The Path Forward: Brain Stimulation in Autism

Autism and Autism Spectrum Disorders (ASD), while once considered extremely rare, are now recognized as relatively common. At Columbia University Medical Center, we are using the cutting edge technology to develop an innovative approach to studying and treating the symptoms of autism.

What Do We Know of Brain Functioning in ASD?

According to the DSM-IV, there are three core symptom clusters in autism and ASD: social deficits, speech/communication deficits and repetitive behaviors.

Converging evidence suggests that autism involves abnormalities in brain volume, (Courchesne 2004) neurotransmitter systems and neuronal growth.(Courchesne and Pierce 2005) In addition, evidence links autism with abnormalities in the cerebellum, the medial temporal lobe, and the frontal lobe.(Penn 2006) Neurochemical findings suggest involvement of multiple neurotransmitter systems (serotonergic, GABA-ergic and cholinergic as the primary ones. (McDougle, Erickson et al. 2005)

Why Is It Difficult to Study Autism?

Present methods of studying brain functioning mostly include structural MRI, functional MRI (fMRI) and Positron Emission Tomography (PET). However, fMRI, though very safe, usually requires performing a certain task while in the scanner, paying attention, pressing a button in response to a stimulus, which is hard for children or low-functioning patients. PET is invasive and uses radioactive substances that have to be injected into the bloodstream.

Here at Columbia, we are developing a new approach to study brain functioning in autism. We are bridging the fields of fMRI and noninvasive brain stimulation techniques, such as Transcranial Magnetic Stimulation and transcranial Direct Current Stimulation (tDCS).

What is Transcranial Magnetic Stimulation (TMS)?

TMS is a noninvasive tool that induces focal electrical currents in the brain by creating a magnetic field. It has been applied to map attention, memory, movement, and speech.(George, Nahas et al. 2003) There are three types of TMS: single-pulse TMS, paired-pulse TMS, and repetitive TMS (rTMS). In single- and paired-pulse TMS, pulses are given to the motor cortex to measure various aspects of motor cortex excitability. In rTMS, trains of pulses at various frequencies are given to acutely probe functioning of cognitive systems, or to treat disorders such as depression, OCD, or schizophrenia (George, Nahas et al. 2003).

Our Protocols

 Our main protocol “Neurocircuitry of Autism” is designed to use fMRI and TMS to study the neurocircuitry of autism symptoms. Using single and double pulse TMS we compare excitability of motor cortex in ASD patients and healthy controls. We also perform fMRI and compare levels of activation of specific brain areas during passive social tasks. Our hypothesis is that patients with ASD have higher excitability of motor cortex and lower level of activation of mirror neuron system during the social tasks. A single session of rTMS is used to see if activating a specific brain area can produce temporarily improvement in social functioning or repetitive behaviors. This will lay the ground work for developing future treatments in autism.

We also have a treatment trial for repetitive/stereotypic behaviors in autism, sponsored by the Autism Speaks. The concept stemmed from the similar studies in Obsessive-Compulsive Disorder (Mantovani, Lisanby et al. 2006), where applying low frequency TMS to the supplementary motor cortex significantly reduced repetitive behaviors.

Finally, we are exploring the language symptoms of autism and have introduced an fMRI strategy to study language processing even in very low functioning subjects. Our preliminary data indicate that high functioning ASD subjects use alternate brain connections for language processing, while low-functioning subjects have not established the alternate pathways. We are preparing a treatment trial to specifically increase functioning in a target brain area identified by the fMRI-guided approach.

Utilizing fMRI image-guided targeting of a specific brain area to treat symptoms of ASD is a break-through in autism investigation and treatment development.

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