Repetitive Transcranial Magnetic Stimulation (rTMS) in the Treatment of First Rank Symptoms on Schizophrenia: Controlled, Randomised, Double Blind Trial

Schizophrenia is a common psychiatric disorder that affects approximately 1% of the general population. This disease can be described in three dimensions: disorganization, delusions and negative signs. The "first rank symptoms" (FRS) were first described by Kurt Schneider. These are core symptoms of schizophrenia that were combined to make pathognomonic signs of the disease and remain at the center of many classifications of the disease. These symptoms are voices or thoughts expressed aloud, voices who argue them, voices that comment on behavior or thoughts, delusional perceptions, experiences of body influences, thoughts influences, impulses from external influences, the will controlled by external forces, thoughts stolen by external forces or others, thoughts interferences by other thoughts, publication thoughts. These symptoms reveal difficulty in distinguishing self and other in action, thought or physical individual. Thus, the FRS are a gateway to agency disorder, disorder of the sense of body ownership and familiarity disorder.

Agency is the ability to distinguish ones own actions from those of others. The sense of body ownership is difficult to distinguish from the sense of agency. It is the knowledge that the arm (for example) which make this action is mine. A disorder of sense of body ownership may lead to the illusion of a phantom limb and it is very interesting to separate both mechanisms of body ownership and agency as wall as the networks involved in agency of those involved in the sense of body ownership. Familiarity is the feeling associated with the sight of someone close. Thus, in familiarity disorder, patient recognizes the facial features of relatives, but feels no sense of familiarity and attributes this to the replacement of the close by an impostor. Familiarity disorders can be understood through the 2-ways model of faces of processing in which the ventral pathway would be affected in the familiarity disorder. The ventral pathway involves a network which extends from the visual cortex to the superior temporal sulcus, the inferior parietal lobe and the cingulate gyrus to join the dorsal pathway in the hypothalamus.

In addition, agency studies imply the superior temporal sulcus and the inferior parietal lobule as regions involved in distinguishing self / others. Nowadays, remains a difficulty to clearly identify the different functions of the regions involved in agency.

Few neuroimaging studies can identify key areas of the sense of body ownership; in fact, protocols are difficult to adapt for use in a scanner. However, there are few studies that highlight, as was expected, extrastriatal body area as well as areas that may be involved in agency. Experiments have difficulty differentiating, as the investigators said, the sense of body ownership from agency, but the investigators have a validated tool, the rubber hand illusion, to differentiate sense of body ownership and agency. This tool has already been validated in healthy subjects , and was the subject of a study in our unit on patients with schizophrenia about to be published. In addition, several studies have shown that the performance at the rubber hand illusion task were modified by repeated Transcranial Magnetic Stimulation (rTMS) applied to the extrastriatal body area (EBA) or to the inferior parietal lobule (IPL) or to the temporo-parietal junction (TPJ).

Transcranial magnetic stimulation or TMS modulate cortical excitability without serious side effects when used at frequencies and intensities recommended in the literature. Low frequency rTMS is a recognized for treatment-resistant auditory hallucinations in schizophrenia. This is therefore an interesting therapeutic innovation that will benefit to residual symptoms, in adjunction to a well conducted medical treatment in schizophrenia.