Recent developments in multifunctional neural probes for simultaneous neural recording and modulation

Understanding neural circuit mechanisms is crucial in neuroscience. Neural probes, which convert extracellular ionic currents into electrical signals, are essential tools for neural activity recording. Recent progress has led to the development of flexible probes, improving the probe-brain interface and enabling long-term recordings. However, to fully understand causal relationships between neural activity and brain function, simultaneous recording and manipulation of specific neuron types are needed. Multifunctional neural probes, integrating recording and stimulating units, offer a powerful platform for this purpose. This review summarizes recent developments in these probes, emphasizing their structural and material designs, and highlighting various modulation modalities.

The review extensively cites existing literature on neural probes, highlighting the transition from rigid to soft probes for improved long-term stability and the development of various multifunctional probes with integrated recording and stimulation capabilities. It covers existing methods for chemical neuromodulator delivery, including intravenous and oral administrations, microinjections, and integrated microfluidic channels. The limitations of existing techniques, such as the blood-brain barrier and potential side effects, are also discussed. Existing work on electrical stimulation, focusing on charge injection capacity and electrode design improvements using nanomaterials, is also reviewed. Optogenetics, its applications, and the challenges of integrating it with neural recording, are covered. Existing research on ECoG electrodes and depth electrodes for optical and electrical neural modulation are also summarized.

The methodology of this paper is a review of existing literature on multifunctional neural probes. The authors systematically searched and analyzed published research articles focusing on probes capable of simultaneous neural recording and modulation using different modalities. The review is organized into sections based on the type of stimulation used (chemical, electrical, optical), with subsections discussing different approaches within each modality and highlighting key examples from the literature. Each section is supported by numerous figures illustrating the design, structure, and performance of the described probes. The figures are sourced from previously published work, showcasing the range of existing designs. The discussion of each modality includes detailed explanations of the materials and techniques employed, their advantages and limitations, and insights into future development directions. The authors critically evaluate the existing literature, identifying current challenges and future prospects in the field.

The review details various designs of multifunctional neural probes. For chemical delivery, advancements range from integrating microfluidic channels into silicon or polymer-based probes for localized drug delivery and real-time recording, to wireless flexible fluidic probes for freely moving animals, and sustained-release systems using drug-loaded nanogels or conducting polymers. For electrical stimulation, improvements focus on increasing charge injection capacity (CIC) through surface coatings with nanomaterials (Pt, Au, IrO2, TiN, CNTs, graphene) and structural engineering (CNTs arrays, carbon nanofibers, porous Pt nanorods). Fiber electrodes (graphene, CNT fibers) offer reduced implantation damage. The integration of stimulation and recording electrodes in ultrathin probes for high spatiotemporal resolution is also discussed, along with the challenges of electrical artifacts and lack of cell-type specificity. Optogenetic modulation utilizes transparent electrodes (ITO, graphene) for ECoG or depth recordings. Different light delivery systems including optical fibers, microLEDs, upconverting nanoparticles (UCNPs), and thermally drawn fibers are reviewed, along with their advantages and limitations regarding penetration depth and invasiveness. In particular, the use of UCNPs that convert near-infrared (NIR) light to visible light for deep brain stimulation is highlighted. Fiber-based multifunctional probes, combining optical stimulation, drug delivery, and neural recording, are also reviewed, demonstrating their potential for low-invasive chronic studies, as well as the use of hydrogel matrices to enhance biocompatibility.

The review successfully addresses the need for simultaneous neural recording and modulation techniques by highlighting the key advancements in multifunctional neural probes. The findings underscore the importance of material selection and structural designs for improved biocompatibility, long-term stability, and high spatiotemporal resolution. The discussion of limitations, including the invasiveness of some methods, lack of single-neuron resolution in certain techniques, and artifacts introduced during stimulation, provides valuable context for the field. The identification of future research needs, such as developing miniature and mechanically compliant probes, improving cell-type-specific modulation, and incorporating additional functionalities like temperature and pH sensors, clearly points towards the exciting possibilities of future research in this field. The review contributes significantly by organizing and presenting a comprehensive overview of a rapidly advancing area of neuroscience research.

Multifunctional neural probes are transforming our understanding of brain function. This review summarizes advancements in chemical, electrical, and optogenetic stimulation techniques, revealing the critical role of material and structural optimization. Despite significant progress, challenges remain, including the need for more biocompatible and miniature probes, and improved cell-type specificity and resolution. Addressing these challenges requires multidisciplinary collaboration.

The review is limited to the published literature and may not fully represent all ongoing research efforts. The rapid pace of technological development in this field means that some very recent work might not have been included. Also, the review mainly focuses on the design and functionality of the probes without delving into detailed biological and physiological responses and consequences of using those probes.