Autism is defined as a Pervasive Developmental Disorder (PDD) that typically occurs in the first three years of life. More specifically, the Diagnostic and Statistical Manual (DSM-IV, American Psychiatric Association, 1994) defines it as "the presence of markedly abnormal or impaired development in social interaction and communication and a markedly restricted repertoire of activity and interests". Some of the most common symptoms include sensory processing difficulties (Baranek 2002; Dawson and Watling 2000), limited social interaction (Gevers et al. 2006), deficits or delays in language development (Smith et al. 2004), and unusual or problematic behaviors (Horner et al. 2002). One in 150 children in the United States today are diagnosed with autism, which is double the incidence of ten years ago (Centers for Disease Control and Prevention (CDC) 2007). Parents of infants with autism often report sensory peculiarities early in development. These reports are among the most salient feathers of autism in the first two years of life (Dahlgren and Gilberg 1989). Most researchers agree that autism is caused by either abnormal brain structure, abnormal "organization" within the CNS or both. Because of the heterogeneity of symptoms, the wide range in their severity and the spectrum of functional deficits, the term Autism Spectrum Disorders (ASDs) is now being used to account for the differences seen in these children (Wing 1997). Although several theories remain regarding what causes autism, much more specific information is now available about the genetic and neurological abnormalities that exist.
Causes of Autism
Genetics
No one gene has been linked to autism (Vastag 2004), but it has long been theorized that it might be an x-linked disorder because of a high ratio of males (Skuse 2000). Only one out of five children with autism is female. Most researchers today believe that autism may begin with a combination of genetic vulnerabilities and environmental triggers (Miller-Kuhaneck & Glennon 2004). Autism however is believed to be prenatal in its origin. Many have suggested that there is a genetic mutation (or mutations) that underlie or cause autism. Statistics suggest that there is a 60-90% chance of having a sibling with an ASD if another child is affected. Geneticists studying autism have discovered specific abnormalities on chromosomes 2, 5, 7, 11, 15, and 17 (Auranen et al. 2002; Badner, Gershon 2002; Buxbaum et al. 2001; Gallagher, Becker, Kearney 2003; Hutcheson, Bradford, Folstein et al. 2003). They believe there may be abnormalities on many more genes. These findings have strongly supported that autism is heterogeneous and that different symptoms, behaviors, and levels of severity displayed by the children may be representative of different types of autism. Today, federal funding for autism research, much of which is genetic in focus, has reached $100 million dollars (Cray 2006).
Neurotoxins
There are also several neurotoxins currently being studied in an effort to determine their possible influence in the development of autism since parents have believed that there was some "substance" that caused their child's autism. A study was completed that examined tissue samples obtained from 700 children with autism to test for the presence of heavy metals (ex. Mercury) due to the "vaccine" theory of autism. While it has been suspected that an immune system response was activated as a result of the injections since some children show chronic inflammation in their brains (Singh, et al. 1998), this theory has not been supported as a cause (Fombonne, Chakrabarti 2001; Hviid, Stellfeld, Wholfahrt, Melbye 2003; Miller 2003; Taylor, Miller et al., 2002; Wilson, Mills, Ross, McGowan, Jadad, 2003). Tissue from children with autism has also been tested for pesticides and other toxic chemicals as possible triggers for autism, with varying levels of evidence which has led to a lack of a definitive conclusion (Edelson, Cantor, 1998).
The influence of opioids has also being examined due to their association with being a by-product of gluten and casein in the diet (Lucarellli et al. 1995). Increased levels of these substances have been found in the urine of some children with autism (Reichelt, Ekrem, & Scott 1990; Reichelt & Kniysberg 2003).
Neurological
It is clearly evident today, as substantiated by both Magnetic Resonance Imaging (MRI) (including functional MRIs) and Positron Emission Technology (PET) scan studies, that the brains of children with autism are different. Electroencephalograms (EEGs) and Magnetoencephalograpy (MEG) have also been used to measure fluctuations in electrical and magnetic responses generated by neural activity in the brain. The evidence suggests that there are abnormalities in both the structure and the function of the brains of individuals with autism. Recent studies have shown that the brains of children with autism are larger (Brambilla et al., 2003; Fidler, Bailey, & Smalley, 2000; Hardan, Minshew, Mallikarjuhn & Keshavan, 2001). This increase in size and growth becomes evident at approximately 6 to 14 months of age Ccourchesne, Carper, & Akshoomoff 2003). This may be due to an excessive number of neurons. Rapid head growth has therefore been suggested as one of the early warning signs. Abnormalities in structure, growth and function have been substantiated in many of the structures of the brain in individuals with autism (Brambilla, et al. 2003). In describing these differences from the lower brain structures to the higher brain structures, differences in the structure and transmission of information have been noted.
The Brainstem
The brainstem is one of the first relay stations for transmitting sensory messages up to higher areas of the brain (Ayres 1972; Bear, Connors, Paradiso 2001). It is where basic integration of information begins. What the brainstem does is below our level of consciousness. The brainstem contains a structure called the reticular formation which has two parts (Bear, Connors, Paridiso 2001). One part of the brainstem is descending and sends messages down through lower levels of the central nervous system. The other part of the reticular formation is ascending and sends messages up to higher structures of the brain. The descending fibers of the reticular formation in the brainstem are concerned with vegetative or autonomic responses and send messages to target organs that are necessary for our survival. The descending fibers are also involved in postural responses involving position, equilibrium and movement. The ascending reticular fibers (also known as the reticular activating system) are concerned with degrees of consciousness and alertness (Noback, 2005). Many of the major sensory pathways -for example for touch, pressure, and movement have axons that end at the nuclei of the reticular activating system. Several studies have suggested that there is an increase in the transmission time of incoming information into the brainstems of children with autism (Akshoomoff et al. 2002). Hashimoto et al. (1995) have shown that the brainstems of the children with autism that they studied were smaller. In a study of ten children with autism and two control groups with ten children each, the children with autism displayed an average of four soft neurological signs, which the authors felt was suggestive of brain stem involvement (Jones, Prior 1985).
The Thalamus and Hypothalamus
Above the brainstem is an area of the brain called the diencephalon which is divided into the thalamus and hypothalmus. The thalamus is also a main relay center for the nervous system, channeling information to and from the motor cortex (Bear, Connors, Paradiso 2001). The hypothalmus has control over the autonomic nervous system (Bear, Connors, Paradiso 2001) which includes the parasympathetic system that maintains homeostasis and calms and organizes us, (Mangelsdorf, Shapiro, Marzolf, 1995: Porges, 1996) and the sympathetic nervous system that responds when we feel we are under threat. It provides us with the flight or fight response (Bear, Connors, Paradiso 2001). The child with a high activity level, who perhaps is hyper-responsive to sensory input, is thought to be dominated by their sympathetic nervous system. This results in frequent flight or fight reactions. So- even though this system is designed to increase our readiness to respond, it can also result in persistent stress responses for the individual who is dominated by this system.
The Cerebellum
In typical people, the cerebellum is a primary site for the integration and modulation of sensory and motor activity. It receives significant amounts of ascending sensory input from the tactile (touch), vestibular (movement - with which it has a direct connection), and proprioceptive (body awareness) systems. The cerebellum also receives signals that are being sent down to the muscles from the motor cortex and helps to modulate that information for postural control before it travels down into the brainstem. It fine tunes motor responses, and helps to control the smoothness with which we move (Bear, Connors, Paradiso 2001). The cerebellum in some children with autism has been found to have an excess of axons within it (Brambilla et al., 2003; Harden, Minshew, Harenski, Keshavan 2001) but their distribution is abnormal. There has also been research that has suggested a reduction in size of the cerebellum (Hashimoto et al. 1995). In addition, the links that should be made from the cerebellum to other structures appear to be decreased (Cray 2006). There are also fewer Purkinje cells in the cerebellum (Bauman , Kemper 1985; Rapin, Katzman 1998). One of the functions of these cells is to arouse the reticular nuclei, which stimulates the arousal of muscle tone and helps a person to change the focus of their attention (Townsend et al. 2001).
The Cerebrum
Within the cerebrum is a structure called the hippocampus. It lies deep within the middle of the brain and is one of the structures that assist us with remembering new information (Bear, Connors, Paradiso 2001). It is slightly larger than normal in some children with autism (Brambilla et al. 2003).
The amygdala which is located in the cerebrum, is part of the limbic system which is involved in emotional responses and helps us to determine what is important and what is not important. The amygdala specifically is associated with arousing us and helping us to determine threatening situations (LeDoux, 1996). The response when activated, is emotional (Brodal, 1992). The amygdala is enlarged in some children with autism (Howard et al., 2000). Research has also shown that the amygdala is activated in children with autism when in social situations and when looking directly at faces (Dalton, Nacewicz, Johnstone, Schaefer, et al. 2005). It is not activated sufficiently in the parietal or frontal lobes where paying attention to faces is normally processed. Several authors have theorized that avoidance of eye contact may be a self-regulatory mechanism that compensates for difficulty with modulating visual input. Others have reported that children with ASD often inspect objects and people in an unusual way with their peripheral vision (LeCouteur et al. 1989; Lord et al. 1994). The conclusion therefore seems to be that here are neurological reasons for lack of eye contact in individuals with autism.
Another area of the cerebrum found to have some abnormalities in its structure, is an area called the basal ganglia. This structure which lies deep within the cerebral hemispheres, serves to connect the cerebellum with the cerebrum in order to regulate automatic movement. The basal ganglia contain a structure called the caudate nucleus. The caudate nucleus in children with autism is enlarged. Increased size of the caudate nucleus in the basal ganglia has been associated with compulsive behaviors, difficulty with changes in routine, and stereotypical motor movements (Sears et al. 1999).
The corpus collosum is an area in the middle of the brain that links the left and right sides for communication between the two hemispheres. It is smaller in children with autism (Harden, Minshew, Keshavan 2000;; Piven, Bailey, Ranson, Arndt 1997) and the neuronal activity that occurs between the two hemispheres of the brain is erratic and poorly connected. Because the corpus collosum links the left and right sides of the brain, there are a number of implications for this abnormality in size and function, including language development, the development of a dominance, and the ability to use bilateral integration.
The Cerebral Cortex
The Cerebral Cortex contains four lobes. These include the frontal, parietal, occipital, and temporal lobes. The somatosensory cortex- which is the ultimate destination for sensory input is located in the parietal lobe. It contains the sensory homunculus which represents and interprets the sensory information that is received by the various body parts (Bear, Connors, Paradiso, 2007). A study by Courchese et al. (1993) showed some volume loss in the parietal lobes of individuals with autism.
The motor cortex - is contained in the frontal lobe of the cerebral cortex (Bear, Connors, Paradiso 2001). It contains the motor homunculus which controls motor function, and is where the tracts for voluntary muscle control originate. The frontal lobes in some children with autism are larger due to an increased number of axons within them (Carper et al., 2002). But despite this increase in the number of axons within the frontal lobes, the connections between them and the parietal (sensory) lobes, and between both of these areas with the thalamus, (a major relay station of the brain), are disrupted.
Summary of Neurological Findings
Although there are several more studies and theories on the neurological causes of autism that are reported in the literature, based on the findings reported in this paper, some major conclusions can be made. It has been suggested that there is an excess of axons in specific areas of the brain which results in over-connection in these areas. However, their links to other areas of the brain appear to be weak (Herbert 2005). There seems to be a lack of coordination among brain regions. There is a lack of synchronization between the various areas of the brain, which seem to impact function. People with autism have difficulty bringing different cognitive functions together in an integrated way. Individuals with autism have problems in planning and organization (Prior, Hoffman 1990; Ozonoff et al. 1991; Hughes et al. 1994). Coordinating volition with movement and sensation can be difficult for some (Cray 2006). In autism each area of the brain seems to do its own thing (Just, Cherkassky, Keller, Minshew 2004). Integration of information therefore does not occur as it should.
Neurological links to sensory processing difficulties in children with autism
Some of the earliest as well as some of the most current theories on autism are based on the premise that children with autism process sensory information differently from others (Brock, Brown, Boucher 2002; Frith 1989; Hermelin, O'Connor 1970; Happe 2005; Just, Cerkassky & Keller 2004). Initial clinical reports of atypical reactions to sensory input date back to Kanner (1943) who first described autism. The first theories on the causes of atypical behaviors among children with autism were based on observations of hypo- or hyper-arousal and unusual reactions to sensory input (Hutt, et al., 1964; Kootz, Marinelli,Cohen 1982; Ornitz 1974). These early reports have since been corroborated by numerous clinical, parental, and first person reports form individuals with autism who have reported unusual attention to, or avoidance of sensory input from various sensory systems (Grandin, 1992; Cesaroni, Garber 1991, O'Neill, Jones, 1997; Williams 1994). Grandin (1995) wrote of her experiences as a person with autism and noted for example that certain textures of clothing could make her anxious, distracted, and fidgety. Based on a review of research that included anecdotal and clinical reports, the prevalence of sensory processing deficits among children with autism is estimated between 42 and 88% (Barenek 2002; Greenspan, Weider 1997; Kientz and Dunn 1997; LeCouteur et al. 1989; Watling, Deita, White 2001) suggest that approximately 39% of children with ASD are under-responsive to sensory input, 20% are hypersensitive, and 36% show a mixed pattern of hypersensitivity and hyposensitivity. Kientz and Dunn (1997) in their study of 3- 13 year old children with autism found that when compared with typical children - the children with autism had significantly more (85% of the responses) on the Sensory Profile to be either hypo or hyper. Rogers et al. (2003) studied 21-50 month-old children with autism and found significant difficulties in tactile sensitivity, taste/smell sensitivity, underactive/seeks stimulation, auditory filtering, and low energy, weak muscle areas of the Sensory Profile. When individuals have deficits in processing and integrating sensory input, problems can occur in learning, behaving, and moving. Poor sensory processing can impact on their ability to participate in social, school, and home activities. Children with autism often demonstrate an extreme aversion to (hyper-responsiveness) or excessive seeking out of sensory input (hypo-responsiveness). (Cesarone, Garber 1991; O'Neill, Jones 1997). From a clinical perspective, the sensory related behaviors exhibited by persons with autism are thought to assist them in coping with their sensory environments by either generating or avoiding sensory input (Erner, Dunn 1998). The effect is that the child is extremely limited in their ability to participate functionally in school, home, or play activities. However when children with sensory integrative dysfunction are given the opportunity to receive appropriate input within the context of meaningful activity, the ability of the CNS to process and integrate sensory input can often be improved - and learning, movement, and "behavior" have the opportunity to be enhanced (Ayres 1972).
Neuroscience research has shown that when animals and humans are allowed to explore and interact with environments that are interesting and meaningful to them, there are significant increases in the formation of synapses. As a result of interacting with the environment and integrating the sensory input that is received, there is an increase in the synaptic connections between the neurons that send the messages and there is also an increase in their efficiency. Animal studies have shown that appropriate sensory input can, and does make positive changes in the synapses (Kandel, Schwartz, Jessell 1995; Kempermann, Gage 1999). These changes are most pronounced when the child is actively engaged rather than passively exposed. In sensory integration theory, an adaptive and automatic response (a successful response) to an environmental change or some form of sensory input is what is expected (Ayres 1972). The children however need assistance through the selection of appropriate activities that correspond to their needs Bundy, Murray 2002). Sensory integration intervention generally provides activities that elicit appropriate responses to tactile, vestibular and proprioceptive input. On the sensory processing spectrum a child can be hypo or hyper-responsive to this input (Dunn 1999). Our knowledge of how the child processes this information is based on careful observation and assessment of his or her responses and behaviors (Ayres 1979).
