Stability of rTMS on Cognition and Brain Networks on Healthy Subjects.

Not Applicable

Terminated

Interventions: Device: ineffective rTMS
Device: active TBS
Device: Sham TBS
Device: fMRI
Device: Effective rTMS
Device: EEG

Brief Summary: Episodic and working memory processes are the most affected cognitive domains in Alzheimer's Disease (AD) and its early stage, Mild Cognitive Impairment (MCI).

Transcranial Magnetic Stimulation (TMS) is a unique tool to interfere with cognitive processes by inducing "virtual and transient lesions", mimicking those observed in MCI. It has proven repeatedly its capacity to interfere with encoding-retrieval memory task. However, to date, only few imaging data exist on the cerebral pathways involved in encoding memory task. Moreover, the stability of TMS effects over time remains to be investigated. If proven to be a stable interfering challenge, TMS could be used to investigate the potential restoring effect of new medication in AD.

The study is the pilot study of a larger clinical trial which aims to prove the utility of rTMS as a potential model for prediction of clinical efficacy using a combination of cognitive and neuroimaging endpoints.

Recruitment & Eligibility

Inclusion Criteria

Healthy male subjects aged between 18 and 40 years-old inclusive.
Education level: at least secondary.
Right-handed (Edinburgh Handedness Inventory).
The subjects are in good health on the basis of the medical interview (medical history, symptoms), the physical examination and vital signs.
No history of psychiatric disorders (assessed by Structured Clinical Interview for DSM IV Disorders (SCID) for Barcelona and by the Mini International Neuropsychiatric Interview (MINI) for Marseille).
No history of neurological disorders
No history of concussion (cranial or facial trauma) without or with loss of consciousness.
Subject without history of brain disease (severe brain trauma, stroke, cerebral tumor...).
Subject without lesion on MRI.
Subject without abnormal electrical activities on standard clinical EEG.
No history of drug or alcohol abuse.
No smoker or ≤ 5 cg/ day.
The subject can complete the neuropsychological test battery during the training session.
Subject without contraindication to MRI.
The subject is able to read and understand the Information Form and comply with the protocol instructions and restrictions.
The subject is covered by a social insurance.
The subject has provided written informed consent.

Exclusion Criteria

History or presence of psychiatric illness (Psychiatric interview).
History or presence of neurologic illness.
The subject, in the opinion of the investigator, is unlikely to comply with the study protocol or is unsuitable for any other reason.
The subject participates in another clinical trial or is still being within a washout period of 1 month since last taking of a previous clinical trial, or subjects who have received more than 4500 Euros in the previous 12 months for participating in clinical trials.
Presence of metallic objects within the body.
Subjects with pacemaker.
Claustrophobia.
Individual and familial history of epileptic seizure.
Any medication listed (see annexe) in the safety guidelines published by the Safety of TMS Consensus Group (Rossi et al., 2009) will be forbidden.
Subject with a correct hit rate during the retrieval session of the memory task

Arm && Interventions

Group	Intervention	Description
ineffective rTMS - Active TBS - EEG	active TBS	-
ineffective rTMS - Active TBS - fMRI	fMRI	-
Effective rTMS - Active TBS - fMRI	Effective rTMS	-
ineffective rTMS - Sham TBS - fMRI	fMRI	-
Effective rTMS - Sham TBS - fMRI	fMRI	-
ineffective rTMS - Active TBS - EEG	ineffective rTMS	-
ineffective rTMS - Sham TBS - EEG	EEG	-
Effective rTMS - Sham TBS - EEG	Effective rTMS	-
ineffective rTMS - Sham TBS - fMRI	Sham TBS	-
Effective rTMS - Sham TBS - fMRI	Sham TBS	-
ineffective rTMS - Sham TBS - EEG	ineffective rTMS	-
Effective rTMS - Sham TBS - EEG	Sham TBS	-
Effective rTMS - Sham TBS - EEG	EEG	-
ineffective rTMS - Active TBS - fMRI	ineffective rTMS	-
ineffective rTMS - Active TBS - fMRI	active TBS	-
Effective rTMS - Active TBS - fMRI	active TBS	-
Effective rTMS - Sham TBS - fMRI	Effective rTMS	-
Effective rTMS - Active TBS - EEG	active TBS	-
Effective rTMS - Active TBS - fMRI	fMRI	-
ineffective rTMS - Active TBS - EEG	EEG	-
ineffective rTMS - Sham TBS - EEG	Sham TBS	-
ineffective rTMS - Sham TBS - fMRI	ineffective rTMS	-
Effective rTMS - Active TBS - EEG	EEG	-
Effective rTMS - Active TBS - EEG	Effective rTMS	-

Primary Outcome Measures

Name	Time	Method
Outputs of the memory task	up to Day 15	outputs: number of correct answers during the retrieval event-related task (Hit rate) and the rate of false recognition of novel pictures (False Alarms rate).

Secondary Outcome Measures

Name	Time	Method
Gene expression	Day 1	Interest genes expression will be investigated depending on the impact of TMS on behavioral and functional brain responses.
Imaging	Day1 and Day 15	Functional MRI (Barcelona): modifications will be highlighted by changes in Blood Oxydation level Dependence (BOLD)signal patterns EEG (Marseille): modifications will be highlighted by changes in EEG markers
CANTAB task	Day 1 and Day 15	* CANTAB / Rapid Visual Information Processing (RVIP) * CANTAB / Spatial Working Memory (SWM) * CANTAB / Paired Associates Learning (PAL)