Coronal image of the brain vasculature of a premature neonate, obtained non-invasively using ultrafast Doppler ultrasound imaging.  Photo credit: Inserm U979 “Wave Physics for Medicine”, Langevin Institute – Waves and Imaging.

Physicians from Inserm Unit 979 “Wave Physics for Medicine” at the ESPCI Paris together with clinician researchers from the neonatal intensive care unit of Robert-Debré AP-HP pediatric hospital and Inserm Unit 1141 have just made a scientific and medical breakthrough: the non-invasive imaging of brain activity in newborns using ultrasound. This will open up new avenues for bedside neurological diagnosis in full-term and premature babies. The details of their research have been published in the October 11, 2017 issue of Science Translational Medicine.

 The technique used, called functional ultrasound imaging of brain activity, was invented in 2009 at the ESPCI Paris in Inserm Unit 979 “Wave Physics for Medicine”, led by Mickael Tanter, Inserm Research Director. Its originality lies in the use of ultrasound technology which, unlike other methods of brain imaging, is simple and portable. Physicians generally use magnetic resonance imaging (MRI) or positron-emission tomography (PET) to image brain activity. Although major technical progress has been made with these methods, they remain restrictive and costly, with long-waiting times for patients.

Similar in appearance to the ultrasound scanners used in obstetrics or echocardiography, the research prototype used has the particularity of being able to acquire images at very high speed. When combined with cutting-edge data processing algorithms, it is possible to map, with very high sensitivity, the subtle variations in blood flow in the small vessels of the brain, variations that are linked to neuronal activity. This new method combines ultrafast image acquisition with very high spatial resolution and a great depth of image. Until now, this had been applied only in pre-clinical studies, using animal models.

Therefore, the research published today establishes the first proof of concept of non-invasive functional ultrasound brain imaging in humans, performed in the neonatology and neonatal intensive care unit of Prof. Olivier Baud at Robert Debré Hospital, AP-HP, currently directed by Prof. Valérie Biran. The brain activity of premature neonates has been recorded in large regions of the brain, at rest and during seizures, at 1,000 images/sec and with a spatial resolution of 150 µm. These hitherto unheard-of data show propagation of cerebral blood flow between and during seizures, and make it possible to locate where they are coming from. Thanks to an ultrafast ultrasound prototype used at the patient’s bedside, images are acquired non-invasively by placing an ultrasound scanner on the baby’s head, above the fontanelle.

For Mickael Tanter and his colleague Charlie Demené, “this first proof of concept of a non-invasive form of neuroimaging that makes it possible to record neuronal activity across an extensive area of the brain, marks the entry of ultrasound into the world of clinical neurosciences with a method that is highly sensitive, portable and can be used directly at the patient’s bedside”.

This study demonstrates the potential of functional ultrasound imaging for the monitoring of premature neonates, who are tricky to examine and in whom it is difficult to diagnose neurological disorders. This technology is not heavy to handle and no patient transportation, contrast agents or ionizing emissions are needed. For Olivier Baud, “functional ultrasound brain imaging could represent a genuine revolution in the field of medicine by bringing new knowledge of neurovascular dynamics, brain development and neuroprotection mechanisms, as well as more early diagnosis of brain functional connectivity alterations”.

© Fotolia

The existence of new “social” neurons has just been demonstrated by scientists from the Institut de neurosciences des systèmes (Aix-Marseille University / INSERM), the Laboratoire de psychologie sociale et cognitive (Université Clermont Auvergne / CNRS), and the Institut de neurosciences de la Timone (Aix-Marseille University / CNRS). Their research on monkeys has shown that when these animals are made to perform a task, the presence or absence of a conspecific—that is, another monkey—determines which neurons are activated. Published in Social Cognitive and Affective Neuroscience, these findings broaden our knowledge of the social brain and help us better grasp the phenomenon of social facilitation.^[1]

Understanding how the brain functions within a social context is a major challenge facing neuroscientists.  Through their unique multidisciplinary collaboration, a primate neurophysiologist and an experimental social psychologist have now discovered two new classes of neurons in the prefrontal cortex: social and asocial neurons.

Most areas of the brain are associated with specific tasks. Some are specialized in the processing of information related to life in society: they make up the so-called social brain. In connection with thesis research conducted by Marie Demolliens,[2] CNRS researchers Driss Boussaoud and Pascal Huguet assigned monkeys the task of matching a picture shown on a touch screen with one of four different items displayed at the corners of the same screen. Executing such a task requires use of the prefrontal cortex but not the “social” areas of the brain. The researchers made daily recordings of neuronal electrical activity in this region of the brain while monkeys performed the task in the presence or in the absence of a conspecific.

Though the monitored neurons of the prefrontal cortex are primarily involved in execution of the visuomotor task, the study showed most of them also reacted strongly to either the presence or absence of another monkey. During the experiment, some of these neurons were only strongly activated in the presence of a conspecific. They have thus been dubbed social neurons. On the other hand, the activity levels of other, asocial neurons only spiked in the absence of a fellow monkey. Even more surprisingly, the greater the intensity of social neuron activity in the presence of a conspecific, the better the subject performed the task. Social neurons are hence at the root of social facilitation. Likewise, the greater the activity of asocial neurons in the absence of conspecifics, the better the subject performed the task—though not as well as in the presence of another, when social neurons are stimulated. The researchers also demonstrated that in the other, rare permutations—activation of social neurons in the absence of conspecifics, or of asocial neurons in their presence—the monkeys did not perform as well.

This work reveals the important connection between social context and neuronal activity, and the consequences on behavior: which neurons the brain uses depends on whether a conspecific is present, even if the task is the same. Thus, rather than being limited to the areas of the brain principally associated with social activity, social neurons might actually be dispersed throughout the brain and play a role in various tasks—whether or not the latter are social in nature.  These findings cast new light on the nature of the social brain as well as certain behavioral disorders characteristic of autism and schizophrenia.

 [1]. Social facilitation refers to enhanced performance of an activity due to the presence of a conspecific. It is observed among all species whose members live in groups (i.e., social species).

[2]. Under the joint supervision of Driss Boussaoud and Pascal Huguet.

Ten days after astronaut Thomas Pesquet take-off into space on the Proxima mission, many questions remain about human adaptation to gravity. The research team at Inserm Unit 1093, “Cognition, Motor Activity and Sensorimotor Plasticity” (Inserm/Université de Bourgogne), focuses on the manner in which movements that depend on this parameter are performed. For 30 years, it was thought that the brain, when giving motor commands, continuously compensated for the effects of gravity. In this study, the researchers reveal that it uses gravity to minimise the efforts our muscles have to make. These results have been published in eLife.

Many human and animal activities need our limbs to move in a precise manner. (Such is the case for professional dancers, who have perfect control of their bodies.) For a movement to be performed correctly, the brain has to generate muscular contractions while taking account of environmental factors likely to affect that movement. One of the most important of these is gravity. The brain develops an internal representation of gravity that it can thus use to anticipate its effects on our bodies. But how does that work? Until now, researchers thought that the brain compensated for the effects of gravity at every moment in order to direct a movement. But the Inserm researchers have proposed a new hypothesis. The brain may use the internal representation of gravity to take advantage of it and save energy.

In order to solve this mystery, the research team asked volunteers to perform arm movements under normal gravity and microgravity conditions. Under normal gravity, 15 volunteers performed right arm movements in 17 different directions.

Each movement was made up of two phases, which determined the total duration of the movement: an acceleration phase (e.g.: raising the arm if the initial trajectory is “upwards”) and a deceleration phase (e.g.: stopping the arm on its pathway). This is known as temporal organisation of movement.

If the brain continuously compensated for the effects of gravity, as was thought, the acceleration and deceleration phases would be of constant duration. Under normal gravity, the acceleration or deceleration phase directed by the brain proved to be more or less, depending on the direction of the movement. This observation corroborates the hypothesis that humans have adapted to exploit gravity by modulating the duration of these phases in order to avoid making unnecessary demands on the muscles.

To confirm and validate these results, the researchers simulated weightlessness in an aircraft. The volunteers repeated the arm movements in the 17 directions. While at the beginning of the experiment, the manner of performing the movements was the same as on Earth, the phases of acceleration and deceleration gradually changed in duration.
 

Volunteer performing movements under microgravity conditions in an aircraft travelling in a parabolic arc

© Jérémie Gaveau / Inserm

“This observation clearly shows that our brain captures information from the environment, reprogrammes itself and adapts to new gravity conditions,” explains Jérémie Gaveau, first author of this work. Once the brain has understood, it incorporates the new parameters and sends commands that allow movements to be performed with as little effort as possible.

 “Comparing these results to those of computer simulations shows sophisticated behaviour on the part of the individual. Indeed, our movements are organised to take advantage of the effects of gravity, in order to minimise the efforts that our muscles need to make,” he concludes.

 This is a genuine paradigm shift. This advance might ultimately be used to correctly programme the “brains” of humanoid robots or assist movement in disabled people.

The Virtual Brain: reconstruction of brain regions and where they are connected. The green cubes indicate the center of brain regions that are connected

©INS UMR1106 INSERM/AMU.

Researchers at CNRS, INSERM, Aix-Marseille University and AP-HM have just created a virtual brain that can reconstitute the brain of a person affected by epilepsy for the first time. From this work we understand better how the disease works and can also better prepare for surgery. These results are published in Neuroimage, on July 28, 2016.

Worldwide, one percent of the population suffers from epilepsy. The disease affects individuals differently, so personalized diagnosis and treatment are important. Currently we have few ways to understand the pathology’s mechanisms of action, and mainly use visual interpretation of an MRI and electroencephalogram. This is especially difficult because 50% of patients do not present anomalies visible in MRI, so the cause of their epilepsy is unknown.

Researchers have succeeded for the first time in developing a personalized virtual brain, by designing a base “template” and adding individual patient information, such as the specific way the brain’s regions are organized and connected in each individual. Mathematical models that cause cerebral activity can be tested on the virtual brain. In this way, scientists have been able to reproduce the place where epilepsy seizures initiate and how they propagate. This brain therefore has real value in predicting how seizures occur in each patient, which could lead to much more precise diagnosis.

Moreover, 30% of epileptic patients do not respond to drugs, so their only hope remains surgery. This is effective if the surgeon has good indications of where to operate.

The virtual brain gives surgeons a virtual “platform.” In this way they can determine where to operate while avoiding invasive procedures, and especially prepare for the operation by testing different surgical possibilities, seeing which would be most effective and what the consequences would be, something that is obviously impossible to do on the patient.

In the long run, the team’s goal is to provide personalized medicine for the brain, by offering virtual, tailored, therapeutic solutions that are specific for each patient. The researchers are currently working on clinical trials to demonstrate the predictive value of their discovery. This technology is also being tested on other pathologies that affect the brain, such as strokes, Alzheimer’s, degenerative neurological diseases, and multiple sclerosis.

This work involves researchers at the Institut de Neurosciences des Systèmes (INSERM/AMU), the Centre de Résonance Magnétique Biologique et Médicale (CNRS/AMU/AP-HM), the Département Epileptologie et du Département Neurophysiologie Clinique at AP-HM, and the Epilepsy Center of Cleveland. It was done in the Fédération Hospitalo-Universitaire Epinext (www.epinext.org).

The Virtual Epileptic Patient: brain regions and their connections are rebuilt by computer. Digital simulations generate an electric signal similar to that generated by the brain during seizures. These simulations allow digital testing of new therapeutic strategies

©INS UMR1106 INSERM/AMU.