Dion Khodagholy - US grants

The ability to send and receive information from inside the body is of key importance for scientific and medical applications. Nearly all implantable electronics devices require communication with the external world to be able to transmit acquired bio-signals for analysis or receive instructions from external devices to modulate their interactions with tissue. However, this task is inherently challenging because the communication method should be (i) non-invasive, meaning no components extruding through tissue, (ii) low-power, to be able to acquire data continuously over an extended period of time (iii) high-speed, to allow transmission of complex biological data acquired, (iv) controllable, to allow communication over a defined depth in the tissue. The overall objective of this work is to develop an ion-based, high-speed communication scheme to enable non-invasive and safe transmission of signals without the need of components that extrude through tissue. The rationale for the proposed work is that ions in biological tissue can be used to transfer information at high speeds and low power to the outside of body. The educational goal of the project is to provide hands-on experience for students by developing fully bio-compatible and inexpensive devices for ionic communication. The proposed research is expected to not only advance the field of bioelectronics by improving understanding of key principles governing communication across the body, but also result in positive impact to society at large.

To understand and modulate physiologic functions, implantable bioelectronic devices should be capable of safely communicating the high spatiotemporal resolution bio-signals with high speed and low power consumption to devices located outside the body. This communication and data transfer should be accomplished through a non-invasive path with no elements that extrude through tissue to minimize discomfort, mobility complications, and risk of tissue damage or infection. Ionic communication, which leverages the ion-rich nature of biological tissue to transmit signals through intact surfaces, could fulfill these requirements and address the limitations of current electronic charge carrier-based approaches. However, there is a clear lack of knowledge regarding how to use ionic communication to establish a high speed, low-power, and biocompatible communication medium across biological tissue. The objective of the proposed research is to combine optimal properties for an abiotic/biotic transmission interface: biocompatibility, conformability, miniaturization, low power consumption, efficient interaction with the body?s ionic signals, and ability to transmit data at speeds relevant to electrophysiological processes. Specific aims for the project are: (1) establish the physical, material and geometrical requirements to enable ionic communication; and (2) define the physical parameters that govern the spatial propagation of ionic signals through tissue. Overall, ionic communication could result in significant medical and social benefits by simplifying data transmission from bioelectronic devices and enabling application to situations in which use of transcutaneous connectors or bulky implanted electronics is prohibitive.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

PROJECT SUMMARY/ABSTRACT A major obstacle to identifying neural network mechanisms responsible for emergence of cognitive function is insufficient capability to acquire large-scale electrophysiologic signals across the course of brain maturation. There is urgent need to develop the technology and experimental protocols to acquire large-scale, chronic neu- rophysiological signals from small, fragile, immature brains via minimally invasive implantable devices. Our long-term goal is to enable such minimally invasive recording and manipulation of large-scale neural networks in developing organisms across critical developmental timeframes. Our overall objective is to establish a neural interface device that can be fully implanted in a mouse pup and can accommodate tissue growth, enabling chronic neurophysiological recording of multiple cortical regions without disrupting the environmental experi- ences required for normal development. Our central hypothesis is that integrating conducting polymer elec- trodes, expandable substrates, and conformable ionic circuits will allow creation of a Conformable, Expandable Neural Interface for the Developing Brain (CENID) that will help us elucidate the coordination of neural activity as the brain grows and matures. This hypothesis was formulated on the basis of preliminary data suggesting that organic electronics can efficiently acquire and process neurophysiologic signals. The rationale for the pro- posed research is that integration of these materials and device components enable our device to acquire data that was previously inaccessible. In order to achieve our objectives, we pursue the following two specific aims: (i) establish expandable, conformable and biocompatible integrated components for high spatiotemporal reso- lution signal acquisition and transmission of the developing brain; (ii) perform in vivo chronic implantation of CENID capable of acquiring and transmitting neurophysiological signals in freely moving mouse pups across maturation. The proposed research is innovative, in our opinion, because it substantially departs from the sta- tus quo of metal-based electrodes and silicon-based electronics by using conformable, fully biocompatible, conducting polymer-based components to create a fully implantable neural interface device compatible with monitoring large-scale cortical networks across development in naturally behaving rodents. This work is ex- pected to be significant because it will provide the groundwork for monitoring of neural networks across time periods associated with brain maturation and emergence of complex brain functions. It will have positive im- pact on development of previous unattainable experimental paradigms and contribute more broadly to im- provement in design of safe, long-term, minimally invasive bioelectronic devices.

Investigating brain circuit development can facilitate understanding of how the brain becomes capable of performing complex cognitive functions. A key missing strategy is the ability to monitor brain activity as an organism transitions to successful performance of behaviors requiring cognitive processes. This project involves using bioelectronic devices that can interface with different brain structures as they naturally grow<br/>to monitor immature rodents as they perform behaviors in naturalistic environments. These devices will be made out of soft, organic materials that can establish an effective interface with biological tissue with minimal damage. The overall goal of this project is to identify neurophysiologic signatures of emerging cognition, using computational analysis on acquired longitudinal data to track developmental trajectories.<br/>The outcomes of this research will improve the efficiency of biomedical devices and provide key insights into principles underlying formation of brain circuits that can support cognition. This work holds promise for guiding public health initiatives that could enable appropriate monitoring of childhood development. From an educational perspective, this project aims to expand training in interdisciplinary initiatives, specifically<br/>focusing on creating partnerships between engineering and neuroscience trainees and highlighting the iterative feedback process required to transition a device from development to functional utilization.<br/><br/>This project aims to addresses focus areas (i) neuroengineering and brain-inspired concepts and designs, and (ii) cognitive and neural processes in realistic, complex environments of NSF Integrative Strategies for Understanding Neural and Cognitive Systems. The overall objective is to use an integrated implantable neural device that enables longitudinal acquisition of neurophysiological data to investigate neural<br/>correlates of cognitive processes as animals become capable of performing advanced naturalistic behaviors. The central hypothesis is that organic electronics in combination with soft, expandable substrates can enable monitoring of local field potentials and action potentials from the developing brain without restricting spontaneous behavior. This data will identify predictors of capacity for neural computation<br/>supporting cognition in individual organisms. The rationale for this high-risk/high-payoff research is that novel monitoring approaches that merge engineering and neuroscience expertise are required to derive insight into how cognitive processes emerge in complex environments. The materials, approaches, and data generated by this work have the potential to provide notable medical and social benefits, such as: (i)<br/>soft, conformable interfaces for acquisition of neurophysiological activity from the human body; ii) approaches to safely expand neuroelectronic devices to use in pediatric age groups; and iii) accessible wearable bioelectronics for preventive medicine and lifestyle management. Generation of novel datasets from animals involved in naturalistic behavioral and social situations will benefit the neuroscience<br/>community and lead to further scientific discoveries. The educational aspects particularly emphasize improving diversity of trainees engaged in STEM research, and providing these trainees with the skills required to form, participate in, and manage projects that require strong interdisciplinary collaboration and involve individuals from disparate training backgrounds. Summative evaluation will be implemented for<br/>these efforts to evaluate overall success in integrating training about core principles of bioelectronics with neuroscientific analysis, with the goal of creating new opportunities for synergy between engineering and neuroscience fields.<br/><br/>This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.