The human brain is an extraordinarily complex structure, whose details has not been fully understood. To date, the scientists could be compared to those pioneers that, centuries ago, drew the first geographic maps during dangerous journeys by sea or overland. Indeed, the tridimensional structure of the brain is so complex and difficult to explore that the availability of detailed maps has always been far to be achieved. Nevertheless, fortunately, something is changing.

Two studies published in 2016 showed significant advances in the human brain mapping thanks to two different imaging techniques. One study provided an accurate definition of 180 different areas for each hemisphere of the brain, while the other one showed a new method to quantify the number of synapses in human brains. Both studies share two important features: they provide data in vivo and in a safe way.

High-resolution mapping of the human brain

A study conducted by Glasser et al. used magnetic resonance imaging (MRI) technique to realize a high-resolution map of 180 regions of the brain. Splitting the brain into many parts is essential in order to understand how these regions interact together and to figure out how the brain works in its entirety.

Brain areas in high-resolution – Human Connectome Project

Glasser’s team analyzed high-resolution images obtained from the Human Connectome Project (HCP), which gathers data from around 1,100 healthy adults. The quality of the images permitted to identify 97 new areas per hemisphere, which were not been detected by previous approaches. The analysis of their architecture, structure and connectivity may help to study the processes of human cognition, development and aging. Moreover, it will be possible to characterize potential changes in the brain structure in case of diseases and cognitive impairment.

In addition to the providing of high-resolution of the brain images and to the advantages of a non-invasive in vivo technique, this method is precise, easily replicable and fully automated. Furthermore, the whole data are accessible to everyone on GitHub (https://github.com/), the HCP (http://humanconnectome.org) and BALSA (https://balsa.wustl.edu/) platforms.

There are also other projects aiming to reconstruct the neuronal connections in the brain of the mammals: among them, BigNeuron (http://bigneuron.org), Neuromorpho (http://neuromorpho.org) and Blue Brain (http://bluebrain.epfl.ch). Unfortunately, other projects on the human brain are still under development, as the european Human Brain Project (https://humanbrainproject.eu), or in stand-by, as the US BRAIN project (https://www.whithouse.gov/BRAIN).

The count of the synapses of the brain

PET evaluation with [11C]UCB-J reveals synapse loss in epilepsy patients

In many cases, the onset of the mental and neurodegenerative diseases is associated with a reduction in the number of synapses. So far, the main method utilized to determine the number of synapses has been the analysis of thin sections of the brain by Transmission Electron Microscopy (TEM). Obviously, the TEM cannot provide an overview of all the brain: it can be used to analyze only small sections of the brain tissue, and there are ethical issues to collect the biopsies.

The Finnema’s team has recently developed an in vivo reliable method for the count of the synapses by combining the well-known positron emission tomography (PET) technique with a new molecule called [11C]UCB-J. [11C]UCB-J binds to SV2A, a molecule that is found in every presynaptic membrane of the neurons. So, the link between [11C]UCB-J and SV2A act as a synaptic marker: the PET analysis quantifies the total number of these links, that is related to the density of the neurons.

This technique allows mapping the density of the synapses in every region of the brain. In the near future, the [11C]UCB-J SV2A PET imaging will help the diagnosis and the monitoring of the neurological disorders, such as the Alzheimer’s disease, that present a loss of the synapses number.

 

References:

Acebes A. Brain Mapping and Synapse Quantification In vivo: It’s Time to Imaging. Front Neuroanat. 2017 Mar 7;11:17. doi: 10.3389/fnana.2017.00017. eCollection 2017.

Glasser, M. F. et al. A multi-modal parcellation of human cerebral cortex. 2016 Nature 536, 171–178. doi: 10.1038/nature18933

Finnema, S. J. et al. Imaging synaptic density in the living human brain. 2016 Sci. Transl. Med. 8:348ra96. doi: 10.1126/scitranslmed.aaf6667

 

 

The elaboration of this post has been financed by the project PI15/01082, as a part of the National Plan of I+D+I and co-financed by the ISCIII – General Deputy Direction for Evaluation and Development of Health Research – and the European Regional Development Fund (ERDF).