Neuromarkers Identification in Major Depressive Disorder Based on Monitoring Measures

The investigators propose a multi-source pattern which integrates neuroimaging data associated with multiple, symptom-related neural processes relevant in depression to improve classification accuracy. The investigators conclude that combining brain activation related to the core-symptoms of depression using the multi-source monitoring data substantially increases classification accuracy while providing a sparse relational neuromarkers-model for future prediction.

The "Multiway stimulator coil®" (Brainsway Ltd.) is a novel TMS stimulator with several new and unique properties. Currently standard TMS devices include a single channel, and can operate only a single coil. The "Multiway stimulator coil®" (Brainsway Ltd.) includes two channels which can operate two independent TMS coils, either simultaneously or sequentially.

The "Multiway stimulator coil®" (Brainsway Ltd.) may be used to obtain a differential activation of various brain regions. For instance it can be used to induce high frequency stimulation of a certain brain region, thus inducing facilitation, while simultaneously stimulate at low frequency in another brain region, leading to inhibition.

In the current study the investigators propose a multi-source pattern which integrates neuroimaging data associated with multiple, symptom-related neural processes relevant in depression to improve classification accuracy. The investigators conclude that combining brain activation related to the core-symptoms of depression using the multi-source monitoring data substantially increases classification accuracy while providing a sparse relational neuromarkers-model for future prediction.

The purpose of the study is to to monitor and optimize the anti depressive effect of brain modulation technique using novel multi model monitoring approach.

Subjects will be treated with one of two designs of the study device (the "Multiway Coil®"):

1. Single Channel with a coil placed over the left PFC (10 Hz).
2. Two channels: a. 10 Hz over the left PFC. b. 1 Hz over the right PFC.

All subjects in the current study will undergo monitoring procedure inclusive of functional MRI and electroencephalogram.

Eligibility Criteria:
Inclusion Criteria:

* Outpatient
* Diagnosed by senior psychiatrist as suffering from major depression episode according to DSM IV using the Structured Clinical Interview for DSM-4 (SCID).
* Rating on HDRS-21\>20.
* Age: 18-68 years.
* Treated for the current depressive episode, at least four weeks, with at least one antidepressant in accepted dose, without improvement, according to their medical chart and ATHF ( antidepressant treatment history form) instruction guidelines .
* Gave informed consent for participation in the study.
* Negative answers on safety screening questionnaire for transcranial magnetic stimulation.

Exclusion Criteria:

* Diagnosis as suffering from other diagnosis on axis 1 ( like: schizophrenia, bipolar disorder, psychotic depression, geriatric depression).
* Diagnosis as suffering from Severe Borderline Personality Disorder or hospitalized due to exacerbation related to of borderline personality disorder.
* Substantial suicidal risk as judged by the treating psychiatrist.
* Attempted suicide in the past year.
* Any current unstable medical or surgical illness.
* History of seizure or heat convulsion.
* History of epilepsy or seizure in first degree relatives.
* History of head injury.
* History of any metal in the head (outside the mouth).
* Known history of any metallic particles in the eye, implanted cardiac pacemaker or any intracardiac lines, implanted neurostimulators, surgical clips, cochlear implants or any medical pumps.
* History of hearing loss.
* History of drug abuse or alcoholism in the last 6 month.
* Pregnancy or not using a reliable method of birth control.
* Systematic and metabolic unstable disorders.
* Inadequate communication with the patient.
* Under custodial care.
* Participation in current clinical study or clinical study within 30 days prior to this study.