Integrated Neurophotonics Takes Brain Imaging to a New Level

Integrated neurophotonics can map real-time brain circuit activity at any depth.

Posted Oct 16, 2020

 Alex Mit/Shutterstock
Brain scan, X-ray (stock photo)
Source: Alex Mit/Shutterstock

A new state-of-the-art brain imaging technique could, someday, make fMRI neuroimaging technology and current optogenetic methods seem antiquated.

This week, a team of Caltech researchers from the Roukes Group announced that they've developed a new real-time method for monitoring and mapping neural circuit activity deep within the brain. This revolutionary method of peering deep inside the brain currently uses very tiny optical microchips that can be implanted inside the mouse brain (at any depth) to optically monitor and control individual neurons using fluorescent molecular and optogenetic actuators.

Scientists have dubbed this new brain imaging method "integrated neurophotonics" and describe how it works in a "Perspective" piece (Moreaux et al., 2020) published on October 14 in the journal Neuron.

"This approach has the potential to enable lens-less functional imaging from within the brain itself [italics authors'] to achieve dense, large-scale stimulation and recording of brain activity with cellular resolution at arbitrary depths," the authors state, with italics to emphasize that functional imaging from within the brain itself is a big deal.

"Current optogenetic studies of the brain are constrained by a significant physical limitation," Caltech senior research scientist and lead author of the paper, Laurent Moreaux, said in a news release. According to the authors, "At present, optogenetics methods cannot readily offer insight into circuits located deeper in the brain, including those involved in higher-order cognitive or learning processes."

Functional magnetic resonance imaging (fMRI) also has limitations due to a lack of neuron-specific information. Each voxel (i.e., 3-D pixel) of an fMRI brain scan contains about 100,000 neurons. Therefore, each voxel can only provide a relatively low-resolution representation of how these 100,000 neurons are behaving on average and en masse.

"The overarching goal of integrated neurophotonics is to record what each neuron in that collection of 100,000 is doing in real-time," principal investigator, Michael Roukes, said in the news release. "Although the work is currently done only in animal models, it could one day help to unravel circuitry deep inside the human brain."

"Dense recording at depth—that is the key," Roukes emphasizes. "We will not be able to record all of the activity of the brain any time soon. But could we focus on some of its important computational structures within specific brain regions? That's our motivation."

Integrated neurophotonics could be a game-changer. Although this method has only been used in mice thus far, someday, it may be possible for neuroscientists to track the activity of individual neurons within human brain circuits. By combining "recent advances in microchip-based integrated photonic and electronic circuitry with those from optogenetics," the Caltech researchers have developed a new method for mapping brain circuit activity that improves upon current optogenetic techniques and traditional fMRI.

"Many of the building blocks [for an approach such as ours] have existed for a decade or more," Roukes notes. "But, until recently, there has just not been the vision, the will, and the funding available to put them all together to realize these powerful new tools for neuroscience."


Laurent C. Moreaux, Dimitri Yatsenko, Wesley D. Sacher, Jaebin Choi, Changhyuk Lee, Nicole J. Kubat, R. James Cotton, Edward S. Boyden, Michael Z. Lin, Lin Tian, Andreas S. Tolias, Joyce K.S. Poon, Kenneth L. Shepard, Michael L. Roukes. "Integrated Neurophotonics: Toward Dense Volumetric Interrogation of Brain Circuit Activity—at Depth and in Real Time." Neuron (First published: October 14, 2020) DOI: 10.1016/j.neuron.2020.09.043