An advance in understanding the origins of language

Researchers from the Cognitive Neuroimaging Unit at NeuroSpin have just identified a network of areas of the brain that are organised in a way that could at least partially explain the specificity of the cognitive functions in the human species. These regions are specifically activated in humans, but not in the macaque monkey, in response to specific variations in the auditory sequences played. They coincide with the classic language areas, particularly Broca’s area. The human faculty of language could therefore have its origins in the emergence of a brain circuit capable of combining, in a single region, information coming from the other regions of the brain into a coherent whole. These results, obtained through a collaboration between the French Atomic Energy Commission (CEA), Inserm, Collège de France, Versailles-Saint-Quentin-en-Yvelines University and Paris-Sud University, are published in Current Biology.

In this study, conducted at NeuroSpin, Stanislas Dehaene (a professor at Collège de France, and director of the Inserm/CEA/Paris-Sud University Cognitive Neuroimaging Unit) and Bechir Jarraya (Professor of Neurosurgery at Versailles-Saint-Quentin-en-Yvelines University), together with Liping Wang and Lynn Uhrigh, used a noninvasive functional imaging method, 3 Tesla functional MRI. They exposed three macaque monkeys and twenty volunteers to regular auditory sequences, e.g. three identical sounds followed by a fourth different sound (a sequence notated as AAAB). Occasionally, they presented a sequence that violated this regularity, either because it included a different number of sounds (e.g. AAAAAB), or because the sequence of sounds was abnormal (e.g. AAAA, which does not end in a B sound).

The monkey’s brain reacted to changes in numbers and sequences, which denotes a certain capacity for abstraction. However, it did so in distinct areas, specialised for either number or sequence. In contrast, the human brain combined the two parameters in regions that coincide with the language areas.

Thus, whereas the monkeys detected isolated properties, such as “four sounds” or “the last one is different,” evolution seems to have endowed our species with a specific ability to combine these pieces of information into a coherent whole, a formula such as “three sounds, then another”—the very beginnings of an inner language?

Thus, although the abstract representation of sound sequences is possible in non-human primates, the evolution of a new brain circuit, connected to the auditory areas, might have enabled our species to acquire the unique ability to compose and recognise the complex sequences characteristic of human languages.Dehaene_LangageCerveau

This figure illustrates the unique ability of the human brain to combine pieces of abstract auditory information. Some regions of the brain are associated with the detection of a change in number of sounds by the brain, independently of a concomitant change in the sequence of sounds (red areas in the figure). Conversely, some regions of the brain detect changes in the sequence of sounds, independently of their number (green areas). In the monkey brain, these two sets of regions are unconnected. Places where they intersect (shown in yellow), i.e. regions that combine the two types of information, “change in sequence of sounds” and “change in number of sounds,” are found only in the human brain. All activations detected are projected on a lateral view of the right hemisphere for purposes of representation. © Liping Wang

Diabetes is associated with neurocognitive disorders in people living with HIV

Does diabetes play a role in the decline of cognitive function in people living with HIV? Researchers at Inserm Unit 897, “Epidemiology and Biostatistics Inserm Research Centre” (Inserm/University of Bordeaux) and the CIC-1401 Clinical Investigation Centre, in collaboration with Bordeaux University Hospital, have shown for the first time that there is a relationship between diabetes and neurocognitive disorders in people living with HIV, regardless of age. These disorders mainly affect functions involving memory and reactivity, and appear as early as the prediabetic stage (hyperglycaemia). This work, funded by ANRS (French National Agency for Research on AIDS and Viral Hepatitis) and carried out within the ANRS Aquitaine cohort, is published in the journal Neurology.
Virus du SIDA

Cell massively infected by HIV, showing the budding of viral particules at the cell surface. © Inserm/Roingeard, Philippe

In 20-50% of cases, people living with HIV show mild neurocognitive disorders, even when their viral load is well controlled by antiretroviral treatment. The causes of these disorders are still incompletely known: age or “traditional” risk factors (education level, vascular risk factors such as diabetes), HIV infection or antiretroviral treatment.

In the general population, several studies have shown that there is a link between diabetes and cognitive decline in older people. Since the prevalence of diabetes in people living with HIV is 5-10%, could diabetes be an explanation for cognitive disorders? A study conducted by Prof. Geneviève Chêne’s team at Inserm Unit 897, “Epidemiology and Biostatistics Inserm Research Centre” (Inserm/University of Bordeaux) and the CIC-1401 Clinical Investigation Centre, together with Bordeaux University Hospital, drew upon the ANRS Aquitaine cohort to answer this question. It reveals for the first time that diabetes is associated with neurocognitive disorders in people living with HIV, regardless of age. This study, funded by ANRS (French National Agency for Research on AIDS and Viral Hepatitis), has just been published in the journal Neurology.

The Aquitaine cohort comprises nearly 9,000 patients distributed among 13 public hospital services, all located in the Aquitaine region of France. The objective of this cohort is to study the course of HIV-1 infection, both naturally and during treatment. For this study, which was carried out at 5 clinical centres of Bordeaux University Hospital between June 2007 and November 2009, 400 people living with HIV were enrolled. They were monitored for two years. Clinical tests (detection and validation of cerebrovascular and cardiac disease, treatments employed, and activities), blood samples, and 10 tests to evaluate cognitive and motor performance were carried out.

Of these 400 people, 39 were diabetic and 33 had hyperglycaemia indicating a “prediabetic” state.

Results show that diabetic patients performed less well than nondiabetic patients in tests involving memory, executive functions, attention, psychomotor speed, language and manual dexterity. Over these two years of monitoring, the researchers observed a slight decline in executive function and memory among these patients.

For people living with HIV who had hyperglycaemia (prediabetic state), overall performance was poorer than in nondiabetic people.

Taking other parameters such as cardiovascular risk factors (hypertension, overweight, hypercholesterolaemia, hypertriglyceridaemia) into consideration does not change these results.

This study demonstrates for the first time the impact of diabetes and the prediabetic state on cognitive performance in people living with HIV. “Basic research should step in to explore the physiopathological mechanisms at play. In particular, to examine objectively whether the lesions created in the small blood vessels by chronic hyperglycaemia are exacerbated by the HIV virus itself. The consequences of HIV on immune activation, as well as certain genetic predispositions, must also be examined,” explains Prof. Geneviève Chêne.

These results already show that active management is needed. 

Geneviève Chêne adds: “In the same way as for the general population, it is vital to strengthen diabetes screening and prevention in people living with HIV. Maintaining a healthy diet, controlling one’s weight and taking regular exercise are universal recommendations.”

One in every two people bring back multi-resistant enterobacteria after a trip in a tropical zone

A large-scale collaborative study, conducted by a French team comprising of the Infectious and Tropical Disease departments of the AP-HP, the hospital bacteriology and hygiene laboratories, the Research Unit of the Bichat – Claude Bernard hospital, the Paris-Diderot University, Inserm, the Pasteur institute and InVS, revealed the acquisition of multi-resistant enterobacteria (MRE) in one in two travellers returning from a stay in a country situated in a tropical region. These results were published in the international journal Clinical Infectious Diseases on 22nd April, 2015.



Enterobacteria are microorganisms naturally present in our digestive tract.  While some are completely harmless, others can be responsible for serious infections. In such cases, the patients are treated with antibiotics. Unfortunately, some of these bacteria are resistant, making treatment of these diseases difficult.

The teams coordinated by Sophie Matheron and Etienne Ruppé carried out a study on 824 healthy people before and after a stay in a tropical region (sub-Saharan Africa, Asia, or South America). These people were asked to answer a medical questionnaire and to provide a stool sample in the week before their departure and within three days of their return. This step was repeated for travellers carrying multi-resistant enterobacteria (MRE) until the samples were negative.

The study revealed an overall acquisition frequency of MRE in the digestive tract during the trip of 51%, i.e. one in two travellers. This increased frequency differs depending on the geographical regions visited: on returning from Asia, over 72% of travellers were carriers, more than 47% of those returning from sub-Saharan Africa were carriers, and a little more than 31% of those returning from South America were carriers.

The acquisition of these microorganisms is favoured by the taking of antibiotics (which alters the natural “barrier” protection effect of the bacteria normally present in the digestive tract), the occurrence of diarrhoea during the trip, and the type of trip.  The open stays (organised trips, the family or the backpacker type) present a greater risk than closed stays in hotel-clubs. The prolonged follow-up showed that 95% of the travellers spontaneously eliminate the MRE in the three months after their return.

This study reminds us of the importance of the prudent use of antibiotics (often consumed in an excessive way in cases of simple diarrhoea) and the importance of respecting the preventative and basic hygiene rules during the trip (wash food, wash hands, drink water from a bottle, etc.). Thanks to dedicated consultations, the international vaccine and advice centres provide this information to travellers. They also give other advice and prescriptions depending on the destination (vaccination, prevention of malaria).

Finally, these results highlight the necessity to study the involvement of MRE in patients reporting an infection in the three months following their return from a tropical region. Thus, the health professionals in towns and hospitals may prescribe a treatment adapted to a possible antibiotic resistance.

It should be noted that travellers carrying MRE are not ill and, on this ground alone, have no reason to consult a doctor.

This study was sponsored by the Public Hospitals of Paris (Assistance Publique-Hôpitaux de Paris – AP-HP) as part of a Hospital Clinical Research Program (Programme Hospitalier de Recherche Clinique – PHRC).

Production of iPS cells: discovery of the 5th element

Since 2006, research has succeeded in generating, from specialised adult cells, induced pluripotent cells (iPS cells), with huge potential applications, particularly for regenerative medicine. However, the process has still not been completely mastered. Two teams of researchers from Inserm, CNRS, Centre Léon Bérard and Claude Bernard Lyon 1 University have discovered a molecule that may favour the production of these induced stem cells. Their work is published in Nature Communications, on 8 July 2015.

Reprogramming an already specialised cell into a stem cell is a scientific feat coveted by many researchers. In 2006, the Japanese scientist Shinya Yamanaka first succeeded in producing these “induced pluripotent cells,” known as iPS cells, capable of becoming any type of cell from the human body, by a process requiring the introduction of a cocktail of four genes into differentiated cells. Until now, only embryonic human cells possessed such a characteristic. iPS cells represent a promising advance. With their help, it should ultimately become possible to replace diseased organs with new organs derived from the patient’s own cells, thereby eliminating all risks of rejection. They would also circumvent the ethical problems raised by the use of cells from human embryos.

Despite this success, cell reprogramming is not yet fully controlled. It is limited by certain constraints, including the phenomenon of programmed cell death, which restricts the number of cells produced. In this context, Fabrice Lavial’s team, in collaboration with Patrick Mehlen’s team, sought to identify new regulators of the genesis of iPS cells.

With this objective, the researchers directed their attention to the factors affected by the four inducing genes involved in the initiation of reprogramming. They then selected from this list those known to have a role in programmed cell death, and with a level of expression that varies over the course of reprogramming. After this screening process, one molecule emerged: netrin-1.

Netrin-1 is a protein naturally secreted by the body. Interestingly, it is able to prevent programmed cell death, among other things. In the first days of reprogramming mouse cells, the researchers observed that their production of netrin-1 was strongly reduced. This deficit limited the efficacy of the process. The researchers then tested the artificial addition of netrin-1 to compensate for its insufficiency in the early phases of reprogramming.

This time, the quantity of iPS cells produced from mouse cells was much more greater. An observation repeated during study of human cells, from which fifteen times more iPS cells were produced by adding netrin-1.

From a therapeutic point of view, it was important to determine whether this treatment affected the quality of cell reprogramming.

“According to several verifications, netrin-1 treatment does not seem to have any impact on the genomic stability the iPS cells or on their ability to differentiate into other tissues,” says Fabrice Lavial, Inserm Research Fellow.

The team continues to test the effect of netrin-1 on the reprogramming of other types of cells, and is endeavouring to gain a better understanding of the mode of action of this molecule in stem cell physiology.Cellule iPS

Colonies of mouse iPS cells obtained in the presence of netrin-1. Top, in white light. Bottom, labelled with pluripotency factor Oct4. ©Inserm/Fabrice Lavial

Vaccines: practices and hesitancy among general physicians in France

At population level, vaccines contribute to reducing mortality associated with infectious diseases such as measles, diphtheria, tetanus, hepatitis B or bacterial meningitis. The community general physician, at the centre of this preventive strategy, remains the main source of information for families. In an article published in the journal Ebiomedecine, Pierre Verger (Inserm Unit 912, “Economics and Social Sciences Applied to Health and Analysis of Medical Information – SESSTIM”) and his collaborators present and analyse the attitudes and practices of over 1,500 general physicians in France, in a context of distrust toward vaccines.Brave little girl receiving injection


Vaccination is the most effective means of preventing, or even eliminating, many infectious diseases. However, in recent years, a growing number of unfavourable opinions regarding the latter has been observed among the general population in France.

Given the widespread scepticism, which is contributing to inadequate coverage for some vaccines, the general physician plays a major role in matters of prevention and information. The survey, conducted by Pierre Verger (Inserm Unit 912, “Economics and Social Sciences Applied to Health and Analysis of Medical Information – SESSTIM”) between April and July 2014, has attempted to capture the practices of general physicians in different vaccination scenarios. The results obtained provide a better understanding of the factors in the reticence—or confidence—of physicians with respect to some vaccines.

Physicians’ recommendations vary with the situation.

1st reassuring finding: Almost all physicians questioned (96%) are confident in their ability to explain the usefulness of vaccines to their patients. Nonetheless, this figure falls to 43% when it comes to speaking about the role of adjuvants, and justifying their use.

2nd finding: The recommendations of general physicians vary with the vaccination scenario: 83% often, or even automatically, recommend the measles, mumps and rubella (MMR) vaccine to adolescents and young adults, but only 57% advise vaccination against type C meningococcal infections for children and young people aged 2-24 years, although the latter is part of the vaccination schedule. “Their hesitation to vaccinate might also reinforce that of patients, and contribute to inadequate vaccine coverage, particularly for controversial vaccines,” according to the authors of this article.

The majority of physicians, however, rather or quite trust the French Ministry of Health (8 in 10 physicians) or the health agencies (9 in 10 physicians) to provide them with reliable information as to the benefits and risks of vaccines.

Some uncertainties persist regarding the risks and usefulness of some vaccines

Some physicians express doubt concerning the risk of serious side-effects from certain vaccines, even when these doubts are refuted by the results of pharmacovigilance and epidemiological studies (e.g. regarding hepatitis B vaccine and the presence of adjuvants in some vaccines). Thus 6% of physicians questioned consider it likely, or even probable, that there is an association between papillomavirus vaccine and the occurrence of neurodegenerative diseases such as multiple sclerosis. Over a quarter of them (26%) also believe that some vaccines recommended by the public authorities are unnecessary, and 20% even believe that children are vaccinated against too many diseases.

The existence of such hesitation on the part of general physicians is directly associated with less regular recommendations for vaccination to their patients. Most of these doubts, like those of the general population, relate to vaccines that have been controversial in France (hepatitis B vaccine, human papillomavirus vaccine).

 However, more surprisingly, a proportion of general physicians hesitate to recommend vaccines of proven safety and efficacy (meningococcal C and measles vaccines). For the moment, these hesitations affect only a minority of general physicians (again depending on the vaccine), but constitute an additional impediment to the maintenance of enough vaccine coverage in the population to protect it against infectious diseases that are still dangerous.

Although this study shows that general physicians trust the authorities, it also underscores their need for training and resources to help them respond to patients who are hesitant about undergoing vaccination.

Climate change and health: what are the implications?

In December 2015, France will host the 21st Session of the Conference of the Parties to the United Nations Framework Convention on Climate Change (COP21). This international conference highlights the willingness of the 200 participating governments to limit climate disruption and its consequences for the Earth’s natural system.

To ensure its success, numerous activities are being arranged prior to COP21. From 7 to 11 July, UNESCO is organising a scientific conference entitled “Our Common Future Under Climate Change.” The aim is to assess the risks from climate change from a scientific point of view, and to propose actions for reducing carbon emissions.

In this context, Inserm is committed to highlighting the crucial role that health and those working in the health sector can play in the coming months and years to make climate-related issues a central concern for our societies. Indeed, we often forget that if global warming is affecting the planet’s ecosystem, the fauna and flora, we are also in the front line of its effects. Conversely, we can also have an influence on climate. For example, by changing our diet to one based on vegetables and less meat, it would be possible to reduce greenhouse gas emissions by 40%[1].

To present the state of the art on the knowledge regarding the impact of climate change on health, and future research in this area, Aviesan (the French National Alliance for Life and Health Sciences) and Inserm (the French National Institute of Health and Medical Research) are organising a mini-symposium in conjunction with the UNESCO conference.

This meeting, “Current and Future Research trends on Climate Change and Health,” will be held in Paris:

Monday 6 July 2015, 2:00–6:00 pm in the auditorium at Paris Biopark, 11 rue Watt, Paris 13th Arrondissement.

Registration: rf.mresni@esserp

In the company of:

Yves Lévy – Chairman and CEO of Inserm, and President of Aviesan

Robert Barouki – Director of Inserm Unit 1124 (Inserm/Paris Descartes University)

And many researchers from Inserm, who will be coming to share the results of their work on the effects of climate change on health.

For more information: the conference program

[1] Green, R, Milner, J, Dangour, AD et al. The potential to reduce greenhouse gas emissions in the UK through healthy and realistic dietary change. Clim Change. 2015; 129: 253–265