Der Einfluss von präfrontaler Gleichstromstimulation (tDCS) auf EEG- und fMRT-Ruhenetzwerke

Das Hauptziel der vorliegenden Dissertation war die Untersuchung des Einflusses der präfrontalen Gleichstromstimulation (tDCS) auf die mögliche Modulation kortikaler Netzwerke. Grundlage dieser kumulativen Dissertation sind die Publikationen: - Keeser D, Padberg F, Reisinger E, Pogarell O, Kirsch V, Palm U, Karch S, Möller HJ, Nitsche MA, Mulert C. Prefrontal direct current stimulation modulates resting EEG and event-related potentials in healthy subjects: a standardized low resolution tomography (sLORETA) study. Neuroimage. 2011 Mar 15;55(2):644-57. - Keeser D, Meindl T, Bor J, Palm U, Pogarell O, Mulert C, Brunelin J, Möller HJ, Reiser M, Padberg F. Prefrontal Transcranial Direct Current Stimulation Changes Connectivity of Resting-State Networks during fMRI. Journal of Neuroscience. 2011 Oct 26;31(43):15284-93. Beide Studien wurden doppelt-verblindet und plazebo-kontrolliert durchgeführt. In den Arbeiten wird mit zwei unterschiedlichen Verfahren, einem neurophysiolo-gischen Ruhe- und einem aktiven Gedächtnistestparadigma (EEG), sowie mit einer funktionellen Konnektivitäts-Magnetresonanztomographie (fcMRT) nachgewiesen, dass präfrontale tDCS kortikale Netzwerke moduliert. Diese Ergebnisse sollen hier wiedergegeben und diskutiert werden. Die Verteilung, Ausrichtung und das Aus-maß der auf tDCS beruhenden Effekte auf die Gehirnphysiologie sind bisher wenig erforscht. Die Erarbeitung weiterer spezifischer Hypothesen bezüglich der neuro-physiologischen Wirkung von präfrontaler tDCS ist entscheidend, um Hinweise auf künftige experimentelle und therapeutische tDCS-Anwendungen zu erhalten.The principal purpose of the present thesis was to investigate the influence of prefrontal direct current stimulation (tDCS) on the modulation of cortical networks. The bases of this cumulative thesis are the two publications: - Keeser D, Padberg F, Reisinger E, Pogarell O, Kirsch V, Palm U, Karch S, Möller HJ, Nitsche MA, Mulert C. Prefrontal direct current stimulation modulates resting EEG and event-related potentials in healthy subjects: a standardized low resolution tomography (sLORETA) study. Neuroimage. 2011 Mar 15;55(2):644-57. - Keeser D, Meindl T, Bor J, Palm U, Pogarell O, Mulert C, Brunelin J, Möller HJ, Reiser M, Padberg F. Prefrontal Transcranial Direct Current Stimulation Changes Connectivity of Resting-State Networks during fMRI. Journal of Neuroscience. 2011 Oct 26;31(43):15284-93. Both studies were carried out in a double-blinded, placebo-controlled manner. In the studies two different procedures, a neurophysiological electroencephalog-raphy (EEG) resting-state and an active EEG memory task paradigm, as well as a functional connectivity magnetic resonance imaging (fcMRI) procedure were used. Both studies proved that prefrontal tDCS modulates cortical networks. These results are presented and discussed. The distribution, direction, and extent of tDCS mediated effects on brain physiology are not well understood. The development of further hypotheses with regard to the neurophysiological effects of prefrontal tDCS is crucial to obtain informations for future experimental and therapeutic tDCS applica-tions

There is no magic in speaker policies : creating gender equality at brain stimulation conferences Editorial II to the supplement from the 2nd European Conference on brain stimulation in psychiatry

Non peer reviewe

The COVID-19 Pandemic Mental Health Questionnaire (CoPaQ): psychometric evaluation and compliance with countermeasures in psychiatric inpatients and non-clinical individuals

BACKGROUND The COVID-19 pandemic has greatly impacted people's lives across a broad spectrum of psychosocial domains. We report the development and psychometric evaluation of the self-report COVID-19 Pandemic Mental Health Questionnaire (CoPaQ), which assesses COVID-19 contamination anxiety, countermeasure necessity and compliance, mental health impact, stressor impact, social media usage, interpersonal conflicts, paranoid ideations, institutional & political trust, conspiracy beliefs, and social cohesion. Further, we illustrate the questionnaire's utility in an applied example investigating if higher SARS-Cov-2 infection rates in psychiatric patients could be explained by reduced compliance with preventive countermeasures. METHODS A group of 511 non-clinical individuals completed an initial pool of 111 CoPaQ items (Open Science Framework: https://osf.io/3evn9/ ) and additional scales measuring psychological distress, well-being, and paranoia to assess construct validity and lifetime mental health diagnosis for criterion validity. Factor structure was determined by exploratory factor analyses and validated by conducting confirmatory factor analysis in the accompanying longitudinal sample (n~= 318) and an independent psychiatric inpatient sample primarily admitted for major depressive-, substance abuse-, personality-, and anxiety disorders (n~= 113). Internal consistency was assessed by Cronbach's Alpha and McDonald's Omega. For the applied research example, Welch t-tests and correlational analyses were conducted. RESULTS Twelve out of 16 extracted subscales were retained in the final questionnaire version, which provided preliminary evidence for adequate psychometric properties in terms of factor structure, internal consistency, and construct and criterion validity. Our applied research example showed that patients exhibited greater support for COVID-19 countermeasures than non-clinical individuals. However, this requires replication in future studies. CONCLUSIONS We demonstrate that the CoPaQ is a comprehensive and valid measure of the psychosocial impact of the pandemic and could allow to a degree to disentangle the complex psychosocial phenomena of the pandemic as exemplified by our applied analyses

Intrinsic network activity reflects the ongoing experience of chronic pain

Analyses of intrinsic network activity have been instrumental in revealing cortical processes that are altered in chronic pain patients. In a novel approach, we aimed to elucidate how intrinsic functional networks evolve in regard to the fluctuating intensity of the experience of chronic pain. In a longitudinal study with 156 fMRI sessions, 20 chronic back pain patients and 20 chronic migraine patients were asked to continuously rate the intensity of their endogenous pain. We investigated the relationship between the fluctuation of intrinsic network activity with the time course of subjective pain ratings. For chronic back pain, we found increased cortical network activity for the salience network and a local pontine network, as well as decreased network activity in the anterior and posterior default mode network for higher pain intensities. Higher pain intensities in chronic migraine were accompanied with lower activity in a prefrontal cortical network. By taking the perspective of the individual, we focused on the variability of the subjective perception of pain, which include phases of relatively low pain and phases of relatively high pain. The present design of the assessment of ongoing endogenous pain can be a powerful and promising tool to assess the signature of a patient's endogenous pain encoding

Prediction of Treatment Outcome in Patients with Obsessive-Compulsive Disorder with Low-Resolution Brain Electromagnetic Tomography: A Prospective EEG Study

The issue of predicting treatment response and identifying, in advance, which patient will profit from treating obsessive-compulsive disorder (OCD) seems to be an elusive goal. This prospective study investigated brain electric activity [using Low-Resolution Brain Electromagnetic Tomography (LORETA)] for the purpose of predicting response to treatment. Forty-one unmedicated patients with a DSM-IV diagnosis of OCD were included. A resting 32-channel EEG was obtained from each participant before and after 10 weeks of standardized treatment with sertraline and behavioral therapy. LORETA was used to localize the sources of brain electrical activity. At week 10, patients were divided into responders and non-responders (according to a reduction of symptom severity > 50% on the Y-BOCS). LORETA analysis revealed that at baseline responders showed compared to non-responders a significantly lower brain electric activity within the beta 1 (t = 2.86, p < 0.05), 2 (t = 2.81, p < 0.05), and 3 (t = 2.76, p < 0.05) frequency bands and ROI analysis confirmed a reduced activity in alpha 2 (t = 2.06, p < 0.05) in the anterior cingulate cortex (ACC). When baseline LORETA data were compared to follow-up data, the analysis showed in the responder group a significantly lower brain electrical resting activity in the beta 1 (t = 3.17. p < 0.05) and beta 3 (t = 3.11. p < 0.05) frequency bands and equally for the ROI analysis of the orbitofrontal cortex (OFC) in the alpha 2 (t = 2.15. p < 0.05) frequency band. In the group of non responders the opposite results were found. In addition, a positive correlation between frequency alpha 2 (rho = 0.40, p = 0.010), beta 3 (rho = 0.42, p = 0.006), delta (rho = 0.33, p = 0.038), theta (rho = 0.34, p = 0.031), alpha 1 (rho = 0.38, p = 0.015), and betal (rho = 0.34, p = 0.028) of the OFC and the bands delta (rho = 0.33, p = 0.035), alpha 1 (rho = 0.36, p = 0.019), alpha 2 (rho = 0.34, p = 0.031), and beta 3 (rho = 0.38, p = 0.015) of the ACC with a reduction of the Y-BOGS scores was identified. Our results suggest that measuring brain activity with LORETA could be an efficient and applicable technique to prospectively identify treatment responders in OCD

Anodal transcranial direct current stimulation sustainably increases EEG alpha activity in patients with schizophrenia

Abstract Aims Transcranial direct current stimulation (tDCS) applied to the prefrontal cortex has been frequently used to elicit behavioral changes in patients with schizophrenia. However, the interaction between prefrontal tDCS and electrophysiological changes remains largely uncharted. The present study aimed to investigate cortical electrophysiological changes induced by tDCS in frontal areas by means of repeated electroencephalography (EEG) in patients with schizophrenia. Methods In total, 20 patients with schizophrenia received 13 minutes of anodal tDCS (1 mA) applied to the left dorsolateral prefrontal cortex (DLPFC). Repeated resting EEG was recorded before (once) and following (at five follow‐up time‐bins) tDCS to trace post‐tDCS effects. We used sLORETA for source reconstruction to preserve the localization of brain signals with a low variance and to analyze frequency changes. Results We observed significant changes after the stimulation in areas highly connected with the stimulated DLPFC areas. The alpha 1 (8.5‐10.0 Hz) activity showed a highly significant, long‐lasting, increase for up to 1 hour after the stimulation in the postcentral gyrus (Brodmann area 2, 3, and 40). Significant yet unstable changes were also seen in the alpha‐2 frequency band precentral at 10 minutes, in the beta‐1 frequency band occipital at 20 minutes, and in the beta‐3 frequency band temporal at 40 minutes. Conclusion We were able to show that anodal tDCS can induce stable EEG changes in patients with schizophrenia. The results underline the potential of tDCS to induce long‐lasting neurophysiological changes in patients with schizophrenia showing the possibility to induce brain excitability changes in this population

Concurrent TMS-fMRI: Technical Challenges, Developments, and Overview of Previous Studies

Transcranial magnetic stimulation (TMS) is a promising treatment modality for psychiatric and neurological disorders. Repetitive TMS (rTMS) is widely used for the treatment of psychiatric and neurological diseases, such as depression, motor stroke, and neuropathic pain. However, the underlying mechanisms of rTMS-mediated neuronal modulation are not fully understood. In this respect, concurrent or simultaneous TMS-fMRI, in which TMS is applied during functional magnetic resonance imaging (fMRI), is a viable tool to gain insights, as it enables an investigation of the immediate effects of TMS. Concurrent application of TMS during neuroimaging usually causes severe artifacts due to magnetic field inhomogeneities induced by TMS. However, by carefully interleaving the TMS pulses with MR signal acquisition in the way that these are far enough apart, we can avoid any image distortions. While the very first feasibility studies date back to the 1990s, recent developments in coil hardware and acquisition techniques have boosted the number of TMS-fMRI applications. As such, a concurrent application requires expertise in both TMS and MRI mechanisms and sequencing, and the hurdle of initial technical set up and maintenance remains high. This review gives a comprehensive overview of concurrent TMS-fMRI techniques by collecting (1) basic information, (2) technical challenges and developments, (3) an overview of findings reported so far using concurrent TMS-fMRI, and (4) current limitations and our suggestions for improvement. By sharing this review, we hope to attract the interest of researchers from various backgrounds and create an educational knowledge base

Differences in electric field strength between clinical and non-clinical populations induced by prefrontal tDCS: a cross-diagnostic, individual MRI-based modeling study

Introduction: Prefrontal cortex (PFC) regions are promising targets for therapeutic applications of non-invasive brain stimulation, e.g. transcranial direct current stimulation (tDCS), which has been proposed as a novel intervention for major depressive disorder (MDD) and negative symptoms of schizophrenia (SCZ). However, the effects of tDCS vary inter-individually, and dose-response relationships have not been established. Stimulation parameters are often tested in healthy subjects and transferred to clinical populations. The current study investigates the variability of individual MRI-based electric fields (e-fields) of standard bifrontal tDCS across individual subjects and diagnoses.Method: The study included 74 subjects, i.e. 25 patients with MDD, 24 patients with SCZ, and 25 healthy controls (HC). Individual e-fields of a common tDCS protocol (i.e. 2 mA stimulation intensity, bifrontal anode-F3/ cathode-F4 montage) were modeled by two investigators using SimNIBS (2.0.1) based on structural MRI scans.Result: On a whole-brain level, the average e-field strength was significantly reduced in MDD and SCZ compared to HC, but MDD and SCZ did not differ significantly. Regions of interest (ROI) analysis for PFC subregions showed reduced e-fields in Sallet areas 8B and 9 for MDD and SCZ compared to HC, whereas there was again no difference between MDD and SCZ. Within groups, we generally observed high inter-individual variability of e-field intensities at a higher percentile of voxels.Conclusion: MRI-based e-field modeling revealed significant differences in e-field strengths between clinical and non-clinical populations in addition to a general inter-individual variability. These findings support the notion that dose-response relationships for tDCS cannot be simply transferred from healthy to clinical cohorts and need to be individually established for clinical groups. In this respect, MRI-based e-field modeling may serve as a proxy for individualized dosing