Descripción del proyecto
Deep brain stimulation (DBS) is a surgical treatment for Parkinson’s disease and other neurological disorders. By applying pulsed, alternating electric currents to targets deep in the brain, DBS induces widespread changes in neural network activity. Although motor symptoms can be reduced by DBS in most patients, some patients suffer from severe side effects or insufficient symptom relief.
Many attempts have been made to optimize the therapeutic effects of DBS, but these attempts have been restricted by a lack of understanding of how DBS exerts its therapeutic effects. Various therapeutic mechanisms have been proposed, but none have fully explained all of the complex effects of DBS. These theories have focused on direct and indirect effects of the strong electric fields near the stimulation contact.
I propose a radically new hypothesis on the therapeutic mechanism of DBS that harnesses current insights from noninvasive brain stimulation. Weak electric fields during noninvasive brain stimulation have recently been shown to desynchronize neural activity from the surrounding network activity. I suggest that weak electric fields during DBS desynchronize cortical activity, which can, in combination with the effects of strong subcortical electric fields, reduce pathological synchrony in motor system networks and thereby restore motor control.
DECODE will integrate large-scale volume conduction modeling to estimate and steer personalized electric fields, biophysical neural network modeling to understand the physiological consequences of weak fields and their interaction with strong field effects, and EEG measurements in humans to verify these models. Finally, based on the obtained knowledge and computational tools, DECODE will clinically test the hypothesis in patients with Parkinson’s disease. If successful, DECODE will start a new era in our understanding of the therapeutic network mechanisms of DBS and trigger clinical breakthroughs to optimize DBS therapy.