Chapter 19, Structural and Functional MRI Studies of Autism Spectrum Disorders

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It has dramatically improved our understanding of brain function. However, several pitfalls limit the value of the technique Both fast gradient echo and fast spin echo techniques have been used extensively in the past with success. The former offers a good signal to noise ratio, but greater sensitivity to larger vessels, the latter offers sensitivity to microvasculature but of a lower signal to noise ratio. Echo-planar imaging EPI is a very fast data acquisition technique which reduces intrabrain motion artifacts and allows whole brain imaging in multislice and even true 3D mode, with a high signal to noise ratio.

However, it requires special and expensive hardware and software for data acquisition and postprocessing. Event related ultrafast echo-planar pulse sequences, with single plane imaging times of 40—80ms, promises to resolve the stimulus-dependent vascular response function. This technique is able to deconvolve neuronal events with time scales of the order of the vascular response.

An alternative strategy for investigating neonates and infants with fMRI is the use of completely silent pulse sequences allowing functional imaging without any gradient noise. The image is composed of a statistical image based on the result from the cross-correlation analysis, overlaid on an anatomical image.

The flicker-goggles are placed over the eyes and the tape serves merely to hold them in place. Care is taken not to apply excessive pressure on the goggles.


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The padded headhold provides the infant with the necessary head stability and prevents head movements. Developmental neuroimaging extends the analysis gained from adults to include the temporal evolution of a structure and associated function. It provides monitoring of the physiological, structural and functional plasticity during early postnatal life by identifying the size and distribution of processing components of discrete elementary operations. The ultimate expectation is that it will reveal typical activation patterns that define sensory inputs, contribute to cognitive tasks and eventually lead to distinct behavioural operations in the child.

Such measures of structure—function relationship may well need to be explored in the normal developing brain, as well as in cases of brain dysfunction and delayed maturation.

SAGE Reference - Autism Spectrum Disorders: General Overview

It is well suited to the study of infants and children. There are, however, constraints in fMRI of neonates and infants. The images should provide high spatial resolution and good contrast, while the total imaging time should be low. Artifacts produced by head movements are a serious obstacle to successfully collecting functional data.


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The high level of acoustic noise from fast switching gradients in echo planar imaging sequences not only frightens children but is also a major source of anxiety for the attending parents. Moreover, typical fMRI experiments require that specific tasks be performed by the subject under investigation over an extended period of time.

All these aforementioned points render neonates and infants poor candidates for MRI studies. A solution to this problem is to examine young children during natural sleep or under sedation. This requires the development of paradigms and fMRI methods that impose no demands on patient co-operation, for example visual stimulation through the closed eyes Fig.

Pentobarbital and chloral hydrate are often used in children during clinical MR examinations to avoid movement artifacts and claustrophobia.

More recently, thiopental has been shown to lower the amplitude of visually evoked potentials10 and to reduce the increase in regional CBF rCBF in response to somatosensory stimulation in rats However, careful analysis of the cortical activity in response to visual stimulation in pentobarbital-sedated adult volunteers has revealed changes in neuronal activity and metabolism to be much smaller than to the reduction in rCBF To perform consistent and reproducible functional experiments with reliable results in neonates and infants, these issues need to be addressed.

Compared to the fMRI signal of older infant see Fig. While the visual activity is more anteriorly located in the calcarine sulcus, the BOLD signal is lower during the periods of stimulation than during the rest periods, i. During the early postnatal months one of the most interesting areas of functional maturation is the development of vision 2. For a long time, the accepted theory on visual processing was that the entire visual system was functional from birth, inefficient at first but maturing rapidly 6 , Research on animals then led to the conclusion that two visual systems co-exist Diamond and Hall14 and later Bronson8 proposed that a secondary, phylogenetically older, extrageniculate visual system, which consists of a number of subcortical structures such as the superior colliculi and thalamic nuclei, may play an important role in neonatal and infantile visual behavior, such as smooth tracking of a slowly moving object.

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However, this system is not capable of providing conscious visual perception in humans. This hypothesis is in line with early metabolic maturation of thalamic afferent pathways and thalamic CBF 11 , 52 indicating thalamic activity in neonates. The secondary visual system mainly processes stimuli falling outside the central area of the retina and has direct connections to various extrastriate visual cortical areas. The involvement of this older subcortical system in visual perception of neonates has been described earlier 16 , Testing the visual performance of premature infants with hypoxic—ischemic and hemorrhagic brain lesions clinically it was found that lesions near the thalami, such as periventricular hemorrhage extending into the basal ganglia were more likely to affect visual behavior than substantial infarction of the occipital cortex.

These findings have been confirmed recently Infants who later became cortically blind seemed to retain their ability to track and show pattern preference until about 2 months postnatally, depending on their gestational age.

It is concluded that these functions do not require cortical integrity, but are most probably mediated through subcortical pathways. Moreover, the time when the affected neonates apparently lost their ability to track objects seems to coincide with the time at which binocular vision is first demonstrable. This is a function which is thought to be cortically mediated.

Thus, cortically mediated visual processes, which involve cognitive processes in order to identify the target object in the foveated area, only start to function during the first 3 months of life. They are mediated via the primary visual pathway passing via the lateral geniculate bodies and entering the cortical visual processing area in V1. Nevertheless, different cortical mechanisms appear to be operational at different postnatal times.

Visual acuity, binocular vision and other visual attributes seem to mature in a predetermined manner Vision probably plays a relatively minor role during postnatal adaptation. However, it is rapidly developing during the first months of life and may become the most important sense with which the infant explores his or her environment and achieves social contact.

Vision then forms the basis for perceptual and future cognitive, intellectual and social function 3. It is not surprising that the primary visual area is one of the earliest neocortical structures to mature and to obtain specific functions. The history of research on autism spectrum disorders ASD is an intriguing example of the value of multidisciplinary and interdisciplinary approaches to developmental disorders.

Though it is likely that autism has existed for a very long time Lane, , the first documentations of it as a syndrome were made in the early in parallel by a psychiatrist and a pediatrician in different countries, in very different situations. Leo Kanner provided detailed descriptions of 11 children seen in his psychiatric clinic in Baltimore who shared qualities of social aloofness, insistence on sameness and language delays or oddities. CQ Press Your definitive resource for politics, policy and people. Remember me?

Functional MRI connectivity of children with autism and low verbal and cognitive performance

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