, M., Machado
, C., Estévez-Hernandez
, T., Leisman
, G., Hernández-
, A., Rodríguez-Rojas
, R., Arias-Morales
, A., Melillo
, A., and R. Naranjo
Autism Spectrum Disorder and the Autonomic Nervous System.
)Institute of Neurology and Neurosurgery, Habana, Cuba; (
)Pontifical Catholic University of Puerto Rico; (
Brain & Rehabilitation Sciences, Nazareth, Israel; (
)F. R. Carrick Institute for Clinical Ergonomics, Rehabilitation, and
Applied Neurosciences (CERAN), Garden City, New York, USA; (
)Biomedical Engineering, ORT-Braude College of
Engineering, Carmiel, Israel; (
)International Center of Neurological Restoration, Havana, Cuba
Dear Chairman, Fellows of the International Academy of Functional Neurology and
Rehabilitation, Colleagues, Friends.
I am very grateful to Professor Machado for his kind previous presentation, and just
would like to add a few words about my father, Prof. Mario Estévez Báez, who was
confident that I could present you some of his ideas about this scientific and social
problem, the Autism Spectrum Disorder.
I ask your permission to read this brief information:
My father was born in Cuba in 1942. He graduated as a Medical Doctor, at the then
single National Faculty of Medicine in Cuba in 1965. In 1972 he became a Specialist in
For some years worked as a scientist in the field of Military Aviation Medicine. From
1977 to 1980 developed special studies in the Institute of Experimental Medicine at the city
of Saint Petersburg in Russia (then Leningrad) under the guide of late Prof. N.P.
Bechtereva, and obtained a PhD degree in Medical Sciences. In parallel, since 1978, he
began to work in the organization of the scientific works associated with the experiments to
be developed in the cosmic flight of the Cuban Cosmonaut “Arnaldo Tamayo Méndez”.
From 1982 to 1992 he continued working in the Soviet Spatial Program
"Intercosmos", and became the head for the coordination of experiments in the field of
Neurophysiology of the Spatial Program. In 1991 the equipment and software with code
name “Cortex-2”, developed under his direct control by Cuban and Soviet specialists,
showed his real possibilities for the study of some neurophysiological functions of
cosmonauts during long-lasting flights, and after that he received several decorations, as
the the Gold Medal of the Academy of Science of Czechoslovak, the Medal of Merit of the
Institutes of Aviation Medicine of Poland and Germany, and the higher decoration for the
scientists in Cuba, the Order Carlos J. Finlay in the First Degree.
The International Academy of Astronautics (France), elected him as a
Correspondent Member in 1991, and four years later, 1995, elected him as a Full Member
He obtained his discharge with Honor from the Cuban Armed Forces in 1998, after
36 years of active service, and later has maintained his scientific production collaborating
with different Health Institutions in Havana, and especially with Professor Machado in the
last five or six years.
In this presentation we will try to show you some facts, commentaries and
technological approaches, related with the study of that frequently forgotten, but integral
and vital part of our Nervous System, the Autonomic Nervous System, in such sensible,
complex and challenging medical problem: the Autism Spectrum Disorder.
A standard query to the Pubmed National Library of Medicine (NLM) database
revealed a relatively high number of items using as medical subject heading (MeSH) the
compound terms “autism” OR “autistic” as shown in the Table.
The addition to the basic query of widely used clinical neurophysiological ancillary
tests showed a very low number of items (from 0.11 to 1.52 %) for a problem whose origin
everybody must suspect that has a brain source.
The autonomic terms added to the basic query also showed, to say the less, that
autonomic complaints could be not present in the ASD.
The graphic at the bottom of the slide shows, that the questions that were object of
this search represent only 4 % of the publications about “autism” included in the database
with the Key Words (MeSH) used.
Then, you should be right to think that our presentation is a futile effort, or only a
waste of time, for all of you. Obviously, this will not be the case (at least, so we hope!).
The Group of Professor Machado, with the joint effort of very dear to us members
of the IAFNR and other friends, recently has contributed to publish a study (the citation is
shown in the upper part of the slide) using quantitative Electroencephalogram qEEG, and
the function of quadratic coherence, oriented to find if there were or not brain connectivity
problems in children with ASD compared with a control healthy paired group. As the by-
products of that publication can be considered the ones that have been summarized in this
Here, we are only going to show some of the graphic possibilities of the software
EEGConn, mentioned earlier as one of the by-products of the joint collaboration. The
graphics are obtained from the software toolbox directly.
In the upper graphics are included the quantitative EEG spectra in the range from
0.5 to 30 Hz of a child with Autism Spectrum Disorder identified with the letter “A”, and to
the right upper part the corresponding EEG of a control healthy child, identified with the
In the lower part of the slide are shown the corresponding spectra for the gamma
band of the same ASD child and the control one.
As can be seen from the colors representing the coherence values, marked highly
values in almost all the EEG bands are observed in the ASD child, in comparison with
those in the control healthy one. In the upper part of the slide are shown the individual
results for the Long-range coherences, while in the lower graphics are represented the
Inter-hemispheric corresponding values. It must be emphasized that all the graphics about
the selected subjects were obtained from the Electroencephalogram of both children in
basal, resting conditions.
In this slide we can also find the same clear differences between the values
represented by different colors for the two children. In the upper panels of the slide are
shown the results for the Short-range intra-hemispheric coherences, while in the lower
panels are shown the values for the transversal Intra-hemispheric coherences.
Why do we believe important to include the study of the integrity of the ANS in
children with ASD?
In the year 2002 a seminal review paper published by Kevin Tracey in Nature,
changed the way in which many biologists and doctors thought about the role of the ANS
in mammals and also in human beings. The concept of the inflammatory reflex, including
the products or molecules generating the reflex, the input arm, the intercalated neurons
and the integrative centers in the Central Nervous System, and the output branch were
In the left panel is shown the neural wiring of the cholinergic anti-inflammatory
pathway, which balances cytokine production in the organism. Cytokines are activated by
pathogens, ischemia, or trauma. The cholinergic brain network responsive to the M1
agonists, inhibit through the efference of the vagus nerve the production of cytokines.
Autonomic visceral afferent signals in the vagus nerve are the afferent branch of
the inflammatory reflex that arrive to the nodose ganglion, and posteriorly enter in the brain
making synapsis with the nucleus tractus solitary (NTS); from there, other fibers reach the
cholinergic brain network. So becomes configured the inflammatory reflex.
In the right panel of the slide we can see the neural structure of the vagal immune
reflex. The afferent arc is also through the vagus nerve and the stimulations are generated
by cytokines. The neural information is relayed to the nucleus tractus solitarius (NTS).
From there, projections lead to the area postrema (AP); this nucleus connects to the
hypothalamus, which activates the hypothalamic-pituitary-adrenal axis. Projections to the
rostro-ventrolateral medulla (RVM) activate the sympathetic nervous system and
epinephrine (EN) is released by the adrenal cortex and norepinephrine (NE) at
postsynaptic Sympathetic Nervous System neurons.
The efferent arc configuration is through the dorsal motor nucleus (DMN), and this
action results in the release of acetylcholine (Ach) at vagal postsynaptic neurons, inhibiting
immune cells through the nicotinic acetylcholine α7 receptors.
The most singular fact is that we can control the functioning of both reflexes
through the assessment of the heart rate variability, and our group has a good experience
in this neurophysiological method for the ANS assessment.
In this slide it is shown how specific neural networks regulate or coordinate
particular actions in the periphery. Advances in neuroimaging and neuroscience have
made it possible to study this neural organization in humans.
Knowledge about the cholinergic antiinflammatory pathway as a specific regulator
of cytokine responses makes it possible to consider that there is a somatotopic
organization of the Central Nervous System regulation and coordination of the behavior of
the immune system.
This slide is the result of the localization of very new and interesting areas related
with the controls of the inflammatory and immune responses by the brain.
Three main statements can be highlighted from the accumulated available literature
in this field, and they are summarized in this slide.