US Hirnforscher der Harvard Universitt hlt Vortrag auf 18.

Legasthenie- und Dyskalkulietrainer Fachtagung in Salzburg2. Juni

2012:
Verffentlicht am 27. Mai 2012 von Redaktion

Seit den neunziger Jahren gilt Prof. Dr. Albert M. Galaburda von der
Harvard Universitt weltweit als einer der bedeutendsten Hirnforscher.
Er zeigte auf, dass bei Menschen mit Schreib- und Leseproblemen ein
Entwicklungsunterschied der linken Hemisphre sichtbar gemacht
werden kann. Hier ist unter anderem das fr die Sprache
verantwortliche Zentrum angesiedelt.
Er fand auch heraus, dass die erblichen Anlagen einer Legasthenie
weitergegeben werden und zwar mindestens durch die Chromosomen 6 und
15. Seine Forschungsergebnisse beruhen auf Autopsiebefunden an
Gehirnschnitten frh verstorbener Legastheniker, welche die Folgerungen
zulassen, dass die Legasthenie eine biologische Ursache habe, die bereits
whrend der vorgeburtlichen Hirnentwicklung wirksam, und die aufgrund der
Besonderheiten der Hirnentwicklung verbunden sei mit spezifischen
Begabungen. Man solle die Legasthenie als eine Normvariante menschlicher
Begabungen auffassen und diese Normvariante im Schulsystem
bercksichtigen und respektieren.
Die Forschungsergebnisse von Prof. Dr. Albert M. Galaburda geben Betroffenen
und deren Umfeld sowie auch Pdagogen und allen an dem Thema Interessierten
eine verstndliche Erklrung fr die Begabungsstruktur dieser Kinder, um
damit am Problemverstndnis der klassischen Legasthenie festzuhalten.
Die Forschungsergebnisse von Prof. Dr. Albert M. Galaburda werden heute durch
eine Reihe von Untersuchungen mit bildgebenden Verfahren besttigt und
untersttzt.
Links:
18. EDL Fachtagung
Dr. Albert M. Galaburda
INTERVIEW WITH ALBERT GALABURDA, MD
December 2, 2005

NLMFF interviewed Albert Galaburda, MD,

Chief of Behavioral Neurology at Beth Israel
Deaconess Medical Center and Emily Fisher
Landau Professor of Neurology and
Neuroscience at Harvard Medical School,
about dyslexia research, its relation to
autism and language, and the future of
autism science.

NLMFF: In the 1980s, you wrote a series of classic papers on cerebral

lateralization with a pioneer in behavioral neurology, the late Norman
Geschwind. Could you please comment on your recollections of your work
with Geschwind, on your experiences and thoughts as you wrote these
papers, and on how many of these ideas have stood the test of time?
Dr. Galaburda: As you may know, Norman Geschwind was my mentor. He
was the head of the department where I did my neurology training, at the
then Boston City Hospital (now Boston Medical Center). In the mid 70s the
then Mayor of Boston, Kevin White, decided that three medical schools at
BCH was administratively unwieldy, so Tufts and Harvard left with their
training programs, leaving Boston University the sole medical school
affiliated with the municipal hospital for the City of Boston. Norman
Geschwind and the rest of us moved to the then Beth Israel Hospital (now
the Beth Israel Deaconess Medical Center) and most of my research
collaborations with NG took place while we were at the BIH. In fact, while my
clinical work was at the BIH, my lab remained at BCH until 1980, at which
time it also moved to BIH.
Norman was very interested in the brain substrates for the phenomenon of
cerebral lateralization (having to do with the notion that one side of the
brain seems to have a dominant role for some cognitive functions, whereas
the other side leads for others). In the 1960s he had rediscovered and
extended the observation that the planum temporale, a region of the brain
that participates in language, was larger on the left side in the majority of
people. My first involvement in this subject with Norman had to do with his
asking me to look for more microscopic bases for cerebral dominance. Thus,
I used methods of cytoarchitectonics, which I learned from the German
anatomists Friedrich Sanides and later Heiko Braak, to show that there
existed in the human and animal brains asymmetries in the sizes of
architectonic areas. There were several papers published on this subject and
my career was launched.
In the 3 years prior to Norman's death, we worked together trying to
compile all the available data from various areas of neuroscience to attempt
to discover all possible biological agents that could affect brain asymmetry.
By doing this we became aware of hormonal and immunological influences,
mainly, and some genetic influences, then and still not well understood, and
we published 3 serial papers in the Archives of Neurology presenting and
interpreting our findings.
In short, hormones, particularly male hormones, we thought, were involved
in the diminishing of brain asymmetry during development, and the same
hormone modulated the development of the immunological system, such
that disorders of the immune system and disorders of brain lateralization,
both modified by male hormones, traveled together. This research was
highly controversial, but so exciting that many investigators felt compelled
to prove it right or wrong.
There were many papers in either direction until the interest of the scientific

community gradually shifted to other questions that could be answered with

emerging methodologies that appeared only in the 80s and 90s, after
Norman's death.
I myself did not pursue many of the areas of research that were set up by
the three papers, mainly because I felt that we didn't have the tools to
answer them adequately. Instead I chose to study specific aspects relating
to brain asymmetry and abnormal brain development with small
experiments using contemporary tools. This led to my work in dyslexia.
There was also another issue: Norman was much more phrenological in his
thinking than I was. He was still highly influenced by (and highly interested
in) the work that had begun at the start of the 19c, known as the
phrenological school (c.f., Franz Josef Gall, Broca, others) that made two
specific claims. The first was that bigger was better, that is, that a bigger
planum meant that it was better (this collapsed when we started to see that
dyslexics, whose main problem was language, had two big plana, not two
small ones, as predicted by the phrenological model). The second claim was
that functions were localized to specific nodes in the brain. Well, work
before Norman died, and work that came out of the introduction of
functional brain imaging, were clearly showing that complex brain functions
are instantiated in distributed networks, rather than localized nodes. It was
not the case that every part of the brain participated in every function, but
it did appear that the circuits were quite large and non-focal. Thus, I
abandoned attempts to show the speciality of small nodes of brain and
focused instead on explaining skills and loss of skills in disease by the
disruption of large networks.
NLMFF: Could you comment on the current state of knowledge about
dyslexia, and on your views regarding the future of dyslexia research?
Dr. Galaburda: Dyslexia research is at an exciting juncture today because
a tentative pathway is in its rough outline now available between a gene
mutation and an alteration of a complex phenotype, in this case
phonological knowledge (a fundamental issue in most dyslexia). There have
been 4 dyslexia susceptibility genes discovered in the past 2 years, all of
which are involved in brain development. Three are involved in neuronal
migration, which my lab showed to be abnormal in dyslexia, and one is
involved in the establishment of neural connections across the hemispheres.
One of these neuronal migration genes, DCDC2, is part of a developmental
pathway that is already rather well understood. Except for the possible
exception of DCDC2, none of these genes are actually markers for dyslexia
(some people who are not dyslexic have the gene mutation), but this issue
will undoubtedly be resolved. The future of dyslexia research, therefore,
seems bright to me. We are in a position to clear up a lot of details in the
pathway (or set of pathways) by which a gene mutation changes brain
development in specific ways that can explain difficulties in phonological
processing. Perhaps working out these details is not as exciting as having
gotten this far, but the work will undoubtedly continue and good answers
that have the potential to be applied to the diagnosis and treatment of
dyslexic individuals will be forthcoming. If one gets bored doing this, there is
always autism to challenge us.

NLMFF: In your opinion, what are the lessons to be learned from dyslexia
research about autism and language?
Dr. Galaburda: We can all agree that however complex phonological
development is in children, its genetic background, its brain developmental
steps, and its interactions with the environment and culture are ultimately
tractable. The dyslexia situation is likely to be a great deal simpler than the
case of autism. However, it is reassuring that science is progressing so that
the biology of complex traits, including complex cognitive traits, is
advancing rapidly. It is possible to think of a gene mutation that changes the
developing brain; it is also possible to think of specific changes in the brain
to explain specific behaviors. It is more difficult, but possible to see how a
gene mutation affects brain development, which in turn affects a behavior.
This is what we need to do for autism. It is the same type of challenge as
that which has been partly met for dyslexia, albeit quantitatively more
difficult. I believe we collectively have the brain power and methodologies,
together with sound theoretical notions, to extend knowledge of brain
development coming from the fields of genetics and developmental
neurobiology to make it relevant to autism.
NLMFF: What are your thoughts on the recent genetic discoveries in
autism?
Dr. Galaburda: Difficult to say at this time, because as usual when things
are getting started the genetic mutations that are discovered account for
very small proportions of the known affected population. Nonetheless, even
though mutations linked to autism are at present explaining only a few
autistic persons, it will be important to study these in great detail. By this I
mean to discover all the downstream effects of the mutation to get us to
specific brain regions the interference with which can explain the observed
symptoms and signs of autism. Once we are sure of the brain regions
involved by converging evidence (functional and structural imaging and
molecular biology both pointing to the same brain regions) we can turn our
attention to other developmental mechanisms acting on those regions
(caused by other genes known to be expressed there during development,
or epigenetic effects known to affect the same regions during development).
NLMFF: Is it possible to understand how the brain creates language and
how genes influence this?
Dr. Galaburda: In principle, yes. However, in practice, we are far from
being able to answer these questions. As you know, even genes currently
linked to disorders of language (and presumably related to the building and/
or function of language circuits), are genes that also express in other
species, which do not have anything resembling human language.
This makes for a much more challenging research program. The first burning
question is whether language emerges in the human brain because large
numbers of genes work together to cause the brain to be larger, to have
therefore more computing capacity, which permits the emergence of new
functions not pre-adapted in other species, including language, musical
ability, math, etc; or, is there a single gene or a relatively small set of genes

that is not present in non- language species that first appear in humans and
builds special modules that support language functions. If we know even
this, we may have a chance to discover how one or the other scenario can
explain the building of a special brain, the human brain. After that we still
have a problem because we do not know the nature of the neural codes that
explain language functions. In other words we need to understand the brain
(and the genes that build it), the behavior (the stuff cognitive psychologists
study) and the neural codes that join the two. I don't see this happening in
my lifetime.
NLMFF: You recently wrote a manuscript entitled, "Unlocking the Secrets of
Autism". Could you please summarize the main points of this paper?
Dr. Galaburda: The main points of the paper are the following. One, that
the core systems of autism are confounded by the fact that they may be
causally related to one another. Thus, social brain problems and
communication problems may be caused by one another or may be
manifestations of the same underlying problem, and stereotypic thoughts
and actions may also relate to the development of social interactions and
communication. One way of interpreting all the data is to state that first and
foremost elements of the social brain do not develop normally in autism and
other things happen through the process of developmental brain plasticity.
Second, that autistic communication problems may represent a form of
disconnexion, a form of apraxia, rather than a fundamental disruption of
knowledge representation in the brain. This means that the normal ways for
learning and expressing communication skills are blocked by aberrant brain
development, and in some autistic individuals one can see that language
and thought is capable of boring through and coming out in alternative
ways, such as writing and reading, for instance. Third, that a valid
interpretation of the available data suggests that the initial problem affects
parts of the brain that are ancient, quite vertically organized (meaning that
damage thereof has a hard time recruiting other systems for help) in the
mesial, inferior frontal cortex and its connections with other parts of the
frontal lobe, the parietal lobe, the temporal lobe, and the occipital lobe.
Finally, the location of this vulnerable zone suggests that it can be hit by
genetic or epigenetic factors early in development leading to comparable
symptoms, the severity and variety of which depend on timing and extent of
early involvement. Among the genetic factors are genes specifically
involved in the development of this brain region and viral, toxic, or
immunological agents that can damage it.
NLMFF: What is your present view regarding the central issues of autism
research?
Dr. Galaburda: The central issues in autism research are clearly to get at
causes, to understand them at multiple levels (molecular--to get diagnostic
markers and pharmacologicals; systems--to get at diagnostic markers and
at rehabilitation approaches), and to quickly translate lab results into clinical
applications. An important early way to get quickly moving on this agenda is
to do away with too much discussion about variability of clinical
manifestations in autism and the fact that it has multiple causes, and to
extract a kernel that unifies all autistic persons. One loses useful

information by doing this, to be sure, but this information can be retrieved

later when it is possible to deal with it instead of being distracted by it.
NLMFF: Given your present view of the central issues of autism research,
what do you feel would be the most promising avenues of research in
autism?
Dr. Galaburda: The success of plans for the future is best predicted by the
success of recent projects. Thus, the powerful tools of molecular biology and
cognitive neuroscience are in the best position to get us where we want to
be. We need to get from gene to brain (even if the gene accounts for a small
number of autistic persons) and we need to get from behavior to brain
(using imaging in living autistic and control participants). Even at the risk of
criticism by those who think autism is about human beings only (they had
the same criticisms about our animal models of dyslexia), there needs to be
more research on animal models, at least regarding preadapted behaviors in
these animals the understanding of which will shed light on behaviors that
suffer in autism.
NLMFF: Thank you so much Al for your reflections, insights, and efforts to
advance dyslexia and autism research.