An axial and a sagittal slice of Broca's area as seen with Magnetic Resonance Imaging (a.u.=arbitrary units). Credit: Costantini I, Morgan L, Yang J, Yael Balbastre Y, et al., Science Advances, 9, 41 (2023).
An international research team has created the first cell-by-cell atlas of a part of the brain known as Broca’s area, critical for processing language and producing speech. The team includes scientists from the University of Florence and the National Research Council (CNR), and the unprecedented single-cell level resolution was achieved at the European Laboratory for Non-Linear Spectroscopy (LENS) in Sesto Fiorentino.
The atlas has been published in Science Advances1, as part of a package of 21 neuroscience studies across various journals. These publications are all under the umbrella of the National Institutes of Health’s BRAIN Initiative Cell Census Network (BICCN), launched in 2017 to create an atlas of the human and non-human primate brain at the cell-type level.
Knowing how several types and sub-types of brain cells work and how they are distributed throughout the brain’s volume is essential to understand how neural circuits generate complex perceptions and behaviours. The team from Italy developed a new technique to analyse and quantify the cellular organization of neurons at a micrometre resolution, while also maintaining a macroscopic view of the spatial organisation of the whole brain. They did so by combining four experimental techniques: magnetic resonance imaging and optical coherence tomography provided 3-D anatomical images at the macroscopic scale, while light-sheet fluorescent microscopy and stereology were used to image and count cell types.
“We have put together a multimodal imaging infrastructure to bridge the resolution gap between macroscopic and microscopic techniques, resulting in a platform that integrates cellular information within a whole-brain reference space,” explains Francesco Saverio Pavone, director of LENS and among the lead authors of the study.
The approach allowed the researchers to collect a cell census of the different neuronal types in the Broca’s area within the whole-hemisphere magnetic resonance imaging of a post-mortem human brain. “Now we can delve deeper into how the cellular architecture changes because of pathologies, and we can increase the resolution of the MRI technique used in clinical applications,” says Pavone. The team’s highly accurate images of a post-mortem brain, he points out, could be used as a reference to interpret MRI scans, or to train machine learning algorithms.
Pavone suggests that the approach, currently applied to a single area of the brain, can be extended to several cerebral areas to gain access to fundamental information on their structure and function. This will also help assess variability between individuals and within a single individual over time, for example because of pathologic changes that occur in neurodegenerative and psychiatric illnesses. Or, Pavone explains, it may be possible to provide data to researchers who develop brain-machines interfaces for patient who have lost their speech and could use a device that decodes signals from the Broca’s area and then re-codes them into words.
