Running effects on cognition and plasticity (ReCaP): study protocol of a longitudinal examination of multimodal adaptations of marathon running.

Regular moderate physical activity (PA) has been linked to beneficial adaptations in various somatic diseases (e.g. cancer, endocrinological disorders) and a reduction in all-cause mortality from several cardiovascular and neuropsychiatric diseases. This study was designed to investigate acute and prolonged exercise-induced cardio- and neurophysiological responses in endurance runners competing in the Munich Marathon. ReCaP (Running effects on Cognition and Plasticity) is a multimodal and longitudinal experimental study. This study included 100 participants (20-60 years). Six laboratory visits were included during the 3-month period before and the 3-month period after the Munich marathon. The multimodal assessment included laboratory measurements, cardiac and cranial imaging (MRI scans, ultrasound/echocardiography) and neurophysiological methods (EEG and TMS/tDCS), and vessel-analysis (e.g. retinal vessels and wave-reflection analyses) and neurocognitive measurements. The ReCaP study was designed to examine novel exercise-induced cardio- and neurophysiological responses to marathon running at the behavioral, functional and morphological levels. This study will expand our understanding of exercise-induced adaptations and will lead to more individually tailored therapeutic options.

Exploring socio-economic inequalities in the use of medicines: is the relation mediated by health status?

OBJECTIVES: This study evaluated mediating effects of the health status on the association between socio-economic status (SES) and medicine use. It was hypothesized that more privileged people show a reduced use of medicines, as compared with the underprivileged, because of their superior health status. It was further hypothesized that people may apply medication based on their type of health complaint (ill physical versus mental status). STUDY DESIGN: Data were taken from the 2012 German Epidemiological Survey of Substance Abuse, a nationally representative cross-sectional study of n = 9084 individuals of the German general population aged 18-64 years. METHODS: Direct and indirect effects of SES on weekly use of analgesics and sedatives/hypnotics were examined by applying generalized structural equation modeling. Self-rated physical and mental health statuses were considered as potential mediators. SES was measured by using educational level as a proxy. All analyses were gender-stratified. RESULTS: Among men, both physical and mental health mediated the path from SES to the use of analgesics and sedatives/hypnotics, respectively, with a stronger effect of physical health on analgesic use and mental health on sedative/hypnotic use. These effects were only partially found among women. CONCLUSIONS: Social inequalities in health seem to have substantial impact on the prevalence of medicine use. Identification and elimination of the reasons for poor health among people of low SES may, therefore, not only help to reduce health inequalities directly. A decline in the use of medicines would also result in less side-effects and a reduced number of people with medicine-related misuse and addiction.

EEG-neurofeedback training and quality of life of institutionalized elderly women (a pilot study).

This pilot study attempted to study the applicability of neurofeedback for elderly persons living in nursing homes. We hypothesized an improve of cognitive functioning and the independence in daily life (IDL) of elderly people by using low beta (12-15HZ) EEG neurofeedback training (E-NFT). The participants (active E-NFT group, n=10; control group, n=6) were community living elderly women without dementia. Neurofeedback training was adjusted ten times within 9 weeks, with a training duration of 21 minutes by use of a single electrode, which was centrally placed on the skull surface. Executive functioning (measured with the Rey and fluency tasks), memory capacity (measured with the 15 words test), and IDL (measured with the Groningen Activity Restriction Scale) were measured before and after ten E-NFT sessions in nine weeks. No effects were found for IDL nor executive functioning. Interestingly, performance on the memory test improved in the experimental group, indicating a possible positive effect of E-NFT on memory in elderly women. This study demonstrates that E-NFT is applicable to older institutionalized women. The outcome of this pilot-study justifies the investigation of possible memory effects in future studies.

[Healthcare models for traumatized refugees in Germany]. / Versorgungsmodelle für traumatisierte Flüchtlinge in Deutschland.

People with a migration background are a risk group for psychiatric disorders. Innovative, transnational and sustainable projects are necessary to ensure adequate care for refugees and asylum seekers. Selected projects of the University of Munich, the Charité Berlin and the University of Konstanz show promising approaches in addition to other initiatives.

[Psychiatric care of refugees in Africa and the Middle East : Challenges and solutions]. / Psychiatrische Versorgung von Flüchtlingen in Afrika und dem Nahen Osten : Herausforderungen und Lösungsansätze.

Violence, flight, famine, and natural disasters as well as the absence of a psychosocial healthcare system are major psychological burdens for refugees. The level of provision of mental healthcare is particularly low in developing countries. Internally displaced people and refugees place high demands on the healthcare system because they often suffer from psychiatric disorders, such as depression, posttraumatic stress disorder, and substance use disorders. We present first initiatives to improve psychiatric care in refugee camps in Ethiopia, Kenya, and Sudan. Moreover, we provide first insights into a project based in Northern Iraq and Germany aimed at the treatment of people who were severely traumatized by the terror regime of the so-called Islamic State (IS).

[Coercive measures in German hospitals for psychiatry and psychotherapy : A pilot study by the DGPPN to evaluate a uniform assessment instrument]. / Zwangsmaßnahmen in deutschen Kliniken für Psychiatrie und Psychotherapie : Eine Pilotstudie der DGPPN zur Erprobung eines einheitlichen Erfassungsinstrumentes.

STUDY OBJECTIVE: A simple instrument to record case-related coercive measures was tested as part of a pilot project of the German Association for Psychiatry, Psychotherapy and Psychosomatics (DGPPN). METHODS: To assess coercive measures data were collected for 3 months in 8 German hospitals for psychiatry and psychotherapy. The type of measures used, the main diagnosis and the legal basis for the coercive measures were documented. RESULTS: In the sample studied, coercive measures were applied in 8% of cases. Coercive measures were most commonly used in patients with a schizophrenic disorder. The principle of justifiable necessity according to § 34 of the German Penal Code was used particularly often as the legal basis for justifying the coercive measures. CONCLUSION: Suitable measurement instruments and reliable data that enable the learning of best practices represent the basis for a reduction of coercive measures.

Neurofeedback for alcohol addiction: Changes in resting state network activity✰.

Alcohol dependence continues to be a major global burden despite significant research progress and treatment development. The aim of this study was to investigate whether neurofeedback training can alter resting state fMRI activity in brain regions that play a crucial role in addiction disorders in patients with alcohol dependence. For this purpose, a total of 52 patients were recruited for the present study, randomized, and divided into an active and a sham group. Patients in the active group received three sessions of neurofeedback training. We compared the resting state data in the active group as part of the NF training on six measurement days. When comparing the results of the active group from neurofeedback day 3 with baseline 1, a significant reduction in activated voxels in the ventral attention network area was seen. This suggests that reduced activity over the course of therapy in subjects may lead to greater independence from external stimuli. Overall, a global decrease in activated voxels within all three analysed networks compared to baseline was observed in the study. The use of resting-state data as potential biomarkers, as activity changes within these networks, may be to help restore cognitive processes and alcohol abuse-related craving and emotions.

Comparative electroencephalography analysis: Marathon runners during tapering versus sedentary controls reveals no significant differences.

INTRODUCTION: Previous studies described various adaptive neuroplastic brain changes associated with physical activity (PA). EEG studies focused mostly on effects during or shortly after short bouts of exercise. This is the first study to investigate the capability of EEG to display PA-induced long-lasting plasticity in runners compared to a sedentary control group. METHODS: Thirty trained runners and 30 age- and sex-matched sedentary controls (SC) were included as a subpopulation of the ReCaP (Running effects on Cognition and Plasticity) study. PA was measured with the International Physical Activity Questionnaire (IPAQ). Resting-state EEG of the runners was recorded in the tapering phase of the training for the Munich marathon 2017. Power spectrum analyses were conducted using standardized low-resolution electromagnetic tomography (sLORETA) and included the following frequency bands: delta: 1.5-6 Hz, theta: 6.5-8.0 Hz, alpha1: 8.5-10 Hz, alpha2: 10.5-12.0 Hz, beta1: 12.5-18.0 Hz, beta2: 18.5-21.0 Hz, beta3: 21.5-30.0 Hz, and total power (1.5-30 Hz). RESULTS: PA (IPAQ) and BMI differed significantly between the groups. The other included demographic parameters were comparable. Statistical nonparametric mapping showed no significant power differences in EEG between the groups. DISCUSSION: Heterogeneity in study protocols, especially in time intervals between exercise cessation and EEG recordings and juxtaposition of acute exercise-induced effects on EEG in previous studies, could be possible reasons for the differences in results. Future studies should record EEG at different time points after exercise cessation and in a broader spectrum of exercise intensities and forms to further explore the capability of EEG in displaying long-term exercise-induced plasticity.

Enhancing educational and vocational recovery in adolescents and young adults with early psychosis through Supported Employment and Education (SEEearly): study protocol for a multicenter randomized controlled trial.

BACKGROUND: Psychotic disorders often develop a chronic course with devastating consequences for individuals, families, and societies. Early intervention programs for people in the first 5 years after the initial psychotic episode (early psychosis) can significantly improve the outcome and are therefore strongly recommended in national and international guidelines. However, most early intervention programs still focus on improving symptoms and relapse prevention, rather than targeting educational and vocational recovery. The aim of the present study is to explore the effects of Supported Employment and Education (SEE) following the Individual Placement and Support (IPS) model in people with early psychosis. METHODS: The SEEearly trial compares treatment as usual (TAU) plus SEE to TAU alone in outpatient psychiatric settings. The study is a six-site, two-arm, single-blinded, superiority randomized controlled trial (RCT). Participants are randomly assigned (1:1) to the intervention or control group. Aiming to recruit 184 participants, with an assumed drop-out rate of 22%, we will be able to detect a 24% difference in the main outcome of employment/education with 90% power. We make assessments at baseline and at 6- and 12-month follow-ups. Outcome data on employment/education, medication, and current psychiatric treatment is obtained monthly through phone based short assessments. The primary outcome is steady participation for at least 50% of the 12-month follow-up in competitive employment and/or mainstream education. Secondary employment outcomes capture length of employment/education, time to first employment/education, monthly wages/educational attainment, and social return on investment (SROI). Secondary non-employment outcomes include subjective quality of life, psychopathology, substance use, relapse, hospitalization, and functional impairment. To be eligible, participants must be between 16 and 35 years, fulfill diagnostic criteria for early psychosis, and be interested in competitive employment and/or mainstream education. DISCUSSION: In SEEearly, we hypothesize that participants with psychosis, who receive TAU plus SEE, present with better primary and secondary outcomes than participants, who receive TAU alone. Positive results of this study will justify SEE as an evidence-based strategy for clinical routine treatment in people with early psychosis. TRIAL REGISTRATION: SEEearly was registered nationally and internationally in the German Clinical Trials Register (DRKS; identifier: DRKS00029660) on October 14, 2022.

Age effects on the P300 potential and the corresponding fMRI BOLD-signal.

Age has been reported to influence amplitude and latency of the P300 potential. Nevertheless, it is not yet fully understood which brain regions are responsible for these effects. The aim of this study was to investigate age-effects on the P300 potential and the simultaneously acquired BOLD signal of functional MRI. 32 healthy male subjects were investigated using an auditory oddball paradigm. The functional MRI data were acquired in temporal synchrony to the task. The evoked potential data were recorded during the intervals in between MR image acquisitions in order to reduce the influence of the scanner noise on the presentation of the tones and to reduce gradient artifacts. The age-effects were calculated by means of regression analyses. In addition, brain regions modulated by the task-induced amplitude variation of the P300 were identified (single trial analysis). The results indicated an age effect on the P300 amplitude. Younger subjects demonstrated increased parietal P300 amplitudes and increased BOLD responses in a network of brain regions including the anterior and posterior cingulate cortex, the insula, the temporo-parietal junction, the superior temporal gyrus, the caudate body, the amygdala and the parahippocampal gyrus. Single trial coupling of EEG and fMRI indicated that P300 amplitudes were predominantly associated with neural responses in the anterior cingulate cortex, the putamen and temporal brain areas. Taken together, the results indicate diminished neural responses in older compared to younger subjects especially in frontal, temporo-parietal and subcortical brain regions.

Computational modelling of schizophrenic symptoms: basic issues.

Emerging "(computational) systems medicine" challenges neuropsychiatry regarding the development of heuristic computational brain models which help to explore symptoms and syndromes of mental disorders. This methodology of exploratory modelling of mental functions and processes and of their pathology requires a clear and operational definition of the target variable (explanandum). In the case of schizophrenia, a complex and heterogeneous disorder, single psychopathological key symptoms such as working memory deficiency, hallucination or delusion need to be defined first. Thereafter, measures of brain structures can be used in a multilevel view as biological correlates of these symptoms. Then, in order to formally "explain" the symptoms, a qualitative model can be constructed. In another step, numerical values have to be integrated into the model and exploratory computer simulations can be performed. Normal and pathological functioning is to be tested in computer experiments allowing the formulation of new hypotheses and questions for empirical research. However, the crucial challenge is to point out the appropriate degree of complexity (or simplicity) of these models, which is required in order to achieve an epistemic value that might lead to new hypothetical explanatory models and could stimulate new empirical and theoretical research. Some outlines of these methodological issues are discussed here, regarding the fact that measurements alone are not sufficient to build models.

Dopaminergic neurotransmission in patients with schizophrenia in relation to positive and negative symptoms.

Schizophrenia is a complex dynamic disorder comprising a wide range of neurobiological alterations including dopaminergic dysfunction. The aim of the study was to investigate dynamic changes of dopaminergic neurotransmission in patients with schizophrenia (n=8, mean age 25.4 ± 5.8 years) in early stages of the disorder, compared to healthy control subjects (n=7, mean age 23.6 ± 2.7 years). A dynamic IBZM SPECT protocol was used to assess the endogenous dopamine release following an amphetamine challenge. Subjects received a bolus activity of 175 MBq followed by a continuous infusion of 45 MBq/h [123I]IBZM. SPECT scans were performed 2 h after bolus injection, and 1 h following the amphetamine challenge (0.3 mg/kg). Striatal IBZM binding to dopamine D2 receptors was assessed with a volume-of-interest (VOI) technique. The change in IBZM binding between pre- and post-challenge scans was used as a measure of endogenous dopamine release triggered by amphetamine. At baseline, patients showed higher mean striatal IBZM binding compared to controls (0.77 ± 0.09 vs. 0.68 ± 0.07, p=0.07). There was a statistically significant difference in IBZM binding between patients, with a predominance of negative vs. positive symptoms (0.84 ± 0.08 vs. 0.71 ± 0.04, p<0.05). Upon amphetamine challenge, mean IBZM binding decreased by about 4.9 ± 7.6% in controls (n=7) compared to a mean of 12.4 ± 5.8% in subjects with schizophrenia (p<0.05). In patients, paranoid symptoms showed a significant negative correlation with IBZM baseline binding, whereas there was a trend towards positive correlation with the decrease of IBZM binding under challenge. Negative symptoms showed positive associations with baseline IBZM binding. The data are in line with previous reports and contribute to the notion of a dynamic instability of the dopaminergic system in patients with schizophrenia, taking into account the psychopathology with respect to positive or negative symptoms.

Prefrontal direct current stimulation modulates resting EEG and event-related potentials in healthy subjects: a standardized low resolution tomography (sLORETA) study.

Prefrontal transcranial direct current stimulation (tDCS) with the anode placed on the left dorsolateral prefrontal cortex (DLPFC) has been reported to enhance working memory in healthy subjects and to improve mood in major depression. However, its putative antidepressant, cognitive and behavior action is not well understood. Here, we evaluated the distribution of neuronal electrical activity changes after anodal tDCS of the left DLPFC and cathodal tDCS of the right supraorbital region using spectral power analysis and standardized low resolution tomography (sLORETA). Ten healthy subjects underwent real and sham tDCS on separate days in a double-blind, placebo-controlled cross-over trial. Anodal tDCS was applied for 20 min at 2 mA intensity over the left DLPFC, while the cathode was positioned over the contralateral supraorbital region. After tDCS, EEG was recorded during an eyes-closed resting state followed by a working memory (n-back) task. Statistical non-parametric mapping showed reduced left frontal delta activity in the real tDCS condition. Specifically, a significant reduction of mean current densities (sLORETA) for the delta band was detected in the left subgenual PFC, the anterior cingulate and in the left medial frontal gyrus. Moreover, the effect was strongest for the first 5 min (p<0.01). The following n-back task revealed a positive impact of prefrontal tDCS on error rate, accuracy and reaction time. This was accompanied by increased P2- and P3- event-related potentials (ERP) component-amplitudes for the 2-back condition at the electrode Fz. A source localization using sLORETA for the time window 250-450 ms showed enhanced activity in the left parahippocampal gyrus for the 2-back condition. These results suggest that anodal tDCS of the left DLPFC and/or cathodal tDCS of the contralateral supraorbital region may modulate regional electrical activity in the prefrontal and anterior cingulate cortex in addition to improving working memory performance.

[Neurobiology of obsessive-compulsive disorder]. / Neurobiologie der Zwangsstörung.

In the last few decades, neurobiological research has considerably improved the understanding of the pathophysiological basis of obsessive-compulsive disorder (OCD), indirectly contributing to the improvement of diverse therapy strategies. A number of functional imaging studies have indicated functional deficits in frontostriatal networks, which can be subsumed in an orbitofrontal model of obsessive-compulsive disorder. A dysfunction is postulated in parallel frontostriatal circuits, leading to an imbalance in direct and indirect feedback loops and a disinhibition of thalamocortical activity. Neurochemical studies have shown that OCD is linked to changes of the central modulatory transmitter system, especially, the serotonin and dopamine system, which probably contribute to a direct and indirect dysregulation in various neural networks. Pharmacologically, the elucidation of these serotonergic and dopaminergic alterations and their interactions are of special interest.

Single-trial coupling of the gamma-band response and the corresponding BOLD signal.

Oscillations in the gamma-band frequency range have been described to be more closely connected to hemodynamic changes as assessed with functional magnetic resonance imaging (fMRI) than other aspects of neuronal activity. In addition, gamma-band oscillations have attracted much interest during the last few years since they are thought to play a crucial role in many aspects of brain function related to perception and cognition. It was the aim of the present simultaneous EEG-fMRI study to identify brain regions specifically involved in the generation of the auditory gamma-band response (GBR) using single-trial coupling of EEG and fMRI. Ten healthy subjects participated in this study. Three different runs of an auditory choice reaction task with increasing difficulty were performed. Brain activity was recorded simultaneously with high density EEG (61 channels) and fMRI (1.5 T). BOLD correlates of the GBR have been predicted using the single-trial amplitude of the GBR. Reaction times (p<0.001), error rates (p<0.05) and self-ratings of task difficulty and effort demands (p<0.001) were related to the level of difficulty in the task. In addition, we found a significant influence of task difficulty on the amplitude of the GBR at Cz (p<0.05). Using single-trial coupling of EEG and fMRI GBR-specific activations were found only in the auditory cortex, the thalamus and the anterior cingulate cortex (ACC) in the most difficult run. Single-trial coupling might be a useful method in order to increase our knowledge about the functional neuroanatomy of "neural ensembles" coupled by 40 Hz oscillations.

12- and 18-month follow-up after residential treatment of methamphetamine dependence: Influence of treatment drop-out and different treatment concepts.

This study investigates the effects of two different residential treatments and of treatment drop-out in a German methamphetamine (MA) dependent sample. 108 subjects from two addiction treatment concepts were recruited at treatment begin and followed-up at 12 (T2) and 18 (T3) months after treatment. Based on follow-up samples (n = 38 at T2, n = 25 at T3), 77.1% at T2 and 68.0% at T3 were MA abstinent. Classifying everyone, who did not participate at follow-ups as having had a relapse, showed MA-abstinence rates of 25.0% (at T2) and 15.7% (at T3). There was no difference in MA-use between treatment conditions nor between treatment completers and drop-outs. Having injected any substance predicted MA-use at T2 (p = .03). The median time of relapse was 1.5 days after hospital release. Depression scores at T2 predicted MA-use at T3 (p = .02). T2 participants that dropped out of treatment had higher craving scores at T2, than T2 subjects who completed treatment (p = .03). The results show positive effects of current inpatient treatment programs without differences between different concepts. More research is needed to clarify the impact of treatment drop-out. Attention should be paid to a successful transition from residential to outpatient services and to a reduction of study attrition.

Short and long-term effects of sham-controlled prefrontal EEG-neurofeedback training in healthy subjects.

OBJECTIVE: In this study we evaluated long-term effects of frontal beta EEG-neurofeedback training (E-NFT) on healthy subjects. We hypothesized that E-NFT can change frontal beta activity in the long-term and that changes in frontal beta EEG activity are accompanied by altered cognitive performance. METHODS: 25 healthy subjects were included and randomly assigned to active or sham E-NFT. On average the subjects underwent 15 E-NFT training sessions with a training duration of 45 min. Resting-state EEG was recorded prior to E-NFT training (t1) and in a 3-year follow-up (t3). RESULTS: Compared to sham E-NFT, which was used for the control group, real E-NFT increased beta activity in a predictable way. This increase was maintained over a period of three years post training. However, E-NFT did not result in significantly improved cognitive performance. CONCLUSION: Based on our results, we conclude that EEG-NFT can selectively modify EEG beta activity both in short and long-term. SIGNIFICANCE: This is a sham controlled EEG neurofeedback study demonstrating long-term effects in resting state EEG.