Precision electronic medicine in the brain

Abstract

Periodically throughout history developments from adjacent fields of science and technology reach a tipping point where together they produce unparalleled advances, such as the Allen Brain Atlas and the Human Genome Project. Today, research focused at the interface between the nervous system and electronics is not only leading to advances in fundamental neuroscience, but also unlocking the potential of implants capable of cellular-level therapeutic targeting. Ultimately, these personalized electronic therapies will provide new treatment modalities for neurodegenerative and neuropsychiatric illness; powerful control of prosthetics for restorative function in degenerative diseases, trauma and amputation; and even augmentation of human cognition. Overall, we believe that emerging advances in tissue-like electronics will enable minimally invasive devices capable of establishing a stable long-term cellular neural interface and providing long-term treatment for chronic neurological conditions.

Figure 1:

Unidirectional and bidirectional neurostimulation approaches. To date, the vast majority of commercially available neurostimulation devices are unidirectional capable of singularly recording or stimulating. For example, unidirectional recording devices (red dashed-line) like the motor cortical prosthetics decode motor intention from motor cortical networks to actuate a robotic arm and restore movement^,. Similarly, unidirectional stimulation devices (blue dashed-line), such as retinal prosthetics map visual-spatial information from cameras to create visual percepts by stimulating retinal receptive fields^,. Bidirectional neurostimulation devices are capable of both sensing and stimulating in a real-time and adaptive manner, thus creating new opportunities leveraging closed-loop approaches.

Figure 2:

Challenges with current neural interfaces. Mismatches in structural, mechanical, and topological features between the brain and interface lead to micromotion and a prolonged chronic immune response limiting the longevity of conventional neural recording probes. Similarly, factors including the physical, chemical, and mechanical composition of the electrode influence probe features such as diameter, shape, cross-sectional area, and size of recording surfaces governing the spatial resolution of the interface^,. Mesh electronics optimize the neural interface design for structural, mechanical, and topological similarity between the implant and neural substrate in order to create an interface that “looks” and “feels” like the cellular and sub-cellular networks comprising the brain.

Figure 3.

Schematic representation of syringe-injectable mesh electronic implant into a human brain. Mesh electronics directly address the structural, mechanical, and topological mismatch between probe and host tissue. The mesh is fabricated with subcellular-sized nanowire field-effect transistor detectors which maintain measurement sensitivity and allow for highly localized sampling, formation of artificial synapses, and minimally invasive intracellular recordings and single-neuron stimulation (stimulation pad depicted by red circle)^,–. The cellular and sub-cellular sized components are incorporated onto 3D ultra-flexible scaffold with a bending stiffness similar to the brain, and the macroporous interconnected arrangement of the mesh allow deep integration and interpenetration of neurons and glia without disruption to the local cytoarchitecture. Schematic representation of mesh electronics implanted in region of heterogenous neuronal sub-types (green and blue dashed-squares). Identifying unique cell-surface protein patterns may enable targeted cellular recording/stimulation interfaces through, for example, expression of complementary antibodies or aptamers on the mesh electronics electrode surfaces and/or polymer-encapsulated mesh structure.