Inhibiting Hippo pathway kinases releases WWC1 to promote AMPAR-dependent synaptic plasticity and long-term memory in mice.

The localization, number, and function of postsynaptic AMPA-type glutamate receptors (AMPARs) are crucial for synaptic plasticity, a cellular correlate for learning and memory. The Hippo pathway member WWC1 is an important component of AMPAR-containing protein complexes. However, the availability of WWC1 is constrained by its interaction with the Hippo pathway kinases LATS1 and LATS2 (LATS1/2). Here, we explored the biochemical regulation of this interaction and found that it is pharmacologically targetable in vivo. In primary hippocampal neurons, phosphorylation of LATS1/2 by the upstream kinases MST1 and MST2 (MST1/2) enhanced the interaction between WWC1 and LATS1/2, which sequestered WWC1. Pharmacologically inhibiting MST1/2 in male mice and in human brain-derived organoids promoted the dissociation of WWC1 from LATS1/2, leading to an increase in WWC1 in AMPAR-containing complexes. MST1/2 inhibition enhanced synaptic transmission in mouse hippocampal brain slices and improved cognition in healthy male mice and in male mouse models of Alzheimer's disease and aging. Thus, compounds that disrupt the interaction between WWC1 and LATS1/2 might be explored for development as cognitive enhancers.

Attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD; also known as hyperkinetic disorder) is a common neurodevelopmental condition that affects children and adults worldwide. ADHD has a predominantly genetic aetiology that involves common and rare genetic variants. Some environmental correlates of the disorder have been discovered but causation has been difficult to establish. The heterogeneity of the condition is evident in the diverse presentation of symptoms and levels of impairment, the numerous co-occurring mental and physical conditions, the various domains of neurocognitive impairment, and extensive minor structural and functional brain differences. The diagnosis of ADHD is reliable and valid when evaluated with standard diagnostic criteria. Curative treatments for ADHD do not exist but evidence-based treatments substantially reduce symptoms and/or functional impairment. Medications are effective for core symptoms and are usually well tolerated. Some non-pharmacological treatments are valuable, especially for improving adaptive functioning. Clinical and neurobiological research is ongoing and could lead to the creation of personalized diagnostic and therapeutic approaches for this disorder.

A New Intervention for Implementation of Pharmacogenetics in Psychiatry: A Description of the PSY-PGx Clinical Study.

(1) Background Pharmacological treatment for psychiatric disorders has shown to only be effective in about one-third of patients, as it is associated with frequent treatment failure, often because of side effects, and a long process of trial-and-error pharmacotherapy until an effective and tolerable treatment is found. This notion emphasizes the urgency for a personalized medicine approach in psychiatry. (2) Methods This prospective patient- and rater-blinded, randomized, controlled study will investigate the effect of dose-adjustment of antidepressants escitalopram and sertraline or antipsychotics risperidone and aripiprazole according to the latest state-of-the-art international dosing recommendations for CYP2C19 and CYP2D6 metabolizer status in patients with mood, anxiety, and psychotic disorders. A total sample of N = 2500 will be recruited at nine sites in seven countries (expected drop-out rate of 30%). Patients will be randomized to a pharmacogenetic group or a dosing-as-usual group and treated over a 24-week period with four study visits. The primary outcome is personal recovery using the Recovery Assessment Scale as assessed by the patient (RAS-DS), with secondary outcomes including clinical effects (response or symptomatic remission), side effects, general well-being, digital phenotyping, and psychosocial functioning. (3) Conclusions This is, to our knowledge, the first international, multi-center, non-industry-sponsored randomized controlled trial (RCT) that may provide insights into the effectiveness and utility of implementing pharmacogenetic-guided treatment of psychiatric disorders, and as such, results will be incorporated in already available dosing guidelines.

[Is Physical Activity a Treatment Option for ADHD?] / Körperliche Aktivität als Therapieoption bei ADHS?

Is Physical Activity a Treatment Option for ADHD? Abstract: Physical activity as an option for the prevention and treatment of psychiatric disorders is increasingly becoming the focus of research. In particular, because of improvements in cognitive functioning, attentional performance, impulsivity, and hyperactivity, physical exercise could be a promising treatment option for attention deficit hyperactivity disorder (ADHD). In this narrative review, we present and evaluate the current state of research on exercise effects in children and adolescents as well as in adults with ADHD. While studies of the short-term effects of a single bout of physical activity indicate robust effects on attention and inhibitory control, results on the impact on further symptoms of ADHD as well as in adults are mixed. Randomized controlled trials of longer-term physical activity are scarce and show high heterogeneity. Nevertheless, they are encouraging for further research in this area.

Altered reward network responses to social touch in major depression.

BACKGROUND: Social touch is an integral part of social relationships and has been associated with reward. Major depressive disorder (MDD) is characterized by severe impairments in reward processing, but the neural effects of social touch in MDD are still elusive. In this study, we aimed to determine whether the neural processing of social touch is altered in MDD and to assess the impact of antidepressant therapy. METHODS: Before and after antidepressant treatment, 53 MDD patients and 41 healthy controls underwent functional magnetic resonance imaging (fMRI) while receiving social touch. We compared neural responses to social touch in the reward network, behavioral ratings of touch comfort and general aversion to interpersonal touch in patients to controls. Additionally, we examined the effect of treatment response on those measures. RESULTS: Clinical symptoms decreased after treatment and 43.4% of patients were classified as responders. Patients reported higher aversion to interpersonal touch and lower comfort ratings during the fMRI paradigm than controls. Patients showed reduced responses to social touch in the nucleus accumbens, caudate nucleus and putamen than controls, both before and after treatment. Contrary to our hypotheses, these effects were independent of touch velocity. Non-responders exhibited blunted response in the caudate nucleus and the insula compared to responders, again irrespective of time. CONCLUSIONS: These findings suggest altered striatal processing of social touch in MDD. Persistent dysfunctional processing of social touch despite clinical improvements may constitute a latent risk factor for social withdrawal and isolation.

Treatment of adult attention-deficit hyperactivity disorder (ADHD) with transcranial direct current stimulation (tDCS): study protocol for a parallel, randomized, double-blinded, sham-controlled, multicenter trial (Stim-ADHD).

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation treatment used as an alternative or complementary treatment for various neuropsychiatric disorders, and could be an alternative or add-on therapy to psychostimulants in attention-deficit hyperactivity disorder (ADHD). Previous studies provided some evidence for improvements in cognition and clinical symptoms in pediatric and adult ADHD patients. However, data from multi-center randomized controlled trials (RCTs) for this condition are lacking. Thus, our aim is to evaluate short- and mid-term effects of tDCS in this multi-center, randomized, double blind, and sham-controlled, parallel group clinical trial with a 1:1 randomization ratio. Primary endpoint is the total score of DSM-IV scale of the internationally established Conners' Adult ADHD Rating Scales (German self-report screening version, CAARS-S-SR), at day 14 post-intervention (p.i.) to detect short-term lasting effects analyzed via analyses of covariance (ANCOVAs). In case of significant between-groups differences at day 14 p.i., hierarchically ordered hypotheses on mid-term lasting effects will be investigated by linear mixed models with visit (5 time points), treatment, treatment by visit interaction, and covariates as fixed categorical effects plus a patient-specific visit random effect, using an unstructured covariance structure to model the residual within-patient errors. Positive results of this clinical trial will expand the treatment options for adult ADHD patients with tDCS and provide an alternative or add-on therapy to psychostimulants with a low risk for side effects.Trial Registration The trial was registered on July 29, 2022 in the German Clinical Trials Register (DRKS00028148).

Exploring the Relationship between Adherence to Therapy, Treatment Acceptability, and Clinical Outcomes in Adults with Attention-Deficit/Hyperactivity Disorder: Results from the COMPAS Multicenter Randomized Controlled Trial.

INTRODUCTION: Cognitive behavioral therapy and dialectical behavior therapy (DBT) can be effective in treating adults with ADHD, and patients generally consider these interventions useful. While adherence, as measured by attendance at sessions, is mostly sufficient, adherence to therapy skills has not been assessed. Furthermore, the relationship between patient evaluation of therapy effectiveness, treatment adherence, and clinical outcomes is understudied. OBJECTIVE: This study aimed to examine treatment acceptability and adherence in relation to treatment outcomes in a large randomized controlled trial comparing a DBT-based intervention with a nonspecific active comparison, combined with methylphenidate or placebo. METHOD: A total of 433 adult patients with ADHD were randomized. Participants reported how effective they found the therapy, and adherence was measured by attendance at therapy sessions and by self-reports. Descriptive, between-groups, and linear mixed model analyses were conducted. RESULTS: Participants rated psychotherapy as moderately effective, attended 78.40-94.37% of sessions, and used skills regularly. The best-accepted skills were sports and mindfulness. Groups receiving placebo and/or nonspecific clinical management rated their health condition and the medication effectiveness significantly worse than the psychotherapy and methylphenidate groups. Improvements in clinical outcomes were significantly associated with treatment acceptability. Subjective (self-reported) adherence to psychotherapy was significantly associated with improvements in ADHD symptoms, clinical global efficacy and response to treatment. DISCUSSION: These results further support the acceptability of DBT for adult ADHD and suggest the need to address adherence to treatment to maximize clinical improvements. Results may be limited by the retrospective assessment of treatment acceptability and adherence using an ad hoc instrument.

Exploring the efficacy of dialectical behaviour therapy and methylphenidate on emotional comorbid symptoms in adults with attention Deficit/Hyperactivity disorder: Results of the COMPAS multicentre randomised controlled trial.

This study evaluated the efficacy of dialectical behaviour group therapy (GPT) vs. individual clinical management (CM) and methylphenidate (MPH) vs. placebo (PLB) on emotional symptoms in adults with ADHD. This longitudinal multicentre RCT compared four groups (GPT+MPH, GPT+PLB, CM+MPH, and CM+PLB) over five assessment periods, from baseline to week 130. Emotional symptomatology was assessed using SCL-90-R subscales. Of the 433 randomised participants, 371 remained for final analysis. At week 13, the GPT+MPH group showed smaller reductions in anxiety symptoms than the CM groups, but the differences disappeared at subsequent assessments. Improvements in emotional symptom were significantly predicted by reductions in core ADHD symptoms in all groups except the GPT+MPH group. The unexpected lack of between-group differences may be explained by a "floor effect", different intervention settings (group vs. individual), and psychotherapy type. Multiple regression analyses suggest a more specific effect of combined interventions (GPT+MPH). Implications for clinical practice are discussed. Clinical trial registration: ISRCTN54096201 (Current Controlled Trials).

The effects of creatine supplementation on cognitive performance-a randomised controlled study.

BACKGROUND: Creatine is an organic compound that facilitates the recycling of energy-providing adenosine triphosphate (ATP) in muscle and brain tissue. It is a safe, well-studied supplement for strength training. Previous studies have shown that supplementation increases brain creatine levels, which might increase cognitive performance. The results of studies that have tested cognitive performance differ greatly, possibly due to different populations, supplementation regimens, and cognitive tasks. This is the largest study on the effect of creatine supplementation on cognitive performance to date. METHODS: Our trial was preregistered, cross-over, double-blind, placebo-controlled, and randomised, with daily supplementation of 5 g for 6 weeks each. We tested participants on Raven's Advanced Progressive Matrices (RAPM) and on the Backward Digit Span (BDS). In addition, we included eight exploratory cognitive tests. About half of our 123 participants were vegetarians and half were omnivores. RESULTS: Bayesian evidence supported a small beneficial effect of creatine. The creatine effect bordered significance for BDS (p = 0.064, η2P = 0.029) but not RAPM (p = 0.327, η2P = 0.008). There was no indication that creatine improved the performance of our exploratory cognitive tasks. Side effects were reported significantly more often for creatine than for placebo supplementation (p = 0.002, RR = 4.25). Vegetarians did not benefit more from creatine than omnivores. CONCLUSIONS: Our study, in combination with the literature, implies that creatine might have a small beneficial effect. Larger studies are needed to confirm or rule out this effect. Given the safety and broad availability of creatine, this is well worth investigating; a small effect could have large benefits when scaled over time and over many people. TRIAL REGISTRATION: The trial was prospectively registered (drks.de identifier: DRKS00017250, https://osf.io/xpwkc/ ).

Developing Advanced AI Ecosystems to Enhance Diagnosis and Care for Patients with Depression.

Major Depressive Disorder (MDD) has a significant impact on the daily lives of those affected. This concept paper presents a project that aims at addressing MDD challenges through innovative therapy systems. The project consists of two use cases: a multimodal neurofeedback (NFB) therapy and an AI-based virtual therapy assistant (VTA). The multimodal NFB integrates EEG and fNIRS to comprehensively assess brain function. The goal is to develop an open-source NFB toolbox for EEG-fNIRS integration, augmented by the VTA for optimized efficacy. The VTA will be able to collect behavioral data, provide personalized feedback and support MDD patients in their daily lives. This project aims to improve depression treatment by bringing together digital therapy, AI and mobile apps to potentially improve outcomes and accessibility for people living with depression.

Chatbot-supported psychoeducation in adult attention-deficit hyperactivity disorder: randomised controlled trial.

BACKGROUND: Although psychoeducation is generally recommended for the treatment of adult attention-deficit hyperactivity disorder (ADHD), participation in clinical psychoeducation groups is impeded by waiting times and the constrained number of patients who can simultaneously attend a group. Digital psychoeducation attempts are promising, but the rapidly expanding number of apps lack evidence and are mostly limited to only a few implemented interactive elements. AIMS: To determine the potential of digital, self-guided psychoeducation for adult ADHD, a newly developed interactive chatbot was compared with a previously validated, conventional psychoeducation app. METHOD: Forty adults with ADHD were randomised, of whom 17 participants in each group completed self-guided psychoeducation based on either a chatbot or conventional psychoeducation app between October 2020 and July 2021. ADHD core symptoms were assessed before and after the 3-week interventions, using both the blinded observer-rated Integrated Diagnosis of ADHD in Adulthood interview and the self-rated ADHD Self-Assessment Scale (ADHS-SB). RESULTS: Observer- and patient-rated ADHD symptoms were significantly reduced from pre- to post-intervention (observer-rated: mean difference -6.18, 95% CI -8.06 to -4.29; patient-rated: mean difference -2.82, 95% CI -4.98 to -0.67). However, there were no group × intervention interaction effects that would indicate a stronger therapeutic benefit of one of the interventions. Likewise, administered psychoeducational knowledge quizzes did not show differences between the groups. No adverse events were reported. CONCLUSIONS: Self-guided psychoeducation based on a chatbot or a conventional app appears similarly effective and safe for improving ADHD core symptoms. Future research should compare additional control interventions and examine patient-related outcomes and usability preferences in detail.

Effects of NMDA-receptor blockade by ketamine on mentalizing and its neural correlates in humans: a randomized control trial.

Schizophrenia is associated with various deficits in social cognition that remain relatively unaltered by antipsychotic treatment. While faulty glutamate signaling has been associated with general cognitive deficits as well as negative symptoms of schizophrenia, no direct link between manipulation of glutamate signaling and deficits in mentalizing has been demonstrated thus far. Here, we experimentally investigated whether ketamine, an uncompetitive N-methyl-D-aspartate receptor antagonist known to induce psychotomimetic effects, influences mentalizing and its neural correlates. In a randomized, placebo-controlled between-subjects experiment, we intravenously administered ketamine or placebo to healthy participants performing a video-based social cognition task during functional magnetic resonance imaging. Psychotomimetic effects of ketamine were assessed using the Positive and Negative Syndrome Scale. Compared to placebo, ketamine led to significantly more psychotic symptoms and reduced mentalizing performance (more "no mentalizing" errors). Ketamine also influenced blood oxygen level dependent (BOLD) response during mentalizing compared to placebo. Specifically, ketamine increased BOLD in right posterior superior temporal sulcus (pSTS) and increased connectivity between pSTS and anterior precuneus. These increases may reflect a dysfunctional shift of attention induced by ketamine that leads to mentalizing deficits. Our findings show that a psychotomimetic dose of ketamine impairs mentalizing and influences its neural correlates, a result compatible with the notion that deficient glutamate signaling may contribute to deficits in mentalizing in schizophrenia. The results also support efforts to seek novel psychopharmacological treatments for psychosis and schizophrenia targeting glutamatergic transmission.

Effects of a video game intervention on symptoms, training motivation, and visuo-spatial memory in depression.

Background: People with Major Depressive Disorder (MDD) often experience reduced affect, mood, and cognitive impairments such as memory problems. Although there are various treatments for MDD, many of them do not address the cognitive deficits associated with the disorder. Playing 3D video games has been found to improve cognitive functioning in healthy people, but it is not clear how they may affect depressed mood and motivation in people with MDD. The aim of this study was to investigate whether a six-week video game intervention leads to improvements in depressed mood, training motivation, and visuo-spatial (working) memory functions in patients with MDD. Methods: A total of 46 clinically depressed individuals were randomly assigned to one of three groups: an experimental "3D video gaming" group (n = 14) which played a video game, an active control group (n = 16) which trained with a computer program "CogPack," and a treatment-as-usual group (n = 16) which received a standard clinical treatment including psychotherapy and/or pharmacotherapy. Participants performed a neuropsychological assessment, including self-report questionnaires asking for depressive symptoms, training motivation, and visuo-spatial (working) memory functions before and after the training intervention. Results: Regarding depressive symptoms, a significant decrease in the proportion of participants who showed clinical levels of depressive symptoms as measured by the Beck Depression Inventory was only found in the 3D video gaming group. Additionally, mean motivational levels of performing the training were significantly higher in the 3D video gaming group when compared with the active control group. Moreover, whereas the 3D Video Gaming group only significantly improved on one visuo-spatial memory test, the active control group improved in all visuo-spatial memory functions. The 3D video gaming group did not perform significantly better than the CogPack group, and the TAU group. Conclusion: Besides a standalone cognitive training, the current findings suggest that cognitive trainings using a video game have potential to increase subjective well-being, show higher levels of training motivation, and lead to improvements in visuo-spatial (working) memory functions in MDD. However, given the mixed and unblinded nature of this study, the results should be interpreted with caution. Further research with larger samples and follow-up measurements is needed.

Electrophysiological evidence for increased auditory crossmodal activity in adult ADHD.

Background: Attention deficit and hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by core symptoms of inattention, and/or impulsivity and hyperactivity. In order to understand the basis for this multifaceted disorder, the investigation of sensory processing aberrancies recently reaches more interest. For example, during the processing of auditory stimuli comparable low sensory thresholds account for symptoms like higher distractibility and auditory hypersensitivity in patients with ADHD. It has further been shown that deficiencies not only exist on an intramodal, but also on a multimodal level. There is evidence that the visual cortex shows more activation during a focused auditory task in adults with ADHD than in healthy controls. This crossmodal activation is interpreted as the reallocation of more attentional resources to the visual domain as well as deficient sensory inhibition. In this study, we used, for the first time, electroencephalography to identify a potential abnormal regulated crossmodal activation in adult ADHD. Methods: 15 adult subjects with clinically diagnosed ADHD and 14 healthy controls comparable in age and gender were included. ERP components P50, P100, N100, P200 and N200 were measured during the performance of a unimodal auditory and visual discrimination task in a block design. Sensory profiles and ADHD symptoms were assessed with inattention as well as childhood ADHD scores. For evaluating intramodal and crossmodal activations, we chose four EEG channels for statistical analysis and group-wise comparison. Results: At the occipital channel O2 that reflects possible crossmodal activations, a significantly enhanced P200 amplitude was measured in the patient group. At the intramodal channels, a significantly enhanced N200 amplitude was observed in the control group. Statistical analysis of behavioral data showed poorer performance of subjects with ADHD as well as higher discrimination thresholds. Further, the correlation of the assessed sensory profiles with the EEG parameters revealed a negative correlation between the P200 component and sensation seeking behavior. Conclusion: Our findings show increased auditory crossmodal activity that might reflect an altered stimulus processing resource allocation in ADHD. This might induce consequences for later, higher order attentional deployment. Further, the enhanced P200 amplitude might reflect more sensory registration and therefore deficient inhibition mechanisms in adults with ADHD.

Relative importance of speech and voice features in the classification of schizophrenia and depression.

Speech is a promising biomarker for schizophrenia spectrum disorder (SSD) and major depressive disorder (MDD). This proof of principle study investigates previously studied speech acoustics in combination with a novel application of voice pathology features as objective and reproducible classifiers for depression, schizophrenia, and healthy controls (HC). Speech and voice features for classification were calculated from recordings of picture descriptions from 240 speech samples (20 participants with SSD, 20 with MDD, and 20 HC each with 4 samples). Binary classification support vector machine (SVM) models classified the disorder groups and HC. For each feature, the permutation feature importance was calculated, and the top 25% most important features were used to compare differences between the disorder groups and HC including correlations between the important features and symptom severity scores. Multiple kernels for SVM were tested and the pairwise models with the best performing kernel (3-degree polynomial) were highly accurate for each classification: 0.947 for HC vs. SSD, 0.920 for HC vs. MDD, and 0.932 for SSD vs. MDD. The relatively most important features were measures of articulation coordination, number of pauses per minute, and speech variability. There were moderate correlations between important features and positive symptoms for SSD. The important features suggest that speech characteristics relating to psychomotor slowing, alogia, and flat affect differ between HC, SSD, and MDD.

Epigenome-wide analysis identifies methylome profiles linked to obsessive-compulsive disorder, disease severity, and treatment response.

Obsessive-compulsive disorder (OCD) is a prevalent mental disorder affecting ~2-3% of the population. This disorder involves genetic and, possibly, epigenetic risk factors. The dynamic nature of epigenetics also presents a promising avenue for identifying biomarkers associated with symptom severity, clinical progression, and treatment response in OCD. We, therefore, conducted a comprehensive case-control investigation using Illumina MethylationEPIC BeadChip, encompassing 185 OCD patients and 199 controls recruited from two distinct sites in Germany. Rigorous clinical assessments were performed by trained raters employing the Structured Clinical Interview for DSM-IV (SCID-I). We performed a robust two-step epigenome-wide association study that led to the identification of 305 differentially methylated CpG positions. Next, we validated these findings by pinpointing the optimal set of CpGs that could effectively classify individuals into their respective groups. This approach identified a subset comprising 12 CpGs that overlapped with the 305 CpGs identified in our EWAS. These 12 CpGs are close to or in genes associated with the sweet-compulsive brain hypothesis which proposes that aberrant dopaminergic transmission in the striatum may impair insulin signaling sensitivity among OCD patients. We replicated three of the 12 CpGs signals from a recent independent study conducted on the Han Chinese population, underscoring also the cross-cultural relevance of our findings. In conclusion, our study further supports the involvement of epigenetic mechanisms in the pathogenesis of OCD. By elucidating the underlying molecular alterations associated with OCD, our study contributes to advancing our understanding of this complex disorder and may ultimately improve clinical outcomes for affected individuals.

Altered interaction of physiological activity and behavior affects risky decision-making in ADHD.

Background: Adult attention-deficit/hyperactivity disorder (ADHD) is often associated with risky decision-making behavior. However, current research studies are often limited by the ability to adequately reflect daily behavior in a laboratory setting. Over the lifespan impairments in cognitive functions appear to improve, whereas affective functions become more severe. We assume that risk behavior in ADHD arises predominantly from deficits in affective processes. This study will therefore aim to investigate whether a dysfunction in affective pathways causes an abnormal risky decision-making (DM) behavior in adult ADHD. Methods: Twenty-eight participants with ADHD and twenty-eight healthy controls completed a battery of questionnaires regarding clinical symptoms, self-assessment of behavior and emotional competence. Furthermore, skin conductance responses were measured during the performance in a modified version of the Balloon Analogue Risk Task. A linear mixed-effects model analysis was used to analyze emotional arousal prior to a decision and after feedback display. Results: Results showed higher emotional arousal in ADHD participants before decision-making (ß = -0.12, SE = 0.05, t = -2.63, p < 0.001) and after feedback display (ß = -0.14, SE = 0.05, t = -2.66, p = 0.008). Although risky behavior was greater in HC than in ADHD, we found a significant interaction effect of group and anticipatory skin conductance responses regarding the response behavior (ß = 107.17, SE = 41.91, t = 2.56, p = 0.011). Post hoc analyses revealed a positive correlation between anticipatory skin conductance responses and reaction time in HC, whereas this correlation was negative in ADHD. Self-assessment results were in line with the objective measurements. Conclusion: We found altered changes in physiological activity during a risky decision-making task. The results confirm the assumption of an aberrant relationship between bodily response and risky behavior in adult ADHD. However, further research is needed with respect to age and gender when considering physiological activities.

Multimodal assessment of adult attention-deficit hyperactivity disorder: A controlled virtual seminar room study.

In the assessment of adult attention-deficit hyperactivity disorder (ADHD) symptoms, the diagnostic value of neuropsychological testing is limited. Partly, this is due to the rather low ecological validity of traditional neuropsychological tests, which usually present abstract stimuli on a computer screen. A potential remedy for this shortcoming might be the use of virtual reality (VR), which enables a more realistic and complex, yet still standardized test environment. The present study investigates a new VR-based multimodal assessment tool for adult ADHD, the virtual seminar room (VSR). Twenty-five unmedicated ADHD patients, 25 medicated ADHD patients, and 25 healthy controls underwent a virtual continuous performance task (CPT) in the VSR with concurrent visual, auditive, and audiovisual distractions. Simultaneously, head movements (actigraphy), gaze behaviour (eye tracking), subjective experience, electroencephalography (EEG), and functional near-infrared spectroscopy (fNIRS) were recorded. Significant differences between unmedicated patients with ADHD and healthy controls were found in CPT performance, head actigraphy, distractor gaze behaviour, and subjective experience. Moreover, CPT performance parameters demonstrated potential utility for assessing medication effects within the ADHD population. No group differences were found in the Theta-Beta-Ratio (EEG) or dorsolateral-prefrontal oxy-haemoglobin (fNIRS). Overall, the results are very promising regarding the potential of the VSR as an assessment tool for adult ADHD. In particular, the combined assessment of CPT, actigraphy, and eye tracking parameters appears to be a valid approach to more accurately capture the heterogeneous symptom presentation of the disorder.

Network-Based Differences in Top-Down Multisensory Integration between Adult ADHD and Healthy Controls-A Diffusion MRI Study.

BACKGROUND: Attention-deficit-hyperactivity disorder (ADHD) is a neurodevelopmental disorder neurobiologically conceptualized as a network disorder in white and gray matter. A relatively new branch in ADHD research is sensory processing. Here, altered sensory processing i.e., sensory hypersensitivity, is reported, especially in the auditory domain. However, our perception is driven by a complex interplay across different sensory modalities. Our brain is specialized in binding those different sensory modalities to a unified percept-a process called multisensory integration (MI) that is mediated through fronto-temporal and fronto-parietal networks. MI has been recently described to be impaired for complex stimuli in adult patients with ADHD. The current study relates MI in adult ADHD with diffusion-weighted imaging. Connectome-based and graph-theoretic analysis was applied to investigate a possible relationship between the ability to integrate multimodal input and network-based ADHD pathophysiology. METHODS: Multishell, high-angular resolution diffusion-weighted imaging was performed on twenty-five patients with ADHD (six females, age: 30.08 (SD: 9.3) years) and twenty-four healthy controls (nine females; age: 26.88 (SD: 6.3) years). Structural connectome was created and graph theory was applied to investigate ADHD pathophysiology. Additionally, MI scores, i.e., the percentage of successful multisensory integration derived from the McGurk paradigm, were groupwise correlated with the structural connectome. RESULTS: Structural connectivity was elevated in patients with ADHD in network hubs mirroring altered default-mode network activity typically reported for patients with ADHD. Compared to controls, MI was associated with higher connectivity in ADHD between Heschl's gyrus and auditory parabelt regions along with altered fronto-temporal network integrity. CONCLUSION: Alterations in structural network integrity in adult ADHD can be extended to multisensory behavior. MI and the respective network integration in ADHD might represent the maturational cortical delay that extends to adulthood with respect to sensory processing.