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Objectives: Genetic variant classification is a challenge in rare adult‐onset disorders as in SCA‐PRKCG (prior spinocerebellar ataxia type 14) with mostly private conventional mutations and nonspecific phenotype. We here propose a refined approach for clinicogenetic diagnosis by including protein modeling and provide for confirmed SCA‐PRKCG a comprehensive phenotype description from a German multi‐center cohort, including standardized 3D MR imaging. Methods: This cross‐sectional study prospectively obtained neurological, neuropsychological, and brain imaging data in 33 PRKCG variant carriers. Protein modeling was added as a classification criterion in variants of uncertain significance (VUS). Results: Our sample included 25 cases confirmed as SCA‐PRKCG (14 variants, thereof seven novel variants) and eight carriers of variants assigned as VUS (four variants) or benign/likely benign (two variants). Phenotype in SCA‐PRKCG included slowly progressive ataxia (onset at 4–50 years), preceded in some by early‐onset nonprogressive symptoms. Ataxia was often combined with action myoclonus, dystonia, or mild cognitive‐affective disturbance. Inspection of brain MRI revealed nonprogressive cerebellar atrophy. As a novel finding, a previously not described T2 hyperintense dentate nucleus was seen in all SCA‐PRKCG cases but in none of the controls. Interpretation: In this largest cohort to date, SCA‐PRKCG was characterized as a slowly progressive cerebellar syndrome with some clinical and imaging features suggestive of a developmental disorder. The observed non‐ataxia movement disorders and cognitive‐affective disturbance may well be attributed to cerebellar pathology. Protein modeling emerged as a valuable diagnostic tool for variant classification and the newly described T2 hyperintense dentate sign could serve as a supportive diagnostic marker of SCA‐PRKCG. [ABSTRACT FROM AUTHOR]

Attention deficit hyperactivity disorder (ADHD) in adulthood is a frequent disorder with a prevalence of 2.5%, which can successfully be treated by pharmacotherapy in 50–70% of cases, depending on the response criteria. Therefore, besides medication nonpharmacological interventions are an important component of the treatment. The essential nonpharmacological interventions are presented and described with respect to the evidence for treatment. According to the S3 guidelines an extensive psychoeducation (PE) functions as the basis of the treatment. If there is still a need for treatment after PE and the clarification of associated disorders, pharmacotherapy is applied. Further psychosocial interventions can then be used as accompaniment or supplement, e.g. when the effectiveness of medication treatment is insufficient. In particular, cognitive behavioral concepts and their variations (dialectic behavioral therapy, metacognitive training, reasoning and rehabilitation therapy) and coaching should be mentioned here, which show increasing evidence for treatment. Neurofeedback can be used if no other psychosocial treatment options are delayed or omitted due to the treatment. Mindfulness training and sport interventions seem to be meaningful as supplementation but similarly to the individualized cognitive training, further research studies are necessary to enable clear statements regarding treatment evidence in adulthood. Further controlled investigations regarding the effectiveness of nonpharmacological interventions on ADHD and associated symptoms and disorders are therefore desirable. [ABSTRACT FROM AUTHOR]

The contribution of the medial temporal lobe (MTL) to the retrieval of autobiographical memories is widely accepted. Results of former patient studies and functional imaging studies suggest different involvement of the MTL during the retrieval of autobiographical context information and the remoteness of these. Varying recency, the MTL contribution during chronological and locational autobiographical context information processing was investigated in this study. Thirteen males (mean = 25 years) judged the event’s place or time in a two-choice recognition task. Subjects made significantly more errors on chronological judgments. Retrieval of chronological information activated the left MTL, while retrieval of locational information activated the MTL bilaterally. Retrieval of more recent than remote context information activated especially the right MTL. Our results underline different MTL contributions on the retrieval of autobiographical context information, depending on the content and on the remoteness of the event that took place. [ABSTRACT FROM AUTHOR]

Cognitive impairment is a common and largely undiagnosed finding in a significant number of dialysis patients. These alterations may result from concomitant cerebrovascular disease, hemodynamic instability, the uremic milieu, or changes induced by the dialysis process. In order to gain further insight into this, we recruited 12 stable chronic hemodialysis patients (without clinical neurological disease) and an age- and gender-matched cohort of 12 control individuals (without renal or neurological problems) in a prospective, single-center study. In order to disentangle the influence of dialysis itself on memory function, each dialysis patient was tested twice: once immediately before dialysis following a long weekend (t1) and again the day after this dialysis (t2). The control individuals were tested in the same time frame. Neuropsychological testing found that the control individuals performed significantly better in verbal learning, motor speed, task switching, verbal comprehension, word fluency, spatial visualization, spatial perception, and reasoning; all independent of the time point. Functional magnetic resonance imaging of the whole brain in seven hemodialysis patients found significantly more bilateral activation of the hippocampus during the verbal working memory task at t2 relative to t1 compared with their seven matched control counterparts. Thus, our study found differential and task-specific activation of memory-relevant brain areas during a dialysis cycle. [ABSTRACT FROM AUTHOR]

Abstract: Hierarchically organized figures (for example, a large E made up of smaller N''s) are frequently used to investigate directed and divided attention. Investigations of neurological and psychiatric patients, and also tachistoscopic and functional neuroimaging studies on healthy subjects, typically find the right hemisphere to be specialized for the processing of global stimuli and the left hemisphere to be specialized for the processing of local stimuli. In the current study, a group of 12 patients with visuo-spatial neglect (NP) after right hemisphere lesions and 12 age and sex-matched control subjects (CO) performed a directed and a divided attention task with hierarchically organized letters. As expected, faster reaction times were found for control subjects than for neglect patients, especially for the directed global attention task. Lower error rates were found for CO and NP for local than for global targets during the divided attention condition. Local on global interference was found for both groups in reaction times. These local processing advantages for older healthy adults have been reported previously. Additionally, an impairment in the divided attention task was found in both groups, but especially for global targets in NP. This impairment is consistent with other evidence of difficulty in disengaging attention shown by patients with visuo-spatial neglect. [Copyright &y& Elsevier]

Background: Sex differences in the symptomatology of adults with attention-deficit/hyperactivity disorder (ADHD) have often been overlooked when studying behavioral abnormalities. However, it is known that women exhibit considerably more stronger symptoms related to emotional competence than men. Since affective functions significantly influence the processing of risky decision-making and risk-engagement, we assume that risky behavior in ADHD is affected by sex differences. Therefore, we specifically investigated sex-specific effects on the interaction between emotionally induced changes in physiology and behavioral performance on a decision-making task. Methods: Skin conductance responses of twenty-nine adults with ADHD (n = 16 male; n = 13 female) and thirty-three adults in the control group (n = 14 male; n = 19 female) were recorded during the performance in a modified version of the Balloon Analogue Risk Task (BART). Additional questionnaires were used to reveal insights in the self-assessment of emotional competence, risk perception, and feedback sensitivity. Emotional arousal and decision-making behavior were analyzed using linear mixed-effects models. Results: Results showed different effects of sex on risk behaviors in controls and ADHD. In contrast to healthy controls, female adults with ADHD showed a significantly greater risk engagement in the BART compared to males with ADHD. This contrary sex relation was not observed in skin conductance responses and revealed a significantly different sex-dependent correlation of body response and behavioral task performance in ADHD. Comparisons with results from self-assessments furthermore indicate a reduced behavioral self-perception in women with ADHD, but not in men. Conclusion: In summary, we found an altered interaction between physiological activity and risky behavior in women with ADHD. Thus, the present study indicates a reduced sensitivity towards the own bodily responses in women with ADHD, which could consequently cause increased risky DM behavior in daily life. The current results suggest that more consideration needs to be given to sex-specific effects on physiological processes and behavior in adults with ADHD. [ABSTRACT FROM AUTHOR]

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/). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Neuropsychological assessments are often surprisingly inaccurate in mapping clinically-reported attention-deficit hyperactivity disorder (ADHD) symptoms, presumably due to their low ecological validity. Virtual reality (VR) might offer a potential solution for this problem, given its capability to generate standardized and yet highly realistic virtual environments. As the first adaptation of existing virtual classroom scenarios to an adult population, we developed a Virtual Seminar Room (VSR) for multimodal characterization of ADHD symptoms. To test its feasibility, N = 35 healthy participants were immersed into the VSR via a head-mounted display and carried out a VR-embedded continuous performance task (CPT) under varying levels of distractions in two experimental blocks (24 min each). CPT performance, electroencephalography (EEG) measures, and head movements (actigraphy) were simultaneously recorded and analyzed offline. Although CPT performance remained constant throughout the task, head movements increased significantly from Block 1 to Block 2. In addition, EEG theta (4–7 Hz) and beta (13–30 Hz) power was higher during Block 1 than Block 2, and during distractor-present than distractor-absent phases. Moreover, P300 amplitudes were higher during Block 1 than Block 2, and P300 latencies were prolonged in distractor-absent compared with distractor-present phases. Although the paradigm awaits further improvements, this study confirms the general feasibility of the VSR and provides a first step toward a multimodal, ecologically valid, and reliable VR-based adult ADHD assessment. [ABSTRACT FROM AUTHOR]

Healthy aging is accompanied by changes in the functional architecture of the default mode network (DMN), e.g. a posterior to anterior shift (PASA) of activations. The putative structural correlate for this functional reorganization, however, is largely unknown. Changes in gyrification, i.e. decreases of cortical folding were found to be a marker of atrophy of the brain in later decades of life. Therefore, the present study assessed local gyrification indices of the DMN in relation to age and cognitive performance in 749 older adults aged 55-85 years. Age-related decreases in local gyrification indices were found in the anterior part of the DMN [particularly; medial prefrontal cortex (mPFC)] of the right hemisphere, and the medial posterior parts of the DMN [particularly; posterior cingulate cortex (PCC)/precuneus] of both hemispheres. Positive correlations between cognitive performance and local gyrification indices were found for (1) selective attention and left PCC/precuneus, (2) visual/visual-spatial working memory and bilateral PCC/precuneus and right angular gyrus (AG), and (3) semantic verbal fluency and right AG and right mPFC. The more pronounced age-related decrease in local gyrification indices of the posterior parts of the DMN supports the functionally motivated PASA theory by correlated structural changes. Surprisingly, the prominent age-related decrease in local gyrification indices in right hemispheric ROIs provides evidence for a structural underpinning of the right hemi-aging hypothesis. Noticeably, the performance-related changes in local gyrification largely involved the same parts of the DMN that were subject to age-related local gyrification decreases. Thus, the present study lends support for a combined structural and functional theory of aging, in that the functional changes in the DMN during aging are accompanied by comparably localized structural alterations. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Previous neuropsychological and functional imaging studies have suggested that the right hemisphere is crucially involved in spatial cognition. By contrast, much less is known about the putative left hemisphere specialization for aspects of temporal cognition. Accordingly, we studied with functional magnetic resonance imaging the neural mechanisms underlying attention to stimulus onset synchrony or orientational congruence with identical pairs of geometric figures. In each trial, two rhombuses were presented, each 4° peripheral to a central fixation cross, in the left and right visual hemifields. In half of the trials, subjects were asked to judge and indicate via button presses whether the rhombuses appeared simultaneously. In the other half of the trials, subjects indicated whether the orientation of the rhombuses was the same (Factor 1, task, temporal synchrony, orientation). In half of the trials, subjects responded with their right hand and in the other half with their left hand (Factor 2, hand, right, left). Data were analyzed using SPM99 and a random-effects model. Attention to orientation differentially activated right temporo-occipital cortex. Attention to stimulus onset synchrony activated left anterior superior temporal gyrus, left inferior parietal cortex, left medial frontal gyrus, and right operculum. Activation of right temporo-occipital cortex for attention to stimulus orientation is in good agreement with previous functional neuroimaging studies of stimulus orientation. More importantly, activation of a predominantly left-hemispheric network with attention to stimulus onset synchrony extends the results of previous functional imaging, psychophysical, and neuropsychological studies of temporal processing. [Copyright &y& Elsevier]

Background: Attention-deficit/hyperactivity disorder (ADHD) is characterized by substantial interindividual heterogeneity that challenges the systematic assessment and treatment. Considering mixed evidence from previous neurofeedback research, we present a novel feedback system that relies on gaze behavior to detect signs of inattention while performing a neuropsychological attention task in a virtual seminar room. More specifically, an audiovisual feedback was given whenever participants averted their gaze from the given task. Methods: Eighteen adults with ADHD and 18 healthy controls performed a continuous performance task (CPT) in virtual reality under three counterbalanced conditions in which either gaze-based feedback, sham feedback, or no feedback was provided. In all conditions, phases of high and low virtual distraction alternated. CPT errors and reaction times, proportions of gaze dwell times (e.g., task focus or distraction focus), saccade characteristics, EEG theta/beta ratios, head movements, and an experience sampling of ADHD symptoms were analyzed. Results: While patients can be discriminated well from healthy controls in that they showed more omission errors, higher reaction times, higher distraction-related dwell times, and more head movements, the feedback did not immediately improve task performance. It was also indicated that sham feedback was rather associated with an aggravation of symptoms in patients. Conclusions: Our findings demonstrate sufficient suitability and specificity for this holistic ADHD symptom assessment. Regarding the feedback, a single-session training was insufficient to achieve learning effects based on the proposed metacognitive strategies. Future longitudinal, multi-session trials should conclusively examine the therapeutic efficacy of gaze-based virtual reality attention training in ADHD. Trial registration: drks.de (identifier: DRKS00022370). [ABSTRACT FROM AUTHOR]

We perceive our daily-life surrounded by different senses (e.g., visual, and auditory). For a coherent percept, our brain binds those multiple streams of sensory stimulations, i.e., multisensory integration (MI). Dependent on stimulus complexity, early MI is triggered by bottom–up or late via top–down attentional deployment. Adult attention-deficit/hyperactivity disorder (ADHD) is associated with successful bottom–up MI and deficient top–down MI. In the current study, we investigated the robustness of the bottom–up MI by adding additional task demand varying the perceptual load. We hypothesized diminished bottom–up MI for high perceptual load for patients with ADHD. 18 adult patients with ADHD and 18 age- and gender-matched healthy controls participated in this study. In the visual search paradigm, a target letter was surrounded by uniform distractors (low load) or by different letters (high load). Additionally, either unimodal (visual flash, auditory beep) or multimodal (audiovisual) flanked the visual search. Linear-mixed modeling was used to investigate the influence of load on reaction times. Further, the race model inequality was calculated. Patients with ADHD showed a similar degree of MI performance like healthy controls, irrespective of perceptual load manipulation. ADHD patients violated the race model for the low load but not for the high-load condition. There seems to be robust bottom–up MI independent of perceptual load in ADHD patients. However, the sensory accumulation might be altered when attentional demands are high. [ABSTRACT FROM AUTHOR]

There is broad consensus that to improve the treatment of adult Attention-Deficit/Hyperactivity Disorder (ADHD), the various therapy options need to be tailored more precisely to the individual patient's needs and specific symptoms. This post-hoc analysis evaluates the multimodal effects of first-line medication (methylphenidate [MPH] vs placebo [PLB]) and psychotherapeutic (group psychotherapy [GPT] vs clinical management [CM]) treatments on the ADHD core symptoms inattention, hyperactivity and impulsivity. For the two-by-two factorial, observer-blinded, multicenter, randomized controlled Comparison of Methylphenidate and Psychotherapy in Adult ADHD Study (COMPAS; ISRCTN54096201), 419 outpatients with ADHD were considered for analysis. ADHD symptoms were assessed by blind observer-rated and patient-rated Conners Adult ADHD Rating Scales before treatment (T1), 13 weeks (T2) and 26 weeks (T3) after T1, at treatment completion after 52 weeks (T4), and at follow-up (130 weeks, T5). MPH was superior to PLB in improving symptoms of inattention at almost all endpoints (observer-rated T2, T3, T4, T5; patient-rated T2, T3, T4), while a significant decrease in hyperactivity and impulsivity was at first found after 6 months of treatment. CM compared to GPT decreased inattention and impulsivity in the early treatment phase only (observer-rated T2, patient-rated T2, T3). In conclusion, while MPH seems to have a direct and sustained effect on inattention, premature medication discontinuation should particularly be avoided in patients with hyperactive-impulsive symptoms. Also, especially in high inattention and/or impulsivity presentations, initial individual patient management might be beneficial. Consequently, considering individual core symptom profiles may enhance the efficacy of treatments in adult ADHD. • Methylphenidate persistently improved adult ADHD symptoms of inattention. • Reduction in hyperactivity and impulsivity after 6 months of methylphenidate intake. • Promoting treatment adherence important in hyperactivity/impulsivity presentations. [ABSTRACT FROM AUTHOR]

The functional specificity of brain areas is diminished with age and accompanied by the recruitment of additional brain regions in healthy older adults. This process has repeatedly been demonstrated within distinct functional domains, in particular the visual system. However, it is yet unclear, whether this phenomenon in healthy aging, i.e., a reduced activation of task-associated areas and increased activation of additional regions, is also present across different functional systems. In the present functional imaging study, comprising 102 healthy subjects, we therefore assessed two distinct tasks engaging the sensory-motor system and the visual attention system, respectively. We found a significant interaction between age and task in the parietal operculum bilaterally. This area as a part of the sensory-motor system showed an age-related decrease in its BOLD-response to the motor task and an age-related increase of neural activity in response to the visual attention task. The opposite response pattern, i.e., reduced visual attention activation and increased response to the motor task, was observed for regions associated with the visual task: the superior parietal area 7A and the dorsal pre-motor cortex. Importantly, task performance was not correlated with age in either task. This age-by-task interaction indicates that a reduction of functional specificity in the aging brain may be counteracted by the increased recruitment of additional regions not only within, but also across functional domains. Our results thus emphasize the need for comparisons across different functional domains to gain a better understanding of age-related effects on the specificity of functional systems. [ABSTRACT FROM AUTHOR]

The left hemispheric dominance for complex motor behavior is undisputed. Clinical observations of complex motor deficits in patients with right hemispheric lesions, however, suggest an additional contribution of the right hemisphere to higher motor control. We assessed, using functional MRI (fMRI), which brain regions are implicated in processing the spatial aspects of complex, object-related actions. Using a blocked, factorial design, 17 healthy volunteers were asked to detect either spatial or sequential errors (factor ERROR) in complex activities of daily living, presented as video sequences with the appropriate object(s) or as pantomimes (factor STIMULUS). Observing complex actions (irrespective of stimulus type) activated a bilateral frontoparietal network. Observing actions with objects (relative to pantomimes) differentially increased neural activity in the fusiform gyrus and inferior occipital cortex bilaterally. Observing pantomimes, i.e., the same actions but without any object, differentially activated right prefrontal cortex, anterior cingulate cortex, the precuneus, and left cerebellum. The left cingulate cortex was differentially activated when subjects assessed the sequencing of actions. By contrast, assessing the spatial configuration of complex actions differentially increased neural activity in right posterior parietal cortex. A significant interaction of ERROR and STIMULUS was revealed for the right inferior parietal cortex only. These findings suggest a specific role of the right hemisphere, especially of right posterior parietal cortex, in processing spatial aspects of complex actions and thus provide a physiological basis for the observed apraxic motor deficits in patients with right hemispheric damage. Hum Brain Mapp, 2006. © 2006 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Background: Studies investigating sensory processing in attention-deficit/hyperactivity disorder (ADHD) have shown altered visual and auditory processing. However, evidence is lacking for audiovisual interplay — namely, multisensory integration. As well, neuronal dysregulation at rest (e.g., aberrant within- or between-network functional connectivity) may account for difficulties with integration across the senses in ADHD. We investigated whether sensory processing was altered at the multimodal level in adult ADHD and included resting-state functional connectivity to illustrate a possible overlap between deficient network connectivity and the ability to integrate stimuli. Methods: We tested 25 patients with ADHD and 24 healthy controls using 2 illusionary paradigms: the sound-induced flash illusion and the McGurk illusion. We applied the Mann–Whitney U test to assess statistical differences between groups. We acquired resting-state functional MRIs on a 3.0 T Siemens magnetic resonance scanner, using a highly accelerated 3-dimensional echo planar imaging sequence. Results: For the sound-induced flash illusion, susceptibility and reaction time were not different between the 2 groups. For the McGurk illusion, susceptibility was significantly lower for patients with ADHD, and reaction times were significantly longer. At a neuronal level, resting-state functional connectivity in the ADHD group was more highly regulated in polymodal regions that play a role in binding unimodal sensory inputs from different modalities and enabling sensory-to-cognition integration. Limitations: We did not explicitly screen for autism spectrum disorder, which has high rates of comorbidity with ADHD and also involves impairments in multisensory integration. Although the patients were carefully screened by our outpatient department, we could not rule out the possibility of autism spectrum disorder in some participants. Conclusion: Unimodal hypersensitivity seems to have no influence on the integration of basal stimuli, but it might have negative consequences for the multisensory integration of complex stimuli. This finding was supported by observations of higher resting-state functional connectivity between unimodal sensory areas and polymodal multisensory integration convergence zones for complex stimuli. [ABSTRACT FROM AUTHOR]

Autosomal-dominant spinocerebellar ataxias (SCA) are neurodegenerative diseases characterized by progressive ataxia. Here, we report on neurometabolic alterations in spinocerebellar ataxia type 1 (SCA1; SCA-ATXN1) and 14 (SCA14; SCA-PRKCG) assessed by non-invasive 1H magnetic resonance spectroscopy. Three Tesla 1H magnetic resonance spectroscopy was performed in 17 SCA14, 14 SCA1 patients, and in 31 healthy volunteers. We assessed metabolites in the cerebellar vermis, right cerebellar hemisphere, pons, prefrontal, and motor cortex. Additionally, clinical characteristics were obtained for each patient to correlate them with metabolites. In SCA14, metabolic changes were restricted to the cerebellar vermis compared with widespread neurochemical alterations in SCA1. In SCA14, total N-acetylaspartate (tNAA) was reduced in the vermis by 34%. In SCA1, tNAA was reduced in the vermis (24%), cerebellar hemisphere (26%), and pons (25%). SCA14 patients showed 24% lower glutamate+glutamine (Glx) and 46% lower γ-aminobutyric acid (GABA) in the vermis, while SCA1 patients showed no alterations in Glx and GABA. SCA1 revealed a decrease of aspartate (Asp) in the vermis (62%) and an elevation in the prefrontal cortex (130%) as well as an elevation of myo-inositol (Ins) in the cerebellar hemisphere (51%) and pons (46%). No changes of Asp and Ins were detected in SCA14. Beyond, glucose (Glc) was increased in the vermis of both SCA14 (155%) and SCA1 (247%). 1H magnetic resonance spectroscopy revealed differing neurochemical profiles in SCA1 and SCA14 and confirmed metabolic changes that may be indicative for neuronal loss and dysfunctional energy metabolism. Therefore, 1H magnetic resonance spectroscopy represents a helpful tool for in-vivo tracking of disease-specific pathophysiology. [ABSTRACT FROM AUTHOR]

Objective: Subjective cognitive decline (SCD) was frequently investigated for memory in healthy aging or in relation to diseases like dementia. It was found to be related to sociodemographic and psychological variables as well as cognitive abilities. The prevalence of SCD in other cognitive domains and their relation to these variables is largely unknown to date. The present study aimed to fill this gap.Methods: A total of 807 subjects (18-85 years of age, M = 57.8 years, female: 43%) completed the Juelich Questionnaire on Subjective Cognitive Decline, to investigate SCD in memory, attention, language, motor, and executive functions. Logistic regression analyses were used to estimate association of depressive symptomatology, emotionality, and general cognitive performance as well as age, gender, and educational attainment with domain-specific SCD.Results: The highest prevalence rate was obtained for the memory domain (65.9%), followed by the attention (54.6%), motor (52.9%), executive (39.7%), and language domain (31.5%). Of the psychosocial factors, only age, depressive symptomatology and emotionality were consistently and strongly associated with domain-specific SCD prevalence.Conclusions: SCD is prevalent not only in the memory domain, but also in other major cognitive domains. Our results also suggest that the suspicion from previous research, that subjective memory decline might be more strongly associated with depressive symptomatology and emotionality than with actual decline of cognitive performance, might also apply to the attention, motor, executive, and language domain. Further investigations using neuropsychological testing for specific cognitive functions and employing longitudinal designs are required for substantiating this suspicion. [ABSTRACT FROM AUTHOR]

• This study compared dialectical behaviour therapy and methylphenidate with placebos in adults whit ADHD. • Effect on the emotional symptoms was assessed with the SCL-90 up to 130 weeks after the baseline. • All groups improved over time, with no significant differences. • Results suggest a specific effect for the psychotherapy and methylphenidate group. 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). [Display omitted] [ABSTRACT FROM AUTHOR]

• ADHD psychoeducation smartphone app is more effective than traditional brochures. • Group psychoeducation effectively reduces ADHD core symptoms. • Homework compliance increases in app-assisted psychoeducation. Psychoeducation is generally recommended in the treatment of adult Attention-Deficit/Hyperactivity Disorder (ADHD), but only few studies have systematically assessed the effects of structured clinical psychoeducation. Moreover, although a considerable number of psychoeducational mobile applications exist, none have provided scientific evidence for their effectiveness or safety. Therefore, the present randomized controlled trial investigated a newly developed, free-to-use psychoeducation app for adults with ADHD as a support to a clinical psychoeducation group. 236 adults with ADHD were contacted for study participation, of whom 60 were finally randomized to a psychoeducation group supported either by our developed smartphone app (n = 30) or by traditional pen-and-paper brochures (n = 30). Psychoeducation treatments were conducted in groups of 10, with 8 weekly one-hour sessions between March 2019 and November 2020. Observer-rated ADHD symptom severity (IDA-R interview) was examined as the primary outcome parameter before and after treatment. Across both interventions, ADHD core symptoms were significantly reduced. Notably, the smartphone-assisted psychoeducation was significantly more effective in improving inattention and impulsivity and led to higher homework compliance than the brochure-assisted psychoeducation. No adverse events were reported. [ABSTRACT FROM AUTHOR]

Autosomal dominant ataxia type 14 (SCA14) is a rare usually adult-onset progressive disorder with cerebellar neurodegeneration caused by mutations in protein kinase C gamma. We set out to examine cerebellar and extracerebellar neurochemical changes in SCA14 by MR spectroscopy. In 13 SCA14 patients and 13 healthy sex- and age-matched controls, 3-T single-voxel brain proton MR spectroscopy was performed in a cerebellar voxel of interest (VOI) at TE = 30 ms to obtain a neurochemical profile of metabolites with short relaxation times. In the cerebellum and in additional VOIs in the prefrontal cortex, motor cortex, and somatosensory cortex, a second measurement was performed at TE = 144 ms to mainly extract the total N-acetyl-aspartate (tNAA) signal besides the signals for total creatine (tCr) and total choline (tCho). The cerebellar neurochemical profile revealed a decrease in glutathione (6.12E−06 ± 2.50E−06 versus 8.91E−06 ± 3.03E−06; p = 0028) and tNAA (3.78E−05 ± 5.67E−06 versus 4.25E−05 ± 5.15E−06; p = 0023) and a trend for reduced glutamate (2.63E−05 ± 6.48E−06 versus 3.15E−05 ± 7.61E−06; p = 0062) in SCA14 compared to controls. In the tNAA-focused measurement, cerebellar tNAA (296.6 ± 42.6 versus 351.7 ± 16.5; p = 0004) and tCr (272.1 ± 25.2 versus 303.2 ± 31.4; p = 0004) were reduced, while the prefrontal, somatosensory and motor cortex remained unaffected compared to controls. Neuronal pathology in SCA14 detected by MR spectroscopy was restricted to the cerebellum and did not comprise cortical regions. In the cerebellum, we found in addition to signs of neurodegeneration a glutathione reduction, which has been associated with cellular damage by oxidative stress in other neurodegenerative diseases such as Parkinson's disease and Friedreich's ataxia. [ABSTRACT FROM AUTHOR]

Trusting reports on internet forums, a substantial number of people have developed unpleasant symptoms of depersonalization (DP) and derealization (DR) after virtual reality (VR) consumption. Likewise, one case series study indicates that even after one single VR session, transient DPDR experiences may occur. Despite these indications, little is otherwise known about the risk of developing DPDR from VR consumption. Therefore, we carried out the present longitudinal randomised controlled trial (N = 80), which examined, whether VR-gaming induces higher DPDR effects than classical PC gaming, and if so, how long DPDR effects persist. DPDR effects were assessed immediately before gaming (T0), immediately after gaming (T1), one day after gaming (T2) and one week after gaming (T3). Moreover, given evidence for an emotional hyporeagibility under DPDR, the participants' emotional and physiological (EDA, HRV) reagibility towards emotional pictures was assessed immediately after gaming. Likewise, to study whether certain personality traits might be associated with the occurrence of VR-induced DPDR effects, we administered a personality inventory to our participants. Results reveal that, after VR gaming, a significantly stronger DPDR experience was reported in the VR group than PC group at T1, while at T2 and T3, no significant DPDR group differences were detectable. Furthermore, no significant group differences were found in respect to emotional and physiological reagibility, nor were any correlations between personality traits and DPDR symptoms found. In summary, although our study provides further evidence that VR consumption can transiently induce DPDR-like symptoms, we find no evidence that these DPDR effects persist in the long term. • Transient symptoms of depersonalization and derealization after both, VR gaming and PC gaming. • Significantly stronger increases of depersonalization/derealization experiences immediately after VR gaming than PC gaming. • No significant group differences in respect to emotional and physiological reagibility. [ABSTRACT FROM AUTHOR]

Background: Corticobasal Syndrome (CBS) is a rare neurodegenerative syndrome characterized by unilaterally beginning frontoparietal and basal ganglia atrophy. The study aimed to prove the hypothesis that there are differences in hemispheric susceptibility to disease-related changes. Methods: Two groups of CBS patients with symptoms starting either on the left or right body side were investigated. Groups consisted of four patients each and were matched for sex, age and disease duration. Patient groups and a group of eight healthy age-matched controls were analyzed using deformation field morphometry and neuropsychological testing. To further characterize individual disease progression regarding brain atrophy and neuropsychological performance, two female, disease duration-matched patients differing in initially impaired body side were followed over six months. Results: A distinct pattern of neural atrophy and neuropsychological performance was revealed for both CBS: Patients with initial right-sided impairment (r-CBS) revealed atrophy predominantly in frontoparietal areas and showed, except from apraxia, no other cognitive deficits. In contrast, patients with impairment of the left body side (l-CBS) revealed more widespread atrophy, extending from frontoparietal to orbitofrontal and temporal regions; and apraxia, perceptional and memory deficits could be found. A similar pattern of morphological and neuropsychological differences was found for the individual disease progression in l-CBS and r-CBS single cases. Conclusions: For similar durations of disease, volumetric grey matter loss related to CBS pathology appeared earlier and progressed faster in l-CBS than in r-CBS. Cognitive impairment in r-CBS was characterized by apraxia, and additional memory and perceptional deficits for l-CBS. [ABSTRACT FROM AUTHOR]

Abstract: Autobiographical episodic memory represents a subsystem of declarative long-term memory and largely depends on combining information from multiple sources. The purpose of this study was to assess neural correlates of declarative long-term memory in patients with amnestic mild cognitive impairment (MCI) and controls using fMRI and a task requiring autobiographical and semantic memory retrieval. Comparison of the network supporting episodic autobiographical and semantic memory irrespective of remoteness (recent and remote) revealed significant activations in right parietal cortex and precuneus bilaterally in the patients. Autobiographical episodic versus semantic memory retrieval in the controls led to significant bilateral activations of the parietal-temporal junction, left temporal pole, anterior cingulate, retrosplenial cortex and cerebellum. In contrast, MCI patients activated left supplementary motor area, left premotor and superior temporal cortex. In MCI patients compared to controls a dysfunction of the retrosplenial cortex during memory retrieval was revealed by a lack of differential activation in relation to recency of memories and memory type. Our data suggest that MCI leads to a loss of specificity in the neural network supporting declarative long-term memory. [Copyright &y& Elsevier]

Human self-consciousness relies on the ability to distinguish between oneself and others. We sought to explore the neural correlates involved in self-other representations by investigating two critical processes: perspective taking and agency. Although recent research has shed light on the neural processes underlying these phenomena, little is known about how they overlap or interact at the neural level. In a two-factorial functional magnetic resonance imaging (fMRI) experiment, participants played a ball-tossing game with two virtual characters (‘avatars’). During an active/agency (ACT) task, subjects threw a ball to one of the avatars by pressing a button. During a passive/ nonagency (PAS) task, they indicated which of the other avatars threw the ball. Both tasks were performed from a first-person perspective (1PP), in which subjects interacted from their own perspective, and a third-person perspective (3PP), in which subjects interacted from the perspective of an avatar with another location in space. fMRI analyses revealed overlapping activity in medial prefrontal regions associated with representations of one's own perspective and actions (1PP and ACT), and overlapping activity in temporal-occipital, premotor, and inferior frontal, as well as posterior parietal regions associated with representation of others' perspectives and actions (3PP and PAS). These findings provide evidence for distinct neural substrates underlying representations of the self and others and provide support for the idea that the medial prefrontal cortex crucially contributes to a neural basis of the self. The lack of a statistically significant interaction suggests that perspective taking and agency represent independent constituents of self-consciousness. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the long-term impact of surgical treatment on seizure outcome and antiepileptic drug (AED) use in patients with pharmacoresistant temporal lobe epilepsy (TLE). Methods: Comparison of seizure outcome and AED us in operated-on TLE patients (n = 148) and nonsurgically treated TLE patients (n = 94) at a baseline visit and a follow-up visit after a mean period of 4.8 years. Results: At follow-up, 44.6% of the surgical patients and 4.3% of the nonsurgical patients had been continuously seizure-free since the baseline visit (including the immediate postoperative period). A further 17.6% of the operated-on and 3.2% of the not operated-on patients had been seizure-free for at least the previous year; 37.8% of the surgical and 92.5% of the nonsurgical patients had had seizures during the previous 12 months (p < 0.001). Of the surgical patients, 8.8% versus none of the nonsurgical patients were AED free at follow-up; 55.4% versus 20.2% were receiving monotherapy, and 35.8% versus 79.8% were receiving polytherapy (p < 0.001). Mean number of AEDs and mean change in number of AEDs were significantly more favorable in operated-on than in non-operated-on patients. Further subgroup analysis revealed that not only the continuously seizure-free surgical patients, but also the operated-on patients with ongoing seizures took fewer AEDs than their respective non-operated-on counterparts. Conclusions: This controlled study for the first time provides comprehensive information on long-term seizure outcome and AED use in surgical TLE patients. It shows a more favorable seizure outcome and AED use in the surgically treated patients. The latter holds true even for the not seizure-free patient subgroup. [ABSTRACT FROM AUTHOR]