(c) Fotolia

A study published in the journal Scientific Reports from Nature publishing group, describes the mechanism by which caffeine counteracts age-related cognitive deficits in animals.

The study coordinated by Portuguese researchers from Instituto de Medicina Molecular (iMM Lisboa) and collaborators from Inserm in Lille, France, along with teams from Germany and United States, showed that the abnormalexpression of a particular receptor – the adenosine A2A, target for caffeine – in the brain of rats induces an aging-like profile namely memory impairments linked to the loss of stress controlling mechanisms.

“This is part of a larger study initiated 4 years ago in which we identified the role of this receptor in stress, but we did not know whether its activation would be sufficient to trigger all the changes. We now found that by altering the amount of this receptor alone in neurons from hippocampus and cortex – memory related areas – is sufficient to induce a profile that we designate as ‘early-aging’ combining the memory loss and an increase in stress hormones in plasma (cortisol)” – explains Luisa Lopes, Group Leader at iMM Lisboa and the coordinator of the study.

When the same animals were treated with a caffeine analogue, which blocks the action of adenosine A2A receptors, both memory and stress related deficits were normalized.

David Blum, from Inserm research director, adds:

“In elderly people, we know there is an increase of stress hormones that have an impact on memory. Our work supports the view that the procognitive effects of A2AR antagonists, namely caffeine, observed in Alzheimer’s and age-related cognitive impairments may rely on this ability to counteract the loss of stress controlling mechanisms that occurs upon aging”

This is important not only to understand the fundamental changes that occur upon aging, but it also identifies the dysfunctions of the adenosine A2A receptor as a key player in triggering these changes. And a very appealing therapeutic target” – concludes Luisa Lopes.

Activation (colored circles at the level of the visual cortex) of the visual system by prosthetic stimulation (in the middle, in red, the insert shows an image of an implanted prosthesis) is greater and more elongated than the activation achieved under natural stimulation (on the left, in yellow). Using a protocol to adapt stimulation (on the right, in green), the size and shape of the activation can be controlled and are more similar to natural visual activation (yellow).

© F. Chavane & S. Roux.

A major therapeutic challenge, the retinal prostheses that have been under development during the past ten years can enable some blind subjects to perceive light signals, but the image thus restored is still far from being clear. By comparing in rodents the activity of the visual cortex generated artificially by implants against that produced by “natural sight”, scientists from CNRS, CEA, Inserm, AP-HM and Aix-Marseille Université identified two factors that limit the resolution of prostheses. Based on these findings, they were able to improve the precision of prosthetic activation. These multidisciplinary efforts, published on 23 August 2016 in eLife, thus open the way towards further advances in retinal prostheses that will enhance the quality of life of implanted patients.

A retinal prosthesis comprises three elements: a camera (inserted in the patient’s spectacles), an electronic microcircuit (which transforms data from the camera into an electrical signal) and a matrix of microscopic electrodes (implanted in the eye in contact with the retina). This prosthesis replaces the photoreceptor cells of the retina: like them, it converts visual information into electrical signals which are then transmitted to the brain via the optic nerve. It can treat blindness caused by a degeneration of retinal photoreceptors, on condition that the optical nerve has remained functional1 . Equipped with these implants, patients who were totally blind can recover visual perceptions in the form of light spots, or phosphenes. Unfortunately, at present, the light signals perceived are not clear enough to recognize faces, read or move about independently.

To understand the resolution limits of the image generated by the prosthesis, and to find ways of optimizing the system, the scientists carried out a large-scale experiment on rodents. By combining their skills in ophthalmology and the physiology of vision, they compared the response of the visual system of rodents to both natural visual stimuli and those generated by the prosthesis.

Their work showed that the prosthesis activated the visual cortex of the rodent in the correct position and at ranges comparable to those obtained under natural conditions. However, the extent of the activation was much too great, and its shape was much too elongated. This deformation was due to two separate phenomena observed at the level of the electrode matrix. Firstly, the scientists observed excessive electrical diffusion: the thin layer of liquid situated between the electrode and the retina passively diffused the electrical stimulus to neighboring nerve cells. And secondly, they detected the unwanted activation of retinal fibers situated close to the cells targeted for stimulation.

Armed with these findings, the scientists were able to improve the properties of the interface between the prosthesis and retina, with the help of specialists in interface physics. Together, they were able to 1 This is the case of patients with Retinitis Pigmentosa or Age-related Macular Degeneration (AMD). Artificial retinas: promising leads towards clearer vision generate less diffuse currents and significantly improve artificial activation, and hence the performance of the prosthesis.

This lengthy study, because of the range of parameters covered (to study the different positions, types and intensities of signals) and the surgical problems encountered (in inserting the implant and recording the images generated in the animal’s brain) has nevertheless opened the way towards making promising improvements to retinal prostheses for humans.

This work was carried out by scientists from the Institut de Neurosciences de la Timone (CNRS/AMU) and AP-HM, in collaboration with CEA-Leti and the Institut de la Vision (CNRS/Inserm/UPMC).

(c) Fotolia

In a study published in the new international scientific journal Neuroscience of Consciousness, Benjamin Rohaut, Inserm researcher, and Lionel Naccache, leader of the team “Picnic lab: Physiological Investigation of Clinically Normal and Impaired Cognition,” both of whom are also clinicians attached to the Neurology Department at Pitié-Salpêtrière Hospital, AP-HP, provide proof that unconscious semantic processing of a word exists, but that it is subject to very strong conscious influences. The work was conducted in collaboration with their colleagues at the Brain and Spine Institute – AP-HP/CNRS/Inserm/UPMC and the Laboratory of Cognitive Psychology (CNRS/AMU).

Experimental psychology is full of situations that make it possible to probe the depth and variety of mental operations performed unbeknown to us, i.e. unconsciously. For example, using subliminal visual presentation techniques, it is possible to “inject” a word into the brain of someone, and then track its fate at psychological and brain levels with the help of behavioural measurements and functional brain imaging. Since the late 1990s, several high-profile studies have also demonstrated that the meaning of a subliminal image, number or word may be unconsciously represented in our mind/brain.

In the study conducted by Lionel Naccache, the researchers provide proof that unconscious semantic processing of a word genuinely exists, but that it is subject to very strong conscious influences.

To do this, they used words such as: “palm, bank, jam, bail, date, ball, tire, bark, bowl, spit  …”. All these words share a common semantic property, have you noticed?

In reality each of these words is “polysemous,” and therefore has two (or more) different meanings. Each time such as word is presented to you, you can therefore understand it in two different ways. Consciously, we perceive only one meaning at a time, as stated by Descartes back in 1649 in Les Passions de l’âme : “We have only one thought of one thing at a time.” The meaning of the word we access consciously at a given moment is likely to be influenced.

Thus, if you read: TREE then PALM you are very likely to access the botanic meaning of the word PALM: “an unbranched evergreen tree with a crown of long feathered or fan-shaped leaves, and typically having old leaf scars forming a regular pattern on the trunk. Palms grow in warm regions, especially the tropics” whereas the HAND – PALM pair will strongly orient your semantic analysis toward the “the inner surface of the hand between the wrist and fingers”.

In this experiment authors presented the volunteers with words triplets while recording their brain activity using an electrode headset. Each test began by presenting the first word, which was always visible and which allowed a particular semantic context to be defined (e.g. HAND). Then the second word was flashed on the screen and was either subliminal or consciously visible. The third word then appeared, and was always consciously visible. It served as a target stimulus to which the subjects had to respond by pressing a button in order to indicate whether it was a real word (e.g. WRIST) or a pronounceable chain of letters which did not correspond to a lexicon word (known as a pseudo-word, such as DRAIE). When the middle word was semantically related to the target word, the subjects responded faster. This is known as a priming effect. This priming effect also appeared in the analysis of brain activities.

When the polysemous word (the middle word of the triplet) was consciously visible, a priming effect was present only when the meaning was consistent with the contextual word presented at the start of each test (Word 1). For example, when the following triplet was presented: HAND-PALM-WRIST, a priming effect of the word WRIST by the word PALM was found, but this effect was absent from triplets such as: HAND-PALM-TREE. Analysis of the electrical activity in the brain confirmed and clarified this result. The absence of priming for the non-contextualised meaning of the polysemous word indicates that this meaning was simply not analysed by the subjects. Conscious semantic processing is therefore strongly influenced by the conscious context.

The core result of this work lies in the discovery that it is the same for the unconscious perception of polysemous words. When the polysemous word (Word 2) was presented in a subliminal manner, the authors found semantic priming effects comparable to those observed under conscious reading conditions: only those meanings of the polysemous word that were consistent with the contextual word were unconsciously analysed.

This series of experiments thus demonstrates that unconscious cognition is not only highly complex, since it can reach the level of semantics (the meaning of words), but also shows that it seems to be extremely sensitive to conscious influences. At every moment, our conscious position influences the nature of the mental operations unconsciously unfolding within us.

“This work, which combines neurosciences with the psycholinguistics of the French language, also illustrates the potential of multidisciplinary scientific approaches,” conclude Lionel Naccache and his collaborators

Fotolia

The relationship between omega-3 fatty acid intake and adaptation to stress or anxiety is becoming clearer. Back in 2011, a team of researchers from INRA and Inserm showed that reducing the intake of omega-3 fatty acids in mice increased their stress. This phenomenon may be linked to impairment of the brain’s ability to produce endogenous cannabinoids, the “endocannabinoids,” brain lipids that control synaptic memory. To better understand the endocannabinoid-dependent links between anxiety and synaptic plasticity, the research team continued its experiments by testing different models of behavioural stress on the rodents. These studies are the subject of an article published in the journal Cell Reports on 21 July.

Mice do not respond equally to stress. An observation made by an INRA/Inserm research team who, after submitting the rodents to a battery of tests related to behaviour stress – isolation, maze or anxiogenic environment – found that some subjects were naturally resilient, or in other words, more resistant to stress. This ability may be related to better plasticity in the neurons of the accumbens nucleus, an area of the brain associated with regulation of the emotions and of stress, where endocannabinoids play a key role in memory at synapse level.

To confirm this relationship, mice showing several anxiety-related symptoms received a treatment to stimulate endocannabinoid production in the accumbens nucleus. Result: the scientists observed an attenuation of anxiety in these mice. For the first time, it has been proven that there is a relationship between anxiety and the levels of endocannabinoids produced by the brain. These results further emphasise the therapeutic potential of molecules that modulate the natural production of endocannabinoids, including dietary omega-3 fatty acids.

A milestone has thus been reached in demonstrating the protective effect of omega-3 fatty acids on the impairment of the brain’s ability to produce endocannabinoids. Ultimately, the idea is to understand how omega-3 fatty acids exert a protective action in response to the impairment of endocannabinoid-dependent plasticity in the accumbens nucleus, a part of the brain that constitutes the neurobiological substrate for anxiety.

This opens new perspectives in understanding the role of omega-3 fatty acids in the management of stress by the brain. The next studies will be aimed at better understanding the role of dietary omega-3 fatty acids in protecting the plasticity of the accumbens nucleus, and hence their ability to stimulate endocannabinoid production in a situation of stress.