Transcranial magnetic stimulation (TMS) offers a way of modulating the way the cerebral cortex works. The magnitude and direction of the effects, whether excitatory or inhibitory, depends on the variables used for stimulation, e.g. intensity, frequency, number of stimuli. By convention repetitive TMS or rTMS in the 0.3-1.0 HZ frequency range are referred to as “slow” and higher frequencies as “fast”.

Transcranial magnetic stimulation is a fairly simple procedure where each session lasts 20 to 30 minutes. Since the level of excitability may vary per patient (also by age and area of the cortex) we usually identify the intensity of the pulse necessary to elicit a noticeable motor response and use it as a reference for further studies in that patient. This measure is called the “motor threshold”. We begin the stimulations by moving the coil over the target area of the brain and adjust the parameters according to the motor threshold.

The procedure itself, rTMS, is regarded as safe, having few side effects. Some patients may report transient tension-type headaches, discomfort due to the sound of the pulses, or a metallic taste in their mouth. At high frequencies, there is also a possibility of inducing seizures (Note: We use lower frequencies for therapy in autism spectrum disorders. Ogawa et al studied the effects of low frequency rTMS and suggested a mechanism of action that involved the activity of cortical inhibitory neurons well past the time of the stimulation. This is in-keeping with our hypothesis that rTMS will increase the activity of inhibitory cells within minicolumns, see http://bit.ly/1fXGf08).

There is a vast literature supporting the use of TMS in mood disorders and the FDA has approved its use in treatment refractory depression. Additional reports have claimed benefits in Attention Deficit Hyperactivity Disorder (ADHD), Post-traumatic Stress Disorder, and Obsessive Compulsive Disorders. It may not be a coincidence that all of the previously named disorders share in having an anxiety component. More recently rTMS has been said to improve symptoms of Parkinson’s disease with effects lasting for at least 3 months after treatment (http://bit.ly/1iqvCuA).

A recognized problem when judging the benefits of rTMS clinical trials is how to establish a control group. Although “sham” TMS coils and equipment are available they do not duplicate the headaches and muscle-twitching (scalp and upper face) associate with the intervention. Furthermore sham interventions are not innocuous and can affect outcome measures (Maragnell et al., 2007 see http://bit.ly/1fXOCJl). According to a consensus panel, the problem is compounded when using subjective measures for outcome assessment (Rossi et al., 2009, see http://bit.ly/1lLO29G).

In order to overcome the criticisms of using a sham control group we have opted on using a waiting list control and instituting electrophysiological measures for outcome. ASD individuals have a long history of studies reporting abnormalities on electrophysiological measures. Many of these are related to an abnormality in the process of decision-making (e.g., so called P300 potential). Furthermore the timing of many of the reported events reveals that they are linked to endogenous brain processes rather than to attributes of the stimulus per se (as in the early event related potentials).

In future blogs I will describe the results of different trials, including our own, involving rTMS and autism. Thus far the treatment remains experimental. Available equipment is very expensive and outside the reach of the practicing psychiatrist. Hopefully the implementation of large clinical trials will help gain approval of rTMS for ASD by the FDA.

References

Ogawa A, Ukai S, Shinosaki K, Yamamoto M, Kawaguchi S, Ishii R, Takeda M: Slow repetitive transcranial magnetic stimulation increases somatosensory high-frequency oscillations in humans. Neurosci Lett 2004, 358:193–196.

I wrote a chapter on TMS and ASD that may be of benefit to the interested reader. Casanova MF, Sokhadze E. Transcranial Magnetic Stimulation: Application in Autism treatment. Valerie Hu (ed.) Frontiers in Autism Research: New Horizons for Diagnosis and Treatment, New Jersey World Scientific, ch. 23, 2014.