To reach high temporal and spatial resolution, N3 will focus on two approaches: noninvasive (Technical Area 1 –TA1) and “minutely” invasive (Technical Area 2 – TA2) neural interfaces. Noninvasive interfaces will include the development of sensors and stimulators that do not breach the skin and will achieve neural ensemble resolution (<1mm3). Minutely invasive approaches will permit nonsurgical delivery of a nanotransducer: this could include a
self-assembly approach, viral vectors, molecular, chemical and/or biomolecular technology delivered to neurons of interest to reach single neuron resolution (<50μm3). In this application, the developed technology will serve as an interface between targeted neurons and the sensor/stimulator. They should be sufficiently small to not cause tissue damage or impede the natural neuronal circuit. The sensors and stimulators developed under the minutely invasive approach will be external to the skull and will interact with the nanotransducers to enable high resolution neural recording and stimulation.
Both noninvasive and minutely invasive approaches will be required to overcome issues with signal scattering, attenuation, and signal-to-noise ratio typically seen with state of the art noninvasive neural interfaces. Systems that are larger or requiring a highly controlled environment – such as magnetoencephalography (MEG), or magnetic resonance imaging (MRI) – and proposals describing incremental improvements upon current technologies, such as electroencephalography (EEG), may not be considered responsive to this BAA and may not be evaluated.
Final N3 deliverables will include a complete integrated bidirectional brain-machine interface system. Non-invasive approaches will include sensor (read) and stimulator (write) subcomponents integrated into a device (or devices) external to the body (Figure 1B). Minutely invasive approaches will develop the nanotransducers for use inside the brain to facilitate read out and write in (Figure 1A). Minutely invasive approaches will also develop the external subcomponents and integrated devices that interact with the internal nanotransducers. N3 developed technologies may move beyond the traditional voltage recordings associated with action potentials, and include different types of signals, such as
light, magnetic/electric fields, radiofrequency, and neurotransmitter/ion concentrations. These atypical signals may require the development of new algorithms to enable accurate decoding and encoding of neural activity. To that end, the N3 program will include a computational and processing unit that must provide task- relevant decoded neural signals for control in a DoD-relevant application. It must also provide the capability to encode signals from a DoD-relevant application and deliver sensory feedback to the brain. The processing unit must decode/encode in real time with minimal system latency (Figure 1C). A block diagram of the expected final prototype is shown in Figure 2.
To prove the capabilities of the N3 system, four major demonstrations will show progress from a benchtop proof-of-concept, to validation in animal models, to a final demonstration of a DoD- relevant application in human subjects. In order to transition the developed technology to clinical readiness, N3 performers will actively collaborate with the Food and Drug Administration (FDA) throughout the program.
ABC
Figure 1. Notional N3 prototype. 1A - Nanotransducers supporting read and write functions (for TA2 devices only). 1B right - Notional concept of at least two subcomponents integrated into one device. 1B left – notional diagram of multiple devices used to achieve multi-focal interaction with the brain. 1C - Processing unit for decoding and encoding computation between the N3 system and relevant DoD application.

(minutely invasive devices only)

Internal
Figure 2. Block diagram of N3 technology
External