Shifted Coupling of EEG Driving Frequencies and fMRI Resting State Networks in Schizophrenia Spectrum Disorders

INTRODUCTION: The cerebral resting state in schizophrenia is altered, as has been demonstrated separately by electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) resting state networks (RSNs). Previous simultaneous EEG/fMRI findings in healthy controls suggest that a consistent spatiotemporal coupling between neural oscillations (EEG frequency correlates) and RSN activity is necessary to organize cognitive processes optimally. We hypothesized that this coupling is disorganized in schizophrenia and related psychotic disorders, in particular regarding higher cognitive RSNs such as the default-mode (DMN) and left-working-memory network (LWMN). METHODS: Resting state was investigated in eleven patients with a schizophrenia spectrum disorder (n = 11) and matched healthy controls (n = 11) using simultaneous EEG/fMRI. The temporal association of each RSN to topographic spectral changes in the EEG was assessed by creating Covariance Maps. Group differences within, and group similarities across frequencies were estimated for the Covariance Maps. RESULTS: The coupling of EEG frequency bands to the DMN and the LWMN respectively, displayed significant similarities that were shifted towards lower EEG frequencies in patients compared to healthy controls. CONCLUSIONS: By combining EEG and fMRI, each measuring different properties of the same pathophysiology, an aberrant relationship between EEG frequencies and altered RSNs was observed in patients. RSNs of patients were related to lower EEG frequencies, indicating functional alterations of the spatiotemporal coupling. SIGNIFICANCE: The finding of a deviant and shifted coupling between RSNs and related EEG frequencies in patients with a schizophrenia spectrum disorder is significant, as it might indicate how failures in the processing of internal and external stimuli, as commonly seen during this symptomatology (i.e. thought disorders, hallucinations), arise.

A deviant EEG brain microstate in acute, neuroleptic-naive schizophrenics at rest

Momentary brain electric field configurations are manifestations of momentary global functional states of the brain. Field configurations tend to persist over some time in the sub-second range (“microstates”) and concentrate within few classes of configurations. Accordingly, brain field data can be reduced efficiently into sequences of re-occurring classes of brain microstates, not overlapping in time. Different configurations must have been caused by different active neural ensembles, and thus different microstates assumedly implement different functions. The question arises whether the aberrant schizophrenic mentation is associated with specific changes in the repertory of microstates. Continuous sequences of brain electric field maps (multichannel EEG resting data) from 9 neuroleptic-naive, first-episode, acute schizophrenics and from 18 matched controls were analyzed. The map series were assigned to four individual microstate classes; these were tested for differences between groups. One microstate class displayed significantly different field configurations and shorter durations in patients than controls; degree of shortening correlated with severity of paranoid symptomatology. The three other microstate classes showed no group differences related to psychopathology. Schizophrenic thinking apparently is not a continuous bias in brain functions, but consists of intermittent occurrences of inappropriate brain microstates that open access to inadequate processing strategies and context information

Decreased functional connectivity of EEG theta-frequency activity in first-episode, neuroleptic-naïve patients with schizophrenia: preliminary results

We explored and refined the hypothesis that during a first episode of acute schizophrenia a disorganization of brain functioning is present. A novel EEG measure was introduced, Global Field Synchronization (GFS), that estimates functional connectivity of brain processes in different EEG frequency bands. The measure was applied to EEG's from 11 never-treated, first-episode, young patients with an acute, positive, schizophrenic symptomatology and from 19 controls, residing in Bern, Switzerland. In comparison to age- and sex- matched controls, patients had significantly decreased GFS in the theta EEG frequency band, indicating a loosened functional connectivity of processes in this frequency. The result was confirmed in an independent, comparable patient group from Osaka, Japan (9 patients and 9 controls), thus making a total of 20 analyzed patients. Previous EEG research in healthy, awake subjects indicated a positive correlation of theta activity with memory functions. Thus, our result suggests a loss of mutual interdependence of memory functions in patients with acute schizophrenia, which agrees well with previous reports of working memory dysfunction in schizophrenia.

Internet-Based Guided Self-Help for Several Anxiety Disorders: A Randomized Controlled Trial Comparing a Tailored With a Standardized Disorder-Specific Approach

Internet-delivered self-help with minimal therapist guidance has shown promising results for a number of diagnoses. Most of the evidence comes from studies evaluating standardized disorder-specific treatments. A recent development in the field includes transdiagnostic and tailored Internet-based treatments that address comorbid symptoms and a broader range of patients. This study evaluated an Internet-based tailored guided self-help treatment, which targeted symptoms of social anxiety disorder, panic disorder with or without agoraphobia, and generalized anxiety disorder. The tailored treatment was compared both with standardized disorder-specific Internet-based treatment and with a wait-list control group. Both active treatment conditions were based on cognitive-behavioral therapy and lasted for 8 weeks. A total of 132 individuals meeting diagnostic criteria for at least one of the anxiety disorders were randomly assigned to 1 of the 3 conditions. Both treatment groups showed significant symptom reductions as compared with the wait-list control group on primary disorder-unspecific measures of anxiety, depression, and general symptomatology and on secondary anxiety disorder-specific measures. Based on the intention-to-treat sample, mean between-group effect sizes were d = 0.80 for the tailored treatment and d = 0.82 for the standardized treatment, versus wait-list controls. Treatment gains were maintained at 6-month follow-up. No differences were found between the 2 active treatment conditions on any of the measures, including a telephone-administered diagnostic interview conducted at posttreatment. The findings suggest that both Internet-based tailored guided self-help treatments and Internet-based standardized treatments are promising treatment options for several anxiety disorders

Die Untersuchung der Schulter in der Praxis

Liegt die Ursache von Schmerzen oder Funktionseinbussen im Schulterbereich selbst, können diese mit einer präzisen klinischen Untersuchung in den meisten Fällen einer bestimmten anatomischen Struktur zugeordnet werden. Vorwiegend im Bild, mit nur knappem Text, werden die einzelnen Tests dargestellt. Dabei wurde zur besseren Merkfähigkeit die jeweils getestete Struktur mit eingezeichnet. Auch die häufigsten in der Praxis vorkommenden Trigger-Punkte mit der entsprechenden pseudoradikulären Symptomatik werden dargestellt. Ziel dieses Artikels ist die Erleichterung der täglichen Arbeit in der Praxis bei häufigen Schulterproblemen.

Comparative Behavioral and Neural Effects of Tryptophan and Catecholamine Depletion in Remitted Depression

Background: Despite immense efforts into development of new antidepressant drugs, the increases of serotoninergic and catechominergic neurotransmission have remained the two major pharmacodynamic principles of current drug treatments for depression. Consequently, psychopathological or biological markers that predict response to drugs that selectively increase serotonin and/or catecholamine neurotransmission hold the potential to optimize the prescriber’s selection among currently available treatment options. The aim of this study was to elucidate the differential symptomatology and neurophysiology in response to reductions in serotonergic versus catecholaminergic neurotransmission in subjects at high risk of depression recurrence. Methods: Using identical neuroimaging procedures with [18F] fluorodeoxyglucose positron emission tomography after tryptophan depletion (TD) and catecholamine depletion (CD), subjects with remitted depression were compared to healthy controls in a double-blind, randomized, crossover design. Results: While TD induced significantly more depressed mood, sadness and hopelessness than CD, CD induced more inactivity, concentration difficulties, lassitude and somatic anxiety than TD. CD specifically increased glucose metabolism in the bilateral ventral striatum and decreased glucose metabolism in the bilateral orbitofrontal cortex, whereas TD specifically increased metabolism in the right prefrontal cortex and the posterior cingulate cortex (PCC). While we found direct associations between changes in brain metabolism and induced depressive symptoms following CD, the relationship between neural activity and symptoms was less clear after TD. Conclusions: In conclusion, this study showed that serotonin and catecholamines play common and differential roles in the pathophysiology of depression.

Prevalence and predictors of fatigue in glioblastoma: a prospective study.

BACKGROUND The main goal of this study was to assess frequency, clinical correlates, and independent predictors of fatigue in a homogeneous cohort of well-defined glioblastoma patients at baseline prior to combined radio-chemotherapy. METHODS We prospectively included 65 glioblastoma patients at postsurgical baseline and assessed fatigue, sleepiness, mean bedtimes, mood disturbances, and clinical characteristics such as clinical performance status, presenting symptomatology, details on neurosurgical procedure, and tumor location and diameter as well as pharmacological treatment including antiepileptic drugs, antidepressants, and use of corticosteroids. Data on fatigue and sleepiness were measured with the Fatigue Severity Scale and the Epworth Sleepiness Scale, respectively, and compared with 130 age- and sex-matched healthy controls. RESULTS We observed a significant correlation between fatigue and sleepiness scores in both patients (r = 0.26; P = .04) and controls (r = 0.36; P < .001). Only fatigue appeared to be more common in glioblastoma patients than in healthy controls (48% vs 11%; P < .001) but not the frequency of sleepiness (22% vs 19%; P = .43). Female sex was associated with increased fatigue frequency among glioblastoma patients but not among control participants. Multiple linear regression analyses identified depression, left-sided tumor location, and female sex as strongest associates of baseline fatigue severity. CONCLUSIONS Our findings indicate that glioblastoma patients are frequently affected by fatigue at baseline, suggesting that factors other than those related to radio- or chemotherapy have significant impact, particularly depression and tumor localization.

Don't forget asking the others! - The added value of significant other's reports on patient interpersonal style for the prediction of therapy process and outcome

Theory: Interpersonal factors play a major role in causing and maintaining depression. It is unclear, however, to what degree significant others of the patient need to be involved for characterizing the patient's interpersonal style. Therefore, our study sought to investigate how impact messages as perceived by the patients' significant others add to the prediction of psychotherapy process and outcome above and beyond routine assessments, and therapist factors. Method: 143 outpatients with major depressive disorder were treated by 24 therapists with CBT or Exposure-Based Cognitive Therapy. Interpersonal style was measured pre and post therapy with the informant‐based Impact Message Inventory (IMI), in addition to the self‐report Inventory of Interpersonal Problems (IIP‐32). Indicators for the patients' dominance and affiliation as well as interpersonal distress were calculated from these measures. Depressive and general symptomatology was assessed at pre, post, and at three months follow‐up, and by process measures after every session. Results: Whereas significant other's reports did not add significantly to the prediction of the early therapeutic alliance, central mechanisms of change, or post‐therapy outcome including therapist factors, the best predictor of outcome 3 months post therapy was an increase in dominance as perceived by significant others. Conclusions: The patients' significant others seem to provide important additional information about the patients' interpersonal style and therefore should be included in the diagnostic process. Moreover, practitioners should specifically target interpersonal change as a potential mechanism of change in psychotherapy for depression.

Changes in self-reported symptoms of depression and physical wellbeing in healthy individuals following a Taiji beginner course – Results of a randomized controlled trial

Introduction: Taiji is a mind-body practice being increasingly investigated for its therapeutic benefits in a broad range of mental and physical conditions. The aim of the present study was to investigate potential preventive effects of Taiji practice in healthy individuals with regard to their depressive symptomatology and physical wellbeing. Methods: A total of 70 healthy Taiji novices (mean age 35.5 years) were randomly assigned to a Taiji intervention group, i.e. Taiji beginner course (Yang-Style Taiji, 2 hours per week, 12 weeks) or a waiting control group. Self-reported symptoms of depression (CES-D) and physical wellbeing (FEW-16) were assessed at baseline, at the end of the intervention, as well as two months later. Results: Physical wellbeing in the Taiji group significantly increased when comparing baseline to follow up (FEW-16 sum scale T(27) = 3.94, p = 0.001, 95% CI 0.17 - 0.55). Pearson’s correlation coefficients displayed a strong negative relationship between self-reported symptoms of depression and physical wellbeing (p’s < 0.001, r‘s ≥ -.54). Conclusions: In this randomized controlled trial we found significant evidence that a Taiji beginner course of three months duration elicits positive effects with respect to physical wellbeing in healthy individuals, with improvements pronouncing over time. Physical wellbeing was shown to have a strong relationship with depressive symptoms. Based on these results, the consideration of Taiji as one therapeutic option in the development of multimodal approaches in the prevention of depression seems justifiable.

Serotonin versus catecholamine deficiency: behavioral and neural effects of experimental depletion in remitted depression

Despite immense efforts into development of new antidepressant drugs, the increases of serotoninergic and catecholaminergic neurotransmission have remained the two major pharmacodynamic principles of current drug treatments for depression. Consequently, psychopathological or biological markers that predict response to drugs that selectively increase serotonin and/or catecholamine neurotransmission hold the potential to optimize the prescriber's selection among currently available treatment options. The aim of this study was to elucidate the differential symptomatology and neurophysiology in response to reductions in serotonergic versus catecholaminergic neurotransmission in subjects at high risk of depression recurrence. Using identical neuroimaging procedures with [(18)F] fluorodeoxyglucose positron emission tomography after tryptophan depletion (TD) and catecholamine depletion (CD), subjects with remitted depression were compared with healthy controls in a double-blind, randomized, crossover design. Although TD induced significantly more depressed mood, sadness and hopelessness than CD, CD induced more inactivity, concentration difficulties, lassitude and somatic anxiety than TD. CD specifically increased glucose metabolism in the bilateral ventral striatum and decreased glucose metabolism in the bilateral orbitofrontal cortex, whereas TD specifically increased metabolism in the right prefrontal cortex and the posterior cingulate cortex. Although we found direct associations between changes in brain metabolism and induced depressive symptoms following CD, the relationship between neural activity and symptoms was less clear after TD. In conclusion, this study showed that serotonin and catecholamines have common and differential roles in the pathophysiology of depression.

Out-of-Body Experiences and Other Complex Dissociation Experiences in a Patient with Unilateral Peripheral Vestibular Damage and Deficient Multisensory Integration

Out-of-body experiences (OBEs) are illusory perceptions of one's body from an elevated disembodied perspective. Recent theories postulate a double disintegration process in the personal (visual, proprioceptive and tactile disintegration) and extrapersonal (visual and vestibular disintegration) space as the basis of OBEs. Here we describe a case which corroborates and extends this hypothesis. The patient suffered from peripheral vestibular damage and presented with OBEs and lucid dreams. Analysis of the patient's behaviour revealed a failure of visuo-vestibular integration and abnormal sensitivity to visuo-tactile conflicts that have previously been shown to experimentally induce out-of-body illusions (in healthy subjects). In light of these experimental findings and the patient's symptomatology we extend an earlier model of the role of vestibular signals in OBEs. Our results advocate the involvement of subcortical bodily mechanisms in the occurrence of OBEs.

The Process-Outcome Mindfulness Effects in Trainees (PrOMET) study: protocol of a pragmatic randomized controlled trial

Background Mindfulness has its origins in an Eastern Buddhist tradition that is over 2500 years old and can be defined as a specific form of attention that is non-judgmental, purposeful, and focused on the present moment. It has been well established in cognitive-behavior therapy in the last decades, while it has been investigated in manualized group settings such as mindfulness-based stress reduction and mindfulness-based cognitive therapy. However, there is scarce research evidence on the effects of mindfulness as a treatment element in individual therapy. Consequently, the demand to investigate mindfulness under effectiveness conditions in trainee therapists has been highlighted. Methods/Design To fill in this research gap, we designed the PrOMET Study. In our study, we will investigate the effects of brief, audiotape-presented, session-introducing interventions with mindfulness elements conducted by trainee therapists and their patients at the beginning of individual therapy sessions in a prospective, randomized, controlled design under naturalistic conditions with a total of 30 trainee therapists and 150 patients with depression and anxiety disorders in a large outpatient training center. We hypothesize that the primary outcomes of the session-introducing intervention with mindfulness elements will be positive effects on therapeutic alliance (Working Alliance Inventory) and general clinical symptomatology (Brief Symptom Checklist) in contrast to the session-introducing progressive muscle relaxation and treatment-as-usual control conditions. Treatment duration is 25 therapy sessions. Therapeutic alliance will be assessed on a session-to-session basis. Clinical symptomatology will be assessed at baseline, session 5, 15 and 25. We will conduct multilevel modeling to address the nested data structure. The secondary outcome measures include depression, anxiety, interpersonal functioning, mindful awareness, and mindfulness during the sessions. Discussion The study results could provide important practical implications because they could inform ideas on how to improve the clinical training of psychotherapists that could be implemented very easily; this is because there is no need for complex infrastructures or additional time concerning these brief session-introducing interventions with mindfulness elements that are directly implemented in the treatment sessions.

Effects of a Transdiagnostic Internet Intervention («velibra») for Anxiety Disorders in Primary Care: Results of a Randomized Controlled Trial

Internet-based cognitive behavioral self-help treatment (ICBT) for anxiety disorders has shown promising results in several trials, but there is yet a lack of studies of ICBT in „real world” primary care settings. In this randomized controlled trial we recruited participants through general practitioners. The aim of the study was to examine whether treatment-as-usual (TAU) in primary care settings plus ICBT is superior to TAU alone in reducing anxiety symptoms and other outcome measures among individuals meeting diagnostic criteria of a least one of three anxiety disorders (social anxiety disorder, panic disorder with or without agoraphobia, generalized anxiety disorder). 150 adults fulfilling diagnostic criteria for a least one of the anxiety disorders according to a diagnostic interview are randomly assigned to one of the two conditions: TAU plus ICBT versus TAU. Randomization is stratified by primary disorder, medication (yes/no) and concurrent psychotherapy. ICBT consists of a transdiagnostic and tailored Internet-based self-help program for several anxiety disorders which also includes cognitive bias modification for interpretation (CBM-I). Primary outcomes are symptoms of disorder-specific anxiety measures and diagnostic status after the intervention (9 weeks). Secondary outcomes include primary outcomes at 3-month follow-up and secondary measures such as general symptomatology, depression, quality of life, adherence to ICBT and satisfaction with ICBT. The study is currently being completed. Primary results along with results for specific subgroups (e.g. primary diagnosis, concurrent medication and/or psychotherapy) will be presented and discussed.

A sorrow shared is a sorrow halved? Internet-based group therapy versus individual therapy for social anxiety disorder: A randomized controlled trial

Purpose: Social anxiety disorder is one of the most researched conditions in the field of Internet-based self-help. Various studies have shown that cognitive-behavioral treatments can be efficacious to reduce social phobic symptoms. Most of the interventions tested include some form of support, whereas the efficacy of a web-based group format has yet to be investigated. The present study aims at investigating the possible added value of therapist-guided group support in an Internet-based guided self-help treatment for SAD. Methods: A total of 150 adults with a diagnosis of SAD are randomly assigned to either a wait-list control group or one of two active treatment conditions. Participants in the two active conditions use the same Internet-based self-help program, either with individual guidance by a therapist or with the support of a therapist-guided group of 6 individuals. In the group condition, participants communicate with each other via an integrated, protected discussion forum. The primary outcome variables are symptoms of SAD and diagnostic status immediately after the intervention (12 weeks) and at 6-month follow-up. Secondary endpoints are general symptomatology, depression, quality of life and adherence to treatment. Furthermore, process variables such as group processes and the working alliance are studied. Results: Results are currently being analyzed. Results at post-treatment will be presented and discussed. Potential moderating and mediating variables of treatment success will be addressed. Conclusion: The results of this study should indicate whether therapist-guided group support could enhance the efficacy of an internet based self-help treatment for SAD. This novel treatment format, if shown efficacious, could represent a cost-effective option and could be further modified to treat other conditions.

Molecular Characterization and Risk Factors of Giardia duodenalis among School Children from La Habana, Cuba

Giardia duodenalis is considered the most common protozoan infecting humans worldwide. Molecular characterization of G. duodenalis isolates has revealed the existence of eight groups (assemblages A to H) which differ in their host distribution. A cross-sectional study was conducted in 639 children from La Habana between January and December 2013. Two assemblage-specific PCRs were carried out for the molecular characterization. The overall prevalence of Giardia infection was 11.9%. DNA from 63 of 76 (82.9%) samples was successfully amplified by PCR-tpi, while 58 from 76 (76.3%) were detected by PCRE1-HF. Similar results by both PCRs were obtained in 54 from 76 samples (71%). According to these analyses, assemblage B and mixed assemblages A + B account for most of the Giardia infections in the cohort of children tested. Our current study identified assemblage B as predominant genotype in children infected with Giardia. Univariate analysis indicated that omission of washing hands before eating and keeping dogs at home were significant risk factors for a Giardia infection. In the future, novel molecular tools for a better discrimination of assemblages at the subassemblages level are needed to verify possible correlations between Giardia genotypes and symptomatology of giardiasis.