Neural interfaces with electrically controllable delivery of manganese ions applied for MEMRI-functionalized deep brain stimulation

Deep brain stimulation (DBS) is a well-developed neurosurgical technique for the treatment of numerous neurological disorders. It is important to understand the cerebral processes triggered by DBS [1]. Manganese-enhanced MRI (MEMRI) allows non-invasive brain imaging through the uncoupling of brain activity. Based on the paramagnetic properties and the similarity to the calcium ions (Ca2 +), Mn2 + accumulating in cells directly gives the responses to their activity via the MRI recording [2]. However, the subcutaneous injection of MnCl2 in concentrations sufficient for MRI analysis tended to be cytotoxic and the diffusion area is usually uncontrollable [3]. Facing the challenge, we developed a conductive hydrogel with electrically controlled Mn2 + release used as a neural interface for MEMRI-functionalized DBS. Through manipulating the pulses of alternative current (AC) stimulation, the neural implant simultaneously allowed DBS and unbiasedly real-time MEMRI. We synthesized a conductive hydrogel via doping Poly(3,4-ethylenedioxythiophene) (PEDOT) into a new type of amphiphilic chitosan to construct a neural interface with ECM-mimicking physical/mechanical properties, stable electrochemical properties, and biocompatibility. In addition, the attached amide (–NH2) and carboxylic groups (–COOH) of the hybrids enabled a chelating affinity with Mn2 + to form a stable complex without leakage at a physiological pH value. Applied with an AC pulse, the raised electric potential resulted in an electrochemically polarized removal of the chelated Mn2 +. Therefore, the on-demand release of Mn2 + was allowed by the pulse frequency. Our finding indicated that the electrical intensity and frequency pulses for DBS enabled trace Mn2 + release from a microprobe which showed a distinct contrast on T1-weight image