Clinical Trials Show Promise for Transcranial Magnetic Stimulation As a Treatment for Autism
Wednesday April 9, 2008

Don Farral – Getty ImagesMore than a year ago, professor Manuel Casanova at the University of Louisville in Kentucky published findings regarding differences in the structure of autistic brains. These findings led him to theorize that a non-invasive treatment called Transcranial Magnetic Stimulation (a treatment used successfully to treat various problems including depression) might help in lessening problemmatic symptoms of autism.

Just this week, Dr. Casanova completed clinical trials which suggest that he was quite right:

Members of the UofL research team placed a coil on the scalps of 10 people with autism to create a low-frequency magnetic field, which they then pulsed by reversing the field’s polarity. After receiving a 20-minute treatment twice a week for five weeks, patients showed fewer symptoms of hyperactivity, sensory overload and repetitive behaviors, said psychologist Lonnie Sears, a project collaborator.
The team assessed symptoms before and after the treatment by measuring patients’ brain activity and their scores on standard neurological and psychological tests.

“Our results are preliminary, but they show a great deal of promise in reducing the severity of symptoms that people with autism find most distressing and, as a result, helping them communicate and relate better — something that most of us take for granted,” Casanova said.

Of particular interest to people on the autism spectrum is this important note:
The team also found that the treatment did not seem to affect areas of “giftedness” in the test group.
“This is important,” Casanova said, “because, despite communication and social problems, some people with autism are very gifted in specific areas of intelligence.

Repetitive Transcranial Magnetic Stimulation Research Clinic at Yale-New Haven Psychiatric Hospital

What is Repetitive Transcranial Magnetic Stimulation?

Transcranial magnetic stimulation (TMS) utilizes an electromagnet placed on the scalp that generates magnetic field pulses roughly the strength of an MRI scan. The magnetic pulses stimulate a small area on the surface of the brain about the size of a quarter. Low frequency (once per second) TMS has been shown to induce small, sustained reductions in activity in the part of the brain that has been stimulated. The photo above shows the TMS system used in the study. Stimulation is administered, above and behind the ear, while people are awake. Currently we are conducting studies to determine whether low-frequency TMS can reduce hallucinated voices. Below are descriptions of these studies and information about how to contact us.

Transcranial Magnetic Stimulation as an Investigational Treatment for Hallucinated “Voices”
What are “Voices?”
Auditory hallucinations are experienced by 50-80% of patients with schizophrenia and 10-15% of patients with a mood disorder. These hallucinations, referred to as voices by patients themselves, consist of spoken speech. Sometimes the voices are familiar-persons whom the patient has known. But often the voices are unrecognizable. They comment, cajole, criticize, and in some cases command the patient. Voices are often highly distressing to the patient, especially when verbal content is negative or intrusive. These experiences disrupt one’s ability to interact with others, to work, to study-even to sleep. In extreme cases they can produce suicidal behavior. In about 25% of cases, voices respond only partially or not at all to currently available drug therapy. Effective treatment alternatives for these hallucinations would therefore provide a significant benefit to patients and their communities. Our neuroimaging studies suggest that voices arise from parts of the brain that are ordinarily involved in perceiving spoken speech. These studies have led us to investigate a new treatment approach. Our strategy is to use low frequency TMS to reduce activation of brain areas appearing to generate voices. Our prediction is that reduced intensity of voices will result. These studies are described in more detail below.

TMS Studies of Voices

Our first study (completed 2/99) compared effects of active versus sham or “placebo” stimulation in 16 patients with severe, persistent voices. In every patient, “voices” were resistant to medication therapy. In the case of the sham stimulation, the scalp but not the brain was stimulated. The patient was not told which type of stimulation was being given in order to determine whether symptom improvements following magnetic stimulation could be due to a “placebo” response. Patients remained on their medication for the duration of the study. Magnetic stimulation was administered while the patient was awake and was directed above and behind the left ear. A total of 40 minutes of stimulation was given over 4 days. Patients showed improvement following active stimulation that exceeded that observed following the placebo form of stimulation.

A second study assessed the effects of more stimulation — a total of 132 minutes of stimulation (compared to 40 minutes) given to the same brain site used in the first study. Stimulation was given over 9 days, and again improvements in AHs following real stimulation greatly exceeded improvements following placebo stimulation. Approximately 53% of patients experienced at least a 50% reduction in their voices compared to 18% of patients receiving the placebo form of stimulation. Duration of improvement ranged from 1 week to over a year. About 50% of patients retained significant improvement for at least three months following the trial.

In our current trial, we use a magnetic resonance imaging (MRI) scan of the brain to locate 2 brain areas that appear to be involved in the production of voices. One area is in a part of the left temporal lobe known as Wernicke’s area, which is ordinarily involved in perceiving spoken speech. The second is a similarly positioned area in the right temporal lobe. The MRI scan is used to position the TMS coil on the scalp above and behind the ears so that it precisely overlies these two brain areas. Our goal is to see if this approach can produce a higher and/or more sustained response compared to our prior studies.

By chance, a portion of the persons enrolled in the study receive the real stimulation and a portion of persons start out receiving a placebo form of stimulation that feels similar to real stimulation but does not produce the direct brain effects. As in our previous studies, the patient and everyone outside of the TMS team will not know what type of stimulation is being administered during this initial time period. During the first 2 weeks, five daily 16-minute sessions of TMS is given to each of two brain areas, one on the left side and the other on the right side that are located using MRI scanning data. During the third week, additional stimulation is given to the left- or right-sided site that appeared to produce the greatest clinical improvement. After this time period, we then tell the patient whether (s)he received the real stimulation or the placebo stimulation. If the patient had received real stimulation, (s)he will be offered a trial of an additional 5 sessions of real stimulation at the stimulation site producing the greatest improvement during the first three weeks of the trial. If the patient had received placebo stimulation, (s)he will be offered the real stimulation for up to 20 stimulation sessions over four weeks. Thus everyone enrolled in the study has the opportunity of finding out whether TMS is helpful in improving voices.

If a patient finds that TMS is helpful but suffers a return in symptoms, he or she may enroll in an additional trial where TMS is given after waiting a six month period. In this trial, we seek to determine if TMS given to both sides of the brain simultaneously can produce even greater improvements in voices.

Who is Eligible?

Persons travel from all over the US to enroll in our TMS trial for voices. Reasonable transportation costs are covered by grant funding. Participants need to be 18-55 years old, have a diagnosis of schizophrenia, schizoaffective disorder, or affective disorder (depression or bipolar disorder), and experience “voices” at least 3-4 times per day. Individuals with a history of seizures or serious medical conditions may not participate in the study. Participants also cannot abuse drugs or alcohol for at least 30 days prior to study enrollment and during the study itself, and will need to stay on a steady dose of psychiatric medication for that period of time also. We do not require patients to be on psychiatric medication in order to enroll in the study, however. A prior history of drug or alcohol problems does not exclude people from enrolling in the study. Another requirement is that the participant needs to undergo an MRI scan. This procedure is painless and does not involve injections, but does require lying on a stretcher in a large electromagnet. This may be difficult for people who are claustrophobic or who are very overweight.

Safety Issues Pertaining to TMS

TMS is generally not painful, but can be uncomfortable insofar as a tingling or knocking sensation is produced against the scalp. Scalp muscle contractions sometimes occur during the treatment. There is a very small risk of a seizure associated with TMS, but for the frequency of stimulation used in this study (one stimulation per second) the risk is significant only for participants who have a prior history of seizures. We remain concerned regarding any risk to concentration or memory, although the occurrence of concentration and memory problems in our studies has been very rare (occurring in less than 5% of participants). If we encounter such problems the trial is stopped. In those few patients where such difficulties seem to have emerged, these complaints have disappeared in 1-2 days following the halt of the trial. No difficulties in perceiving speech have arisen from TMS in any of our studies to date.

Pain relief induced by repetitive transcranial magnetic stimulation of precentral cortex.

Lefaucheur JP,
Drouot X
Keravel Y
Nguyen JP

Services de Physiologie, Explorations Fonctionnelles, Hopital Henri Mondor, 51 avenue de Lattre de Tassigny, 94010 Creteil, France. 

Chronic electrical stimulation of the precentral (motor) cortex using surgically implanted electrodes is performed to treat medication-resistant neurogenic pain. The goal of this placebo-controlled study was to obtain such antalgic effects by means of a non-invasive cortical stimulation using repetitive transcranial magnetic stimulation (rTMS). Eighteen patients with intractable neurogenic pain of various origins were included and underwent a 20 min session of either 10 Hz, 0.5 Hz or* sham rTMS over the motor cortex in a random order. A significant decrease in the mean pain level of the series was obtained only after 10 Hz rTMS. This study shows that a transient pain relief can be induced by 10 Hz rTMS of the motor cortex in some patients suffering from chronic neurogenic pain.

PMID: 11588611 [PubMed – indexed for MEDLINE]

The Use of rTMS to Improve Theory of Mind Among Adults With Autism and Asperger’s Disorder

This study is currently recruiting participants.
Verified by Bayside Health, December 2008
First Received: December 14, 2008   Last Updated: December 15, 2008   History of Changes
Sponsored by: Bayside Health
Information provided by: Bayside Health Identifier: NCT00808782

Theory of mind (ToM) refers to the ability to infer other’s mental states. It includes a recognition that other individuals experience thoughts, feelings, intentions, and desires that may be different to our own. ToM is often impaired among individuals with an autism spectrum disorder (such as autism and Asperger’s disorder), and may underlie aspects of social dysfunction in this population. Indeed, it has been suggested that impaired ToM is the core deficit of autism and Asperger’s disorder.

Imaging studies suggest that the bilateral medial prefrontal cortex, the most important brain region in ToM processing, is underactive in autism. The current study examines whether repetitive transcranial magnetic stimulation (rTMS) to the bilateral medial prefrontal cortex can modulate ToM ability among healthy adults, and improve ToM ability among adults with autism or Asperger’s disorder. With the prevalence of autism increasing, there is a clear need to develop appropriate therapeutic interventions to improve social functioning.

This study involves a double-blind study using high-frequency rTMS in an attempt to improve ToM among adults with either autism or Asperger’s disorder. Theory of mind will be measured using behavioural tasks that require the participant to infer what someone is thinking or feeling by observing their behaviour. These tasks will administered both before and after rTMS to determine whether any change in theory of mind has occurred.

Thirty adults with either autism (n = 15) or Asperger’s disorder (n = 15) will initially undergo functional and structural MRI to determine the site on the scalp that lies over the medial prefrontal cortex (to which rTMS will be administered). They will then attend our lab each consecutive weekday for a two-week period, during which they will 15 minutes high-frequency (5 Hz) rTMS (either active or sham) to the medial prefrontal cortex. ToM and clinical measures will be collected before the first session, soon after the last session, and one month after the last session.

Based on prior imaging data, it is expected that high-frequency rTMS (compared with sham rTMS) to the medial prefrontal cortex will improve ToM ability and reduce social dysfunction among adults with autism or Asperger’s disorder. Should these hypotheses be supported, it will indicate the suitability of rTMS as a neurobiological intervention designed to improve ToM and social function among individuals with autism and related disorders.