Autistic disorder (autism) and related pervasive developmental disorders (PDDs) are profound neuropsychiatric conditions characterized by impairments in social skills and communication, as well as repetitive interests and activities. The most commonly diagnosed PDDs, autism, Asperger's disorder, and PDD not otherwise specified (NOS), are often referred to as autism spectrum disorders (ASDs). Epidemiological research suggests that ASDs affect at least 60 per 10,000 youth, with estimates as high as 100 per 10,000 (Baron-Cohen et al., 2009
; Fernell and Gillberg, 2010
). In addition, ASDs are considered highly heritable polygenetic disorders, with concordance rates for autism in monozygotic twins ranging from 60% to greater than 90% (Bailey et al., 1995
; Ritvo et al., 1985
In 1943, Leo Kanner first described autism in a case report of 11 patients who had a “fundamental inability to relate themselves in the ordinary way to people and situations from the beginning of life.” In this landmark work, Kanner provided an enduring characterization of autism that is closely reflected in the current criteria of the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision) (DSM-IV-TR) (American Psychiatric Association, 2000
). This description included symptoms of autistic aloneness, echolalia, pronoun reversal, and need for sameness, among others. Of importance, Kanner believed that autism was congenital in nature and astutely noted the presence of “relatively large heads” in five of the eleven children in his case report; a key observation that would later be supported by research into the neurobiological underpinnings of autism.
In light of Kanner's (1943)
original observation that some patients with autism had enlarged heads, researchers began investigations of head circumference as a means to determine whether individuals with autism are macrocephalic (head size greater than two standard deviations above the mean). The findings from these studies, which included both children and adults, revealed that approximately 15%–20% of subjects with autism exhibited macrocephaly (Aylward et al., 2002
; Bailey et al., 1993
; Fombonne, 2000
; Lainhart et al., 1997
). However, it was difficult to meaningfully interpret these results because head circumference is considered to provide a fairly accurate indication of brain size in early childhood, but not in adolescence or adulthood (Bartholomeusz et al., 2002
These intriguing findings compelled researchers to further explore the brains of individuals with autism in an in vivo fashion and on a larger scale than could be done before. Early studies employed computerized tomography (CT), an imaging modality that used ionizing radiation, to ascertain neuroanatomy. Although gross abnormalities were initially found, many subjects suffered from other potential causes of brain damage (e.g., infectious, genetic, neurologic) that likely confounded the results (Damasio et al., 1980
). Subsequent CT studies used rigorous screening procedures to enroll subjects with idiopathic autism (Campbell et al., 1982
; Rosenbloom et al., 1984
). Overall, these studies did not show significant gross anatomical abnormalities and supported Kemper and Bauman's (1998)
hypothesis of an aberrant neuropathology at the microscopic level in the autistic brain. Taken together, these early studies only modestly contributed to the knowledge base in autism. Ultimately, CT was found to have concerning limitations such as poor spatial resolution and use of ionizing radiation that greatly restricted its use. New imaging technologies would clearly be needed to advance the understanding of brain structure and function in individuals with ASDs.
In fact, a new technology was evolving from two seminal studies of nuclear magnetic resonance conducted in 1946 (Huettel et al., 2009
). By the 1970s, research advances in the area had led to the first biological images captured by magnetic resonance imaging (MRI) techniques. Magnetic resonance imaging has a high degree of spatial resolution and contrast sensitivity, as well as an absence of ionizing radiation. However, it was not until the 1980s that the clinical use of structural (s) MRI for brain imaging became widespread. Diffusion tensor imaging (DTI), a MRI technique for assessing white matter microstructure in the brain, underwent investigation during the 1980s (Pierpaoli et al., 1996
; Taber et al., 2002
). In the 1990s, researchers found that changes in blood oxygenation could be measured in the brain using functional (f) MRI. The advent of these novel neuroimaging techniques using MRI would soon herald a new era of investigation into the neuroanatomy and neurocircuitry of ASDs.
This review provides a synopsis of relevant sMRI and fMRI studies in ASDs to date, with an emphasis on well-designed, controlled research. Structural MRI findings that are summarized include studies of total brain volume (TBV) and specific neuroanatomic structures, as well as DTI. Functional MRI results, encompassing task-based, as well as resting state studies of the default-mode network (DMN), are subsequently reviewed.