Growing pains in neurosciences?

Photo ParisTech Review / Editors / March 11th, 2014

The human brain now forms the grand, new frontier of biology in the 21st century. Rapid advances in neurosciences have led to some decisive progress in fields as varied as education or treatment of psychiatric disorders. We can expect prodigious gains in terms of economic productivity, as well as social and medical progress, if we identify not only the key to unleash all the power of this unique organ but also how to prevent, alleviate or heal the pathologies that impair its functions, illnesses such as Alzheimer, schizophrenia or autism. But debate rages as the ambitions of neurosciences expand overtly.

On both sides of the Atlantic, two flagship projects – among many others – underpin growing enthusiasm in favour of brain studies. In the USA, the National Institutes of Health (NIH) are financing the Human Connectome project, the objective assigned being to map neuron connections in a healthy human adult brain. Concomitantly, at Ecole Polytechnique Fédérale de Lausanne (EPFL), Switzerland, research scientists, in a ‘Blue Brain Project’ are busy recreating a virtual human brain in a super-computer.

The combined effect of the numerous expectations that arise through this acceleration of brain research round the world are bringing on stage and under the sunlights, so to say, a wide variety of new research areas, that come under the heading of “neurosciences.” The challenge here is to better understand the links between biology, thought and human behaviour. Schematically, neurosciences would like to provide a total vision of thinking, acting, feeling human beings. That is the view-point of the more ambitious of the neuroscientists. From the biologists’ point of view, neurosciences will enable studies of the nervous system, structures and functions, staring from a molecular scale and working up to the functional organs, among which first and foremost the brain, and then the whole body as a biological ensemble.

connectome
An image from the Connectome Project

At its early days, neurosciences were a simple branch specialty in neurology that arose from discussions about frontiers in psychiatric disorders. Over a span of some fifteen years, they have now come to represent a fertile crossroads intermeshing new ideas and concepts from biology, medicine, psychology, chemistry, computer sciences and mathematics. This ongoing mutation only reflects the growing conceptual and methodological arsenal of tools that enable scientists to investigate our nervous system from several view-points: cells, development, anatomy, physiology, cognition, genetics, evolution, computation, or in general medicine.

Already, as we move through the second decade of this century, neurosciences have provided some very important data about how the brain works and have led to certain innovative treatments with notable positive results for patients suffering from normally irreversible lesions. We can cite two examples to illustrate. Blind patients can now partially recover vision thanks to a camera that transmits the image data to a 60 pixel subretineal implant placed. Motor-paralyzed patients can now recover hand and arm action sufficient to reach food, just by thinking of the motion needed in the limb.

Growing pains
However, given the wide range of possibilities, their political ‘urgency’ and media-prone visibility, neurosciences are now going through what we might call growing pains.

Neurosciences are pervasive, suggests French sociologist Alain Ehrenberg, notably because, as he puts it “in a world where being self-reliant is obligatory, where questions of self-control of our emotions and impulses have become major societal issues. Thus we must assume that there is a mental health dimension now in all our institutions. Neurosciences could totally upset classic public policies and our conception of the social world around us.”

Nonetheless, we should admit, adds Alain Erhenberg, that the promises of the preceding decade (1990-1999) did not match expectations, hopes and aspirations and critical voices became audible all around. “Criticism was levelled at the scientific validation of the diagnoses. The very concept of diagnosis is changing with the recently released 5th edition of Diagnostic and statistical manual of mental disorders (DSM, published by the American Psychiatric Association) which tends not to reason in terms of syndromes but more on risk factors that cover several syndromes.” To frame this differently, progress enabled by neurosciences have allowed us to make precise diagnosis by establishing links between a given neurological disorder and a given illness, while at the same time losing the idea of making a simple precise diagnosis.

Another issue relates to the statistical validity of the investigation findings. A paper in Nature Reviews Neuroscience pointed out that the samples used by research scientists in neurosciences are far too small and hence the effect of lack of statistic depth, obviating in essence the reproducibility of experiments and, consequently, slows down progress in this field of research. The paper, co-authored by members of teams from the universities of Stanford (USA), Bristol (UK) and Oxford (UK) after analysis of 700 published studies, showed that these studies generally did not exceed a value of 20% in terms of statistical validity, which implies that the results are only valid once every five times. It is ipso facto impossible to base a therapy on such unstable, uncertain results.

Another form of criticism is levelled at the scientific acumen of the scientists themselves. Most of the research works have a background in biology but, if we except people like Stanislas Dehaene, who is a high level mathematician by training, very few are competent in mathematics. Studies of the nervous system are confronted constantly with configurations where the number of dimensions involved, plus the associate parameters, is always much higher than two. In order, on one hand to fully understand symptoms with their true degree of complexity and, on the other, to be able to handle the big data (‘number crunching’), you really need powerful mathematico-physical tools. Without the latter, neurosciences run the risk of levelling out with approximate diagnoses that simply indicate causal effects – e.g., prescribing dopamine which is the brain’s reward molecule – that have a strong emotional impact for the public at large, but there is not a sufficient guarantee for reliability or even safety of this treatment.

The interest shown by the public for brain topics round the world has also produced a series of admass publications, focusing mostly on personal development, with articles that extrapolate – without taking due precaution – on the results of recent research. Some of these admass authors have gained notoriety in public places though their conclusions are as simplistic as they are popular. It is indeed this popularity that is destabilizing research. In the fight for recognition between neurosciences and pseudo-psychology, a ‘new high’ was reached in the summer of 2012. In a conference that will surely do down in history, Professor Dorothy Bishop, neuropsychologist at the University of Oxford, demonstrated one by one a series of false cerebral ‘mechanisms’ that were being circulated in relation to children with dyslexia, even including papers in highly reputed science publications, such as the Proceedings of the National Academy of Sciences (PNAS), where, as she said “most people would kill just to get a paper published in PNAS.” The misuses are particularly outspoken when they invoke pictures taken during sophisticated brain scan techniques and, above all, in the most sophisticated of these, viz., functional magnetic resonance imaging (fMRI). There is a high risk of mistaking case and effect since the excitation of a given brain area may result from the physiological decision, but may also be its cause. We should add at this point errors in reasoning that relate to petitio principii (begging the question) thereby making the conclusion of an experiment largely dependent on the metaphysical, moral and social postulates of the scientists themselves.

Criticism occasionally moves onto a philosophical plane. In France, for example, a regular and violent indictment for “reductionism” accuses neurosciences of refocusing as biological a series of phenomena that hitherto belonged to other scientific fields such as linguistics, anthropology, psychology, sociology and psychiatry. The accusation goes further, inasmuch as the collective aspects are reduced to individuals and the individual again reduced to his or her brain; inasmuch also that psychological facts are aligned with neuron-related facts, in short these authors are building a “biological myth” of the brain that refutes its social dimension, mistaking rain, mind and placing our conscience on the same level as the physical neurons. The recurrent debate that rages in the USA to determine whether neurosciences will in fine reduce ad absurdum our free will (a key and central point in Protestant theology) illustrates this extreme sensitivity of Society – albeit with nuances, naturally, from country to country – as to the ultimate destiny of the brain.

As happens to all sciences when moving forwards and upwards, neurosciences also run the gantlet of being accused of mercantile practice. Are they, for example, socially responsible? If we judge by ethics and personal integrity, Society is right to question the commercial, social, technological and even political uses that could follow in the wake of neuroscience discoveries and possible applications. Here again, the response varies from country to country and their societies. A good example here is neuro-marketing, the aim of which is to identify the deep-rooted mechanisms of a purchasing act, a process which is totally illegal in France (Art.16-14 of the ‘Civil Code’), whereas it is accepted and used regularly in the USA.

Neurosciences vs. psychiatry?
The upsurge of neurosciences regularly fires territorial arguments with nearby specialties. The most significant fight was launched via the publication of DSM-5 Diagnostic and statistical manual of mental disorders, Spring 2013 in the American psychiatric milieus, sponsored by the American Psychiatric Association (APA). DSM-5 provides a classification of mental disorders which constitutes a very important tool inasmuch as it is referred top, in the USA and elsewhere, as the reference manual for reimbursement by the insurance companies and by courts in cases of litigation. Its contents are also taught in many schools of medicine, including in France.

The new edition (DSM-5) introduces new categories of mental disorder such as “minor cognition disorders (physiological loss of memory as age advances), bereavement troubles, or certain violent disturbances in children.

Not only does the DSLM-5 deeply divide the American psychiatric profession, but also disturbs the American government via the National Institute of Mental Health (NIMH) who have decided to ignore its recommendations – a “first” in history that will no doubt reshuffle all brain research. The Director of NIMH, Thomas Insel, declared: “The weak point of DSM is its lack of validation. Contrary to our own (NIMH) definitions of ischemic cardio-pathology, or lymphoma or AIDS, the diagnoses proposed by DSLM are based on a consensus of several clinical symptoms grouped together, by without any objective laboratory conducted measurements. In every other field of medicine, this would be equivalent to making diagnoses based on the level of pain felt in the chest or on the qualitative analysis of a fever/high temperature. And we well know that taken alone, these symptoms rarely indicate the real nature of the ailment or the choice of treatment.”

This radical decision of the American Government, basing research into mental illnesses on categories other than PTSD has been interpreted as a victory for neuroscientists. The “Brain Initiative” financed by the Obama Administration (100 M $US) is there to provide a classic, strong thrust to brain research, i.e.,in practical terms, to find undisputed biological markers for each mental disorder.

The tenets of traditional psychiatry qualify this stance as « extreme biological approach ». In their opinion, neurosciences, despite ambitious announcements and political support, somehow also lack a global paradigm that could provide a solid base for future research work. In the same way that astronomy first defined what a planet was before advancing to planetary formation and then to explaining the solar system, they recall that medicine also advances in the same way: first, there are the empirical diagnoses based on symptoms, the epidemiological approach (who catches what, how and where?) and as a final stage, the pathophysiology that identifies the underlying causes for the ailment and suffering. The latter stage unfortunately is absent from studies of all mental diseases.

The clash of what is legitimate and what is not, as it is developing in the USA but may affect the whole world, is laying paradoxically the bases of a later reconciliation and consolidation of this merging scientific specialty. To gain a better knowledge of mental disorders calls for a qualitative leap and the associate technologies to helps scientists progress significantly. Nonetheless, these illnesses can never be totally understood using only biological, genetic or brain image terminology. The simple reason for this assertion is that they result, in essence, from a complex combination of cerebral functions the environmental factors.

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