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Miguel Garcia Pimenta,1 Trevor Brown,2 Martijn Arns,3– 5 Stefanie Enriquez-Geppert1,6 1Department of Clinical and Developmental Neuropsychology, University of Groningen, Groningen, the Netherlands; 2NeuroCare Group, Melbourne, Australia; 3Department of Psychiatry, Amsterdam UMC, University of Amsterdam, Location AMC, Amsterdam Neuroscience, Amsterdam, the Netherlands; 4Research Institute Brainclinics, Brainclinics Foundation, Nijmegen, the Netherlands; 5Department of Cognitive Neuroscience, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, the Netherlands; 6Department of Biomedical Sciences of Cells & Systems, Section of Cognitive Neuropsychiatry, University of Groningen, Groningen, the NetherlandsCorrespondence: Miguel Garcia PimentaDepartment of Clinical and Developmental Neuropsychology, Faculty of Behavioural and Social Sciences, University of Groningen, Grote Kruisstraat 2/1, Groningen, 9712 TS, the NetherlandsTel +31 50 363 6537Email m.garcia.pimenta@rug.nlPurpose: Recent reviews have proposed that scientifically validated standard EEG neurofeedback (NF) protocols are an efficacious and specific treatment for attention-deficit hyperactivity disorder (ADHD). Here, we review the current evidence for the treatment efficacy and clinical effectiveness of NF in ADHD to investigate whether NF treatment personalization (standard protocols matched to the electrophysiological features of ADHD) and combination with other interventions (psychosocial, sleep hygiene and nutritional advice) might yield superior long-term treatment outcomes relative to non-personalized NF and medication monotreatments.Methods: The electronic databases PubMed and PsycINFO were systematically searched using our key terms. Of the 38 resulting studies, 11 randomized controlled trials (RCTs) and open-label studies were eligible for inclusion. Studies were analyzed for effect sizes and remission rates at the end of treatment and at follow-up. The effects of personalized and multimodal NF treatments were compared to non-personalized NF monotreatments and with two benchmark medication studies.Results: The analysis of RCTs indicated that the long-term effects of personalized NF interventions were superior to non-personalized NF and comparable to those of medication alone or in combination with behavioral intervention. The analysis of open-label trials further indicates that the interaction of NF with parental interventions, sleep and nutritional advice might yield superior clinical effectiveness relative to NF and medication monotreatments.Conclusion: Personalized and multimodal NF interventions seem to yield superior treatment efficacy relative to NF alone and superior clinical effectiveness relative to medication. We propose that treatment outcomes may be further enhanced by adjusting NF non-specific factors (eg, reinforcement contingencies) to specific ADHD characteristics (eg, reward sensitivity). Future NF research should focus on the systematic evaluation of the treatment outcomes of personalized and multimodal treatments.Keywords: neurofeedback, ADHD, treatment efficacy, effectiveness, personalized, multimodal

Executive function deficits, common in psychiatric disorders, hinder daily activities and may be linked to diminished neural plasticity, affecting treatment and training responsiveness. In this pioneering study, we evaluated the feasibility and preliminary efficacy of psilocybin-assisted frontal-midline theta neurofeedback (NF), a neuromodulation technique leveraging neuroplasticity, to improve executive functions (EFs). Thirty-seven eligible participants were randomized into an experimental group (n = 18) and a passive control group (n = 19). The experimental group underwent three microdose sessions and then three psilocybin-assisted NF sessions, without requiring psychological support, demonstrating the approach's feasibility. NF learning showed a statistical trend for increases in frontal-midline theta from session to session with a large effect size and non-significant but medium effect size dynamical changes within sessions. Placebo effects were consistent across groups, with no tasks-based EF improvements, but significant self-reported gains in daily EFs—working memory, shifting, monitoring and inhibition—showing medium and high effect sizes. The experimental group's significant gains in their key training goals underscored the approach's external relevance. A thorough study with regular sessions and an active control group is crucial to evaluate EFs improvement and their specificity in future. Psilocybin-enhanced NF could offer significant, lasting benefits across diagnoses, improving daily functioning. This article is part of the theme issue 'Neurofeedback: new territories and neurocognitive mechanisms of endogenous neuromodulation'. [ABSTRACT FROM AUTHOR]

Objective The Face-Name Associative Memory test (FNAME) has recently received attention as a test for early diagnosis of Alzheimer's disease. So far, however, there has been no systematic investigation of the effects of aging. Here, we aimed to assess the extent to which the FNAME performance is modulated by normal ageing. Method In a first step, we adapted the FNAME material to the Dutch population. In a second step, younger (n  = 29) and older adults (n  = 29) were compared on recall and recognition performance. Results Significant age effects on name recall were observed after the first exposure of new face-name pairs: younger adults remembered eight, whereas older adults remembered a mean of four out of twelve names. Although both age groups increased the number of recalled names with repeated face-name exposure, older adults did not catch up with the performance of the younger adults, and the age-effects remained stable. Despite of that, both age groups maintained their performance after a 30-min delay. Considering recognition, no age differences were demonstrated, and both age groups succeeded in the recognition of previously shown faces and names when presented along with distractors. Conclusions This study presents for the first time the results of different age groups regarding cross-modal associative memory performance on the FNAME. The recall age effects support the hypothesis of age-related differences in associative memory. To use the FNAME as an early cognitive biomarker, further subscales are suggested to increase sensitivity and specificity in the clinical context. [ABSTRACT FROM AUTHOR]

The EEG theta band displays distinct roles in resting and task states. Low resting theta and transient increases in frontal-midline (fm) theta power during tasks are associated with better cognitive control, such as error monitoring. ADHD can disrupt this balance, resulting in high resting theta linked to drowsiness and low fm-theta activity associated with reduced cognitive abilities. Theta/beta ratio (TBR) neurofeedback aims to normalize resting state activity by downregulating theta, which could potentially unfavorably affect task-related fm-theta. This study examines the TBR neurofeedback's impact on both resting and fm-theta activity, hypothesizing that remission depends on these effects. We analyzed data from a multi-center, double-blind randomized controlled trial with 142 children with ADHD and high TBR (ICAN study). Participants were randomized into experimental or sham NF groups. EEG measurements were taken at rest and during an Oddball task before and after neurofeedback, assessing global electrodes for resting theta and fm electrodes during error dynamics. Post-intervention changes were calculated as differences, and ANOVAs were conducted on GROUP, REMISSION, and CONDITION variables. Final analysis included fewer participants for all analyses. Resting state analysis showed no significant effects on global or fm-theta after TBR neurofeedback. Error dynamics analysis was inconclusive for global and fm-theta in both remitters and non-remitters. Results suggest that the current TBR neurofeedback protocol did not reduce aberrant resting state theta, and emphasize the need for refined protocols targeting specific theta-band networks to reduce resting-state theta without affecting fm-theta related to cognitive control., Competing Interests: Declarations. Conflict of interest: S.E.-G, J.K., H.v.D., R.dB. declare that they have no conflict of interest. They also declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. L.E.A. has contracts to carry out research from Yamo, Maplight, Supernus and consult in CHADD and Yamo. L.E.A. also uses amplifiers from Thought Technology and Brainmaster, ADHD Suite from TT, EEger software, EEG equipment from BRC. L.E.A also uses broad-spectrum micronutrients and placebo from Hardy Nutritionals. M.A. is scientific adviser and shareholder to Sama Therapeutics, and scientific adviser to Synaeda Research and Neumarker., (© 2024. The Author(s).)

Piloting is a complex task that demands robust cognitive functions to handle multiple tasks simultaneously in a constantly changing environment. As a result, cognitive abilities, particularly executive functions (EFs), have gained significant importance in relation to flight performance. However, the specific EFs most critical for predicting flight performance remain unclear. Understanding the exact nature of this relationship has the potential to advance research on pilot selection procedures, cockpit design, and influence cognitive training approaches to ultimately improve flight safety. This systematic review aims to pinpoint the most pertinent EFs for various aspects of airplane piloting. A systematic narrative literature review was conducted with a framework focusing on four EFs: working memory updating, set-shifting, response inhibition, and conflict monitoring, as well as three key aspects of flight performance: flying, navigating, and communicating. The findings suggest that multiple EFs predict flight performance outcomes. Notably, working memory updating significantly predicts the management of communication tasks and the making of critical decisions requiring mental flexibility. However, other specific EFs remain understudied. To advance this research area, we recommend conceptualizing EFs and flying measures based on existing theoretical frameworks, using measures sensitive to specific EFs, evaluating flying performance in simulated or real flights, controlling or accounting for factors that affect EFs and flying performance, and investigating the ameliorative potential of EFs with end results on flight performance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Enriquez-Geppert, Smit, de Boer, Daneshnia, Lafont and Dehais.)

The Learning and Associative Memory (LAM) test is a face-name associative memory test created to detect early Alzheimer's disease (AD). In a recent study, it was administered to cognitively healthy individuals with different levels of amyloid-β (Aβ) and tau burden. The key findings for LAM were: 1) selective correlations with Aβ levels, 2) unique discriminatory power between A + and A- individuals, 3) significantly higher areas under the curve in receiver operating curve analysis. Future research should focus on comparing performance on the LAM and face-name associative memory tests to determine the most effective method for detecting early signs of AD.

Fatigue is a pervasive symptom experienced by many individuals after COVID-19. Despite its widespread occurrence, fatigue remains a poorly understood and complex phenomenon. Our aim is to evaluate the subjective experience of mental fatigue after COVID-19 and to assess its significance for daily life functioning. In this online questionnaire study ( N  = 220), the Fatigue Severity Scale (FSS), World Health Organization Quality-of-Life assessment (WHOQoL) and a subjective severity rating of the COVID-19 disease progression were used. For our statistical analyses we utilized independent samples t-tests, one-way ANOVA with post-hoc analyses, and a multiple regression. As expected our findings revealed the COVID group reported significantly higher levels of subjective fatigue compared to the control group. Moreover, there was a significant difference between experienced fatigue across the four severity groups. Participants who had a milder course of disease also experienced severe subjective fatigue. Subjective fatigue explained 40% variance in quality-of-life. In conclusion, severe subjective fatigue appears to be associated with increased self-reported COVID-19 symptom severity and lower quality-of-life but is already observable in milder cases. This underscores, firstly, the importance of considering also less severe cases and, secondly, the need to develop rehabilitation and psychological interventions for fatigue.

Objective: The cognitive characterization of Alzheimer's disease risk states, such as amnestic mild cognitive impairment (aMCI) and subjective cognitive decline (SCD), is fundamental for timely diagnosis and interventions. The Face Name Associative Memory Exam (FNAME) is sensitive to early Alzheimer's disease brain changes, and an extended version captures a fuller range of associative memory abilities. We aimed to assess group effects in the extended FNAME in older adults with SCD, aMCI, and older adult controls (CON)., Method: Two concurrently created versions of the extended FNAME were used to test three groups of older adults (CON = 35, SCD = 37, aMCI = 31) at two sites (Mexico = 59, Netherlands = 44). Extended FNAME memory abilities were analyzed in five analyses of variance. Group and site were considered as independent variables. For the recall ability, subtest levels were entered as a within-subject variable. The remaining abilities (Face Recognition, Name Recognition, Spontaneous Name Recall, and Face-Name Matching) were analyzed in independent models., Results: In all models, the main effect for group was significant with large effect sizes, driven by a worse performance of aMCI participants. No significant differences were found between SCD and CON. The main effect for site was only significant in Face Recognition., Conclusions: The worse performance of aMCI in the extended FNAME implies an impairment in associative memory abilities beyond recall. The similar performance of CON and SCD might be explained by the recruitment of SCD participants that did not spontaneously seek help for memory decline. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

& STATEMENT OF IMPACTSARS-COV-2 infection can result in acute and long-lasting cognitive complaints, causing ongoing impairments in daily life which poses a challenge to society. Consequently, the evaluation and characterization of cognitive complaints, specifically in the domain of executive functions (EFs) affecting daily life, is imperative in formulating an effective neuropsychological response.In total 442 participants aged 18-65+ years from the Netherlands, Germany, Mexico, and Spain were included in an online questionnaire. Among others, the questionnaire consisted of demographics, the Behavior Rating Inventory of Executive Functioning for Adults (BRIEF-A), measures of subjective disease progression severity and experienced subjective impairment in daily activities. To assess whether daily life activities are affected by EF impairments, the main BRIEF-A composite score (GEC) was analyzed. To determine whether disease-related COVID-19 factors predict EFs complaints in daily life, a stepwise regression analysis was performed with i) experienced disease severity, ii) time since disease, and iii) health risk factor as predictors.The study revealed noteworthy differences in the occurrence of EFs problems in daily life between both groups, as indicated by the GEC, which exhibited a medium effect size even 6 months post-COVID-19 diagnosis even in mild disease progression. The scores of the BRIEF-A subscales follow a domain-specific profile, and includes clinically relevant impairments in: Working memory, Plan/Organize, Task Monitor, Shift, which are affected by the experienced severity of the disease. This cognitive profile has important implications for targeted cognitive training in rehabilitation and has the potential for an applicability to other viruses as well.

Impairments in executive functions (EFs) are common across disorders and can greatly affect daily functioning. Frontal-midline (FM) theta neurofeedback (NF) has been shown effective in enhancing EFs in healthy adults, prompting interest in exploring its potential as an alternative treatment for EFs in (sub)clinical samples. This study aims to determine the effects of FM theta NF on EFs in a sample of 58 adults (aged 20-60 years) with pronounced subjective EF complaints in daily life. Using a pre/post/follow-up design with a sham NF group, the present study assessed upregulation of FM theta in an eight-session individualized FM theta NF training and its immediate and long-term transfer effects on objective and subjective measures of EFs. These included behavioral performance on EF tasks assessing working memory updating (N-back task), set-shifting (Switching task), conflict monitoring (Stroop task), and response inhibition (Stop-signal task), as well as FM theta power during these tasks, and subjective EFs in daily life (BRIEF-A). The results indicate that there are only differences in FM theta self-upregulation between the NF group and sham group when non-responders are excluded from the analysis. Regarding behavioral transfer effects, NF-specific improvements are found in working memory updating reaction time (RT) and conflict monitoring RT variability at 6-month follow-up, but not immediately after the NF training. The effects on FM theta power during the EF tasks and subjective changes in EFs in daily life were not specific to the NF training. As a next step, research should identify the best predictors to stratify NF training, as well as explore ways to improve NF responsiveness, for instance by increasing neuroplasticity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Smit, Dapor, Koerts, Tucha, Huster and Enriquez-Geppert.)

Impairments in executive functions (EFs) are common across psychological disorders. Research into the neural oscillations underlying EFs has the potential to help understand these impairments and contribute to the development of interventions. The aim of this study is to assess theta power and functional theta connectivity in the sensor space of the regions of the superordinate network for the core EFs: conflict monitoring, response inhibition, set-shifting, and working memory updating. We recruited adults with self-reported everyday EFs complaints and formed two groups: one with attention deficit hyperactivity disorder (ADHD) (n=27) and another without any diagnosis (n=22), and compared them to controls (n=21) on the Stroop, Stop-signal, Switching, and N-back task using EEG. Power and functional connectivity analyses were conducted for four regions of interest: frontal-midline, frontolateral left and right, and parietal region. For all four EFs, the groups showed a dynamical increase in theta power over time in the four regions of interest, as well as in functional theta connectivity between these regions. Group differences were found especially for conflict monitoring, with differences in theta power in the frontal-midline and frontolateral right region. These neural markers are also associated with behavioural performance and complaints in daily life. For set-shifting, group differences were less pronounced and for response inhibition and working memory updating no group differences were observed., Competing Interests: Declaration of interest None., (Copyright © 2023. Published by Elsevier B.V.)

Introduction: Currently, major depressive disorder (MDD) treatment plans are based on trial-and-error, and remission rates remain low. A strategy to replace trial-and-error and increase remission rates could be treatment stratification. We explored the heartbeat-evoked potential (HEP) as a biomarker for treatment stratification to either antidepressant medication or rTMS treatment., Methods: Two datasets were analyzed: (1) the International Study to Predict Optimized Treatment in Depression (iSPOT-D; n = 1,008 MDD patients, randomized to escitalopram, sertraline, or venlafaxine, and n = 336 healthy controls) and (2) a multi-site, open-label rTMS study (n = 196). The primary outcome measure was remission. Cardiac field artifacts were removed from the baseline EEG using independent component analysis (ICA). The HEP-peak was detected in a bandwidth of 20 ms around 8 ms and 270 ms (N8, N270) after the R-peak of the electrocardiogram signal. Differences between remitters and non-remitters were statistically assessed by repeated-measures ANOVAs for electrodes Fp1, Cz, and Oz., Results: In the venlafaxine subgroup, remitters showed a lower HEP around the N8 peak than non-remitters on electrode site Cz (p = 0.004; d = 0.497). The rTMS group showed a non-significant difference in the opposite direction (d = -0.051). Retrospective stratification to one of the treatments based on the HEP resulted in enhanced treatment outcome prediction for venlafaxine (+22.98%) and rTMS (+10.66%)., Conclusion: These data suggest that the HEP could be used as a stratification biomarker between venlafaxine and rTMS; however, future out-of-sample replication is warranted., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

In recent years there has been an increasing interest in understanding the role apathy plays in mediating the relationship between cognitive impairment and functional outcome. In general, most studies measure cognition with traditional cognitive tests that give explicit instructions and guide the participants toward generating a response. However, given that apathy is defined by a decrease in self-initiated behavior, it is crucial to evaluate cognition with ecological tasks that do not explicitly direct the patient´s motivation to generate behaviors to assess the actual effect. This study investigated whether an ecological cognitive assessment (the Jansari Executive Function Assessment, JEF©) would uniquely contribute to the relationship between cognition, apathy, and functional outcome in schizophrenia. The Apathy Evaluation Scale (AES), neuropsychological tests and the JEF© were administered to 20 patients with schizophrenia. Hierarchical multiple regression and mediation analysis were performed to test the associations between the variables of interest. Results showed that JEF© explained a significant portion of the variance in AES (25%). In addition, apathy explained 36% of the variance in functional outcome. However, AES did not mediate between cognition and functional outcome. Our results highlight the importance of assessing cognition with tasks that require integration of cognitive functions needed for real life demands., Competing Interests: The authors have declared that no competing interests exist.

Although the presence of anosognosia in amnestic mild cognitive impairment (aMCI) may be predictive of conversion to Alzheimer's disease (AD), little is known about its neural correlates in AD and aMCI. Four different groups were compared using volumetric and diffusion magnetic resonance imaging metrics in regions of interest (hippocampus and cingulum cortex gray matter, cingulum bundle white matter): aMCI subjects with anosognosia ( n = 6), aMCI subjects without anosognosia ( n = 12), AD subjects with anosognosia ( n = 6), and AD subjects without anosognosia ( n = 9). aMCI subjects with anosognosia displayed a significantly lower gray matter density (GMD) in the bilateral hippocampus than aMCI subjects without anosognosia, which was accounted for by bilateral hippocampal differences. Furthermore, we identified that the mean hippocampal gray matter density of aMCI subjects with anosognosia was not statistically different than that of AD subjects. The groups of aMCI and AD subjects with anosognosia also displayed a lower GMD in the bilateral cingulum cortex compared to subjects without anosognosia, but these differences were not statistically significant. No statistically significant differences were found in the fractional anisotropy or mean diffusivity of the hippocampus or cingulum between subjects with and without anosognosia in aMCI or AD groups. While these findings are derived from a small population of subjects and are in need of replication, they suggest that anosognosia in aMCI might be a useful clinical marker to suspect brain changes associated with AD neuropathology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Flores-Vázquez, Ramírez-García, Marrufo-Meléndez, Alcalá-Lozano, Lietz, Rodríguez-Agudelo, Acosta-Castillo, Renken, Aleman, Enriquez-Geppert and Sosa-Ortiz.)

Introduction: The Face Name Associative Memory Exam (FNAME) is sensitive to associative memory changes early in the Alzheimer's disease spectrum, but little is known about how healthy aging affects FNAME performance. We aimed to assess aging effects on an extended version of the test, which captures further associative memory abilities beyond the recall and recognition domains measured in the original version., Method: We adapted FNAME versions in Spain and Mexico, adding new subtests (Spontaneous Name Recall, Face-Name Matching). We compared the performance of 21 young adults (YA) and 27 older adults (OA) in Spain, and 34 YA and 36 OA in Mexico. Recall was analyzed using a mixed-model ANOVA including subtest scores as dependent variables, age group as a fixed-factor independent variable, and recall subtest as a three-level repeated-measure independent variable. The rest of the associative memory domains were analyzed through t-tests comparing the performance of YA and OA., Results: In Spain, we found significant effects for age group and recall subtest , with large effect sizes. The recognition subtests (Face Recognition, Name Recognition) displayed ceiling effects in both groups. The new subtests displayed medium-to-large effect sizes when comparing age groups. In Mexico, these results were replicated, additionally controlling for education. In both studies, recall performance improved after repeated exposures and it was sustained after 30 minutes in YA and OA., Conclusions: We document, in two different countries, a clear aging pattern on the extended FNAME: regardless of education, OA remember fewer stimuli than YA through recall subtests. The new subtests provide evidence on associative memory changes in aging beyond recall.

Neurofeedback has begun to attract the attention and scrutiny of the scientific and medical mainstream. Here, neurofeedback researchers present a consensus-derived checklist that aims to improve the reporting and experimental design standards in the field., (© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Many individuals with severe mental disorders have difficulties in vocational and social functioning, which are regarded the most important outcomes, together with clinical symptoms. To understand the underlying mechanisms, research is increasingly focused on factors influencing functional outcomes. One established association has been shown between cognition and community functioning with negative symptoms as a possible mediator. Although it has been shown that negative symptoms consist of two subdomains, thus far negative symptoms have been assessed as one unitary construct. This study considers for the first time subdomains of negative symptoms as putative mediators (expressive deficits, amotivation) of the association between cognition (neuro- and social cognition) and functional outcome (living situation, occupation, social functioning). We expected that specific subdomains of negative symptoms (e.g. amotivation) would mediate the effect of cognition on specific functional outcomes (e.g. social functioning) independently from illness duration. To assess this, we included two independent cohorts, consisting of participants with different illness duration. These two independent cohorts consisted of patients with a recent-onset psychotic disorder: PROGR-S (first time treated; N = 1129) and GROUP (illness duration preferably <5 years; N = 1200). Using linear regression, mediation analyses were performed with two cognition domains (neurocognition and social cognition) as predictors, negative symptoms (Expressive deficits and Amotivation as indexed with items from the Positive and Negative Syndrome Scale) as mediators and three measures of functional outcomes (living situation, occupation and social functioning) as outcome measures. The analyses were repeated with the same outcome measures three years later. Three main results were obtained. I) Both in the cross-sectional and longitudinal analyses, the associations of neurocognition (both cohorts) and social cognition (GROUP) with social functioning were mediated by amotivation. II) The association between cognition and living situation was mediated by Expressive deficits in one cohort (GROUP) but not in the cohort assessing first-episode psychosis (PROGR-S). III) The association between cognition and occupation was mediated by Amotivation in PROGR-S and by Expressive deficits in GROUP. CONCLUSION: The current results show a less robust mediating role for specific negative symptom domains regarding the associations of cognition with occupation and living situation that may depend on the duration of psychotic illness. However, Amotivation, mediates the association between cognition and social functioning, which holds true for patients experiencing a first-onset and patients with a longer illness duration alike. The results may have implications for the development of therapeutic approaches focusing on amotivation to improve social functioning. GENERAL SCIENTIFIC SUMMARY: This study stresses the importance of distinguishing subdomains of negative symptoms, cognition and functioning. Our results show that specific negative symptom dimensions mediate the effects of cognition on specific functional outcomes., Competing Interests: Declaration of competing interest AA received speakers fees from Lundbeck. All other authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose of Review: Current traditional treatments for ADHD present serious limitations in terms of long-term maintenance of symptom remission and side effects. Here, we provide an overview of the rationale and scientific evidence of the efficacy of neurofeedback in regulating the brain functions in ADHD. We also review the institutional and professional regulation of clinical neurofeedback implementations., Recent Findings: Based on meta-analyses and (large multicenter) randomized controlled trials, three standard neurofeedback training protocols, namely theta/beta (TBR), sensori-motor rhythm (SMR), and slow cortical potential (SCP), turn out to be efficacious and specific. However, the practical implementation of neurofeedback as a clinical treatment is currently not regulated. We conclude that neurofeedback based on standard protocols in ADHD should be considered as a viable treatment alternative and suggest that further research is needed to understand how specific neurofeedback protocols work. Eventually, we emphasize the need for standard neurofeedback training for practitioners and binding standards for use in clinical practice.

Background: Negative symptoms in schizophrenia concern a clinically relevant reduction of goal-directed behavior that strongly and negatively impacts daily functioning. Existing treatments are of marginal effect and novel approaches are needed. Noninvasive neurostimulation by means of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are novel approaches that may hold promise., Objectives: To provide a quantitative integration of the published evidence regarding effects of rTMS and tDCS over the frontal cortex on negative symptoms, including an analysis of effects of sham stimulation., Methods: Meta-analysis was applied, using a random effects model, to calculate mean weighted effect sizes (Cohen's d). Heterogeneity was assessed by using Cochrans Q and I 2 tests., Results: For rTMS treatment, the mean weighted effect size compared to sham stimulation was 0.64 (0.32-0.96; k = 22, total N = 827). Studies with younger participants showed stronger effects as compared to studies with older participants. For tDCS studies a mean weighted effect size of 0.50 (-0.07 to 1.07; k = 5, total N = 134) was found. For all frontal noninvasive neurostimulation studies together (i.e., TMS and tDCS studies combined) active stimulation was superior to sham, the mean weighted effect size was 0.61 (24 studies, 27 comparisons, 95% confidence interval 0.33-0.89; total N = 961). Sham rTMS (baseline - posttreatment comparison) showed a significant improvement of negative symptoms, d = 0.31 (0.09-0.52; k = 16, total N = 333). Whereas previous meta-analyses were underpowered, our meta-analysis had a power of 0.87 to detect a small effect., Conclusions: The available evidence indicates that noninvasive prefrontal neurostimulation can improve negative symptoms. This finding suggests a causal role for the lateral frontal cortex in self-initiated goal-directed behavior. The evidence is stronger for rTMS than for tDCS, although this may be due to the small number of studies as yet with tDCS. More research is needed to establish moderator variables that may affect response to neurostimulation and to optimize treatment parameters in order to achieve stable and durable (and thus clinically relevant) effects., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Age-related neurocognitive effects have been observed at different levels ranging from reduced amplitudes of even-related potentials and brain oscillations, to topography changes of brain activity. However, their association remains incompletely understood. We investigated time-frequency and time-course effects in functional networks underlying the P300 and their involvement in reactive control. Electroencephalographic (EEG) data of three different age groups (30 young: 18-26 years, 30 mid-aged: 49-58 years, 30 elderly: 65-75 years) was measured while they performed a cued colour/thickness switching task. Neural data was analysed concerning the targets. To consider restart, mixing, and switching processes, the targets´ position after a cue (first or third target) as well as their context in the single-task (distractor cue) or the mixed-task block (switch- or repeat cue) was analysed. P300 EEG data was decomposed by means of group-independent component and time-frequency analyses focusing on theta and beta oscillations. RTs generally slowed down with age (main effect group), and effects were specifically strong in targets after a switching cue (larger Cohens d). Peaking at around 300 ms, we detected five functionally independent networks reflecting the multicomponent process underlying task-switching. These networks differed in terms of their topography (parietal and frontal), their involvement in task processes (switch-specific, mixing-, restart-, and single-task processes) and in terms of frequency effects. All were affected by age, as indicated by amplitude changes of the target-P300 and power reductions most consistently shown in beta oscillations. Most extensive age-related changes were observed in one parietal network sensitive to mixing and restart processes. Changes included a topography shift, P300 and beta amplitudes, and were ongoing in the elderly group.

Background: depression is associated with worse executive function, but underlying mechanisms might differ by age., Aims: to investigate whether vascular disease burden affects the association between depression and executive dysfunction differentially by age., Method: among 83,613 participants of Lifelines (population-based cohort study), linear regression analyses were applied to examine the association between executive function (Ruff Figural Fluency test, dependent variable) and depression according to DSM-IV criteria (Mini International Neuropsychiatric Interview, independent variable)., Results: adjusted for demographic characteristics, major depressive disorder was associated with a lower level of executive function in both younger and older adults. Minor depressive disorder was only associated with worse executive function in younger adults. Adding vascular disease burden to the final model with major depressive disorder, reduced this strength of this association by 5.9% in younger and 5.0% in older adults., Conclusions: major depression was associated with worse executive function across the lifespan, but minor depression only in younger adults. The impact of vascular burden on the association did not differ between younger and older adults. Therefore, vascular risk reduction is important in both age groups., (© The Author 2017. Published by Oxford University Press on behalf of the British Geriatrics Society.All rights reserved. For permissions, please email: journals.permissions@oup.com)

The ability to inhibit behavior is crucial for adaptation in a fast changing environment and is commonly studied with the stop signal task. Current EEG research mainly focuses on the N200 and P300 ERPs and corresponding activity in the theta and delta frequency range, thereby leaving us with a limited understanding of the mechanisms of response inhibition. Here, 15 functional networks were estimated from time-frequency transformed EEG recorded during processing of a visual stop signal task. Cortical sources underlying these functional networks were reconstructed, and a total of 45 features, each representing spectrally and temporally coherent activity, were extracted to train a classifier to differentiate between go and stop trials. A classification accuracy of 85.55% for go and 83.85% for stop trials was achieved. Features capturing fronto-central delta- and theta activity, parieto-occipital alpha, fronto-central as well as right frontal beta activity were highly discriminating between trial-types. However, only a single network, comprising a feature defined by oscillatory activity below 12 Hz, was associated with a generator in the opercular region of the right inferior frontal cortex and showed the expected associations with behavioral inhibition performance. This study pioneers by providing a detailed ranking of neural features regarding their information content for stop and go differentiation at the single-trial level, and may further be the first to identify a scalp EEG marker of the inhibitory control network. This analysis allows for the characterization of the temporal dynamics of response inhibition by matching electrophysiological phenomena to cortical generators and behavioral inhibition performance. Hum Brain Mapp 38:1333-1346, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Neurofeedback is attracting renewed interest as a method to self-regulate one's own brain activity to directly alter the underlying neural mechanisms of cognition and behavior. It not only promises new avenues as a method for cognitive enhancement in healthy subjects, but also as a therapeutic tool. In the current article, we present a review tutorial discussing key aspects relevant to the development of electroencephalography (EEG) neurofeedback studies. In addition, the putative mechanisms underlying neurofeedback learning are considered. We highlight both aspects relevant for the practical application of neurofeedback as well as rather theoretical considerations related to the development of new generation protocols. Important characteristics regarding the set-up of a neurofeedback protocol are outlined in a step-by-step way. All these practical and theoretical considerations are illustrated based on a protocol and results of a frontal-midline theta up-regulation training for the improvement of executive functions. Not least, assessment criteria for the validation of neurofeedback studies as well as general guidelines for the evaluation of training efficacy are discussed.

Frontal-midline (fm) theta oscillations as measured via the electroencephalogram (EEG) have been suggested as neural "working language" of executive functioning. Their power has been shown to increase when cognitive processing or task performance is enhanced. Thus, the question arises whether learning to increase fm-theta amplitudes would functionally impact the behavioral performance in tasks probing executive functions (EFs). Here, the effects of neurofeedback (NF), a learning method to self-up-regulate fm-theta over fm electrodes, on the four most representative EFs, memory updating, set shifting, conflict monitoring, and motor inhibition are presented. Before beginning and after completing an individualized, eight-session gap-spaced NF intervention, the three-back, letter/number task-switching, Stroop, and stop-signal tasks were tested while measuring the EEG. Self-determined up-regulation of fm-theta and its putative role for executive functioning were compared to an active control group, the so-called pseudo-neurofeedback group. Task-related fm-theta activity after training differed significantly between groups. More importantly, though, after NF significantly enhanced behavioral performance was observed. The training group showed higher accuracy scores in the three-back task and reduced mixing and shifting costs in letter/number task-switching. However, this specific protocol type did not affect performance in tasks probing conflict monitoring and motor inhibition. Thus, our results suggest a modulation of proactive but not reactive mechanisms of cognitive control. Furthermore, task-related EEG changes show a distinct pattern for fm-theta after training between the NF and the pseudo-neurofeedback group, which indicates that NF training indeed tackles EFs-networks. In sum, the modulation of fm-theta via NF may serve as potent treatment approach for executive dysfunctions.

There has been a lively debate whether conceptual representations of actions or scenes follow a left-to-right spatial transient when participants depict such events or scenes. It was even suggested that conceptualizing the agent on the left side represents a universal. We review the current literature with an emphasis on event representation and on cross-cultural studies. While there is quite some evidence for spatial bias for representations of events and scenes in diverse cultures, their extent and direction depend on task demands, one's native language, and importantly, on reading and writing direction. Whether transients arise only in subject-verb-object languages, due to their linear sentential position of event participants, is still an open issue. We investigated a group of illiterate speakers of Yucatec Maya, a language with a predominant verb-object-subject structure. They were compared to illiterate native speakers of Spanish. Neither group displayed a spatial transient. Given the current literature, we argue that learning to read and write has a strong impact on representations of actions and scenes. Thus, while it is still under debate whether language shapes thought, there is firm evidence that literacy does.

Neurofeedback training procedures designed to alter a person's brain activity have been in use for nearly four decades now and represent one of the earliest applications of brain-computer interfaces (BCI). The majority of studies using neurofeedback technology relies on recordings of the electroencephalogram (EEG) and applies neurofeedback in clinical contexts, exploring its potential as treatment for psychopathological syndromes. This clinical focus significantly affects the technology behind neurofeedback BCIs. For example, in contrast to other BCI applications, neurofeedback BCIs usually rely on EEG-derived features with only a minimum of additional processing steps being employed. Here, we highlight the peculiarities of EEG-based neurofeedback BCIs and consider their relevance for software implementations. Having reviewed already existing packages for the implementation of BCIs, we introduce our own solution which specifically considers the relevance of multi-subject handling for experimental and clinical trials, for example by implementing ready-to-use solutions for pseudo-/sham-neurofeedback., (© 2013.)

Cortical oscillations demonstrate a relationship with cognition. Moreover, they also exhibit associations with task performance and psychiatric mental disorders. This being the case, the modification of oscillations has become one of the key interests of neuroscientific approaches for cognitive enhancement. For such kind of alterations, neurofeedback (NF) of brain activity constitutes a promising tool. Concerning specific higher cognitive functions, frontal-midline theta (fm-theta) has been suggested as an important indicator of relevant brain processes. This paper presents a novel approach for an individualized, eight-session NF training to enhance fm-theta. An individual's dominant fm-theta frequency was determined based on experiments tapping executive functions. Effects of the actual NF training were compared to a pseudo-NF training. Participants of the pseudo-NF training experienced a comparable degree of motivation and commitment as the subjects of the actual NF training, but found the "training" slightly easier. In comparison to the pseudo-NF training, proper NF training significantly enhanced fm-theta amplitude in the actual training sessions, as well as during the whole course of training. However, unspecific changes in the alpha and beta frequency ranges found with both the actual NF and the pseudo-NF training groups emphasize the relevance of active control groups for neurofeedback studies., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Humans differ in their ability to learn how to control their own brain activity by neurofeedback. However, neural mechanisms underlying these inter-individual differences, which may determine training success and associated cognitive enhancement, are not well-understood. Here, it is asked whether neurofeedback success of frontal-midline (fm) theta, an oscillation related to higher cognitive functions, could be predicted by the morphology of brain structures known to be critically involved in fm-theta generation. Nineteen young, right-handed participants underwent magnetic resonance imaging of T1-weighted brain images, and took part in an individualized, eight-session neurofeedback training in order to learn how to enhance activity in their fm-theta frequency band. Initial training success, measured at the second training session, was correlated with the final outcome measure. We found that the inferior, superior, and middle frontal cortices were not associated with training success. However, volume of the midcingulate cortex as well as volume and concentration of the underlying white matter structures act as predictor variables for the general responsiveness to training. These findings suggest a neuroanatomical foundation for the ability to learn to control one's own brain activity.

Conflict monitoring and motor inhibition are engaged in the performance of complex tasks. The midcingulate cortex (MCC) has been suggested to detect conflicts, whereas the right inferior frontal cortex (IFC) seems to be of relevance for the inhibition process. The current experiment investigates the neural underpinnings of their interplay via a modified flanker paradigm. Conflict was manipulated by the congruency of flanking stimuli relative to a target (congruent vs. incongruent) and motor inhibition by a within-trial response change of the initiated response (keep response vs. stop-change). We used event-related functional magnetic resonance imaging, decomposition with high model order ICA, and single trial analysis to derive a functional parcellation of the whole-brain data. Results demonstrate the segmentation of the MCC into anterior and posterior subregions, and of the IFC into the pars opercularis, pars triangularis, and pars orbitalis. The pars opercularis and pars triangularis of the right IFC constituted the foundation of inhibition-related networks. With high conflict on incongruent trials, activity in the posterior MCC network, as well as in one right IFC network was observed. Stop-change trials modulated both the MCC as well as networks covering extended parts of the IFC. Whereas conflict processing and inhibition most often are studied separately, this study provides a synopsis of functionally coupled brain regions acting in concert to enable an optimal performance in situations involving interference and inhibition., (Copyright © 2012 Wiley Periodicals, Inc.)

Cognitive enhancement is a popular topic, attracting attention both from the general public and the scientific research community. Higher cognitive functions are involved in various aspects of everyday life and have been associated with manifest behavioral and psychiatric mental impairments when deteriorated. The improvement of these so-called executive functions (EFs) is of high individual, social, and economic relevances. This review provides a synopsis of two lines of research, investigating the enhancement of capabilities in executive functioning: a) computerized behavioral trainings, and b) approaches for direct neuromodulation (neurofeedback and transcranial electrostimulation). Task switching, memory updating, response inhibition, and dual task performance are addressed in terms of cognitive functions. It has been shown that behavioral cognitive training leads to enhanced performance in task switching, memory updating, and dual tasks. Similarly, direct neurocognitive modulation of brain regions that are crucially involved in specific EFs also leads to behavioral benefits in response inhibition, task switching, and memory updating. Response inhibition performance has been shown to be improved by neurostimulation of the right inferior frontal cortex, whereas neurostimulation of the dorsolateral prefrontal cortex exerts effects on task switching and memory updating. Due to a lack of consistency in experimental methods and findings, a comparison of different training approaches concerning their effectiveness is not yet possible. So far, current data suggest that training gains may indeed generalize to untrained tasks aiming at the same cognitive process, as well as across cognitive domains within executive control., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Response inhibition paradigms, as for example stop signal and go/no-go tasks, are often used to study cognitive control processes. Because of the apparent demand to stop a motor reaction, the electrophysiological responses evoked by stop and no-go trials have sometimes likewise been interpreted as indicators of inhibitory processes. Recent research, however, suggests a richer conceptual background. Evidence denotes an association of a frontal-midline N200/theta oscillations with premotor cognitive processes such as conflict monitoring or response program updating, and an anterior P300/delta oscillations with response-related, evaluative processing stages, probably the evaluation of motor inhibition. However, the data are still insufficient to unambiguously relate these electroencephalographic measures to specific inhibitory functions. Beta band activity only recently has become a focus of attention in this task context because of its association with the motor system and regions involved in inhibitory control. Its functional role in response inhibition tasks needs further exploration though. Hence, as things stand, any deduction of differences regarding actual inhibitory capabilities or loads between subject groups or conditions based on electroencephalographic measures has to be treated with caution., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Despite a growing number of studies, the neurophysiology of adult vocabulary acquisition is still poorly understood. One reason is that paradigms that can easily be combined with neuroscientfic methods are rare. Here, we tested the efficiency of two paradigms for vocabulary (re-) acquisition, and compared the learning of novel words for actions and objects. Cortical networks involved in adult native-language word processing are widespread, with differences postulated between words for objects and actions. Words and what they stand for are supposed to be grounded in perceptual and sensorimotor brain circuits depending on their meaning. If there are specific brain representations for different word categories, we hypothesized behavioural differences in the learning of action-related and object-related words. Paradigm A, with the learning of novel words for body-related actions spread out over a number of days, revealed fast learning of these new action words, and stable retention up to 4 weeks after training. The single-session Paradigm B employed objects and actions. Performance during acquisition did not differ between action-related and object-related words (time*word category: p = 0.01), but the translation rate was clearly better for object-related (79%) than for action-related words (53%, p = 0.002). Both paradigms yielded robust associative learning of novel action-related words, as previously demonstrated for object-related words. Translation success differed for action- and object-related words, which may indicate different neural mechanisms. The paradigms tested here are well suited to investigate such differences with neuroscientific means. Given the stable retention and minimal requirements for conscious effort, these learning paradigms are promising for vocabulary re-learning in brain-lesioned people. In combination with neuroimaging, neuro-stimulation or pharmacological intervention, they may well advance the understanding of language learning to optimize therapeutic strategies.

Current theoretical positions assume that action-related word meanings are established by functional connections between perisylvian language areas and the motor cortex (MC) according to Hebb's associative learning principle. To test this assumption, we probed the functional relevance of the left MC for learning of a novel action word vocabulary by disturbing neural plasticity in the MC with transcranial direct current stimulation (tDCS). In combination with tDCS, subjects learned a novel vocabulary of 76 concrete, body-related actions by means of an associative learning paradigm. Compared with a control condition with "sham" stimulation, cathodal tDCS reduced success rates in vocabulary acquisition, as shown by tests of novel action word translation into the native language. The analysis of learning behavior revealed a specific effect of cathodal tDCS on the ability to associatively couple actions with novel words. In contrast, we did not find these effects in control experiments, when tDCS was applied to the prefrontal cortex or when subjects learned object-related words. The present study lends direct evidence to the proposition that the left MC is causally involved in the acquisition of novel action-related words., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Conflict and inhibition are considered to exert strong influences on the neurophysiological N200 and P300 brain responses as evoked in go/nogo and stop-signal tasks. In order to separate their underlying neural and functional mechanisms, the current experiment manipulated both conflict and inhibition. To do so, the go/nogo and stop-signal tasks were merged into one paradigm. Conflict was manipulated by varying go-trial frequencies across blocks (75% vs. 25%). Motor inhibition was manipulated by using go, nogo and stop trials each representing a different load of inhibition. Event-related potentials (ERPs) as well as current density reconstructions (CDRs) of fifteen healthy participants were analyzed. Overall, infrequent trials evoked significantly more pronounced N200s than frequent trials. The P300 predominantly revealed significant variations between trial types (go, nogo, stop). Estimated source activations of the MCC and the IFC supported the ERP results; N200-related effects were revealed in both regions, whereas the condition-specific variations of the P300 were only observed in the IFC. The results indicate that the N200 primarily reflects conflict-related effects whereas the P300 predominantly represents motor inhibition., (Copyright 2010 Elsevier Inc. All rights reserved.)