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Functional Magnetic Resonance Imaging (fMRI)

brain scan

Study of Brain Functional Development

We specialize in using functional magnetic resonance imaging (fMRI) to reveal the neural underpinnings of autism. Our studies have been conducted with the participation of adults and adolescents with autism, as well as infants and toddlers at risk for the disorder. In this way we can discover how the brain changes across development.

In addition, we have used fMRI to study brain functional development in typically developing infants and toddlers. Results from our studies of normal development are foundational to our understanding of the mechanisms that go awry in autism.

What is fMRI?

fMRI stands for "functional magnetic resonance imaging" and is a technique used by scientists and medical professionals to map activity in the brain.

When our brains are active, such as when we talk or complete a math problem, the parts of the brain that are being used require more energy in the form of glucose. In order to meet this increased energy demand, active brain tissue receives an increase in blood flow, which carries with it oxygen and glucose rich blood.

Using a magnetic resonance imaging scanner tuned to be sensitive to small differences in signal quality due to brain activity, scientists can measure the change in blood flow, specifically the resulting increase in oxygen content, and make inferences about the location of brain activity.

It is important to note that “brain activity” as used in fMRI research studies is an umbrella term and includes various types of neuronal activity such synaptic excitation, synaptic inhibition and action potential of the neuron soma. Measures of fMRI activity are an indirect measure of neuronal activity, but can nonetheless be a very powerful tool to map brain function.

When brain cells, or neurons, are active, they require increased levels of glucose and oxygen to be delivered through the blood stream. Through a process called the hemodynamic response, blood vessels selectively deliver glucose and oxygen to brain regions with high demands. This results in a localized increase in the ratio of oxygenated (versus deoxygenated) hemoglobin, which carries oxygen in the blood.

Oxygenated and deoyxgenated hemoglobin have different magnetic properties due to the presence of iron in hemoglobin which is less exposed (and less magnetic) when oxygenated. Thus, oxygen rich blood and oxygen poor blood have different magnetic resonances and changes in the ratio of oxyhemoglobin and deoxyhemoglobin can be measured by tuning the imaging sequence so that it is sensitive to small magnetic inconsistencies in a region. The resulting blood-oxygenation level dependent, or BOLD, signal is the central metric used in establishing an image of brain function using fMRI.

Sleep fMRI with infants illuminates how autism first emerges

Autism spectrum disorders (ASDs) impact one out of every 59 children born today. It is a disorder that affects how the brain grows and works, yet the functional brain characteristics of autism during the time when symptoms first appear, namely 12-36 months, is almost completely unknown. This is because fMRI studies have been conducted almost exclusively with high functioning adolescents and adults with autism.

The reason for this major gap in knowledge is that despite its power to map brain function, fMRI cannot be successfully used with awake, alert toddlers, whether autistic or typically developing. This is due to the strong requirement for subjects to remain still during an entire fMRI experiment, a task beyond the capabilities of infants and toddlers.

To successfully scan infants and toddlers with autism, the UC San Diego Autism Center of Excellence (UCSD ACE) has developed a new method that we call the Sleep fMRI method.

Sleep fMRI studies with typically developing toddlers

To identify the key systems that fail in autism, an understanding of the neural bases for typical language acquisition at this critical time period is needed. We addressed this question in our sleep fMRI study of typical toddlers (Redcay, Haist and Courchesne, 2008). In response to speech, typical toddlers in our study displayed extended networks of activation to complex speech information.

Specifically, functional activity was prominent in a number of different frontal and cerebellar regions that are involved in social, emotional, attention, novelty detection or sequence tracking functions in adults, whereas activity in 3-year-old typical children was prominent primarily in classic adult receptive language cortices, including the superior temporal gyrus (STG).

It may be that activation of these long-distance extended networks is important in establishing long distance connectivity, organizing long-distance synchronized interactivity, and stabilizing specialized and lateralized functional networks during early development.

Moreover, this evidence supports a more general assumption in the neurodevelopmental literature that frontal cortex development is key to the rapid acquisition of a variety of higher-order complex skills.

Overall, however, several sleep fMRI studies with typically developing toddlers demonstrate that the STG, particularly on the left side of the brain, is active and functionally responsive to language within the first year of life. The degree to which this pattern is similar, or different, in toddlers with autism may hold the key to understanding what genes and other factors are operating to adversely impact normal language and social development in autism.

Sleep fMRI studies with ASD toddlers

fMRI image of brain lit up when baby hears a sound

Initial sleep fMRI studies at the UCSD ACE have focused on understanding how the brain responds to language. In a series of studies ACE scientists have found functional defects in the superior temporal gyrus (STG), a brain region key for language processing. Results from studies note that defects are both early emerging and a core defect in the disorder, with abnormalities found in our studies in children as young as 14-months.

These defects largely take the form of reduced activation in the left STG relative to controls and a proclivity for greater right hemisphere activation relative to the left in some cases, the opposite of what is found in typically developing toddlers. For more information, see the original pioneering study by Redcay & Courchesne (2008).



New Discoveries

fMRI with School-Age Children, Adolescents and Adults During Face Processing Reveal Surprising Properties about Brain Function in the Disorder

For many, the ability to process a face is fundamental to the human social experience. It is the face that conveys socio-emotional meaning and acts as a portal between one's internal state and the surrounding environment.

Early studies of face processing in autism revealed a startling effect:

There was a reduced or completely absent functional activity in the brain region that strongly supports face processing, namely, a region in the middle lateral fusiform gyrus often referred to as the fusiform face area (FFA). See papers by Pierce et al., 2001 and Schultz et al., 2000 for examples of this early work.

New studies now show a remarkable effect:

Namely, extrinsic factors that serve to increase attention, motivation, or interest can cause more normal functional activation in brain regions and networks in high functioning autistic individuals.

For example, showing adults and children with autism familiar faces such as pictures of their mother has been shown to result in normal levels of fusiform activity. See studies by Pierce and colleagues, 2004 and 2008. Other scientists have also shown that increasing gaze fixation to the face by inserting a dot on the face and instructing subjects to attend to the face also results in more normal fusiform activity. See papers by Hadjikhani and colleagues 2004 and 2007.

One interpretation of this finding is that the fusiform gyrus, an important brain region involved in face processing in normal individuals, can and does function in autism, but whether or not it does so depends more on systems that mediate fusiform function, such as attention, motivation, and reward systems, rather than the fusiform region per se.

images of a brain responding to facial expressions

The above image (left in the picture) shows the location in the brain that is responsive to faces in typical individuals. This region, called the "Fusiform Face Area" (FFA) is located in a particular location in the temporal lobe called fusiform gyrus and is shown in this functional activation map. Although both sides of the brain are commonly active in response to faces, it is the right side that is usually more active in response to faces (note radiological convention where left and right are reversed in the image).

This image was taken from early face processing research conducted by Karen Pierce and colleagues at the ACE.

The image on the right of the picture is of the human brain, post mortem, where the fusiform face area is colored in pink.