Abstracts and biosketches BCN Symposium 2017: Parallel session II

Prof.dr. Stephan van Gils
Mathematics & Computer Science
University of Twente, the Netherlands

Stephan van Gils studied mathematics at the VUA (Vrije Universiteit Amsterdam) and did his PhD at the CWI (Centrum Wiskunde & Informatica). Currently he is the head of the Applied Analysis group at the University of Twente. The research focus of the group is on mathematical  neuroscience and imaging, both with medical applications.

Coordinated Reset revisited: a computational, neurobiological and clinical study
Continuous application of high-frequency deep brain stimulation (DBS) often effectively reduces motor symptoms of Parkinson's disease patients. While there is a growing need for more effective and less traumatic stimulation, the exact mechanism of DBS is still unknown. Already more than a decade ago Peter Tass proposed that a different stimulation protocol called coordinated reset is more efficient. We have tested this in a computational model, assuming  spike-timing-dependent plasticity (STDP) at GABAergic GPe–GPe synapses.

In an exemplary set of biologically plausible model parameters, we show that STDP in the GPe has a direct influence on neural activity and especially the stability of firing patterns. STDP stabilizes both uncorrelated firing in the healthy state and correlated firing in the parkinsonian state. Alternative stimulation protocols such as coordinated reset stimulation can clearly profit from the stabilizing effect of STDP. These results are widely independent of the STDP learning rule.

Once the model settings, e.g., connection architectures, have been described experimentally, our model can be adjusted and directly applied in the development of novel stimulation protocols. More efficient stimulation leads to both minimization of side effects and savings in battery power.

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Prof.dr. Mariska van Steensel

Department of Neurology and Neurosurgery
Brain Center Rudolf Magnus
University Medical Center Utrecht, the Netherlands

Mariska van Steensel’s mission is to use the wealth of neuroscientific knowledge directly for the benefit of people with disease or disability. After several years of fundamental research on circadian rhythmicity, the main focus of her research since 2007 has been the development of an implantable Brain-Computer Interface (BCI) for communication in severely paralyzed people, based on electrocorticographic electrodes. Initially, she conducted research on the proof-of-concept of implantable BCIs. More recently, as assistant professor, she has been coordinator of several projects: First, they are making the transition from implantable BCI research to BCI application by investigating the usability of a prototype implantable BCI system in the daily life of people with severe paralysis. Second, they aim to develop the next generation implantable BCIs, utilizing the detailed organization of the sensorimotor areas for higher-dimensional BCI control. In addition, she works on improving strategies of presurgical mapping of brain functions.

A brain-implant for communication in severe paralysis: Performance and usability
Diseases such as amyotrophic lateral sclerosis (ALS) and events such as a brain-stem stroke may lead to (nearly) complete paralysis in the presence of intact cognition. This situation is called the locked-in syndrome (LIS). People with LIS often report a satisfactory quality of life, which is, however, strongly determined by the ability to communicate. Existing approaches that facilitate communication in people with LIS are based on residual motor function and do not function well for all affected, and in all situations. Brain-computer interfaces (BCIs) may provide people with LIS with an alternative, completely brain-based method, to control their communication devices. For optimal use in the daily life at home by people with LIS, BCIs need to be reliable, user friendly for both the user and the caretaker, available 24/7, comfortable and esthetically attractive, or, even better, invisible. Implantable BCIs have the potential to meet these requirements, but up till recently, the usability and performance of these devices in the daily life of the target population had not been demonstrated. I will discuss the results of the first study worldwide that aims to investigate home-use of a fully implantable BCI system for communication by people with LIS. The participant was a woman with late-stage ALS, who was implanted with subdural strips of electrodes over the sensorimotor area and an implantable amplifier/transmitter device that was placed subcutaneously under the clavicle. After a period of familiarization, training and optimizing parameter settings, she was (and still is) able to use the implant to communicate, at her home, with her family and caretakers, without expert help. In addition, she uses the system to call her caregiver when she needs attention. She uses the system mainly in situations where her eye-tracking device does not function adequately (e.g. outside) and reports high user satisfaction with the device. We conclude that a fully implantable BCI may offer adequate performance accuracy as well as satisfactory usability for home-use by people with LIS.

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Prof.dr. Gertjan van Dijk

GELIFES-Neurobiology
Department of Behavioural Neurosciences
University of Groningen, the Netherlands

Gertjan van Dijk is Professor of Integrative Neurobiology at the Groningen Institute for Evolutionary Life Sciences (GELIFES) at the University of Groningen. His main interests are the neurobiology of energy balance and behavioural energetics.  Current projects include modeling of obesity and associated metabolic comorbidities in rodents, and treatment of (aspects of) these by using novel nutritional supplements, pharmacotherapy, bariatric surgery, and/or deep brain stimulation.  In addition, several projects focus on the role of diet and physical activity in cognitive and affective functioning, both in humans and rodent models.  Besides his work as researchers, he teaches and coordinates several courses in the biology and life science curricula. He is member of the scientific advisory board of the Dutch Diabetes Foundation, and of several societies focusing on brain and behavior including the Society for the Study of Ingestive Behaviour.

DBS as treatment option for Obesity
Binge eating disorder (BED) is the most common eating disorder in modern industrialized societies. It is characterized by recurrent episodes of rapid and excessive food consumption. There is a significantly higher prevalence of BMI of ≥40 among individuals BED compared to people without any eating disorder. The neurobiology of BED may encompass impaired processing of reward and motivation leading to addictive-like mechanisms, which may be caused by mesolimbic dopaminergic system changes, presumably homologous to those seen in drug addiction. Deep Brain Stimulation (DBS) is currently regarded as a relatively novel but promising surgical treatment of addiction. Because of potentially similar circuitries underlying drug addiction and BED, we aimed to investigate Nucleus Accumbens DBS in a rodent model for binge eating behavior. After first establishing a binge eating protocol in male Wistar rats - consisting of one-hour food deprivation preceding one hour access to a high fat and sugar diet (HFS binge) at the penultimate hour before the dark phase - subsequent animals had electrodes placed in the Nucleus Accumbens core (NAcc core), lateral shell (NAcc lShell) or medial shell (NAcc mShell), and were habituated to HFS bingeing. DBS was applied either before and/or during the binge and was varied in stimulation current and frequency. With respect to the NAcc core, the most striking inhibitory effect on HFS bingeing (-39%, p=0.008) was achieved when stimulating with a current of 250 µA before the binge at 10Hz, while no effects were found when stimulation was performed during the binge. DBS in the NAcc lShell showed strongest suppression of the HFS binge (-44%, p=0.003) when stimulating with either 125 or 250 µA during HFS binge at 50Hz, but no effects were observed when stimulation was performed before the binge. No significant results were achieved when stimulating NAcc mShell, however these rats showed profound escape behavior upon stimulation. These data indicate that DBS of the NAcc core suppresses the “wanting” aspects of binging whereas DBS of the NAcc lShell suppresses “liking” aspects of binging. “Wanting” changes the food reward potency, and these aspects have indeed been found to reside in the NAcc core. Furthermore, incentive hotspots associated with “liking” have previously been identified in lateral parts of the NA. We conclude that DBS in the NAcc may be a promising tool for the treatment of BED in humans.

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Dr. Bernadette van Wijk

Department of Neurology
Charité - University Medicine Berlin, Germany

Dr. Bernadette van Wijk pursued her undergraduate and postgraduate studies in Human Movement Sciences at VU University Amsterdam. During her PhD she focused on the role of beta oscillations in the motor system of healthy individuals using techniques such as EEG, MEG and EMG. After graduating she moved to University College London to work with Dr. Vladimir Litvak on simultaneous LFP and MEG recordings in Parkinson’s disease patients with deep brain stimulation electrodes implanted in the subthalamic nucleus. Currently she is continuing this line of research together with Prof. Andrea Kühn at the Charité - University Medicine Berlin. Using advanced signal processing techniques such as cross-frequency coupling and dynamic causal modelling, she investigates physiological and pathological activity patterns within the cortico-basal ganglia network.

Beta and high-frequency oscillations as biomarkers in Parkinson’s disease
The subthalamic nucleus (STN) is one of the primary targets for deep brain stimulation (DBS) treatment in Parkinson’s disease. Local field potentials recorded from the STN have revealed a strong association between beta band oscillations and bradykinesia/rigidity symptoms. Both dopaminergic medication and DBS reduce beta band amplitude along with improvements in clinical motor scores. However, it remains unclear how excessive beta band oscillations mechanistically lead to motor impairment. Here, I propose that more insight into Parkinsonian neurophysiology might be obtained by focusing on another spectral peak that can frequently be observed: high-frequency oscillations (HFO) within the 150-400Hz range. Activity within this frequency range is especially relevant as it typically shows a movement-related increase in amplitude. I will present our findings indicating that HFO may express abnormally strong phase-amplitude coupling with ongoing beta band oscillations that correlates with severity of bradykinesia/rigidity. In addition, our intraoperative recordings identified that HFO and beta band oscillations are likely to arise from separate, but spatially close, neural populations. Future work will be necessary to determine whether HFO can help fine-tune deep brain stimulation targeting.