Research ReportStructural and functional magnetic resonance imaging of autism spectrum disorders
Research Highlights
► MRI research has generated insights into the neurobiology of ASDs. ► Structural MRI studies found increased total brain volume and early rapid brain growth. ► Alterations in gray and white matter have been consistently identified. ► Functional MRI research found abnormalities in cortical activation and specialization. ► Abnormalities of the default-mode network have been found during the resting state.
Introduction
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, Lainhart et al., 2006). 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).
Recognizing that autism first emerges early in life, investigators studied head circumference in infants who later developed autism. As a whole, head circumference in this group was found to be average or slightly below average at birth (Courchesne et al., 2003, Dawson et al., 2007, Dementieva et al., 2005, Hazlett et al., 2005, Lainhart et al., 1997). However, brain growth was then found to accelerate on or before 1 year of age, with 15%–20% developing macrocephaly by 4–5 years of age.
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.
Section snippets
Total brain volume
In light of prior research suggesting early abnormal brain enlargement, investigators launched sMRI studies in an effort to better delineate brain abnormalities in ASDs. Although autism had been considered a static process, new insights gleaned from head circumference data suggested a dynamic process of age-dependent brain growth abnormalities. To further explore this possibility, Courchesne et al. (2001) conducted a sMRI study that quantified developmental abnormalities in TBV in boys with
Discussion
The concept of autism as a brain-based disorder began with a highly significant early observation, namely the finding of “relatively large heads” in some children with autism. Although this finding would later be verified via studies of head circumference, new technologies were clearly needed to further our understanding of ASDs. Several decades would pass after Kanner's original observations before investigators would begin to actively utilize MRI techniques in an effort to elucidate the
Experimental procedures
A PubMed search was conducted from 1966 to 2010 using the search terms autism, autism spectrum disorders, default-mode network, diffusion tensor imaging, functional magnetic resonance imaging, neuroimaging, pervasive developmental disorders, and structural magnetic resonance imaging, with additional publications obtained from articles identified in the search.
Acknowledgments
This work was supported in part by a research grant (RO1 MH072964) from the National Institute of Mental Health (NIMH) (Dr. McDougle), a Career Development Award (K23 MH082119) from the NIMH (Dr. Stigler), and a Daniel X. and Mary Freedman Foundation in Academic Psychiatry Fellowship Award (Dr. Stigler).
References (206)
Fear, faces, and the human amygdala
Curr. Opin. Neurobiol.
(2008)- et al.
Outcome classification of preschool children with autism spectrum disorders using MRI brain measures
J. Am. Acad. Child Adolesc. Psychiatry
(2004) - et al.
Diffusion tensor imaging of the corpus callosum in autism
Neuroimage
(2007) - et al.
Social perception from visual cues: role of the STS region
Trends Cogn. Sci.
(2000) - et al.
Neuroanatomy of autism
Trends Neurosci.
(2008) - et al.
Autism and megalencephaly
Lancet
(1993) - et al.
White matter structure in autism: preliminary evidence from diffusion tensor imaging
Biol. Psychiatry
(2004) - et al.
Superior temporal sulcus anatomical abnormalities in childhood autism: a voxel-based morphometry MRI study
Neuroimage
(2004) - et al.
Gray and white matter imbalance—typical structural abnormality underlying classic autism?
Brain Dev.
(2008) - et al.
Brain anatomy and development in autism: review of structural MRI studies
Brain Res. Bull.
(2003)
Default-mode brain dysfunction in mental disorders: a systematic review
Neurosci. Biobehav. Rev.
On beyond mirror neurons: internal representations subserving imitation and recognition of skilled object-related actions in humans
Brain Res. Cogn. Brain Res.
Localized enlargement of the frontal cortex in early autism
Biol. Psychiatry
Cerebral lobes in autism: early hyperplasia and abnormal age effects
Neuroimage
Altered cerebellar feedback projections in Asperger syndrome
Neuroimage
Less white matter concentration in autism: 2D voxel-based morphometry
Neuroimage
A functional and structural study of emotion and face processing in children with autism
Psychiatry Res.
Mapping early brain development in autism
Neuron
Rate of head growth decelerates and symptoms worsen in the second year of life in autism
Biol. Psychiatry
Accelerated head growth in early development of individuals with autism
Pediatr. Neurol.
Social stimuli interfere with cognitive control in autism
Neuroimage
Atypical modulation of cognitive control by arousal in autism
Psychiatry Res.
Normal movement selectivity in autism
Neuron
Autism spectrum disorder diagnoses in Stockholm preschoolers
Res. Dev. Disabil.
A meta-analysis of the corpus callosum in autism
Biol. Psychiatry
Total brain volume and corpus callosum size in medication-naive adolescents and young adults with autism spectrum disorder
Biol. Psychiatry
Morphological evidence for brainstem involvement in infantile autism
Biol. Psychiatry
Atypical [corrected] participation of visual cortex during word processing in autism: an fMRI study of semantic decision
Neuropsychologia
Volumetric alterations of the orbitofrontal cortex in autism
Prog. Neuropsychopharmacol. Biol. Psychiatry
Neural mechanisms of empathy in adolescents with autism spectrum disorder and their fathers
Neuroimage
The phenotype and neural correlates of language in autism: an integrative review
Neurosci. Biobehav. Rev.
Activation of the fusiform gyrus when individuals with autism spectrum disorder view faces
Neuroimage
Posterior fossa magnetic resonance imaging in autism
J. Am. Acad. Child Adolesc. Psychiatry
Abnormal brain size effect on the thalamus in autism
Psychiatry Res.
An MRI and proton spectroscopy study of the thalamus in children with autism
Psychiatry Res.
A preliminary longitudinal magnetic resonance imaging study of brain volume and cortical thickness in autism
Biol. Psychiatry
Corpus callosum volume in children with autism
Psychiatry Res.
Brain activation during semantic processing in autism spectrum disorders via functional magnetic resonance imaging
Brain Cogn.
Human neural systems for face recognition and social communication
Biol. Psychiatry
Cortical gray and white brain tissue volume in adolescents and adults with autism
Biol. Psychiatry
Striatal volume on magnetic resonance imaging and repetitive behaviors in autism
Biol. Psychiatry
Magnetic resonance imaging of the posterior fossa in autism
Biol. Psychiatry
The neuroanatomy of autism: a voxel-based whole brain analysis of structural scans
NeuroReport
Diagnostic and Statistical Manual of Mental Disorders
Abnormal functional connectivity of default mode sub-networks in autism spectrum disorder patients
Neuroimage
MRI volumes of amygdala and hippocampus in non-mentally retarded autistic adolescents and adults
Neurology
Effects of age on brain volume and head circumference in autism
Neurology
Autism as a strongly genetic disorder: evidence from a British twin study
Psychol. Med.
Prevalence of autism-spectrum conditions: UK school-based population study
Br. J. Psychiatry
Relationship between head circumference and brain volume in healthy normal toddlers, children, and adults
Neuropediatrics
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