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Arns M.,University Utrecht | Arns M.,Research Institute Brainclinics | Feddema I.,Research Institute Brainclinics | Kenemans J.L.,University Utrecht
Frontiers in Human Neuroscience | Year: 2014

Recent studies suggest a role for sleep and sleep problems in the etiology of attention deficit hyperactivity disorder (ADHD) and a recent model about the working mechanism of sensori-motor rhythm (SMR) neurofeedback, proposed that this intervention normalizes sleep and thus improves ADHD symptoms such as inattention and hyperactivity/impulsivity. In this study we compared adult ADHD patients (N = 19) to a control group (N = 28) and investigated if differences existed in sleep parameters such as Sleep Onset Latency (SOL), Sleep Duration (DUR) and overall reported sleep problems (PSQI) and if there is an association between sleep-parameters and ADHD symptoms. Secondly, in 37 ADHD patients we investigated the effects of SMR and Theta/Beta (TBR) neurofeedback on ADHD symptoms and sleep parameters and if these sleep parameters may mediate treatment outcome to SMR and TBR neurofeedback. In this study we found a clear continuous relationship between self-reported sleep problems (PSQI) and inattention in adults with- and without-ADHD. TBR neurofeedback resulted in a small reduction of SOL, this change in SOL did not correlate with the change in ADHD symptoms and the reduction in SOL only happened in the last half of treatment, suggesting this is an effect of symptom improvement not specifically related to TBR neurofeedback. SMR neurofeedback specifically reduced the SOL and PSQI score, and the change in SOL and change in PSQI correlated strongly with the change in inattention, and the reduction in SOL was achieved in the first half of treatment, suggesting the reduction in SOL mediated treatment response to SMR neurofeedback. Clinically, TBR and SMR neurofeedback had similar effects on symptom reduction in ADHD (inattention and hyperactivity/impulsivity). These results suggest differential effects and different working mechanisms for TBR and SMR neurofeedback in the treatment of ADHD © 2014 Arns, Feddema and Kenemans.


Arns M.,Research Institute Brainclinics | Arns M.,University Utrecht | Cerquera A.,Antonio Nariño University | Gutierrez R.M.,Antonio Nariño University | And 2 more authors.
Clinical Neurophysiology | Year: 2014

Objective: Several linear electroencephalographic (EEG) measures at baseline have been demonstrated to be associated with treatment outcome after antidepressant treatment. In this study we investigated the added value of non-linear EEG metrics in the alpha band in predicting treatment outcome to repetitive transcranial magnetic stimulation (rTMS). Methods: Subjects were 90 patients with major depressive disorder (MDD) and a group of 17 healthy controls (HC). MDD patients were treated with rTMS and psychotherapy for on average 21 sessions. Three non-linear EEG metrics (Lempel-Ziv Complexity (LZC); False Nearest Neighbors and Largest Lyapunov Exponent) were applied to the alpha band (7-13. Hz) for two 1-min epochs EEG and the association with treatment outcome was investigated. Results: No differences were found between a subgroup of unmedicated MDD patients and the HC. Non-responders showed a significant decrease in LZC from minute 1 to minute 2, whereas the responders and HC showed an increase in LZC. Conclusions: There is no difference in EEG complexity between MDD and HC and the change in LZC across time demonstrated value in predicting outcome to rTMS. Significance: This is the first study demonstrating utility of non-linear EEG metrics in predicting treatment outcome in MDD. © 2013 International Federation of Clinical Neurophysiology.


Van Tricht M.J.,University of Amsterdam | Ruhrmann S.,University of Cologne | Arns M.,Research Institute Brainclinics | Arns M.,University Utrecht | And 12 more authors.
Schizophrenia Research | Year: 2014

Background: Prediction studies in subjects at Clinical High Risk (CHR) for psychosis are hampered by a high proportion of uncertain outcomes. We therefore investigated whether quantitative EEG (QEEG) parameters can contribute to an improved identification of CHR subjects with a later conversion to psychosis. Methods: This investigation was a project within the European Prediction of Psychosis Study (EPOS), a prospective multicenter, naturalistic field study with an 18-month follow-up period. QEEG spectral power and alpha peak frequencies (APF) were determined in 113 CHR subjects. The primary outcome measure was conversion to psychosis. Results: Cox regression yielded a model including frontal theta (HR = 1.82; [95% CI 1.00-3.32]) and delta (HR = 2.60; [95% CI 1.30-5.20]) power, and occipital-parietal APF (HR = .52; [95% CI .35-.80]) as predictors of conversion to psychosis. The resulting equation enabled the development of a prognostic index with three risk classes (hazard rate 0.057 to 0.81). Conclusions: Power in theta and delta ranges and APF contribute to the short-term prediction of psychosis and enable a further stratification of risk in CHR samples. Combined with (other) clinical ratings, EEG parameters may therefore be a useful tool for individualized risk estimation and, consequently, targeted prevention. © 2014 Elsevier B.V.


Spronk D.,Research Institute Brainclinics | Arns M.,Research Institute Brainclinics | Arns M.,University Utrecht | Barnett K.J.,Brain Resource | And 2 more authors.
Journal of Affective Disorders | Year: 2011

The aim of this study was to investigate if biomarkers in QEEG, genetic and neuropsychological measures are suitable for the prediction of antidepressant treatment outcome in depression. Twenty-five patients diagnosed with major depressive disorder were assessed twice, pretreatment and at 8-wk follow-up, on a variety of QEEG and neuropsychological tasks. Additionally, cheek swab samples were collected to assess genetic predictors of treatment outcome. The primary outcome measure was the absolute decrease on the HAM-D rating scale. Regression models were built in order to investigate which markers contribute most to the decrease in absolute HAM-D scores. Patients who had a better clinical outcome were characterized by a decrease in the amplitude of the Auditory Oddball N1 at baseline. The 'Met/Met' variant of the COMT gene was the best genetic predictor of treatment outcome. Impaired verbal memory performance was the best cognitive predictor. Raised frontal Theta power was the best EEG predictor of change in HAM-D scores. A tentative integrative model showed that a combination of N1 amplitude at Pz and verbal memory performance accounted for the largest part of the explained variance. These markers may serve as new biomarkers suitable for the prediction of antidepressant treatment outcome. © 2010 Elsevier B.V. All rights reserved.


van Dinteren R.,Research Institute Brainclinics | van Dinteren R.,Radboud University Nijmegen | Arns M.,Research Institute Brainclinics | Arns M.,University Utrecht | And 3 more authors.
Frontiers in Aging Neuroscience | Year: 2014

In the present study the frontal and parietal P300, elicited in an auditory oddball paradigm were investigated in a large sample of healthy participants (N = 1572), aged 6-87. According to the concepts of the compensation-related utilization of neural circuits hypothesis (CRUNCH) it was hypothesized that the developmental trajectories of the frontal P300 would reach a maximum in amplitude at an older age than the amplitude of the parietal P300 amplitude. In addition, the amplitude of the frontal P300 was expected to increase with aging in adulthood in contrast to a decline in amplitude of the parietal P300 amplitude. Using curve-fitting methods, a comparison was made between the developmental trajectories of the amplitudes of the frontal and parietal P300. It was found that the developmental trajectories of frontal and parietal P300 amplitudes differed significantly across the lifespan. During adulthood, the amplitude of the parietal P300 declines with age, whereas both the frontal P300 amplitude and behavioral performance remain unaffected. A lifespan trajectory of combined frontal and parietal P300 amplitudes was found to closely resemble the lifespan trajectory of behavioral performance. Our results can be understood within the concepts of CRUNCH. That is, to compensate for declining neural resources, older participants recruit additional neural resources of prefrontal origin and consequently preserve a stable behavioral performance. Though, a direct relation between amplitude of the frontal P300 and compensatory mechanisms cannot yet be claimed. © 2014 van Dinteren, Arns, Jongsma and Kessels.


Jongsma M.L.A.,Radboud University Nijmegen | Postma S.A.E.,Radboud University Nijmegen | Souren P.,Radboud University Nijmegen | Arns M.,Research Institute Brainclinics | And 5 more authors.
PLoS ONE | Year: 2011

Chronic pain has been associated with impaired cognitive function. We examined cognitive performance in patients with severe chronic pancreatitis pain. We explored the following factors for their contribution to observed cognitive deficits: pain duration, comorbidity (depression, sleep disturbance), use of opioids, and premorbid alcohol abuse. The cognitive profiles of 16 patients with severe pain due to chronic pancreatitis were determined using an extensive neuropsychological test battery. Data from three cognitive domains (psychomotor performance, memory, executive functions) were compared to data from healthy controls matched for age, gender and education. Multivariate multilevel analysis of the data showed decreased test scores in patients with chronic pancreatitis pain in different cognitive domains. Psychomotor performance and executive functions showed the most prominent decline. Interestingly, pain duration appeared to be the strongest predictor for observed cognitive decline. Depressive symptoms, sleep disturbance, opioid use and history of alcohol abuse provided additional explanations for the observed cognitive decline in some of the tests, but to a lesser extent than pain duration. The negative effect of pain duration on cognitive performance is compatible with the theory of neurodegenerative properties of chronic pain. Therefore, early and effective therapeutic interventions might reduce or prevent decline in cognitive performance, thereby improving outcomes and quality of life in these patients. © 2011 Jongsma et al.


Dinteren R.,Research Institute Brainclinics | Dinteren R.,Radboud University Nijmegen | Arns M.,Research Institute Brainclinics | Arns M.,University Utrecht | And 2 more authors.
PLoS ONE | Year: 2014

Background: The P300 component of the event-related potential is a large positive waveform that can be extracted from the ongoing electroencephalogram using a two-stimuli oddball paradigm, and has been associated with cognitive information processing (e.g. memory, attention, executive function). This paper reviews the development of the auditory P300 across the lifespan. Methodology/Principal Findings: A systematic review and meta-analysis on the P300 was performed including 75 studies (n = 2,811). Scopus was searched for studies using healthy subjects and that reported means of P300 latency and amplitude measured at Pz and mean age. These findings were validated in an independent, existing cross-sectional dataset including 1,572 participants from ages 6-87. Curve-fitting procedures were applied to obtain a model of P300 development across the lifespan. In both studies logarithmic Gaussian models fitted the latency and amplitude data best. The P300 latency and amplitude follow a maturational path from childhood to adolescence, resulting in a period that marks a plateau, after which degenerative effects begin. We were able to determine ages that mark a maximum (in P300 amplitude) or trough (in P300 latency) segregating maturational from degenerative stages. We found these points of deflection occurred at different ages. Conclusions/Significance: It is hypothesized that latency and amplitude index different aspects of brain maturation. The P300 latency possibly indexes neural speed or brain efficiency. The P300 amplitude might index neural power or cognitive resources, which increase with maturation. © 2014 van Dinteren et al.


Olbrich S.,University of Leipzig | Arns M.,University Utrecht | Arns M.,Research Institute Brainclinics
International Review of Psychiatry | Year: 2013

Major depressive disorder (MDD) has high population prevalence and is associated with substantial impact on quality of life, not least due to an unsatisfactory time span of sometimes several weeks from initiation of treatment to clinical response. Therefore extensive research focused on the identification of cost-effective and widely available electroencephalogram (EEG)-based biomarkers that not only allow distinguishing between patients and healthy controls but also have predictive value for treatment response for a variety of treatments. In this comprehensive overview on EEG research on MDD, biomarkers that are either assessed at baseline or during the early course of treatment and are helpful in discriminating patients from healthy controls and assist in predicting treatment outcome are reviewed, covering recent decades up to now. Reviewed markers include quantitative EEG (QEEG) measures, connectivity measures, EEG vigilance-based measures, sleep-EEG-related measures and event-related potentials (ERPs). Further, the value and limitations of these different markers are discussed. Finally, the need for integrated models of brain function and the necessity for standardized procedures in EEG biomarker research are highlighted to enhance future research in this field. © 2013 Institute of Psychiatry.


Arns M.,Research Institute Brainclinics | Arns M.,University Utrecht | Drinkenburg W.H.,Janssen Research and Development | Fitzgerald P.B.,Monash University | Kenemans J.L.,University Utrecht
Brain Stimulation | Year: 2012

Background: The application of rTMS in Depression has been very well investigated over the last few years. However, little is known about predictors of non-response associated with rTMS treatment. Objective: This study examined neurophysiological parameters (EEG and ERP) in 90 depressed patients treated with rTMS and psychotherapy and sought to identify predictors of non-response. Methods: This study is a multi-site open-label study assessing pre-treatment EEG and ERP measures associated with non-response to rTMS treatment. Results: Non-responders were characterized by 1) Increased fronto-central theta EEG power, 2) a slower anterior individual alpha peak frequency, 3) a larger P300 amplitude, and 4) decreased pre-frontal delta and beta cordance. A discriminant analysis yielded a significant model, and subsequent ROC curve demonstrated an area under the curve of 0.814. Conclusions: Several EEG variables demonstrated clear differences between R and NR such as the anterior iAPF, fronto-central Theta and pre-frontal cordance in the Delta and Beta band (representative of increased relative pre-frontal perfusion). The increased P300 amplitude as a predictor for non-response requires further study, since this was the opposite as hypothesized and there were no correlations of this measure with clinical improvement for the whole sample. Combining these biomarkers in a discriminant analysis resulted in a reliable identification of non-responders with low false positive rates. Future studies should prospectively replicate these findings and also further investigate appropriate treatments for the sub-groups of non-responders identified in this study, given that most of these biomarkers have also been found in antidepressant medication studies. © 2012 Elsevier Inc. All rights reserved.


Arns M.,University Utrecht | Arns M.,Research Institute Brainclinics | Kenemans J.L.,University Utrecht
Neuroscience and Biobehavioral Reviews | Year: 2014

In this review article an overview of the history and current status of neurofeedback for the treatment of ADHD and insomnia is provided. Recent insights suggest a central role of circadian phase delay, resulting in sleep onset insomnia (SOI) in a sub-group of ADHD patients. Chronobiological treatments, such as melatonin and early morning bright light, affect the suprachiasmatic nucleus. This nucleus has been shown to project to the noradrenergic locus coeruleus (LC) thereby explaining the vigilance stabilizing effects of such treatments in ADHD. It is hypothesized that both Sensori-Motor Rhythm (SMR) and Slow-Cortical Potential (SCP) neurofeedback impact on the sleep spindle circuitry resulting in increased sleep spindle density, normalization of SOI and thereby affect the noradrenergic LC, resulting in vigilance stabilization. After SOI is normalized, improvements on ADHD symptoms will occur with a delayed onset of effect. Therefore, clinical trials investigating new treatments in ADHD should include assessments at follow-up as their primary endpoint rather than assessments at outtake. Furthermore, an implication requiring further study is that neurofeedback could be stopped when SOI is normalized, which might result in fewer sessions. © 2012 Elsevier Ltd.

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