Neurobiological Perspectives on Autism
Lauren HellewAutism is a pervasive developmental disorder characterized by restricted, repetitive, and stereotyped patterns of behavior, along with severe impairments in reciprocal social interaction, verbal and non-verbal communication, and cognitive development (1,2,3) . If the brain is responsible for behavior then it should follow that disordered autistic behaviors should be explainable in terms of brain abnormalities and disordered neurobiological processes. While findings are generally speculative and the etiology of the disorder remains somewhat of an enigma, there is significant evidence that autism is associated with neurobiological dysfunction.
Autistic individuals are often highly socially withdrawn to the extent that they may appear to live in a world of their own. Infants typically fail to develop normal attachments to parents or caregivers. They may seem indifferent to other's gestures of affection towards them, and may even resist being held or otherwise engaged in physical or emotional interaction. They tend to make little or no use of eye contact, smiling, facial expressions, gestures, and other signals of social intent. They continue to manifest many of the same social impairments throughout childhood, adolescence, and adulthood. For example, they typically fail to develop normal peer relationships and they generally demonstrate an impairment in social-emotional reciprocity. Normal displays of emotion or empathy are uncommon: they do not generally offer comfort to others, nor do they seek others for comfort in their own times of distress. Similarly, they lack the ability to share in the enjoyment of other's pleasure and they resist sharing their own enjoyment with others.
Restricted, repetitive, and stereotypical patterns of behavior and interest are also typical in autism. Autistic individuals often demonstrate repetitive motor mannerisms, including body rocking and hand/finger flapping or twisting. They can demonstrate apparent compulsive adherence to certain routines, and may become highly distressed upon changes to such rituals. They may become preoccupied with unusual objects, and/or very specific (and often bizarre) interests. In higher functioning individuals, such insistence on sameness may be manifested as a narrow range of interests, whereas, in lower functioning individuals, it may result in a preoccupation with, and attachment to, an unusual object or parts of objects.
Individuals with autism generally demonstrate delayed or deviant verbal and non-verbal communication. In fact, poor communication skills are found in nearly all autistic children, and some autistic individuals never acquire functional speech. Those who do acquire speech often have pragmatic difficulties with the language, and are generally unable to use it in a socially communicative fashion. They may display abnormalities in the volume, stress, rate, rhythm, and intonation of their speech. Bizarre uses of language are also common. For example, ecolalia (repeating heard words or phrases), and palelalia (repeating oneself), are often seen in autism. In addition, disturbances in responses to sensory stimuli (particularly hypersensitive hearing or hyperacusis) are also common in autism.
There is evidence that autism is associated with specific structural brain abnormalities. Relatively recent research in this area has been conducted by Dr. Eric Courchesne, in conjunction with the San Diego Children's Hospital and the University of California in San Diego (4,5,6) . Using magnetic resonance imaging (MRI) to contrast the brains of normal subjects with those of individuals with autism, Courchesne has found that certain areas of the cerebellum are distinctly underdeveloped in autistics. The cerebellum is a relatively large portion of the brain located near the brain stem that is primarily responsible for motor movements, but may also play a role in speech, learning, emotions, and attention. Thus, cerebellar abnormalities may help to explain the aberrant motor activity, impaired cognitive abilities, and apparent lack of emotion that are characteristic of autism.
In particular, results of comparative brain imaging studies have shown that two areas of the cerebellum, vermal lobules VI and VII, are significantly smaller in autistic individuals. These regions of the cerebellum are connected to brain regions that specifically govern attention, arousal, and the assimilation of sensory stimulation. Based on such results, Courchesne has developed a "Theory of Overstimulation" that emphasizes the idea that autistic individuals are chronically overstimulation by confusing and inconsistent activity of their disordered brains. He suggests that individuals with autism are abnormally subject to stimulation because of specific brain deficiencies and that, as a result, they try to shield themselves from additional stimuli. Courchesne takes the theory one step further to suggest that there is a brain mechanism through which repetitive and rhythmical behavior can have a calming effect on the cerebral cortex. Thus, certain characteristic features of autism, including sensitivity to sensory stimuli and repetitive behavior, may be explained in terms of structural abnormalities in the cerebellum.
There is also evidence that autistic individuals have dramatically reduced levels of Purkinje cells in the cerebellum. These cells, which are rich in the neurotransmitter serotonin, transmit inhibiting messages from the cerebellum to areas of the cerebral cortex. Given that the cerebral cortex is thought to be the center of thinking and judging, the dearth of communication with this area may help to explain some of the cognitive deficits characteristic of autism.
Evidence has also suggested that autism may be related to specific neurological damage to the limbic system (4,7) . A great deal of research in this area has been conducted by Drs. Bauman and Kemper of Harvard Medical School and Boston University School of Medicine, respectively. These researchers have examined post-mortum brains of autistic individuals and have found the amygdala and the hippocampus to be underdeveloped. In particular, they have reported finding densely packed, unusually small neurons in the amygdala and hippocampus of autistic individuals. While the exact implications of these findings remain somewhat speculative, examination of the normal functions of these structures as well as related animal research may help to explain how such neurological damage may be connected to the traits and behaviors associated with autism.
The amygdala is thought to play a role in the control of aggression and emotion. This is significant in that autistics are often either overly aggressive or passive and may appear emotionless. When the amygdala is damaged or removed, animals exhibit social withdrawal, compulsive behaviors, failure to learn about dangerous situations, memory deficits, and difficulty adjusting to novel situations - characteristics that are similar to those seen in autism. The amygdala may also function in response to various types of sensory stimuli, another system which appears to function abnormally in autistics (7) . The hippocampus is thought to be primarily responsible for learning and memory. It has been hypothesized by Dr. Bernard Rimland that autistic individuals have a specific cognitive deficit related to learning and memory. When the hippocampus is damaged or removed, animals demonstrate an inability to store new information into memory and they often display characteristics commonly seen in autism, including stereotypic, self-stimulatory behaviors, and hyperactivity (7) .
Additional brain abnormalities that may be associated with autism have been found via imaging studies of the brains of people suffering from tuberous sclerosis (TS) (8) . TS patients are known to have a much higher risk of developing autism than the general public. A comparison of TS patients with autism and those without autism has shown that those with autism are more likely to have tube-like growths of enlarged brain cells on the temporal lobes of their brains than are TS patients without autism. Such data suggests that some TS suffers develop these abnormal growths and that these growths may be linked to autism.
A recent brain imaging study involving identical twins, one of which was autistic and the other of which was not, has further examined the structural brain abnormalities associated with autism (9) . This study, which was conducted by Wendy Kates and her colleagues at Johns Hopkins University, the Kennedy Kreiger Institute, and Stanford University, found that the autistic twin had a smaller amygdala and a smaller hippocampus relative to his normal brother. In addition, parts of the cerebellum that are involved in shifting attention were found to be smaller in the autistic twin than the non-autistic twin. Furthermore, both twins had a reduced frontal cortex, an area responsible for executive functions including organizing, planning, and problem solving, and a reduced superior temporal gyrus, a region responsible for processing language. Interestingly, the non-autistic twin did show some autistic-like behavioral and communication problems. Such evidence implicates the above brain regions in the etiology of autism and suggests that there may be a mild form of autism that may affect relatives of autistic individuals.
Several findings have implicated neurochemical dysfunctions in individuals with autism. Additionally, there is some evidence that therapeutic medications which act directly on these neurochemical systems (including fenfluramine, haloperidol, risperidone, clonidine, and naltrexone) can effectively decrease the aggressive, obsessive-compulsive, and self-stimulating behaviors associated with autism in controlled drug trials.
Autism has been associated with abnormalities of the brain domaminergic system (10,11) . Specifically, it is thought that autistic individuals have increased levels of brain dopamine. This is demonstrated by the fact that intellectually subnormal autistic children with severe hyperactivity and stereotypes have been shown to have high cerebrospinal fluid levels of levels of the dopamine metabolite homovanillic acid. Furthermore, the use of dopamine antagonists such as haloperidol has been shown to have modest success in decreasing hyperactivity, negativism, and stereotyped behaviors, and facilitating learning in autistics. The dopaminergic system is known to affect motor behavior. Abnormalities of this system are associated with excess motor activity and stereotyped behaviors, traits often observed in autistic patients.
It has also been hypothesized that autism is related to a dysfunctional serotonergic system, and that such dysfunction may be responsible for the sensory and perceptual abnormalities seen in these patients (4,10,11) . Evidence for this theory comes in part from studies that have shown increased platelet serotonin concentrations in autistic individuals. Additionally, studies of fenfluramine, a medication that reduces brain serotonin, have shown that the drug may be beneficial in treating some cases of autism.
There is also evidence that some autistic individuals have elevated levels of beta-endorphins, an endogenous opiate-like substance in the body (4,10,11) . It has been shown that neonatal rats and chicks exposed to high levels of opiates show autistic-like symptoms after they are born. In particular, they exhibit unusual motor flurries similar to the hyperactivity seen in autistic children and they fail to show normal separation anxiety when removed from their mothers. In addition, opiate addicts often demonstrate social withdrawal, self-stimulation, and high levels of pain tolerance - symptoms often associated with autism. While such evidence suggests that opiate antagonists such as naltrexone may be beneficial in treating autism, such a treatment has not proven to be very effective.
Abnormalities of the noradrenergic system have also been associated with autism (4,10,11) . In particular, norepinephrine agonists have been shown to worsen the behaviors of autistic patients, and increases in norepinephrine plasma concentrations have been reported in autistics. However, treatment of autism with norepinephrine antagonists such as clonidine has not proven to be very effective.
A great deal of attention has recently been focused on the polypeptide hormone secretin as a possible treatment for autism (12,13,14) . Secretin is a hormone messenger secreted by "S" cells in the duodenum during digestion. The function of secretin is to increase the production and secretion of alkaline digestive fluids by the pancreas, thus facilitating the neutralization of partially digested food that has been acidified by hydrochloric acid in the stomach. Initial use of secretin as a treatment for autism was based on a report of three autistic children who were subjected to a test of pancreatic function that involved the intravenous administration of secretin, and who subsequently demonstrated significant behavioral improvements including increased eye contact and expressed language. Since that report, approximately 2,500-3,000 autistic children have been treated with secretin with generally positive results. While the mechanism through which secretin exerts its therapeutic effects is unclear, it is hypothesized that the hormone may affect the brain. There is some preliminary evidence from animal studies to suggest that there are secretin receptors in the brain. Despite the questionable nature of the mechanism responsible for the apparent effectiveness of secretin, the fact that such a neurobiological intervention can have a potentially dramatic effect on behavior suggests that the behavior is directly mediated by neurobiological processes.
Thus, it seems that there are several structural and neurochemical abnormalities associated with autism that can help to explain the specific behaviors and deficits characteristic of the disorder. This demonstrated link between brain and behavior is significant on several levels. In terms of the etiology of the specific disorder, localization of physiological dysfunction suggests biological, rather than psychological, social or otherwise non-biological causality. Given that only a few decades autism was commonly thought to result from unaffectionate "refrigerator" mothers, this move towards biologically based explanations is certainly significant. On a more general level, the neurobiological basis of autism is suggestive of a more general brain-behavior connection.
WWW Sources1)Autism Research Institute 
3)Autism Society of America 
4)AUTISM: Overview of Autism 
5)The Cerebellum and Autism 
6)Autism and the Brain 
7)Autism and the Limbic System 
12)Secretin: A Treatment for Autism?  (Autism Biomedical Information Network)
13)Secretin Information  (Autism Research Institute)
14)The Use of Secretin to Treat Autism  (National Institute of Child Health and Human Development)
01/19/2006, from a Reader on the Web
To whom it may concern: My name is Erin and I am a Special Education major at Towson University. I just read the article "Neurobiological Perspectives on Autism" and while I thought the article was informative and overall well written, I do have one suggestion. When you are writing or speaking about individuals with disabilities, it is more appropriate and respectful to use people first language. People first language simply means that you identify the person before the disability, since a person is not defined by their handicaps. For example, rather than saying "autistic individuals" or "autistics," say "individuals with autism" or "individuals who are autistic." The author of the article varied her use of people first language with non-people first language. Overall, the use of people first language extends the respect for the disability and its research to the individuals and their families who are living with the disability. Thanks.