Clinical Research

Group Walther

Ongoing Projects

(ClinicalTrials.gov Identifier: NCT03921450)
Background  In addition to symptoms such as hallucinations, delusions, and thought disorder, patients with schizophrenia frequently suffer from motor abnormalities. One of these motor abnormalities is psychomotor slowing (PS), which may affect both gross and fine motor behavior. Motor abnormalities are associated with abnormal functional and structural connectivity within the cerebral motor network. While PS causes significant distress and predicts poor outcome, researchers are just starting to understand its pathobiology. Recent studies suggested increased neural activity in the premotor cortex to underlie severe motor inhibition. Thus, a possible way to ameliorate PS is repetitive transcranial magnetic stimulation (rTMS), which may temporarily alter brain activity. This project will combine a motor battery, advanced neuroimaging, and rTMS to probe the cerebral motor network contributions to PS. 
Hypothesis  We hypothesize that (1) PS would be linked to increased functional connectivity in the motor network, (2) inhibitory rTMS to the premotor cortex will alleviate PS by reducing motor network functional connectivity, (3) patients responding to rTMS treatment of PS will have superior clinical and functional outcomes at 6-month follow-up.
Design of the study  We plan to investigate four groups of schizophrenia patients (total 88) in a randomized, double blind, 3-arm sham-controlled trial of 15 rTMS sessions in 3 weeks with pre and post intervention MRI scans and a clinical follow-up at 6 months. One group will first be kept on a 3 week waiting list and then enter the study. Longitudinal MRI scans and motor tests separated by 3 weeks will also be applied to a control group of 40 healthy subjects for comparisons with the patient groups

Preliminary Data  The pilot data on this study design (See Walther et al.2020, https://doi.org/10.1093/schizbullopen/sgaa020) suggest that three weeks of daily inhibitory rTMS over the premotor cortex might improve psychomotor slowing in schizophrenia.
Funding    http://p3.snf.ch/project-182469
Study team                                         Collaborators
Niluja Nadesalingam                           Prof. Roland Wiest, Institute of Diagnostic and
Stephanie Lefebvre, PhD                                                    Interventional Neuroradiology
Danai Alexaki, MD                              Prof. Jessica Bernard, Texas A & M University
Daniel Baumann, MD                         Prof. Roger Kalla, Dept. of Neurology, Bern
Sebastian Walther, MD                       Prof. Andrea Federspiel, Translational Research Center                                                                                                                

Subtle motor abnormalities are frequently found in the psychosis spectrum. This research is devoted to objective assessment of different motor abnormalities and to testing the predictive value for transition into psychosis in subjects at risk and for the course of the disorder in patients.

Collaborators: PD Dr. Jochen Kindler, Prof. Vijay Mittal

Aberrant motor behavior is a key dimension of schizophrenia spectrum disorders. Our group has a track record of investigating motor behavior and dysfunction of the motor system in psychoses. We apply instrumentation, clinical rating scales and advanced neuroimaging to learn about the neurobiology of various motor abnormalities in psychoses. Importantly, motor behavior has the potential to serve as readily accessible marker of psychosis staging. We aim to assess various motor domains such as parkinsonism, abnormal involuntary movements, soft signs, catatonia and psychomotor slowing.

See publications for review articles

Collaborators: Dr. Katharina Stegmayer, Dr. Petra Viher, Dr. Lea Schäppi, Dr. Tobias Bracht, Prof. Andrea Federspiel

 

In order to understand the abnormal motor behavior, we also need to consider normal motor behavior. Therefore, we are testing several of our paradigms in healthy subjects.

Collaborators: Dr. Katharina Stegmayer, Dr. Petra Viher, Dr. Andrea Cantisani, Dr. Leila Tarokh

Gesture behavior is defective in the majority of schizophrenia patients. This project aims to explore the neural correlates applying sophisticated multimodal neuroimaging methods. We focus on the praxis network that includes brain areas devoted to motor behavior, spatial integration and semantics.

Collaborators: Dr. Petra Viher, Dr. Katharina Stegmayer, PD Tim Vanbellingen, Prof. Stephan Bohlhalter, Prof. Andrea Federspiel, Prof. Marek Kubicki

Schizophrenia patients are critically impaired in decoding nonverbal social information, such as hand gestures, prosody, body postures or facial expressions. In addition, we detected that patients also use hand gestures incorrectly. In fact, some patients have clear deficits in both perceiving and producing hand gestures, predicting unfavorable outcome. In a series of studies, we are exploring the link between social cognitive deficits and nonverbal communication skills using clinical assessments and behavioral experiments.

Collaborators: Dr. Katharina Stegmayer, Dr. Petra Viher, Dr. Sarah Eisenhardt, PD Tim Vanbellingen, Prof. Stephan Bohlhalter

The project examines the type of gesture deficits and motor abnormalities in subjects with autism spectrum disorders. Behavioral experiments and clinical rating scales are applied.

Collaborators: Dr. Daniela Reinhold, Avram Tolev, Prof. Thomas Müller

During depressive episodes patients also face a number of social interaction problems. We detected gesture deficits in a small group of depression patients with severe psychomotor retardation. The current project will examine whether gesture impairment may also occur in less severe major depression.

Collaborators: Dr. Petra Viher, Hanta Bachofner

Patients with multiple sclerosis often suffer from comorbid psychiatric disorders such as major depression or anxiety. These comorbidities could contribute to poor social interaction. In addition, gesture performance and fine motor skills are frequently impaired in multiple sclerosis. This project will assess quality of life, motor activity and nonverbal communication in social interactions of patients with multiple sclerosis.

Collaborators: Dr. Anke Salmen, Dr. Robert Hoeppner, Dr. Katharina Stegmayer, Prof. Andrew Chan

Formal thought disorder refers to abnormalities of speech and thought. These abnormalities range from thought blocking to excessive loose associations, i.e. inhibition to excitation. Similar to nonverbal communication deficits formal thought disorder may critically impair social interaction. Using multimodal neuroimaging techniques we explore white matter alterations and perfusion changes associated with distinct dimensions of formal thought disorder.

Collaborators: Dr. Katharina Stegmayer, Dr. Petra Viher, Prof. Andrea Federspiel

Paranoid experiences of threat are rarely disclosed by patients suffering from paranoia. We developed a bed-side test on personal space, detecting paranoid threat among schizophrenia patients with 93% sensitivity and 83% specificity (see publications). Currently, we are exploring the neurophysiologic and neural correlates of aberrant interpersonal space in paranoia among patients with schizophrenia and subjects at risk for psychosis.

Collaborators: Dr. Katharina Stegmayer, Dr. Lea Schäppi

Negative symptoms relate to poor interaction with the external environment of patients and also to loss of interest and motivation. Motor behavior contributes to broad concepts of negative symptoms. Here, we explore neural correlates of negative symptoms such as apathy, loss of initiative or reduced expression in relation to alterations of the cerebral reward system and related brain areas.

Collaborators: Dr. Tobias Bracht, Dr. Katharina Stegmayer, Dr. Petra Viher, Prof. Andrea Federspiel, Prof. Stefan Kaiser

In a traditional medical model clinical suicide prevention is focused on the treatment of associated psychiatric disorders. However, although psychiatric diagnoses are major risk factors for suicide, prevention projects aimed at improving detection and treatment of psychiatric disorders have a limited potential to reduce suicidal behaviour. In contrast to the medical approach to suicidality we have developed a patient-centred treatment model, based on the theory of goal-directed action. Within this theoretical frame the therapeutic approach is aimed at establishing a therapeutic alliance, starting with the patients’ self-narrative of the suicidal crisis. Suicidal behaviour is understood as triggered by adverse experiences, which seriously threaten a person’s major life-goals. Our research is aimed at a better understanding of the psychology of the suicidal mind, including psychological pain, coping strategies, and neuropsychological mechanisms. The ultimate aim is to translate these patient-oriented insights into better and more effective treatments for suicidal patients.