Neurotechnologies for research and clinical applications

How can we make viable neural interfaces that last a lifetime?

Neurotechnology has the potential to provide a greater understanding of the structure and function of the complex neural circuits in the brain, as well as impacting the field of BMI to bring neuroprosthetic systems into the clinical realm.

Clinically-viable neurotechnologies that last a lifetime should be able to withstand a variety of biotic and abiotic effects that lead to performance degradation at the electrode-tissue interface. Moreover, these technologies should be wireless, require minimum power, and support large-scale bidirectional dataflow, i.e., “reading” and “writing” from/to the brain. In many cases, these systems will be fully implantable in the intracranial space as well as have batteryless operation. They should also be modular enough to allow the measurement and stimulation of different types of neural signals across different spatio-temporal scales.

In collaboration with Berkeley colleagues Michel Maharbiz, Jan Rabaey, Elad Alon, and Rikky Muller we have developed a number of unique technologies that have considerably advanced the state-of-the-art in BMIs. These include flexible sensor arrays, ultra-low power and low noise data acquisition channels, wireless powering of and communication with miniature-implanted devices, and complete system integration.

Vanishingly small neural interfaces

The highlight of our neurotechnology efforts with Michel Maharbiz is Neural Dust, a technology platform for wireless power and communication with implantable, extreme miniature sensors using ultrasound.

In essence, the technology consists of a millimeter-size implantable sensor that can be inserted deep into the body, such as in a particular nerve or organ, through a minimally invasive procedure. Neural dust uses ultrasound sent from an external device to receive power and communicate via backscatter real-time information such as electrophysiological data, pH, pressure, temperature, and oxygen levels from the body. Since ultrasound goes through the body like a charm, we only need to use minuscule amounts of power to energize the device and receive information from it.

For applications in cortical/subcortical BMIs, our goal is to achieve completely untethered recording through a large number of unanchored, free-floating miniature (< 100 µm3) motes. Overall, the long-term technology vision is to build multiple high bandwidth channels with the human body.

Recent collaborative efforts led by the Muller and Maharbiz groups have expanded the Neural Dust platform with electrical stimulation capabilities, resulting in StimDust. StimDust is the smallest volume, most efficient wireless nerve stimulator to date, capable of stimulating major therapeutic targets in the peripheral nervous system.

In the Fall of 2017, Michel Maharbiz and Jose Carmena co-founded iota Biosciences, a startup to commercialize the neural dust technology platform. iota aims to empower the future of bioelectronic medicine, transforming how the world monitors and treats disease.

A picture of Neural Dust. Click to read the article, “Engineers implanted tiny sensors in rats’ nerves and muscles. Are humans next?”, in The Washington Post.
From “Wireless recording in the peripheral nervous system with ultrasonic neural dust.” Click to view in Neuron.
StimDust.

Selected Publications

A system for neural recording and closed-loop intracortical microstimulation in awake rodents (2009)

Venkatraman S., Long J.D., Elkabany K., Yao Y. and Carmena J.M. (2009) A system for neural recording and closed-loop intracortical microstimulation in awake rodents. IEEE Transactions on Biomedical Engineering 56(1), pp. 15-22.

Abstract

There is growing interest in intracortical microstimulation as a means of providing sensory input in neuroprosthetic systems. We believe that precisely controlling the timing and parameters of stimulation in closed loop can significantly improve the efficacy of this technique. Here, we present a system for closed-loop microstimulation in awake rodents chronically implanted with multielectrode arrays. The system interfaces with existing commercial recording and stimulating hardware. Using custom-made hardware, we can stimulate and record from electrodes on the same implanted array and significantly reduce the stimulation artifact. Stimulation sequences can either be preprogrammed or triggered by neural or behavioral events. Specifically, this system can provide feedback stimulation in response to action potentials or features in the local field potential recorded on any of the electrodes within 15 ms. It can also trigger stimulation based on behavioral events, such as real-time tracking of rat whiskers captured with high-speed video. We believe that this system, which can be recreated easily, will help to significantly refine the technique of intracortical microstimulation and advance the field of neuroprostheses.

Investigating neural correlates of behavior in freely behaving rodents using inertial sensors (2010)

Venkatraman S., Jin X., Costa R.M. and Carmena J.M. (2010) Investigating neural correlates of behavior in freely behaving rodents using inertial sensors. Journal of Neurophysiology 104, pp. 569-575.

Abstract

Simultaneous behavior and multielectrode neural recordings in freely behaving rodents holds great promise to study the neural bases of behavior and disease models in combination with genetic manipulations. Here, we introduce the use of three-axis accelerometers to characterize the behavior of rats and mice during chronic neural recordings. These sensors were small and light enough to be worn by rodents and were used to record three-axis acceleration during freely moving behavior. A two-layer neural network-based pattern recognition algorithm was developed to extract the natural behavior of mice from the acceleration data. Successful recognition of resting, eating, grooming, and rearing are shown using this approach. The inertial sensors were combined with continuous 24-h recordings of neural data from the striatum of mice to characterize variations in neural activity with circadian cycles and to study the neural correlates of spontaneous action initiation. Finally, accelerometers were used to study the performance of rodents in traditional operant conditioning, where they were used to extract the reaction time of rodents. Thus the addition of accelerometer recordings of rodents to chronic multielectrode neural recordings provides great value for a number of neuroscience applications.

Neural Dust: An Ultrasonic, Low Power Solution for Chronic Brain-Machine Interfaces (2013)

Seo D.J., Carmena J.M., Rabaey J.M., Alon E., and Maharbiz M.M. (2013) Neural Dust: An Ultrasonic, Low Power Solution for Chronic Brain-Machine Interfaces. arXiv:1307.2196 [q-bio.NC].

Abstract

A major hurdle in brain-machine interfaces (BMI) is the lack of an implantable neural interface system that remains viable for a lifetime. This paper explores the fundamental system design trade-offs and ultimate size, power, and bandwidth scaling limits of neural recording systems built from low-power CMOS circuitry coupled with ultrasonic power delivery and backscatter communication. In particular, we propose an ultra-miniature as well as extremely compliant system that enables massive scaling in the number of neural recordings from the brain while providing a path towards truly chronic BMI. These goals are achieved via two fundamental technology innovations: 1) thousands of 10 – 100 \mu m scale, free-floating, independent sensor nodes, or neural dust, that detect and report local extracellular electrophysiological data, and 2) a sub-cranial interrogator that establishes power and communication links with the neural dust.

Model validation of untethered, ultrasonic neural dust motes for cortical recording (2014)

Seo D.J., Carmena J.M., Rabaey J.M., Maharbiz M.M. and Alon E. (2014) Model validation of untethered, ultrasonic neural dust motes for cortical recording. Journal of Neuroscience Methods pii: S0165-0270(14)00284-2. doi: 10.1016/j.jneumeth.2014.07.025.

Abstract

A major hurdle in brain-machine interfaces (BMI) is the lack of an implantable neural interface system that remains viable for a substantial fraction of the user’s lifetime. Recently, sub-mm implantable, wireless electromagnetic (EM) neural interfaces have been demonstrated in an effort to extend system longevity. However, EM systems do not scale down in size well due to the severe inefficiency of coupling radio-waves at those scales within tissue. This paper explores fundamental system design trade-offs as well as size, power, and bandwidth scaling limits of neural recording systems built from low-power electronics coupled with ultrasonic power delivery and backscatter communication. Such systems will require two fundamental technology innovations: (1) 10-100 μm scale, free-floating, independent sensor nodes, or neural dust, that detect and report local extracellular electrophysiological data via ultrasonic backscattering and (2) a sub-cranial ultrasonic interrogator that establishes power and communication links with the neural dust. We provide experimental verification that the predicted scaling effects follow theory; (127 μm)(3) neural dust motes immersed in water 3 cm from the interrogator couple with 0.002064% power transfer efficiency and 0.04246 ppm backscatter, resulting in a maximum received power of ∼0.5 μW with ∼1 nW of change in backscatter power with neural activity. The high efficiency of ultrasonic transmission can enable the scaling of the sensing nodes down to 10s of micrometer. We conclude with a brief discussion of the application of neural dust for both central and peripheral nervous system recordings, and perspectives on future research directions.

Wireless recording in the peripheral nervous system with ultrasonic neural dust (2016)

Seo D.J.*, Neely R.M.*, Shen K., Singhal U., Alon E., Rabaey J.M., Carmena J.M.* and Maharbiz M.M.* (2016) Wireless recording in the peripheral nervous system with ultrasonic neural dust. Neuron 91, pp. 529-539.

Abstract

The emerging field of bioelectronic medicine seeks methods for deciphering and modulating electrophysiological activity in the body to attain therapeutic effects at target organs. Current approaches to interfacing with peripheral nerves and muscles rely heavily on wires, creating problems for chronic use, while emerging wireless approaches lack the size scalability necessary to interrogate small-diameter nerves. Furthermore, conventional electrode-based technologies lack the capability to record from nerves with high spatial resolution or to record independently from many discrete sites within a nerve bundle. Here, we demonstrate neural dust, a wireless and scalable ultrasonic backscatter system for powering and communicating with implanted bioelectronics. We show that ultrasound is effective at delivering power to mm-scale devices in tissue; likewise, passive, battery-less communication using backscatter enables high-fidelity transmission of electromyogram (EMG) and electroneurogram (ENG) signals from anesthetized rats. These results highlight the potential for an ultrasound-based neural interface system for advancing future bioelectronics-based therapies.

Reliable Next-Generation Cortical Interfaces for Chronic Brain-Machine Interfaces and Neuroscience (2017)

Maharbiz M.M., Muller R., Alon E., Rabaey J.M., and Carmena J.M. (2017) Reliable Next-Generation Cortical Interfaces for Chronic Brain-Machine Interfaces and Neuroscience. Proceedings of the IEEE 105 :1:73-82. doi: 10.1109/JPROC.2016.2574938 [Review]

Abstract

This review focuses on recent directions stemming from work by the authors and collaborators in the emerging field of neurotechnology. Neurotechnology has the potential to provide a greater understanding of the structure and function of the complex neural circuits in the brain, as well as impacting the field of brain-machine interfaces (BMI). We envision ultralow-power wireless neural interface systems that are life-lasting, fully integrated, and that supports bidirectional data flow with high bandwidth. Moreover, we believe in the importance of building neural interface technology that is truly tetherless, has a very small recording footprint, and little to no mechanical coupling between the sensor and the external world. We believe these developments will impact both neuroscience and neurology, revealing fundamental insight about how the nervous system functions in health and disease.

Recent advances in neural dust: towards a neural interface platform (2017)

Neely R.M., Piech D.K., Santacruz S.R., Maharbiz M.M., and Carmena J.M. (2018) Recent advances in neural dust: towards a neural interface platform. Current Opinion in Neurobiology 50:64-71. doi: 10.1016/j.conb.2017.12.010. [Review]

Abstract

The neural dust platform uses ultrasonic power and communication to enable a scalable, wireless, and batteryless system for interfacing with the nervous system. Ultrasound offers several advantages over alternative wireless approaches, including a safe method for powering and communicating with sub mm-sized devices implanted deep in tissue. Early studies demonstrated that neural dust motes could wirelessly transmit high-fidelity electrophysiological data in vivo, and that theoretically, this system could be miniaturized well below the mm-scale. Future developments are focused on further minimization of the platform, better encapsulation methods as a path towards truly chronic neural interfaces, improved delivery mechanisms, stimulation capabilities, and finally refinements to enable deployment of neural dust in the central nervous system.

Up next: Neurophysiology of motor control