Manipulating brain circuits using smartphones

A wireless soft neural implant that can be controlled using a smartphone was developed. It is the first wireless neural device capable of indefinitely delivering multiple drugs and multiple color lights to chronically control brain circuits with high specificity, thereby accelerating efforts to uncover brain diseases such as Alzheimer’s and Parkinson’s.

Article | Spring 2020

Optogenetics and neuropharmacology are powerful techniques that can dissect complex neural circuitry using light and drugs, respectively. Because of their high specificity for controls of neuronal cells in time and space, these methods have immense potential for basic neuroscience studies and clinical applications.

Conventional approaches to optogenetics and neuropharmacology involve optical fibers and metal tubes to deliver light and drugs, respectively. However, these tools not only limit the subject’s movement due to the need for physical connections with external equipment, but also cause increase tissue damage and inflammation because of the mechanical mismatch between rigid devices and soft brain tissue. For these reasons, these are not appropriate for implantation in the brain for long periods of time.

To address these issues, a research team under Professor Jae-Woong Jeong in the School of Electrical Engineering at KAIST invented a small, smartphone-controlled brain implant that can wirelessly deliver drugs and light indefinitely for “chronic” optogenetics and pharmacology (Figure 1 and Video 1). This device, incorporating Lego-like replaceable drug cartridges and an ultrathin soft probe (with the thickness of a human hair) with tiny LEDs and microfluidic channels, allow neuroscientists to study the same brain circuits for several months through optical and chemical manipulations.

 

Controlled with a simple user interface on a smartphone, neuroscientists can easily trigger any specific combination or precise sequencing of light and drug deliveries in any implanted target animal without the need to be physically inside the laboratory (Video 2). Using these wireless neural devices, researchers could also easily setup fully automated animal studies where the behavior of one animal could trigger light and/or drug delivery in other animals. This was enabled by a closed-loop control system, which monitored the target subject with a camera, and depending on its specific behaviors, the devices implanted in the surrounding animals were triggered wirelessly based on custom-defined algorithms.

The research team succeeded in controlling place preference of freely behaving mice through wireless light and drug delivery to the brain. Mice that have light-sensitive neurons associated with place preference behavior could be controlled by neuroscientists to make them stay on one side of a cage through light stimulation on these neurons. The mice lost their place preference behavior when the researchers used a smartphone to trigger the delivery of a drug that blocked the action of the neurons.

This research was published on August 05, 2019 in Nature Biomedical Engineering under the title, “Wireless optofluidic brain probes for chronic neuropharmacology and photostimulation” (Nature Biomedical Engineering 3, 655-669 (2019)).

Video 1. Smartphone App Graphical User Interface for wireless, selective and programmable control of optofluidic devices.

Video 2. Wireless selective control triggering of intra-VTA drug release in a group of four mice during an open field test. The video highlights the device capability for selective wireless drug delivery to manipulate brain circuits in freely moving animals with no physical disturbance.