(French) : VIH et Pays du Sud : Le suivi biologique des patients est coût-efficace sous certaines conditions de prix

Musical memory deficits start in auditory cortex

Congenital amusia is a disorder characterized by impaired musical skills, which can extend to an inability to recognize very familiar tunes. The neural bases of this deficit are now being deciphered. According to a study conducted by researchers from CNRS and Inserm at the Centre de Recherche en Neurosciences de Lyon (CNRS / Inserm / Université Claude Bernard Lyon 1), amusics exhibit altered processing of musical information in two regions of the brain: the auditory cortex and the frontal cortex, particularly in the right cerebral hemisphere. These alterations seem to be linked to anatomical anomalies in these same cortices. This work, published on XX April 2013 in the journal Brain, adds invaluable information to our understanding of amusia and, more generally, of the “musical brain”, in other words the cerebral networks involved in the processing of music.

Etude des structures cérébrales de sujets sains ou pathologiquesEtude des structures cérébrales de sujets sains ou pathologiques©Auzias/Inserm

Congenital amusia, which affects between 2 and 4% of the population, can manifest itself in various ways: by difficulty in hearing a “wrong note”, by singing “out of tune” and sometimes by an aversion to music. For some of these individuals, music is like a foreign language or a simple noise. Amusia is not due to any auditory or psychological problem and does not seem to be linked to other neurological disorders. Research on the neural bases of this impairment only began a decade ago with the work of the Canadian neuropsychologist Isabelle Peretz.

Two teams from the Centre de Recherche en Neurosciences de Lyon (CNRS / Inserm / Université Claude Bernard Lyon 1) have studied the encoding of musical information and the short-term memorization of notes. According to previous work, amusical individuals experience particular difficulty in hearing the pitch of notes (low or high) and, although they remember sequences of words normally, they have difficulty in memorizing sequences of notes.

In a bid to determine the regions of the brain concerned with these memorization difficulties, the researchers conducted magneto-encephalographs (a technique that allows very weak magnetic fields produced by neural activity to be measured at the surface of the head) on a group of amusics while they were performing a musical task. The task consisted in listening to two tunes separated by a two-second gap. The volunteers were asked to determine whether the tunes were identical or different.

The scientists observed that, when hearing and memorizing notes, amusics exhibited altered sound processing in two regions of the brain: the auditory cortex and the frontal cortex, essentially in the right hemisphere. Compared to non-amusics, their neural activity was delayed and impaired in these specific areas when encoding musical notes. These anomalies occurred 100 milliseconds after the start of a note.

These results agree with an anatomical observation that the researchers have confirmed using MRI: amusical individuals have an excess of grey matter in the inferior frontal cortex, accompanied by a deficit in white matter, one of whose essential constituents is myelin. This surrounds and protects the axons of the neurons, helping nerve signals to propagate rapidly. The researchers also observed anatomical anomalies in the auditory cortex. This data lends weight to the hypothesis according to which amusia could be due to insufficient communication between the auditory cortex and the frontal cortex.

Amusia thus stems from impaired neural processing from the very first steps of sound processing in the auditory nervous system. This work makes it possible to envisage a program to remedy these musical difficulties, by targeting the early steps of the processing of sounds and their memorization.

Are babies endowed with consciousness?

Babies have long been considered as beings with limited skills and behaviors that are principally automatic and of a reflex type, and are not accompanied by a subjective conscious experience. Nevertheless, CNRS scientists in the Laboratoire de Sciences Cognitives et Psycholinguistiques (CNRS/Ecole Normale Supérieure, Paris/EHESS), working in collaboration with scientists from NeuroSpin (Inserm/CEA) have now shown that as from an age of 5 months, infants are endowed with form of consciousness similar to that seen in adults. These findings are published in Science on 19 April 2013.

Un bébé de 5 mois qui a participé à cette étude avec sa mère.

A 5-month old baby who participated in the study with his mother.

© Sofie Gelskov

How can we determine whether babies are conscious of their environment even though they do not yet know how to talk and are incapable of communicating their thoughts? To solve this complex problem, the scientists used an alternative approach which consisted in determining whether the neural markers of consciousness seen in adults might also be present in babies. Indeed, recent research in adults has revealed a two-stage response by the brain to the perception of an external event. During the first 200 to 300 milliseconds, perceptual processing is wholly unconscious and accompanied by neural activity that increases in a linear manner; i.e. according to an amplitude which increases constantly depending on the length of time the objects are presented to them. A later, second stage (after 300 ms) is characterized by a non-linear response corresponding to the threshold of consciousness. Only periods of presentation that are sufficiently long to reach this threshold will give rise to a later response and be accompanied by conscious perception. This late and non-linear response by the brain is considered to be a neural marker of consciousness.

During this study, the presence of this marker of consciousness was tested in 80 infants aged 5, 12 and 15 months. To achieve this, they were asked to look at faces presented to them for varying periods of time (or in other words, for periods shorter or longer than their threshold of perception), while the electrical responses of their brains were recorded by electroencephalography. In all the age groups, the scientists saw the same late and non-linear response as in adults, thus confirming the presence of this “neural signature of consciousness” in the babies. However, although this response is recorded at around 300 ms in adults, it occurred much later in the babies, only being established after at least a second in the youngest infants.
These findings reveal that the cerebral mechanisms underlying perceptive consciousness are already present at a very early stage in infants. But at that time they are relatively slow, before accelerating gradually during development.

Quinze souris astronautes pour soigner les hommes

(French) Légionellose : reprogrammation inédite des cellules hôtes à l’avantage de la bactérie Legionella pneumophila

Liver disease: understanding it will enable the provision of better treatment

A certain number of patients hospitalised for cirrhosis complications soon develop a syndrome characterised by acute liver failure and/or the failure of other vital organs (ACLF)[1]. This syndrome had no specific diagnostic criteria hitherto. In this prospective study, led by Dr Richard Moreau, INSERM Research Director (Mixed Research Unit 773 “Centre de Recherche biomédicale Bichat-Beaujon”; INSERM/Université Paris Diderot) who is also a practitioner attached to the Hepatology Department of the Beaujon Hospital (AP-HP), researchers studied a cohort of 1343 patients from 12 European countries. The results, published in the learned journal Gastroenterology, describe, for the first time, the specific profile of sufferers from this syndrome that is associated with cirrhosis. This also makes it possible to more clearly define the actual rules of attribution of the organs in those most severely affected, for whom there is a high risk of early death.

Cirrhosis is an irreversible liver disease. It is characterised by chronic inflammation that destroys the liver cells and produces anarchic regeneration in the form of nodules. The disease causes the liver to lose function and is accompanied by multiple complications. When these complications manifest (bleeding in the digestive tract, bacterial infection, accumulation of liquid in the abdomen, etc.), this is known as decompensated cirrhosis and the patients are hospitalised.

A certain number of these patients quickly develop a syndrome characterised by acute liver failure and/or failure of other vital organs1 (ACLF – acute-on-chronic liver failure). The syndrome is associated with a high risk of death at one month and no diagnostic criteria were clearly established hitherto that might make it possible to describe the condition.

Through a consortium[1], the researchers in Mixed Research Unit 773 “Centre de Recherche biomédicale Bichat-Beaujon” (INSERM/Université Paris Diderot), analysed data from 1343 patients hospitalised due to acute cirrhosis complications between February and September 2011 in 29 Hepatology Departments in 12

European countries[2]. This enabled them to define robust diagnostic criteria for ACLF, indicating that one-third of the patients enrolled in the study had developed this syndrome.

The researchers noted that, compared to patients not suffering from ACLF, those who developed acute failure of an organ or organs were younger, were most frequently prey to alcoholism, suffered from a larger number of bacterial infections and had higher levels of white blood cells, as well as other markers of organ inflammation.

Quite unexpectedly, failure was most severe in patients without a previous history of cirrhosis complications. A high number of organ malfunctions (liver, kidneys, brain) were observed in these patients, including white blood cells in the blood and a mortality rate within one month of admission to hospital that was15 times greater than in patients who had a previous history.

“The identification of the criteria to define acute failure of an organ or organs enabled us to show that this is a separate syndrome from cirrhosis complications. In addition to organ failure and the high associated mortality, the development of the disease depends on the patient’s age and medical history”, explains Richard Moreau, INSERM Director of Research, and the Principal Investigator for the study.

We hope to be able to better identify those at risk of early death in order to improve their treatment. Furthermore, these results could lead to improving the current rules for assigning organs for grafting in the severest cases”, he concludes.


 Crédit photo : ©Fotolia

Liver and cirrhosis

The liver is a vital organ whose main functions are the storage and production of glucose as well as the synthesis and breakdown of other substances (triglycerides, cholesterol, lipoproteins, coagulation factors).
There are about 700,000 cases of cirrhosis in France, of which 30% are at the severe stage, resulting in 10,000 to 15,000 deaths a year. Diagnosis is on average at the age of 50. Not everyone at risk of cirrhosis develops the disease. In fact, it only manifests in 10% to 20% of cases.
The only current treatment for cirrhosis is a liver transplant. The first eligible patients are those whose life expectancy at three months is the lowest. Each year, around 1,000 patients receive liver transplants in France.

Please consult the information on the 


[1]    Consortium known as CLIF (“Chronic Liver Failure”) including French researchers and their European colleagues; Richard Moreau is the main investigator in the first study conducted under the aegis of this Consortium.

[2] France, Belgium, United Kingdom, Italy, Spain, Germany, Netherlands, Ireland, Switzerland, Austria, Denmark, Czech Republic


[1]    Acute-on-chronic liver failure affecting the kidneys, brain, lungs and/or circulatory system

The latest trends in healthy life expectancy in the European Union

A key priority for the European Union is to ensure its ageing population keeps as healthy as possible and it has set a target to increase the number of healthy life years (HLY) by 2 years from 2010 to 2020. The European Joint Action on “healthy life years” (EHLEIS) coordinated by the National Institute of Health and Medical Research (INSERM, France), the Member States and the European Commission together monitor and analyze trends in health expectancies in Europe. The latest results on healthy life expectancy at age 65 years and above will be revealed at the second annual meeting of EHLEIS in Paris on Thursday, April 18, 2013 (Salle Pierre Laroque, 14, Avenue Duquesne – 75007 PARIS at 13:30) at the invitation of the French Ministry of Health.

Doctor with female patient

• In the EU as a whole life expectancy at age 65 in 2011 was 18.0 years for men and 21.4 years for women, an increase of more than a year from 2005 (1.3 years for men and 1.2 years for women).

• Life expectancy in good perceived health (years lived where people perceive themselves in good or very good health) has also significantly increased since 2005, by 1.5 years for men and 1.6 years for women, more than the increases in life expectancy.

• On a less positive note healthy life years (years free of activity limitation) at age 65 have remained stable between 2005 and 2011, increasing by only 0.2 years, to 8.8 years for men, and decreasing by 0.2 years, to 8.6 years, for women. This means that the years lived with activity restriction have increased between 2005 and 2011.

• Life expectancy without chronic illness, significantly decreased between 2005 and 2010 but increased markedly between 2010 and 2011 so that the 2011 values (7.2 years for men and 8.0 years for women) were similar to those in 2005

. Again this means that the number of years lived with chronic illness increased between 2005 and 2011. These apparently contradictory results might be explained by better management of health problems and/or associated disability (activity limitations), so that the health problems and disability associated with increases in life expectancy at age 65 have not generated an increase lower quality of life. It is likely that people, better informed today about their actual health status, report more chronic health problems and at earlier stages.

Table 1: Life and health expectancies at age 65 in Europe (EU25) from 2005 to 2011 * – by sex (Figures corresponding to Figure 1)

tableau 1 ENG

Figure 1: Changes in life and health expectancies at age 65 in Europe (EU25) from 2005 to 2011 * – by sex *Provisional figures for 2011

Changes in life and health expectancies at age 65 in Europe (EU25) from 2005 to 2011 * - by sex *Provisional figures for 2011

For more information

The HLY (Healthy Life Years) is an important European policy indicator and was selected as part of the Lisbon Strategy (2000-2010) to assess the quality of life and functional health status of Europeans. The HLY is also part of the European Community Health Indicators (ECHI) and was set as the overarching target of the partnership of Innovation Union (research and development component of the strategy Europe 2020) on Active and Healthy Ageing, the target being an increase in HLY in the European Union of two years by 2020. HLYs are obtained by applying the prevalence of disability observed in the general population to a standard life table to distribute the years lived into those lived with disability and those lived free of disability. The same principles are applied to compute the life expectancy without chronic disease and the life expectancy in good perceived health. The health information used (prevalence of activity limitation, longstanding health problems, self perceived health) comes from the annual EU-SILC survey whose implementation is coordinated by EUROSTAT. Self perceived health is measured by the question: How is your health in general? Very good, good, fair, bad, very bad. Chronic diseases are measured by the question: Do you have long standing health problems? Yes, no. The prevalence of disability is measured by a general question on activity limitations: To what extent have you been limited for at least 6 months, due to health problem, in activities people usually do? Severely limited, limited but not severely, not limited at all. EUROSTAT calculates and disseminates the HLY as it does for all European policy indicators. The objective is to provide in year t (i.e., 2013) the HLY indicators of year t-2 (i.e., 2011). The Joint Action EHLEIS, supported and supervised by the European Commission, disseminates widely the results for all ages (not just birth and age 65 years) through country reports, dedicated websites, Wikipedia, and other media, encourages correct interpretation through training material and an interpretation guide, promotes their use in policies and, lastly and most importantly, produces in-depth analyses of trends and gaps in HLYs and their determinants.

The surprising ability of blood stem cells to respond to emergencies

A research team of Inserm, CNRS and MDC lead by Michael Sieweke of the Centre d’Immunologie de Marseille Luminy (CNRS, INSERM, Aix Marseille Université) and Max Delbrück Centre for Molecular Medicine, Berlin-Buch, today revealed an unexpected role for hematopoietic stem cells: they do not merely ensure the continuous renewal of our blood cells; in emergencies they are capable of producing white blood cells “on demand” that help the body deal with inflammation or infection. This property could be used to protect against infections in patients undergoing bone marrow transplants, while their immune system reconstitutes itself. The details of the research is published in Nature on april 10th 2013.


Cells in our blood feed, clean and defend our tissues, but their lifespan is limited. The life expectancy of a red blood cell rarely exceeds three months, our platelets die after ten days and the vast majority of our white blood cells survive only a few days.

The body must produce replacement cells in a timely manner. This is the role of hematopoietic stem cells, more commonly called blood stem cells. Nestled in the core of the bone marrow (the soft tissue in the center of long bones such as the chest, spine, pelvis and shoulder), they dump billions of new cells into the bloodstream every day. To accomplish this strategic mission, they must not only multiply but also differentiate, i.e. to produce specialized white blood cells, red blood cells or platelets.

For many years, researchers have been interested in how this process of specialization is triggered in stem cells. Michael Sieweke and his team previously discovered that the latter do not engage randomly in a particular differentiation pathway but “decide” their fate under the influence of internal factors and signals from the environment.

An important issue remains: how do stem cells manage to respond appropriately to emergencies? For example, are they able to meet the demand by producing white blood cells like macrophages to eat microbes during infection?

Until now, the answer was clear: the stem cells could not decode such messages and were content to differentiate randomly. Michael Sieweke’s team has demonstrated that, far from being insensitive to these signals, stem cell perceive them and in return manufacture the cells that are most appropriate for the danger that is faced.

“We have discovered that a biological molecule produced in large quantities by the body during infection or inflammation directly shows stem cells the path to take,” said Dr. Sandrine Sarrazin, Inserm researcher, co-author of the publication. “As a result of this molecule, called M-CSF (Macrophage Colony-Stimulating Factor), the switch of the myeloid lineage (the PU.1 gene) is activated and the stem cells quickly produce the cells that are best suited to the situation such as macrophages.”

Now that we have identified this signal, it may be possible in the future to accelerate the production of these cells in patients facing the risk of acute infection,” said Dr. Michael Sieweke, CNRS Research Director. “This is the case for 50,000 patients worldwide each year* who are totally defenseless against infections just after bone marrow transplantation. Thanks to M-CSF, it may be possible to stimulate the production of useful cells while avoiding to produce those that can inadvertently attack the body of these patients. They could therefore protect against infections while their immune system is being reconstituted”.

About the discovery

This seemingly simple discovery is quite original, both in its approach and by the technology it required. To reach their conclusions the team had to measure the change of state in each cell. This was a double challenge: the stem cells are not only very rare (there is only one stem cell per 10,000 cells in the bone marrow of a mouse), but they are also completely indistinguishable from their descendants.

“To differentiate the protagonists we used a fluorescent marker to indicate the status (on or off) of the myeloid cell switch: the protein PU.1. First in the animal, then by filming the accelerated cell differenciation under a microscope, we showed that stem cells “light-up” almost immediately in response to M-CSF,” said Noushine Mossadegh-Keller, CNRS assistant engineer, co-author of this publication. “To be absolutely sure, we recovered the cells one by one and confirmed that the myeloid genes were activated in all the cells that had turned green: once they perceived the warning message, they changed identity.”

Adolescents aujourd’hui, adultes demain

Is the mother’s immune system capable of protecting the foetus from cytomegalovirus infection?

An infection from the cytomegalovirus (CMV), a virus belong to the herpesviridae family, usually goes unnoticed in a healthy subject, but in pregnant women, it can be harmful to the foetus. Nabila Jabrane-Ferrat, research officer of the CNRS Physiopathology Centre at Toulouse Purpan (Inserm unit / université Toulouse III – Paul Sabatier / CNRS), working with The “Immunity, Gestation, Therapy” research team led by Philippe Le Bouteiller, an Inserm research director, has demonstrated that certain immune cells from the mother located at the foeto-maternal interface are capable of fighting the infection in order to protect the foetus. This work was published in the review Plos Pathogens on April 4, 2013.

Pregnancy induces major modifications in the uterus that are necessary to provide the needs of the foetus. Following the implantation of a fertilized egg, the wall of the uterus (the endometrium) is massively infiltrated with a specific population of immune cells known as decidual Natural Killer cells (dNK), that come from the mother.

The functions of these immune cells are finely regulated during pregnancy. In the endometrium, their function is not to kill, but to protect to allow successful implantation of the embryo. dNK cells release soluble factors that help the embryo to implant into the maternal tissue. They contribute to exchanges between the mother and the fœtus and are in direct contact with the placenta. By providing an enriched microenvironment, dNK cells play a major part in pregnancy.

The authors of the study published this month wondered whether these cells that are “armed to kill” could have their gregarious instinct aroused in the event of an attack by a pathogenic agent. To this end, they studied the action of the dNK cells when the mother was infected by CMV during pregnancy.

Congenital infection by the CMV is a major public health problem that affects between 0.2 and 0.5 percent of newly-borns in France and is a known cause of foetal fatality. CMV contamination occurs by close contact with affected persons or healthy carriers. Therefore, pregnant women must respect the classic rules of hygiene to avoid infection during their pregnancy, since the risk of foetal contamination is between 30 to 50%.

There are no clinical signs of CMV in a healthy adult; but it is dangerous for the foetus if the mother becomes infected. The virus passes into the mother’s bloodstream, crosses the placental barrier and infects the cells in the foetus, causing serious damage, even death to the foetus. Congenital CMV infection induces placental development problems and remodelling of the uterine arteries that can be detected by ultrasound scanning.

Researchers have observed phenotype and functional changes in maternal dNK cells. In addition, analysis of tissues from terminations of pregnancy due to CMV has shown that dNK cells are capable of migrating to the actual site of the infection in the placenta.

Quite unexpectedly, the researchers found that dNK cells become cytotoxic in order to kill off infected cells and fight infection.

For Cover

© N. Jabrane-Ferrat / Inserm. In red and greed above: the NK cells attempting to make their way to the infected cell (in glue and green).

These results suggest that dNK cells could protect the foetus from maternal CMV infection. They open the way for the development of new treatments. The next step is to figure out how to trigger a massive cytotoxic reaction by the dNK cells when faced with the virus.