Publication date: 28th June 2024
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).
This research was funded by the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 881603 (Graphene Flagship Core 3) and grant number 101070865 (MINIGRAPH). ICN2 is supported by the Severo Ochoa Centres of Excellence programme (Grant CEX2021-001214-S), funded by MCIN/AEI/10.13039.501100011033, and by the CERCA Programme of Generalitat de Catalunya. N. R. acknowledges grant PRE2020-093708 founded by MCIN/AEI /10.13039/501100011033 and by FSE. E. M. C. acknowledges grant FJC2021-046601-I funded by Agencia Estatal de Investigacion of Spain and the European Union Next-GenerationEU/PRTR. This work has made use of the SpanishICTS Network MICRONANOFABS, partially supported by MICINN and the ICTS NANBIOSIS, specifically by the Micro-NanoTechnology Unit U8 of the CIBER-BBN. This research was supported by CIBER -Consorcio Centro de Investigación Biomédica en Red- (CB06/01/0049), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación. We would like to thank Prof. Alex Casson from the Department of Biomedical Engineering at the University of Manchester for loaning us the potentiostat used in the experiments. The project that gave rise to these results received the support of a fellowship from the ”la Caixa” Foundation (ID 100010434). The fellowship code is LCF/BQ/DI21/11860021