Clinical trial NCT01648868: Transcranial Magnetic Stimulation (rTMS) and Autism.
Official title: Transcranial Magnetic Stimulation (rTMS) and Autism.Implication of the Superior Temporal Sulcus in Normal and Abnormal Social Perception
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Autism Spectrum Disorder
Keywords: TMSAutism
Eye-tracking
Social perception
Social cognition
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2012-07-24
Enrollment: 97
Sex: ALL
Minimum age (years): 18
Maximum age (years): 30
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In this protocol we aim to use rTMS to better characterize STS role in normal and abnormal social cognition. With that purpose, we will measure the effect of inhibitory and excitatory rTMS on the fixation time on social scenes (using eye-tracking methodology) or on the ability to recognize human voice/sounds.

Detailed description: Autism is characterized by severe impairments in verbal and non verbal communication and in social interactions. Results from cerebral imaging studies have suggested that abnormalities located on the superior temporal Sulcus (STS) level would be implicated in social impairments in autism. This abnormalities are both anatomical and functional: 1) rest hypoperfusion detected by positron emission tomography (PET); 2) abnormal activation during social tasks (fMRI) and 3) structural abnormalities shown on anatomical MRI. The STS is implicated in social cognition in normal subjects. Our hypothesis is that these anatomo-functional abnormalities would appear very early in brain development and could be one of the first steps in the cascade of neuronal dysfunction in autism. Transcranial Magnetic Stimulation (rTMS) is a technique which is used in cognitive neuroscience research as well as in therapeutic approaches in certain neurological and psychiatry diseases. It consists on applying a magnetic impulse on the brain trough the scalp in a non-invasive and painless by placing a coil on the surface of the head. This magnetic fields induce an electrical field which modifies activity of those neurons inside the magnetic field and induce an electrophysiological change in the target area. This process allows a non-invasive interaction with the human brain in action during focal stimulations. In cognitive neuroscience research, we are interested in the modifications caused by rTMS in cognitive performances in order to better precise the functional role of the target region. The intensity and the frequency of the impulse can be controlled (frequency \<1 Hz = inhibitory effect ; frequency \> 3 Hz = excitatory effect). The functional characteristics of a given region and it's eventual dysfunctions may be identified thank to the abnormalities in reactivity and cortical connectivity. The goal of this project is to study inhibitory and excitatory effects of rTMS applied to the STS in healthy controls and patients with autism. This effect will be measured by two main parameters of social cognition: 1) visual perception of social scenes, measured by eye-tracking methodology; 2) auditory perception of human voice. We will study 50 healthy voluntaries controls and 50 patients with a non-syndromic autism (18 to 25 years old; IQ \> 60), diagnosed by DSM-IV and ADI-R. All participants will undergo an structural MRI and a rTMS session on the STS. In both cases, the STS will be localised based on the structural MRI. The total duration of the rTMS session is about two hours. All data will be analysed by the adapted statistical methods. This study will allow a better understanding of the role of STS in social cognition in healthy subjects as well as it's implication in the social impairments which characterize autism. Finally, the rTMS may become, in a near future, a innovative therapeutic strategy in autism.

Eligibility criteria: Inclusion Criteria:

Patients with autism

* Age from 18 to 30 years old
* Autism diagnosed by DSM-IV and ADI-R
* IQ \> 60 or able to have an MRI
* Social security registration
* Consent form signed by patient or legal tutor

Healthy controls

* Age from 18 to 30 years old
* Medical exam previous to the interventions
* Social security registration
* Consent form signed

Exclusion Criteria:

All Patients

* Indication against MRI (pace-maker, metallic pieces in the body, working with metals)
* Indications against rTMS (epilepsy, epilepsy family history, craniotomy scarf, pace maker or neuron stimulator, intraocular or intra-cerebral strange metallic piece, cochlear implant, cardiac valve, chirurgical metallic arterial material, metallic material susceptible to concentrate radio-frequency impulse)
* Claustrophobia
* Pregnant woman
* Women in a fertile age with no efficient contraception method
* Use of drugs diminishing cortical excitability
* Participation in another clinical trial that forbids the participation in this one
* Have already being treated by some electrical or magnetic stimulation technique ( transcutaneous or radicular stimulation)

Primary outcomes:
measure: Fixation time in eyes, mouth and face areas
timeFrame: 1 day
Secondary outcomes:
measure: Eye-tracking or voice human perception correlation
timeFrame: 1 day
measure: Fractional anisotropy covariation
timeFrame: 1 day
measure: Fractional anisotropy comparison
timeFrame: 1 day
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital Necker-Enfants Malades
Study officials:
affiliation: Necker-Enfants Malades Hospital
name: Nathalie BODDAERT, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Institut National de la Santé Et de la Recherche Médicale, France
name: Monica ZILBOVICIUS, PhD
role: STUDY_DIRECTOR
References: