Wireless lightweight implantable pulse generators enable chronic dual-target deep brain stimulation in rodent disease models

Deep brain stimulation (DBS) is a well-established treatment option for neurological disorders. Despite its widespread use, the underlying mechanisms of action remain still unknown. Further exploration of the clinical applications of DBS and improvement of its efficacy require preclinical research in animal models. However, studies on rodents have been limited due to a lack of lightweight, small, standardized experimental neurostimulators for long-term deep brain stimulation. We have therefore developed and tested two versions of a simplified, lightweight wireless microstimulation platform (small implantable pulse generator (s-IPG) 1.6 g and tiny IPG (t-IPG) 0.9 g) that uses slightly imbalanced output waveforms to enable long-term DBS. In benchtop testing using standard DBS paradigms, the s-IPG achieved 62 days voltage-compliant stimulation (n = 16 rats). In 6-OHDA Parkinson’s Disease model in rats, subthalamic nucleus (STN) stimulation improved motor performance acutely (n = 16/16, p = 0.0076) and after 30 days of continuous long-term stimulation (n = 6/8, p = 0.03). Long-term nucleus accumbens (NAc) s-IPG stimulation in obese mice confirmed successful cell activation after 5 weeks (cFos, n = 2). This system may in the future contribute to optimizing the long-term application of DBS and lead to a deeper understanding of the underlying mechanism of action.