Deep brain stimulation (DBS) is an established neuroelectronic therapy for the treatment of several neurological disorders, including Parkinson's Disease (PD), which is the focus of this work. Current Parkinson's DBS implants, despite their relatively broad clinical adoption, exhibit problems of invasiveness and precision in targeting specific brain regions, which is crucial for maximizing therapeutic benefits while minimizing side effects and lack of focalized and adaptive treatments that can avoid continuous brain stimulation and improve safety over extended periods of time. In this work, we propose the use of microelectrode thin film technology based on reduced graphene oxide, a highly porous material that offers exceptional charge injection and very low impedance, enabling accurate brain recording for biomarker monitoring and focal microstimulation. Our thin film technology consists of 10 µm thin, highly flexible neural leads featuring a high-density array of microelectrodes of 25 µm in diameter.

Experiments were conducted in control and Parkinsonian rats, under anesthesia and in awake state, to investigate specific biomarkers and to evaluate the effect of neuromodulation. Thanks to the recording capabilities of the graphene microelectrodes and its high density, it was possible to precisely localize the subthalamic nucleus (STN), a key structure in Parkinson’s disease, through the recording of single-cell action potentials.  

By comparing PD and control rats, we were to observe a robust increase in neuronal burst activities in the STN of the Parkinsonian rats, which was enabled by the use of microelectrode recordings. Electrical stimulation through those microelectrodes inside the STN induced desynchronization in neuron firing, effectively modulating STN activity to levels comparable to non-Parkinsonian animals.

The stimulation exhibits focal precision, activating an area up to 100 µm away. This allows targeted treatment of small brain regions, such as the STN, without affecting other neural structures. These effects last for several minutes post-stimulation, encouraging the implementation of a closed-loop system to improve therapy efficacy and energy battery consumption. Future studies will be conducted to evaluate the presence of behavioral changes produced in the awake state.

References

Viana, D. et al. Nanoporous graphene-based thin-film microelectrodes for in vivo high-resolution neural recording and stimulation. Nat. Nanotechnol. (2023) doi:10.1038/s41565-023-01570-5.

 Rodríguez-Meana, B. et al. Engineered Graphene Material Improves the Performance of Intraneural Peripheral Nerve Electrodes. Adv. Sci. 2308689, 1–19 (2024).