A Systematic Review of The Potential Use of Neurofeedback in Patients with Schizophrenia.

Schizophrenia (SCZ) is a neurodevelopmental disorder characterized by positive symptoms (hallucinations and delusions), negative symptoms (anhedonia, social withdrawal) and marked cognitive deficits (memory, executive function, and attention). Current mainstays of treatment, including medications and psychotherapy, do not adequately address cognitive symptoms, which are essential for everyday functioning. However, recent advances in computational neurobiology have rekindled interest in neurofeedback (NF), a form of self-regulation or neuromodulation, in potentially alleviating cognitive symptoms in patients with SCZ. Therefore, we conducted a systematic review of the literature for NF studies in SCZ to identify lessons learned and to identify steps to move the field forward. Our findings reveal that NF studies to date consist mostly of case studies and small sample, single-group studies. Despite few randomized clinical trials, the results suggest that NF is feasible and that it leads to measurable changes in brain function. These findings indicate early proof-of-concept data that needs to be followed up by larger, randomized clinical trials, testing the efficacy of NF compared to well thought out placebos. We hope that such an undertaking by the field will lead to innovative solutions that address refractory symptoms and improve everyday functioning in patients with SCZ

Evaluating self-regulation in adolescents with conduct problems or severe disruptive behavior disorders - possible neural targets for future interventions

Disruptive behavior is a common phenomenon in human nature and frequently occurs during adolescence. It is associated with conduct problems (CP) in healthy as well as clinical populations. When CP exceed the normal range and disruptive behaviors are severe, Disruptive Behavior Disorder (DBD), including Conduct Disorder (CD) and Oppositional Defiant Disorder (ODD), is often diagnosed. Individuals who fulfill diagnostic criteria of DBD also frequently display a conspicuous pattern of behavior that is characterized by a callous, uncaring and unemotional interpersonal style, including deficits in empathy, emotional affectivity and conscientiousness. These behaviors have been labeled the affective dimension of psychopathy or callous-unemotional traits (CU traits) in research. Overall, evidence-based psychological treatments for DBD (with and without increased CU traits) only reach small to moderate effect sizes and there is currently not enough evidence to support one specific form of treatment over another. To date, real-time functional magnetic resonance imaging (rtfMRI-NF) is increasingly considered as a promising tool for the training of brain self-regulation in order to treat psychiatric conditions. It has already been applied to train self-regulation of compromised inhibitory or emotional brain regions, and of emotion regulation strategies in adult psychopaths and adolescents diagnosed with ADHD. For the purpose of investigating and evaluating new innovative forms of treatments for adolescents with DBD, this thesis followed a two-way approach. First (study 1), a large dataset of healthy young adolescents (mean age: 14.44 (0.41), range 13.08-15.72 years) with varying level of CP was analyzed with respect to possible neural correlates of frontal control over CP during affective processing of negative facial emotions. Second (study 2), an individualized rtfMRI-NF training aiming at the learning of self-regulation of emotional processing regions (amygdala or insula) and, as a result, at the improvement of affective processing was conducted with adolescent patients (mean age: 14.62 (1.64), range: 12.04-17.99 years) diagnosed with DBD and elevated CU traits (ICU total score >20 in self-rating and/or >24 in parent-rating) over a course of 10 weeks and compared with a clinical TAU group. In study 1, we observed no significant differences in brain responses to negative facial affect in adolescents with high versus low CP. However, regression analyses along the CP dimension across the groups revealed a significant nonlinear effect: left orbitofrontal cortex (OFC) responses increased with increasing CP up to the clinical range, and, decreased again only for the highest CP range. This increasing left OFC activity found during affective processing in an epidemiological adolescent sample with low to clinically relevant levels of CP might represent frontal control mechanisms preventing the outbreak of disruptive or conduct disorder despite conduct problems. In study 2, the NF and the TAU group showed comparable and significant clinical improvement on DBD-related behavioral scales over time, in line with non-inferiority. Within the NF group, successful learning of self-regulation in the target region was found for NF of the amygdala, but not for NF of the insula. The data suggest that the self-regulation of emotional processing regions might be more promising when receiving feedback from the amygdala (as compared to the insula). Additional exploratory analyses also suggested involvement of prefrontal areas in the learning of self-regulation of emotion processing regions. However, clinical improvement in NF was not specific to the amygdala group. In the emotion matching task, both treatment groups showed decreased activities after treatment in prefrontal emotion-regulation related areas, potentially indicating higher efficiency of processing affective stimuli after treatment. The results suggest clinical improvement and non-inferiority of rtfMRI-NF training compared to other treatment options for adolescents with diagnosis of DBD, but further studies are needed to clarify underlying mechanisms and cost effectiveness. As a future perspective, further investigation of the role of structural and functional connections between subcortical and prefrontal areas with respect to the cognitive regulation of affective arousal might be fruitful for the development of future specific treatment strategies aiming at the improvement of adaptive reactivity, emotion regulation and social behavior. Also, the OFC could form a promising target for further NF approaches aiming at the control of emotions

Treatment biomarkers for ADHD: Taking stock and moving forward

The development of treatment biomarkers for psychiatric disorders has been challenging, particularly for heterogeneous neurodevelopmental conditions such as attention-deficit/hyperactivity disorder (ADHD). Promising findings are also rarely translated into clinical practice, especially with regard to treatment decisions and development of novel treatments. Despite this slow progress, the available neuroimaging, electrophysiological (EEG) and genetic literature provides a solid foundation for biomarker discovery. This article gives an updated review of promising treatment biomarkers for ADHD which may enhance personalized medicine and novel treatment development. The available literature points to promising pre-treatment profiles predicting efficacy of various pharmacological and non-pharmacological treatments for ADHD. These candidate predictive biomarkers, particularly those based on low-cost and non-invasive EEG assessments, show promise for the future stratification of patients to specific treatments. Studies with repeated biomarker assessments further show that different treatments produce distinct changes in brain profiles, which track treatment-related clinical improvements. These candidate monitoring/response biomarkers may aid future monitoring of treatment effects and point to mechanistic targets for novel treatments, such as neurotherapies. Nevertheless, existing research does not support any immediate clinical applications of treatment biomarkers for ADHD. Key barriers are the paucity of replications and external validations, the use of small and homogeneous samples of predominantly White children, and practical limitations, including the cost and technical requirements of biomarker assessments and their unknown feasibility and acceptability for people with ADHD. We conclude with a discussion of future directions and methodological changes to promote clinical translation and enhance personalized treatment decisions for diverse groups of individuals with ADHD

Optimization of near-infrared spectroscopy-based neurofeedback for use in the treatment of attention-deficit hyperactivity disorder

Die Aufmerksamkeitsdefizit-Hyperaktivitätsstörung (ADHS) zählt zu den am häufigsten vorkommenden psychischen Störungen im Kindes- und Jugend-, aber auch im Erwachsenenalter, ca. 2,5-5% der Weltbevölkerung sind davon betroffen. Die Erkrankung wirkt sich in drei Kernbereichen aus: Hyperaktivität, Impulsivität und Unaufmerksamkeit, mit tiefgreifenden Beeinträchtigungen in verschiedenen Bereichen des Lebens, am deutlichsten in der Schule, bei der Arbeit und in interpersonellen Beziehungen. Es existieren verschiedene Behandlungsansätze, welche die vielseitige Symptomatologie der ADHS anzugehen versuchen. Die Medikation stellt dabei die gängigste Behandlungsmethode dar, ist jedoch nicht selten mit Nebenwirkungen verbunden. Die Methode des Neurofeedbacks (NF) ist zwar unlängst kein neuartiges Verfahren mehr, ist aber eine Behandlungsmethode, welche, aufgrund der fraglichen Wirksamkeit, in den letzten Jahren viele Diskussionen anregt hat. Da die Methode jedoch an der Schnittstelle zur Verhaltenstherapie und der neusten neurophysiologischen Forschung liegt, bietet sie die Möglichkeit fortwährend um die aktuellsten wissenschaftlichen Erkenntnisse erweitert zu werden. Die vorliegende Dissertation strebt die Optimierung des NIRS-basierten NF Paradigmas zur Behandlung von ADHS durch die Untersuchung folgender Punkte an: 1) Wie können NIRS-basierte Paradigmen in VR implementiert werden? 2) Welche sind die zugrundeliegenden Mechanismen, die für einen erfolgreichen NF Trial und Paradigma verantwortlich sind? 3) Wie können Methoden kombiniert werden um NF Paradigmen weiter zu entwickeln? Die Dissertation umfasst vier Studien. In Studie 1 untersuchten wir die Effektivität eines Nahinfrarotspektroskopie-(NIRS)-basierten NF Paradigmas, realisiert im virtuellen Klassenzimmer, zur Behandlung hoch-impulsiver Universitätsstudenten. In Studie 2 wurde ein ’Standard’- NIRS-basiertes NF Paradigma für ADHS in seinen Einzelteilen überprüft und Empfehlungen für die Weiterentwicklung eines NF Studiendesigns diskutiert sowie Netzwerke, welche mit Erfolg und Misserfolg bei NF Trials assoziiert sind, untersucht. In Studie 3 untersuchten wir das post-Fehlerverhalten bei ADHS-Patienten im Vergleich zu gesunden Kontrollpersonen (healthy controls, HC). Im Einzelnen betrachteten wir die ’P300-informed’ NIRS-Analyse um die Unterschiede zwischen ADHS-Patienten und HC genauer zu untersuchen. Zusätzlich wurde die Studie konzipiert um die Effektivität von EEG/NIRS für den zukünftigen Einsatz in einem multimodalen NF Studiendesign für ADHS zu überprüfen. In Studie 4 wird das Studiendesign für eine großangelegte und momentan laufende Studie mit Schulkindern mit ADHS beschrieben, in welcher das Paradigma aus Studie 1 zum Einsatz kommt. Dies liefert eine erste Zusammenfassung über die umfangreiche Datenerhebung, welche zu neuen Erkenntnissen bei NIRS-NF bei ADHS führen soll

Probing fMRI brain connectivity and activity changes during emotion regulation by EEG neurofeedback

Despite the existence of several emotion regulation studies using neurofeedback, interactions among a small number of regions were evaluated, and therefore, further investigation is needed to understand the interactions of the brain regions involved in emotion regulation. We implemented electroencephalography (EEG) neurofeedback with simultaneous functional magnetic resonance imaging (fMRI) using a modified happiness-inducing task through autobiographical memories to upregulate positive emotion. Then, an explorative analysis of whole brain regions was done to understand the effect of neurofeedback on brain activity and the interaction of whole brain regions involved in emotion regulation. The participants in the control and experimental groups were asked to do emotion regulation while viewing positive images of autobiographical memories and getting sham or real (based on alpha asymmetry) EEG neurofeedback, respectively. The proposed multimodal approach quantified the effects of EEG neurofeedback in changing EEG alpha power, fMRI blood oxygenation level-dependent (BOLD) activity of prefrontal, occipital, parietal, and limbic regions (up to 1.9% increase), and functional connectivity in/between prefrontal, parietal, limbic system, and insula in the experimental group. New connectivity links were identified by comparing the brain functional connectivity between experimental conditions (Upregulation and View blocks) and also by comparing the brain connectivity of the experimental and control groups. Psychometric assessments confirmed significant changes in positive and negative mood states in the experimental group by neurofeedback. Based on the exploratory analysis of activity and connectivity among all brain regions involved in emotion regions, we found significant BOLD and functional connectivity increases due to EEG neurofeedback in the experimental group, but no learning effect was observed in the control group. The results reveal several new connections among brain regions as a result of EEG neurofeedback which can be justified according to emotion regulation models and the role of those regions in emotion regulation and recalling positive autobiographical memories

Increased neuromodulation ability through EEG connectivity neurofeedback with simultaneous fMRI for emotion regulation

Emotion regulation plays a key role in human behavior and life. Neurofeedback (NF) is a non-invasive self-brain training technique used for emotion regulation to enhance brain function and treatment of mental disorders leading to behavioral changes. Most neurofeedback studies were limited to using the activity of a single brain region of fMRI data or the power of a single or two EEG electrodes. In a novel study, we use the connectivity-based EEG neurofeedback through retrieving positive autobiographical memories and simultaneous fMRI to upregulate positive emotion. The feedback was calculated based on the coherence of EEG electrodes rather than the power of single/two electrodes. We demonstrated the efficiency of the connectivity-based neurofeedback to traditional activity-based neurofeedback through several experiments. The results confirmed the effectiveness of connectivity-based neurofeedback to enhance brain activity/connectivity of deep brain regions with key roles in emotion regulation e.g., amygdala, thalamus, and insula, and increase EEG frontal asymmetry as a biomarker for emotion regulation or treatment of mental disorders such as PTSD, anxiety, and depression. The results of psychometric assessments before and after neurofeedback experiments demonstrated that participants were able to increase positive and decrease negative emotion using connectivity-based neurofeedback more than traditional activity-based neurofeedback. The results suggest using the connectivity-based neurofeedback for emotion regulation and alternative therapeutic approaches for mental disorders with more effectiveness and higher volitional ability to control brain and mental function.Comment: 21 pages, 5 figure

Exploring brain functions in autism spectrum disorder : a systematic review on functional near-infrared spectroscopy (fNIRS) studies

A growing body of research has investigated the functional development of the brain in autism spectrum disorder (ASD). Functional near-infrared spectroscopy (fNIRS) is increasingly being used in this respect. This method has several advantages over other functional neuroimaging techniques in studying brain functions in ASD, including portability, low cost, and availability in naturalistic settings. This article reviews thirty empirical studies, published in the past decade, that used fNIRS in individuals with ASD or in infants with a high risk of developing ASD. These studies investigated either brain activation using multiple tasks (e.g., face processing, joint attention and working memory) or functional organization under a resting-state condition in ASD. The majority of these studies reported atypical brain activation in the prefrontal cortex, inferior frontal gyrus, middle and superior temporal gyrus. Some studies revealed altered functional connectivity, suggesting an inefficient information transfer between brain regions in ASD. Overall, the findings suggest that fNIRS is a promising tool to explore neurodevelopment in ASD from an early age

Neural dysfunction during temporal discounting in paediatric Attention-Deficit/Hyperactivity Disorder and Obsessive-Compulsive Disorder

Both Attention-Deficit/Hyperactivity Disorder (ADHD) and Obsessive-Compulsive Disorder (OCD) are associated with choice impulsivity, i.e. the tendency to prefer smaller immediate rewards over larger delayed rewards. However, the extent to which this impulsivity is mediated by shared or distinct underlying neural mechanisms is unclear. Twenty-six boys with ADHD, 20 boys with OCD and 20 matched controls (aged 12–18) completed an fMRI version of an individually adjusted temporal discounting (TD) task which requires choosing between a variable amount of money now or £100 in one week, one month or one year. Activations to immediate and delayed reward choices were compared between groups using a three-way ANCOVA. ADHD patients had steeper discounting rates on the task relative to controls. OCD patients did not differ from controls or patients with ADHD. Patients with ADHD and OCD showed predominantly shared activation deficits during TD in fronto-striato-insular-cerebellar regions responsible for self-control and temporal foresight, suggesting that choice impulsivity is mediated by overlapping neural dysfunctions in both disorders. OCD patients alone showed dysfunction relative to controls in right orbitofrontal and rostrolateral prefrontal cortex, extending previous findings of abnormalities in these regions in OCD to the domain of choice impulsiveness