Recent developments in autism research

Manuel F. Casanova, editor. Now available from Nova Science Publishers.

From the cover

The hardest thing to do is to live immersed in the present. Even while tending to our chores we always try to tip toe into the future. People with autism tend to live unceremoniously in the present. Although fixed in the moment, their language does not partake in the industriousness of give-and-take conversation. The end result is a language that is all “muscular,” lacking the “twang” of the vernacular. People misconstrue their communication attempts as bordering on rashness; as being too rough. Moreover, superficiality for autistic persons is a pejorative term. They find it difficult to take cues from people talking to them. In a world made routine by verbal constructs, their way of thinking is judged to be unfamiliar. For they experience the world with heightened sensations and depict the world at an angle. This is the pathos of the condition, because a different way of thinking does not copy, it rivals.

This book is about people with autism. It deals primarily with those lines of research suggestive of an underlying brain disorder. Besides emphasizing the results obtained with different research techniques, the book also explores the tantalizing quandaries of the disorder. Is there an increased incidence in autism? What do we know about the savant qualities of some autistic patients? Recent discoveries challenge all of us to reconceive our image of an autistic person. However, the same results also challenge us to pursue those clues that are most likely to provide for meaningful interventions. In this sense the selection of chapters has been biased towards techniques that can provide outcome measures of treatment efficacy.

Table of contents

Introduction

Author: Manuel F. Casanova

Preface

Author: Benedetto Vitiello

1. The epidemiology of pervasive developmental disorders

Author: Eric Fombonne

2. The savant syndrome in autistic disorder

Author: Darold A. Treffert

3. The brain during life in autism: Advances in neuroimaging research

Authors: Janet E. Lainhart, Mariana Lazar, Erin D. Bigler, Andrew Alexander

4. EEG in autism: Is there just too much going on in there?

Author: Caroline Brown

5. GABAergic dysfunction in autism

Author: S. Hossein Fatemi

6. Minicolumnar pathology in autism

Author: Manuel F. Casanova

7. The use of animal models to understand autism spectrum disorder

Author: Elizabeth M. Powell

8. Neural network modeling of autism

Authors: Lennart Gustafsson, Andrew P. Papliński

9. Autism research: Future directions

Authors: Eric London

Introduction

Manuel F. Casanova

Copyright © 2004 Nova Science Publishers

One writer has defined autism as “a developmental disorder…whose core features…are impairment in socialization, communication and imagination.”1 However, no phrases or sentences by themselves define autism. One may argue that longer descriptions are more defensible, are better able to detail the complexity of the syndrome, and provide a better basis for diagnosis. Still, after all is said and done, definitions usually fail to describe the part autism plays in the behavior of the afflicted individual: how it affects their beliefs, the way they perceive the world, and the way the world perceives them. In similar fashion, textbooks will cite a number of reasons to study autism: the number of affected patients, degree of social impairment, and chronicity. They fail; nevertheless, to stress its inextricable links to other areas of human thought and conduct. We can’t talk about autism without discussing cognitive psychology, memory, or intelligence.

Autism is a condition that hits the patient in places that can’t be hidden; in his/her behavior. It is a condition worn for public scrutiny, blending personal aspects of the patient’s life with his/her social environment. It provides for guilt in patients and for Job-like ponderings in their parents. How do you measure the extent of damage to a patient’s life or that of the parent’s?

Figure 1Present day thinking portrays the problem of autism in the context of a triangle. In this triangle each interconnected vertex alternatively represents the autistic person, pathophysiological theories on causation, and symptoms. This faulty “syllogism” inadequately represents the autistic person. In this context, medical theories extend piety to the patients. They tend to be denominationally driven and self-referential. Ultimately, theories may serve as decorative art if they are not clinically relevant. How can these ideas be reconciled with the tremendous gifts observed in some patients? In danger of mixing metaphors: how can we square the triangle? How can we reconcile those positive aspects of the condition, the charisma of autism, with its shortcomings?

Figure 2Like previous attempts, this book does not fairly represent autism. A handful of chapters could not possibly do so. Rather this book will focus on certain themes: those physical aspects which make an individual autistic. Although we are willing to entertain both psychological and biological explanations, this book will deal primarily with the biological. Even when these explanations overlap, ultimately, they perform different functions; one biased towards the need to know and the other towards the need to cure.

Clinicians have proposed different psychological theories to explain mental illnesses from the perspective of the mind. Some of them are imaginative explanations of facts that have not or can not be explained neurobiologically. Ultimately such explanations blur the line between cause and effect. Unsurprisingly, the number of psychological theories about a condition is a direct reflection on how little is known about its etiology. When little is know about a condition, theories proliferate, become grouped, and are publicized as new developments. Theories, stemming from this perspective, are difficult to falsify. Are they dogma or scientific explanations? In psychology, the more compelling the description, the more persistent is the underlying presumption. Moreover, psychological explanations have become fair game for the opinion of anybody who is willing to espouse a trendy name, e.g., refrigerator mothers, catch 22. These theories are not the end of psychoanalytic ruminations but rather represent a return to the same.

One could not argue, however, that only the biological perspective is correct or that it has escaped neuroscientific inquiry unscathed. The lack of reproducible findings has allowed for a proliferation of biological theories. In this regard, neuropathology echoes Dostoyevsky’s unsettling remark that if there is no God, then everything is allowed.2 If we do not have pathology, we should favorably consider every inquiry and every result. Unfortunately, this approach preserves falsehoods by building tale upon tale. Maybe finding pathology for autism is akin to existential horror. Finding pathology would locate the workings of minds in the brain. This approach leads to the astonishing hypothesis that “You, your joys and your sorrows, your memories and ambitions, your sense of personal identity and free will are in fact no more than the behavior of a vast assembly of nerve cells and their associated molecules.”3 This thesis undermines humans’ tendency to flatter themselves, to assert their uniqueness. Desmond Morris once said that we tend to think of ourselves as fallen angels, not risen apes.4

Physicians are unwilling to accept a diminished role in fixing neurological and psychiatric problems akin to that of car mechanics. Yet no such qualms deter us from accepting organic explanations to deafness or hemiplegia. We take for granted that a steam shovel and a crane will dig faster and lift more weight than a human. However, the eyebrow of the world goes up when a computer beats the world chess champion. Broaching the subject of the mind makes the difference.

In the last decade a series of discoveries has destabilized the dominant image of autism within the medical and lay community. One of the better developments has been the introduction of two complementary diagnostic instruments, the ADI-R5 and the ADOS.6 In both instruments domain scores indicate severity of impairment based on symptom frequency and degree of interferences with daily living. ADI-R is better at fulfilling DMS-IV diagnostic criteria while ADOS is a briefer scale that takes into account developmental level.

Core deficits are now defined in terms of information processing impairment. At present there is enough scientific evidence to accord the status of “theory” to three different psychological conjectures on autism: deficits in theory of mind, executive function, and central coherence. First, deficits in theory of mind can be seen as exaggerations of gender based differences that are seemingly hard-wired into our brains. Asperger7 was the first brave soul to suggest that his syndrome was the extreme of the male personality. Simon Baron-Cohen8 has publicized this theory based on his own pioneering research spanning the spectrum from gossip to aggression, from evolution to everyday life, and from brain sciences to theory of mind. These differences reflect the way we systematize and develop empathy. Second, executive functions have a locus within the prefrontal cortex. Experimental work by Goldman-Rakic9 indicates that, according to the anatomical area involved, the frontal lobe exhibits different working-memory domains. Visuospatial processing is performed by the dorsolateral prefrontal cortex. Working memory for the features of objects and faces occurs in the more lateral and inferior cortices, while semantic encoding and retrieval involves still more inferior and insular regions. It is easy to envision how a defect in working memory/executive functions can provide for abnormalities in language, thinking, and behavior. Lastly, central coherence is analogous to the binding phenomena studied in neurosciences. Weak central coherence, a pattern typical of autism, is a cognitive style that emphasizes low-level features in lieu of high-level integrative processing. Higher level integrative processing appears to be mediated by the synchronization of neuronal discharges on high- (gamma-) frequency EEG. Unsurprisingly investigators have recently reported a disorder of binding related gamma EEG oscillatory activity in autism.

It is noteworthy that Shakow,10 working in the 1930’s and 40’s, generated a segmental set theory that seemingly joined both executive functions and central coherence. His theory stated that in order to successfully perform daily activities one needs to break down activities into segments while retaining the big picture or set. In some conditions, the big picture is easily lost. The underlying deficit appears related to hemispheric, rather than global, function. The right hemisphere interprets global patterns while the left hemisphere infers details of stimuli.

It is my biased opinion that the putative presence of minicolumnar abnormalities in the cortex of autistic patients offers an explanation to all of the previously mentioned core psychological theories. Thus no longer are there psychological theories nor neuropathological research; rather, there is an amalgam of ideas. Psychological research has now gained neuropathological underpinning while neuropathological research has significant psychological correlations.

Psychological theories now focus away from the inner life of emotions into action. They place an individual within the constraints of the environment, interacting with other people. Whenever evidence requires it, theories become malleable, confluent, and no longer painted into a corner. Theories have become commonsensical providing for easy and clear to enunciate observations. Arguments now rest on a bedrock; a starting point of further investigation.

We can now view autism as the result of a variation in the blueprint of the brain. Solving this enigma may partially map the mind’s interior. The beauty of these recent findings lies, as E. O. Wilson11 would say, in the way they trace causation through many levels of organization. They invite researchers of many disciplines to bring their own tools and expertise to the fray thus providing a multidimensional view of the condition. This book will describe the evolution of some of these discoveries. It will reconstruct their path and, in so doing, share in an amazing journey. The champagne is on ice; let’s hope to uncork the bottle sometime in the near future.

  1. Frith U. Autism and Asperger Syndrome. Cambridge, UK: Cambridge University Press; 1991.
  2. Dostoyevsky F. The Brothers Karamazov, book 2, chapter 6.
  3. Crick F. The Astonishing Hypothesis: The Scientific Search for the Soul. New York, NY: Scribner; 1994.
  4. Morris D. The Naked Ape: A Zoologist’s Study of the Human Animal. London, UK: Jonathan Cape; 1967.
  5. Lord C, Rutter M, le Couteur A. Autism diagnostic interview—revised: A revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. Journal of Autism and Developmental Disorders. 1994;24:659-685.
  6. Lord C, Risi S, Lambrecht L, et al. The autism diagnostic observation schedule—generic: a standard measure of social and communication deficits associated with the spectrum of autism. Journal of Autism and Developmental Disorders. 2000;30:205-223.
  7. Asperger H. Die “autistischen Psychopathen” im Kindesalter. Archiv für Psychiatrie und Nervenkrankheiten. 1944;117:76-136.
  8. Baron-Cohen S. The Essential Difference. New York, NY: Basic Books; 2003.
  9. Goldman-Rakic PS, Selemon LD. Functional and anatomical aspects of prefrontal pathology in schizophrenia. Schizophrenia Bulletin. 1997;23:437-458.
  10. Shakow D. The Nature of Deterioration in Schizophrenic Conditions. New York, NY: Coolidge Foundation; 1946. Nervous and Mental Disorders Monographs 70.
  11. Wilson EO. Consilience: The Unity of Knowledge. New York, NY: Alfred A. Knopf, Inc, 1998.

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Contact persons for this Web site are Manuel F. Casanova (principal investigator) and Andrew E. Switala (administrator).