Neuromodulation & Behavior

This pre-clinical research group headed by Ingo Willuhn is embedded in a larger clinical research team at the AMC Psychiatry and driven by the central question: “How do we control our behavior?”. The Neuromodulation and Behavior group is specifically interested in compulsivity” and the effects of “deep-brain stimulation” on compulsive behavior.

What is compulsivity? Compulsivity is behavior that we perform despite the unwillingness to act or despite its negative outcome. Compulsive behavior is often performed persistently and repetitively and is characterized by the incapacity of altering our behavior according to an intended plan. But how does compulsivity develop? What is its neurobiological basis? To answer these questions, we investigate different aspects of compulsivity (i.e., habit formation, response inflexibility, loss of voluntary control, and aggravation by stress and anxiety) and measure neuronal activity in the brain simultaneously.

Compulsivity is a core feature in several neuropsychiatric disorders, such as obsessive-compulsive disorder (OCD), addiction, eating disorders, and impulsivity disorders. In therapy-resistant cases of a number of neurological and psychiatric disorders, deep-brain stimulation (DBS) has been shown to be effective. However, despite extensive clinical and experimental research, our understanding of the mechanisms of action of DBS is still limited.

How does deep-brain stimulation (DBS) affect compulsivity? What is the neurobiological basis of the therapeutic effects of high-frequency stimulation in psychiatric disorders? What are the best and safest brain targets for changing pathological behavior in OCD, addiction, anxiety and eating disorders? As these disorders are characterized by profound behavioral alterations due to disturbances of affect, motivation and cognition, our research is focused on neurobiological substrates of motivational behavior in general.

Our group is embedded in the larger research team of Professor Damiaan Denys (chair of the Department of Psychiatry at the Amsterdam Medical Center, AMC) and therefore has close ties with clinicians and clinical researchers, providing optimal conditions for a translational and multidisciplinary approach. Specifically, we translate clinical findings from studies in humans into relevant animal models, and vice versa we aim to apply the conclusions from our basic science findings in the clinical setting. Our research tools include behavioral (e.g., signal attenuation, Vogel conflict) and genetic (SAPAP3 mice) animal models and methods for intracerebral stimulation (e.g., DBS, optogenetics, pharmacogenetics) in freely moving rodents, in combination with tests for emotional and cognitive behavior (in set-ups such as elevated plus maze and operant chambers), neurochemical measurements (e.g., microdialysis, fast-scan cyclic voltammetry), and electrophysiological recordings (single-unit activity and local field potentials (LFPs) combined with simultaneous reverse dialysis). Furthermore, we established pharmacologic and functional magnetic resonance imaging (phMRI and fMRI) in rodents to detect the effects of drugs, DBS, and optical stimulation throughout the brain.