**2.1 Etiologies**

Autism has a strong complex genetic basis. Abnormalities in gene expression affect the molecular, synaptic, cellular, and brain network levels. There is variability in results of brain imaging studies [magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI)] in autism, which report structural cerebral changes and functional connectivity disruptions. Alterations in overall gray and white matter volume and in regional lobes and gyri were witnessed.

Early brain overgrowth, especially in an early age of 2–3 years old toddlers remains, however, one of the most replicated findings. Compared with typically developing children, global gray matter (GM) and white matter (WM) volumes were significantly increased and also right superior temporal gyrus regional GM and WM volumes. Higher fractional anisotropy value was also observed in the corpus callosum, posterior cingulate cortex, and limbic lobes of autistic children

**21**

[18, 19].

*Autism: A Neurodevelopmental Disorder and a Stratum for Comorbidities*

[8]. The converging findings of structural and white matter abnormalities in autism suggest that alterations in neural anatomy of different brain regions may be

involved in the associated behavioral and cognitive deficits in this disorder.

Nevertheless, recent neural models of autism spectrum disorders have moved the focus from a lesion model to connectivity disorder model. Aberrant conductivity between different brain regions in autism is currently the most frequently addressed neurodevelopmental model. Minshew and Williams [9] have implicated intra-hemispheric connectivity to be mainly involved in the disorder. Vissers et al. [10] have studied functional and structural brain connectivity in individuals with high functioning individuals with ASD. They supported the findings that long-range cortico-cortical functional and structural pathways displayed weaker connectivity in people with ASD than in controls, but with less evidence for local overconnectivity. Other researchers have supported a local overconnectivity and long-range underconnectivity pattern of brain functioning in autism through the use of high-resolution electroencephalography (EEG) [11]. Cortical underconnectivity between brain regions, especially the frontal cortex and more posterior areas, is relatively well established in autism. This supports the view that there is weaker coordination between different parts of the brain that should be working together to accomplish complex social and language tasks. This is opposite to what is occur-

In this cerebral connectivity disorder of autism, the cerebellum has also been strongly implicated. Although the role of cerebellum as error detector and coordinator of movement and balance was the typical portrait of cerebellar function, yet recognition of nonmotor functions of the cerebellum has recently come into view. While some parts of the cerebellum are predominantly connected to sensorimotor cortex, other connections project to cognitive and affective regions and comprise a large fraction of cerebellar connectivity [13]. Impairment of these connections was

As a model for aberrant conductivity in autism, we could consider the reported comments about deviations in corpus callosum, white matter, and neurotransmitters. So, brain connectivity includes connectivity between the two hemispheres done mainly by the corpus callosum (CC), or between multiple areas in the brain accomplished by tracts in white matter and by synapses and neurotransmitters. People need this connectivity as different regions of the brain need to communicate in order to identify a face, understand, and respond to others and to different social situations. Disruption of white matter tracts in regions related to social functioning is implicated in autism [14]. In autism, defective joint attention was related to decreased connectivity and synchronization between posterior involuntary attention related to responding to joint attention (RJA) and anterior volitional joint

The corpus callosum (CC) constitutes the main commissural tract between the two hemispheres (more than 200 million axons). A study by Hardan et al. [16] that investigated the corpus callosum by MRI-based morphometry has identified decreased total volume of CC and several of its seven subdivisions. This was found in other studies and could reflect in the form of social deficits, repetitive behavior,

There are neural circuits for social cognition, which involves attention, memory, motivation, and emotion. Abnormalities in social brain structures and circuitry that are modulated by several neurotransmitters and neuromodulators have been linked, through human fMRI and animal research, to disorders of social functioning as in autism [17]. Neurotransmitter systems involved in autism spectrum disorders have been identified as GABA, glutamate, serotonin, catecholamines, and acetyl choline

*DOI: http://dx.doi.org/10.5772/intechopen.82496*

ring during normal development [12].

attention related to initiating joint attention (IJA) [15].

and sensory processing abnormalities.

also reported in autism.

## *Autism: A Neurodevelopmental Disorder and a Stratum for Comorbidities DOI: http://dx.doi.org/10.5772/intechopen.82496*

*Neurodevelopment and Neurodevelopmental Disorder*

autistic children [4].

ASD children [6].

**2. Body**

**2.1 Etiologies**

**1.2 Restricted repetitive behavior**

Abnormality in face perception is a core feature in autism. Face processing includes unchangeable facial features as those relating to gender and identity and changeable facial features such as emotional expression and gaze direction. Autistic children ignore looking at faces of others and are unable to understand facial expressions. Fixation time on the eye area of the face is reduced in ASD individuals. Opposite to what occurs in typically developing individuals, processing of gaze direction in autism experimentally produced more activation in fusiform gyrus for averted than for direct look. This was termed "covert attention," as autistic indi-

During recognition of neutral faces, the autistic children exhibit a reduced activation of fusiform gyrus, superior temporal sulcus, amygdala, and occipital lobes, the primary areas for face recognition. In spite of this fact, autistic children showed typical activation when looking at familiar faces like that of a mother. Inferior temporal, middle, and inferior frontal gyri are also involved in face processing. It is important to note that reduced connectivity in brain networks between areas of face processing emerged as a holistic approach to explain the atypical face perception in

The social processing involves social cognition and social motivation. Social cognition involves processes like attention, memory, and theory of mind, by which the person infers the internal state of others. Social motivation resembles directing attention to socially relevant stimuli and enjoying social activities. Both activities depend on the function of face processing. So it is related to the areas of face processing in addition to striatum (social interaction) and orbitofrontal cortex (social motivation) [5]. Impaired connectivity in social executive functions is present in

Autistic individuals resist change in their daily routine or the familiar surroundings. They do not explore while playing, and the toys are manipulated with little creativity or symbolic function. They are cognitively inflexible, as they may be preoccupied with parts of objects, or attached to unusual objects or movements, as watching the rotatory activity of fans. They could show stereotypic repetitive behavior that may be injurious to self or others. They tend to have a repetitive sensory motor behavior, insistence on sameness, and sometimes self-injurious acts [7].

Autism has a strong complex genetic basis. Abnormalities in gene expression affect the molecular, synaptic, cellular, and brain network levels. There is variability in results of brain imaging studies [magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI)] in autism, which report structural cerebral changes and functional connectivity disruptions. Alterations in overall gray and white matter

Early brain overgrowth, especially in an early age of 2–3 years old toddlers remains, however, one of the most replicated findings. Compared with typically developing children, global gray matter (GM) and white matter (WM) volumes were significantly increased and also right superior temporal gyrus regional GM and WM volumes. Higher fractional anisotropy value was also observed in the corpus callosum, posterior cingulate cortex, and limbic lobes of autistic children

volume and in regional lobes and gyri were witnessed.

viduals are visually attentive and perceptive, but in an atypical manner.

**20**

[8]. The converging findings of structural and white matter abnormalities in autism suggest that alterations in neural anatomy of different brain regions may be involved in the associated behavioral and cognitive deficits in this disorder.

Nevertheless, recent neural models of autism spectrum disorders have moved the focus from a lesion model to connectivity disorder model. Aberrant conductivity between different brain regions in autism is currently the most frequently addressed neurodevelopmental model. Minshew and Williams [9] have implicated intra-hemispheric connectivity to be mainly involved in the disorder. Vissers et al. [10] have studied functional and structural brain connectivity in individuals with high functioning individuals with ASD. They supported the findings that long-range cortico-cortical functional and structural pathways displayed weaker connectivity in people with ASD than in controls, but with less evidence for local overconnectivity. Other researchers have supported a local overconnectivity and long-range underconnectivity pattern of brain functioning in autism through the use of high-resolution electroencephalography (EEG) [11]. Cortical underconnectivity between brain regions, especially the frontal cortex and more posterior areas, is relatively well established in autism. This supports the view that there is weaker coordination between different parts of the brain that should be working together to accomplish complex social and language tasks. This is opposite to what is occurring during normal development [12].

In this cerebral connectivity disorder of autism, the cerebellum has also been strongly implicated. Although the role of cerebellum as error detector and coordinator of movement and balance was the typical portrait of cerebellar function, yet recognition of nonmotor functions of the cerebellum has recently come into view. While some parts of the cerebellum are predominantly connected to sensorimotor cortex, other connections project to cognitive and affective regions and comprise a large fraction of cerebellar connectivity [13]. Impairment of these connections was also reported in autism.

As a model for aberrant conductivity in autism, we could consider the reported comments about deviations in corpus callosum, white matter, and neurotransmitters. So, brain connectivity includes connectivity between the two hemispheres done mainly by the corpus callosum (CC), or between multiple areas in the brain accomplished by tracts in white matter and by synapses and neurotransmitters. People need this connectivity as different regions of the brain need to communicate in order to identify a face, understand, and respond to others and to different social situations. Disruption of white matter tracts in regions related to social functioning is implicated in autism [14]. In autism, defective joint attention was related to decreased connectivity and synchronization between posterior involuntary attention related to responding to joint attention (RJA) and anterior volitional joint attention related to initiating joint attention (IJA) [15].

The corpus callosum (CC) constitutes the main commissural tract between the two hemispheres (more than 200 million axons). A study by Hardan et al. [16] that investigated the corpus callosum by MRI-based morphometry has identified decreased total volume of CC and several of its seven subdivisions. This was found in other studies and could reflect in the form of social deficits, repetitive behavior, and sensory processing abnormalities.

There are neural circuits for social cognition, which involves attention, memory, motivation, and emotion. Abnormalities in social brain structures and circuitry that are modulated by several neurotransmitters and neuromodulators have been linked, through human fMRI and animal research, to disorders of social functioning as in autism [17]. Neurotransmitter systems involved in autism spectrum disorders have been identified as GABA, glutamate, serotonin, catecholamines, and acetyl choline [18, 19].

In the area of communication abilities, the gifts of memory, understanding, emotional expression, and learning are used on a daily basis. Sometimes, these abilities are disrupted due to deviant central nervous system development (neurodevelopmental disease), which includes long-range underconnectivity and local overconnectivity. Conditions like autism spectrum disorders (ASDs), and attention-deficit hyperactivity disorder (ADHD), can emerge secondary to these disruptions.
