Abstracts and biosketches BCN Symposium 2017: Parallel session III

Dr. Branislava Ćurčić-Blake
Department of Neurosciences
University Medical Center Groningen, the Netherlands

Branislava Ćurčić-Blake is a neuroscientist interested in brain connectivity in psychiatric and neurological diseases. She holds a PhD in Physics, and is an Assistant Professor at the Department of Neuroscience, UMCG, Groningen, Netherlands. She is specialized in brain connectivity in health and disease, including neurodegenerative disorders. She has extensive experience in data acquisition and analysis, both in humans and model systems. She is expert in state-of-the-art MRI data analysis, involving a variety of MRI techniques. Current research efforts focus on improving cognitive functioning in patients with multiple sclerosis and elderly people with mild cognitive impairment (MCI), in both cases using transcranial electric current stimulation.

tECS in Neuropsychiatric Disorders
Transcranial electric current stimulation (tECS) of the brain is a “rediscovered” therapeutic approach for regional modulation of neocortical excitability or brain oscillations. It is relatively easy to apply and the side-effects are minor, thus it has potential to be applied in clinical settings. tECS implies the delivery of a weak current transcranially in three different modalities: direct current (tDCS), alternating current (tACS), and random noise (tRNS), each with different working mechanisms. In this lecture I will summarize the use of these approaches in healthy participants and psychiatric and neurological patients. I will focus on the effects of this treatment to elevate cognitive functioning, including memory and executive function in cognitively impaired patients across diagnostics. Finally, I will describe the clinical trials using tECS that are in progress at the UMCG.

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Prof.dr. Eddy van der Zee
Groningen Institute for Evolutionary Life Sciences, Molecular Neurobiology

University of Groningen, the Netherlands

Prof.dr. Eddy van der Zee is interested in various aspects of neurobiology, with emphasis on learning, memory and (healthy) aging. One of his current research line is about the effects of sensory stimulation, in the form of whole body vibration, on cognitive function .

The Van der Zee lab studies various aspects in the field of learning and memory. Special focus of research is on clinical and preclinical studies in the fields of whole body vibration, motion simulation, Alzheimer’s disease and aging. In all studies we are especially interested in the link between brain functioning and behavior, both fundamentally and from a biomedical perspective. We primarily study experimentally-induced changes in key memory proteins such as neurotransmitter receptors, kinases, and various other down-stream regulators. The way we approach this is by combining cognitive behavioral tests with brain manipulation (genetically, pharmacologically, or via non-pharmacological interventions) in mice and rats (or other types of rodents if necessary). We are studying declarative, procedural, motor and episodic-like memory using a large variety of commonly used memory tasks as well as our newly developed tasks and paradigms. Brains are generally analyzed by way of Western blotting, Elisa or Immunocytochemistry. Within the framework of learning and memory, aging is a central topic. Interventions to prevent or slow down aging-related aspects of cognitive neurodegeneration are tested, either pharmacologically or through behavioral interventions like exercise and vibration therapies. Brain regions of main interest are the hippocampus, striatum, neocortex, amygdala and hypothalamus. In all projects we try to understand the link between brain functioning and behavior, and to decipher the underlying cellular and molecular mechanisms. Current research topics are: a) Cognitive dysfunctions in PKU mice and dietary interventions. For these studies we use the two available PKU mouse models (C57Bl6 and BTBR background) in direct comparison to the human PKU situation where possible, b) Cognitive dysfunctions in Post-Operative Cognitive Decline (POCD) mimicked in rats. Notably the role of neuroinflammation in POCD is studied, c) Active (running wheel) and passive (whole body vibration) exercise and cognition. In close collaboration with Human Movement Sciences we study the underlying mechanisms of different types of exercise in improving cognitive and motor performance, notably in relation to Alzheimer’s disease (mouse and human studies), and d) Cognitive changes in aging in relation to multiple memory systems and their interaction, with emphasis on Alzheimer’s disease.

Multi-sensory brain stimulation and neuromodulation by way of mild whole body vibrations
Whole body vibration (WBV) is a technique to provide sensory stimulation to the body (and brain) through regular, low-amplitude vibrations using a vibrating platform. We first examined the impact of WBV on mouse brains. Mice were placed in a cage connected to a vibrating platform and exposed to 10 minutes WBV (30 Hz–1.9 g) per day for five weeks. Controls existed of sham WBV. After WBV, brains were analyzed for Glut-1 (a glucose transporter protein), c-fos (an immediate early gene indicative for neuronal activity), ChAT (Choline-Acetyltransferase, the rate-limiting enzyme for the production of Acetylcholine; Heesterbeek er al., 2017), and TH (Tyrosine-Hydroxylase, the rate-limiting enzyme for the production of dopamine). WBV increased the expression of Glut-1, ChAT (in many forebrain target regions) and TH (striatum). C-fos expression was enhanced selectively in the brain. Balance beam tests revealed that the performance improved gradually over time, and was significant after three (young mice of 3-4 months of age) or five weeks (old mice of ca. 24 months of age) of WBV treatment (Keijser et al., 2017). This functional gain was still present two weeks after WBV intervention was stopped. Results of spatial memory testing showed significantly improved cognition. Next, we performed human studies, and showed that two minutes passive WBV (sitting on a chair mounted on the vibration platform) with 30 Hz frequency improved executive functioning in the Stroop test by about 8 % (acute effects; Regterschot et al., 2014). A series of experiments with healthy adults in which we used a duration of four minutes of passive WBV in a chronic treatment protocol (5 weeks, 3 days per week, n = 5), revealed even stronger improvements in Stroop test performance (maximally 14% improvement). Moreover, the effects were still significantly present after one week without WBV treatment, illustrating the potential of passive WBV to improve cognition. WBV may predominantly stimulate vibration-sensitive mechanoreceptors in the skin activating the brain, such as the Meissner corpuscles sensitive to 10–80 Hz vibrations and specifically responsive to 30–40 Hz vibrations. Taken together, WBV seems a multi-sensory (e.g. vibrations and proprioception) way to affect neuromodulation and to stimulate brain functioning.

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Prof.dr.ir. Michel van Putten

Clinical Neurophysiology
University of Twente, the Netherlands

Michiel van Putten studied Medicine in Leiden and Applied Physics in Delft. In 2000, he got his PhD in Applied Physics from Delft, and registered as a clinical neurologist. He is head of the department of Clinical Neurophysiology of the Medisch Spectrum Twente, a large teaching hospital, and chair of the Clinical Neurophysiology group at the University of Twente.

The research focuses on advancing our understanding of processes involved in cerebral ischaemia and cortical excitability, where the EEG is an important measurement tool. Our translational approach includes clinical measurements in patients in coma in the ICU and epilepsy, computational modeling, and in-vitro research with cultured neuronal networks.

For more information and recent publications, please visit www.utwente.nl/tnw/cnph
or https://www.researchgate.net/profile/Michel_Van_Putten

TMS in Epilepsy
TMS as a neurostimulation tool in epilepsy has potential as both a therapeutic and diagnostic tool.

I will shortly address candidate working mechanisms of repetitive TMS (rTMS) in inducing long lasting changes in cortical excitability, and review some open label trials and a few placebo controlled studies that support a possible therapeutic role for rTMS in epilepsy.

Next, I will discuss TMS/EMG and TMS/EEG as a tool to assess the cortical excitation-inhibition ratio (cortical excitability), using the motor evoked potential and the transcranial evoked response as readouts, respectively, and how this may be used for epilepsy diagnostics and evaluation of treatment efficacy. This will be complemented by own research data from two ongoing clinical studies in first seizure patients and drug naive patients diagnosed with epilepsy.   In both patient populations, we study if single or paired pulse TMS/EEG can provide a diagnostic biomarker and can predict treatment efficacy.

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Dr. Jacco de Haan

Medical Oncology
University Medical Center Groningen, the Netherlands

Jacco de Haan is a medical oncologist at the University Medical Center Groningen. Previously, he studied the impact of neuromodulation by nutritional and pharmacological means on the acute inflammatory response. Currently, his main interest is the improvement of the care for oncological patients by manipulation of the immune system. His research projects include preclinical mechanistic studies on the interplay between the autonomic nervous system, immune system and organ integrity, and clinical studies directed at implementation of immunomodulatory interventions like enriched enteral nutrition.

Neuromodulation of the inflammatory response
Intensive research at the frontiers of immunology and neuroscience has identified multiple points of interaction and communication between the immune system and the nervous system. Neuronal circuits regulate innate and adaptive immunity, which has lead to the identification of new therapeutic possibilities in inflammatory and autoimmune diseases. Recent clinical trials using bioelectronic devices that modulate the vagal antiinflammatory pathay to ameliorate inflammation and restore tissue integrity in several disease entities including rheumatoid arthritis and inflammatory bowel disease. In addition, nutritional stimulation of the vagal antiinflammatory pathway is currently investigated in patients with an acute inflammatory response provoked by major surgery. This presentation will review current knowledge of the neural regulation of immunity and inflammation and its potential therapeutic implications.