Methods

Nerve cells in the brain transmit information through fine electrical potentials. This electrical activity can be measured with the EEG. The EEG is measured non-invasively from the scalp and is thus harmless. In psychiatric everyday life, the EEG is being used to find out whether psychiatric symptoms arise because there are primary organic reasons or influencesof substances that impair the functionality of the brain (e.g., toxic substances, epilepsy, or a tumor). In psychiatric research, the EEG can be employed to distinguish different states of information processing that are activated during specifically designed experiments. These information-processing steps are observed in certain conditions and with certain tasks. It is interesting to know which processing steps are changed in specific groups of patients and how these changes relate to psychopathological symptoms. At the University Hospital and Polyclinic for Psychiatry in Bern, we have separate laboratories for clinical routine investigations and research.

Research’s primary focus is not the diagnosis and treatment but the insight into the mechanisms that lead to psychopathological symptoms. Research projects need the approval of an ethics commission and are always voluntary for the examined persons. Independent of their causes, psychiatric symptoms result from a misfit between the brain's information processing and the environment, which leads to inadequate experiences and behavior (this implies that both patient and environment must be considered.) With neurophysiological methods, it is possible to assess and influence not only the experiences and behavior of a subject but also the processing steps that produce them.

Lab / Infrastructure

Clinical EEG Laboratory

For the clinical EEG, a 32-channel digital EEG system is used. Per year, approx. 600 routine measurements are accomplished. Apart from these routine measurements, further standardized investigations (P300, CPT) are available. For the evaluation of the EEG, analysis PCs, and a database are available. The clinical EEG measurements are accomplished by trained medical-technical assistants.

Involved team members: Yvonne Fontana, Head FND – Electrophysiology Laboratory, Melanie Haynes, dipl. biol.

Research EEG Laboratory

For research purposes, we have:

  • an EEG recording chamber with a 32-channel modular neurofeedback system
  • an EEG recording chamber with a 96-channel digital EEG system and a variety of soft- and hardware for stimulation
  • a total of 4 modular 32-channel amplifiers
  • Analysis software and PCs
  • Regular introductory courses in the analysis of EEG data
  • Support for design, data acquisition, analysis, and interpretation of experiments

Other EEG facilities are available in the groups of Christoph Nissen and Leila Tarokh

The experimental psychology group offers methodological and theoretical collaboration to clinical project groups in these fields, with a specific focus on longitudinal data and time series, psychotherapeutic change mechanisms, embodied cognition in therapeutic exchange, and mindfulness-based interventions.

Concerning psychotherapeutic change, we conduct empirical projects that illustrate which of the common change factors of psychotherapy are activated by the various therapeutic techniques. These projects address dyadic and group psychotherapies with psychiatric patients, treated in day hospitals as well as ambulatory settings and inpatient units. For the analysis of change mechanisms, we specialize in time series modeling through vector autoregression and related methods. In embodiment research, we study processes of motoric and nonverbal synchrony in psychotherapy sessions and other dyadic social interactions. We have developed specific methods for measuring synchrony: SUSY (surrogate synchrony) detects social coupling based on cross-correlational statistics and surrogate tests. MEA (Motion Energy Analysis) is a method to monitor movement in video recordings.  In mindfulness research, a comprehensive questionnaire (the CHIME) was developed by our group and is currently used in projects on mindfulness-based psychotherapy (MBCT) and, as a short form, in ecological assessments.

Neurofeedback is similar to biofeedback. Both techniques are used to learn to control some of our body's functions. During biofeedback, one is typically connected to electrical sensors that help receive information about the body (e.g., the heart rate). This feedback helps to make subtle changes in the body, such as relaxing certain muscles. In contrast to biofeedback, neurofeedback measures brain activity either via EEG or via fMRI.

Real-time fMRI neurofeedback

With real-time fMRI neurofeedback, participants learn to regulate their brain activity in a given brain area. The current brain activity is measured in real-time and data pre-processing as well as data analysis is performed with dedicated software. Feedback is provided to the participant in the scanner via a projector in the form of a thermometer icon, with the temperature reading indicating the current level of brain activity. The participants perform several training runs, which are composed of baseline blocks and up- or down-regulation blocks. During the regulation blocks, the target-level indicator of the thermometer display moves up or down, indicating that the participants should in- or decrease activity in the targeted brain region. With the help of feedback information, participants can learn to voluntarily control their brain activity in the targeted brain area.  

Several techniques are currently available that provides images of the structure and the function of the human brain. Neuroimaging is the acronym for it. Imaging can be performed by the non-invasive method of Magnetic Resonance (MRI). The principles of MRI are fully described by interaction processes between matter (i.e. nuclei composed of protons and neutrons) and photons (the carrier of the electromagnetic forces) radiation. Due to the small dimensions of both interaction particles quantum physical description is needed. Moreover, a large number of interaction particles (i.e. mass phenomenon) are required in order that MR scanner may record the MR signal. Fortunately, the human brain contains large number of water molecules (i.e. protons) so that in most cases there is a genuine MR signal. Due to the non-invasive nature of the method, MRI can be repeatedly applied to a large cohort of subjects: from neuropediatric up to elderly patients. The technique has been successfully applied in medicine, neuroscience, psychology and psychiatry.

In structural MRI images of the gray matter (GM) and of the white matter (WM) are recorded. Dedicated MR sequences are sensitive to both tissue types are typically acquired at high resolution (i.e. 1 mm x 1 mm x 1mm iso-voxel). Both maps require rigorous pre-processing and artefacts removal, before quantitative and qualitative features are extracted.

Functional MRI are tipically acquired in 2D slices for a large number of volumes that eventually form a time series. A paradigm containing different stimuli (i.e. the task) is presented to the subjects and the human brain is then assumed to involve distinct brain regions for solving the task. The paradigm can be a repetition of the same stimulus for a certain interval (i.e. block-design) or can be a fast, balanced and randomly presented sequence of different stimuli (i.e. fast-event-related fMRI design [er-fMRI]). No matter which design type is applied, a rigorous pre-processing pipeline is needed before a 1-level analysis, and subsequently, a 2-level analysis can be computed. A majority of studies are performed on fMRI signal based on “blood oxygenation level-dependent” contrast [BOLD-fMRI].

However, fMRI can also be performed with non-BOLD techniques: such as Arterial Spin Labelling (ASL). This method allows the absolute quantification of cerebral blood flow (CBF) in units of [ml/100 g/min]. Moreover, by combining BOLD fMRI and CBF fMRI measurements under hypercapnia condition (i.e. administration of 5 % CO2), additional physiological features such as the cerebral metabolic rate of Oxygen (CMRO2).

can be estimated. Therefore, knowledge of the neurovascular-coupling can be assessed.

Find hereafter a few examples of maps as obtained by Neuroimaging methods.

Anatomy GM  WM
cube of MRI images

Methods of non-invasive brain stimulation used in our group include transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). TMS and tDCS are used to disrupt cerebral functioning to examine the role of the stimulation target in physiological or pathological conditions, an approach that has been referred to as virtual lesion.

TMS is a noninvasive method of delivering electrical stimuli to the brain through the intact scalp. Depending on the stimulation parameters, TMS is able to excite or inhibit the brain. Repetitive (r)TMS is able to change and modulate activity beyond the stimulation period which is why it sometimes is referred to as offline-TMS. Therefore, rTMS has therapeutic potential in patients with neurological and psychiatric disorders. It is, however, unclear by which mechanism rTMS induces these lasting effects on the brain. Several lines of evidence support the hypothesis that rTMS affects the brain by changes in synaptic plasticity, by long-term potentiation and long-term depression. Plasticity is the ability of the brain to reorganize itself, enabling short- and long-term remodeling of neural communication that outlasts an experimental manipulation or period of training.

An alternative stimulation approach is tDCS. Here, weak direct currents are applied to the brain for several minutes non-invasively. Dependig on the electrode, this leads to shifts in membrane potentials without causing neuronal firing like in TMS. Cathodal tDCS hyperpolarizes whereas anodal tDCS depolarizes the membrane. This mechanisms has been indirectly proven by Nitsche and Paulus from the University of Göttingen, Germany by combining TMS and tDCS and measuring motor evoked potentials in the contralateral limb. They showed that tDCS caused an alteration of the motor evoqued potentials of plus minus 20 percent. In our own research we study tDCS as a method to modulate and potentially treat auditory hallucinations in schizophrenia (Figure 1).

Cathodal (negative) transcranial direct current stimulation (tDCS) supposedly causes hyperpolarization at Wernicke's area.
Figure 1. Cathodal (negative) transcranial direct current stimulation (tDCS) supposedly causes hyperpolarization at Wernicke's area. Wernicke's area and other language regions are hyperactive in auditory verbal hallucinations in schizophrenia. The reference electrode (anode) is placed at the contralateral frontal area (not shown) (Figure taken from Homan et al. 2012, Eur Arch Psychiatry Clin Neurosci).

Sleep and mental health are bidirectionally related - disrupted sleep is often a core feature of many psychiatric disorders and sleep difficulties exacerbate psychiatric symptoms.  The overarching aim of our research is to gain new insight into the pathophysiology of mental health disorders by investigating and modulating sleep. To achieve this, we take a multimodal approach using high-density sleep EEG, auditory closed loop stimulation and actigraphy coupled with in-depth behavioral phenotyping. Furthermore, translating our findings into clinical practice is a priority of our research activities.

The Bern Psychopathology Scale (BPS) is a clinical rating scale developed to group psychotic symptoms in the domains of language, affectivity, and motor-behavior.

These domains are of particular interest for understanding the fundamental communication breakdown during psychotic disorders, since they can be linked to known, higher order brain systems, i.e. the language, the limbic and the motor system. These systems are anatomically and functionally separate, and their interactions are the basis for cognition and communication. We assume that schizophrenia is due to a functional imbalance of one or more of these systems resulting in disruptions of their interaction, and to the characteristic symptoms like incoherence, paranoid anxiety or grandiosity, and movement disorders.

The psychopathological assessment is based on objective, subjective and indirect symptoms, which are assigned to the 3 domains. Each phenomenon is defined by the respective normal psychic function, and a mutually exclusive symptom pair, indicating a "positive" or "negative" deviation from normal, e.g. hyperkinesia and akinesia, logorrhea and mutism or incoherence and perplexity. Thus, the 3 domains are not categories, but dimensions, each spanning from negative to positive, and capable to represent combinations of deviations in different domains.

The scale was tested for interrater reliability and internal consistency in a group of 168 psychotic patients. The items of the scale were reliable and principal component analysis (PCA) was best explained by a solution resembling the three candidate systems. In conclusion, the scale is apt to distinguish symptom domains related to the activity of defined brain systems. This first validation is presented in the publication cited below.

The scale was developed as a research instrument in order to investigate possible neurophysiological correlates of domain-specific psychotic syndromes. Further, the clinical utility of the scale in terms of differential pharmacology or psychotherapy is a possible research field.

The Handbook contains considerations which led to the structure of the scale in the present form. The original scale as used in a first study testing the reliability and internal consistency is presented in German and English.

Further information about the Bern Psychopathology Scale (BPS), publications and related research can be found in the Systems Neuroscience of Psychosis (SyNoPsis) project.