether behavioral tagging with novelty can be used to tackle memory problems observed in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). 34 patients with ADHD and 34 typically developing participants (age 9-15 years) explored either a previously familiarized or a novel virtual environment 45 min after they had learned a list of 20 words. Participants took a free recall test both immediately after learning the word list and after 24 h. Patients who explored a familiar environment showed significantly impaired memory consolidation compared to typically developing peers. Exploration of a novel environment led to significantly better memory consolidation in children and adolescents with ADHD. However, we did not observe a beneficial effect of novel environment exploration in typically developing participants. Our data rather suggested that increased exploration of a novel environment as well as higher feelings of virtual immersion compromised memory performance in typically developing children and adolescents, which was not the case for patients with ADHD. We propose that behavioral tagging with novel virtual environments is a promising candidate to overcome ADHD related memory problems. Moreover, the discrepancy between children and adolescents with and without ADHD suggests that behavioral tagging might only be able to improve memory consolidation for weakly encoded information.