Multifunctional Wireless Gut-Brain Neurotechnology

The peripheral organs of the body are in a constant bidirectional cross-talk with the brain. This generates a cognitive map of body’s physiological state which is vital for survival. Although internally arising organ-to-brain sensory cues are consciously imperceptible, they have been shown to influence higher level neurocognitive processes such as motivation and affect. These findings create opportunities for co-opting organ-to-brain neural circuits to develop new paradigms for autonomic neuromodulation therapies. However, probing and understanding critical brain-body circuits presents a neurotechnology challenge due to contrasting design criteria imposed on the implantable devices by drastic anatomical differences between the skull-encased brain tissue and mobile, delicate peripheral organs in behaving animal models.

In this talk I will describe our efforts in addressing this challenge. Seeking inspiration from nerve fibers, we design a soft, flexible polymer fiber-based organ-brain neurotechnology. In order to match the inherent signaling complexity of the nervous system we envisaged probes that integrate multiple functionalities while still retaining a miniature device foot print to facilitate chronic bio-integration. To create such a multifunctional and multi-organ neurotechnology we combine the scalability and customization of fiber drawing with functional sophistication of solid-state microdevices. With this approach we successfully produce hundreds of meters of flexible polymer filamentary probes integrating microscale light emitting devices, thermal sensors, microelectrodes, and microfluidic channels. The ability to process thermoplastic elastomers with the same route enables deterministic tunability of device mechanics and allows probes for targeting deep-brain structures and/or various regions of the murine intestine. We custom design a light-weight and modular wireless control circuit, NeuroStack, that offers bidirectional wireless control and real-time programmability of in-fiber microdevices along with an intuitive user interface. The brain fibers offer gene delivery for cell-type specific optogenetic neuromodulation, single-neuron recordings, thermometry, and tetherless control of mesolimbic reward pathway in the brain. The soft gut fibers grant access to anatomically challenging and delicate intestinal lumen, allowing intraluminal optofluidic control of sensory epithelial cells that guide feeding behaviors. Using this technology, we uncover that optogenetic stimulation of vagal afferents from the intestinal lumen is sufficient to drive reward behavior in untethered mice.

We anticipate that these illustrative applications will foreshadow widespread use of wireless multifunctional microelectronic fibers to study the roles of specific cells in bidirectional communication between the peripheral organs and the brain. This will not only empower the field of interoception, but also pave the way for mechanistically guided improved autonomic neuromodulation therapies.

Atharva obtained his Integrated BS-MS degree in Chemical Sciences at the Indian Institute of Science Education and Research-Kolkata. Atharva’s undergraduate research was centered around functional inorganic materials and spanned the fields of supramolecular polyoxometalate chemistry, colloidal quantum-dot chemistry, and photovoltaics. Fascinated by the idea of utilizing optoelectronic devices for understanding how the brain works, Atharva switched fields and joined the Bioelectronics group at MIT as a graduate student under the mentorship of Prof. Polina Anikeeva. His doctoral research is at the intersection of Materials Science, Medical Devices, and Systems Neuroscience. He develops soft, stretchable, and multifunctional microsystems in unusual form factors to modulate and monitor functions of the nervous system in the brain, spinal cord, and the gastrointestinal tract. These microscale probes are produced via scalable fabrication approaches and are wirelessly addressable. Some notable examples include flexible waveguides that enable luminal gut optogenetics, electrochemical brain probes that deliver gaseous neurotransmitters, and wireless multi-modal multi-organ gut-brain devices. The broader goal is to deploy this technology to decipher neural circuits underlying interoception and help guide clinically relevant autonomic neuromodulation therapies.