Autism Spectrum Disorder (ASD) is a condition that affects behavioural aspects of an individual including social interaction, communication and interests. The symptoms of ASD usually present before the age of three years in an individual. [1]
There is no cure for ASD however there are therapies available. The therapies include applied behaviour analysis, structured teaching, social skills instruction, occupational therapy and sensory integration therapy, and medical management of other conditions associated with ASD such as epilepsy. [2]
Although a definitive cause of autism has not yet been discovered, there is evidence to suggest that there is structural and functional differences between an autistic brain and an individual of normal development. This report will review this evidence on the underlying causes of autism.
Cerebellum
The cerebellum has several roles. It stores sequences of movements that an individual has learnt and participates in the fine tuning and coordination of movements produced in other parts of the brain, integrates all these movements to produce fluidness that we are not aware that we are doing. Pathologies of the cerebellum have revealed that it is involved in motor coordination. The cerebellum is divided into three specific regions, each with specific structure connection and functions.
1. The archicerebellum (vestibulocerebellum) –connected to the vestibule of the inner ear has involvements in balance.
2. The palaeocerebellum (spinocerebellum) consists of mainly the vermis, axial structure. It is connected to the spinal cord with controls of postural muscle and influences on muscle tonus. Is it also involved in muscle tensing at all times and releasing muscles required for execution of certain movements.
3. The neocerebellum (cerebrocerebellum) – consists of the cerebellar hemispheres and is connected to the cortex and contributes to the co-ordination of voluntary movements. It ensures that there is a set of muscles initiates movements and opposing set acts as a break so target action is precise. [3]
Basic body movements must be controlled in a very precise manner for any gesture, including the sequence and duration of these movements. The cerebellum provides control over the timing of the movements by a loop circuit that connects to the motor cortex and modulates the signals that the motor cortex sends to the motor neurons. [4]
In some autistic children, cognitive delays have been partly attributed to insufficient development of certain parts of the cerebellum.
Some signs of cerebellar involvement have been found in the areas of language, attention, memory, and emotions regarding cognitive activity. The cerebellum has an ability to learn and remember, which is based on the distinctive cell architecture of the cerebellar cortex. The cerebellum is involved in specific cerebellar zones which influence social interaction, and sensitive-period disruption of internal brain communication can account for autism’s key features. [4] There have been many studies which have shown abnormalities in the size of the brain in patients of ASD. Hypoplasia of the central cerebellar vermis lobules (VI+VII) was the first neuroanatomical change detected in the brains of ASD patients. [5] Structural imaging investigations have shown decreases in both cerebellar grey and white matters showed a 24% decrease in mean Purkinje cell size in autistic brains. The Purkinje cell is the output neuron of the cerebellum, and it uses the inhibitory neurotransmitter, GABA. Studies have shown that some autistic subjects had greater than a 50% reduction in Purkinje cell size compared to control cases. There have been studies that have found Purkinje neuron reductions in autistic subjects which some also demonstrated reduction in diffusion. Also, the enzyme used to synthesize GABA has been found to be reduced by >50% in dentate neurons to which the Purkinje cells communicate in the post-mortem brains of ASD patients versus control cases. [6]
Amygdala
The amygdala is an almond-shaped mass of cells which is located deep within in the temporal lobes of the brain of which there are two amygdalae, each section in each brain hemisphere. It processes emotions such as fear, pleasure and anger. The amygdala is vital to determine what memories are stored and where they are stored in the brain. This determination is based on the relevance of an event and the impact it has on an individuals’ emotions. [4]
The amygdala is associated with fear and hormonal secretions and is involved in autonomic nervous system. Scientific studies have discovered the neurons in the amygdala that are responsible for fear conditioning.
Fear conditioning is when an individual learns to fear something through repeated experiences. Experiences cause brain circuits to change and create new memories.
An example of this process is when an individual hears an unpleasant sound, the amygdala heightens the perception of the sound which is then deemed distressing and memories are created associating that sound with unpleasantness. If the noise is experienced again in the future, it activates the autonomic fight or flight response through the sympathetic nervous system. [7] This activation leads to accelerated heart rate, dilated pupils, and increased metabolic rate and blood flow to the muscles; all of which are coordinated by the amygdala.
Sensory information is received by the amygdala from the thalamus and the cerebral cortex. The thalamus is involved in sensory perception and movement with parts of the brain and spinal cord. The cerebral cortex processes the information received from the senses and is involved in processes such as decision-making, problem-solving and planning. [7]
Malfunction of the amygdala and its associated structures in ASD patients may be indicative of impairments in social interaction, rewarding convention, memory and facial and emotional recognition patterns. There have been many studies analysing the role of abhorrent amygdala growth patterns in patients of ASD. [5]
The amygdala has abnormal developmental time that includes enlargement that persists through late childhood. Several studies have shown a 13–16% enlargement of the amygdala in young autistic cases (3–5 years of age). Amygdala grows by 40% between 8 and 18 years of age in typically developing boys, whereas autistic boys show a stagnation of growth of the amygdala. Even though the amygdala volume differs significantly in the younger ages between ASDs and controls, the volume normalises in the adolescent and adult age groups because of differential growth patterns between the two groups. Recent studies suggest that amygdala enlargement is associated with elevated anxiety and poor social and communication skills. Using stereological methods, there has been a discovery of a significant 14% decrease in total neuron number in the lateral nucleus and a significant 12% decrease in neuron number in the total amygdala in 9 autism brains versus 10 typically developing control brains. Amygdala volume was significantly smaller in the autistic subjects versus controls (of the same age) based on MRI imaging studies in adolescents and adults. Therefore the amygdala size and cell number differ in ASDs versus controls, but the difference depends upon the age of the ASD subject. [6] The Growth Model of Autism can be shown on Figure 1 in comparison to typically normal brain development.
Growth Model of Autism
Autism involves three phases of early brain growth pathology.
1 Early brain overgrowth at the beginning of life.
2 Slowing or arrest of growth during early childhood.
3 Possible degeneration in some brain regions by preadolescence and continuing into adulthood. [8]
Figure 1 This is a graph that shows the neural maldevelopment in autism compared to the normal development. [8]
Conclusion
There is a lot of evidence to suggest that the neuropathological differences in early ages of patients leads to the development of autism. Hypoplasia of the cerebellum evidently leads to reduced numbers of Purkinje cells and this leads to reduction in the connectivity of the brain, specifically GABA neurotransmitter and enzymes associated with GABA in patients of autism. It may be worth researching to increase GABA levels or enzymes to be able to cure the autism. Amygdala abnormalities particularly the enlargement during early childhood has been suggested to be an underlying cause of autism. Genetic screening could be carried out on patients of autism who show evidence of enlargement of the amygdala in fMRI scans and these could be used to find connections of specific genes and enlarged amygdalae in comparison to case controls. The studies that have been carried out in the reviews have shown that there were not many subjects that these studies have been tested out on. This could affect the validity of the studies.