Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Prospective Multicenter Double Blind Randomized Controlled Trial to Explore the Tolerability, Safety and Efficacy of the H1-Coil Deep Transcranial Magnetic Stimulation (TMS) in Subjects With Schizophrenia Experiencing Auditory Hallucinations
Brief Summary: Until recently stimulation of nervous tissue deeper than approximately 2 cm from the scalp (will hence be called non-deep TMS) was not possible (3).A new coil ("H"-coil invented in Weizmann Institute of Science, Neurobiology Department, Rehovot, Israel ) capable of stimulating more than twice this depth (Up to 5 cm)was recently developed.Deep TMS is using this h-coil.

Auditory hallucinations are reported by 50% to 70% of patients with schizophrenia and generally consist of spoken speech or "voices." . Patients usually describe the hallucinatory experience as distressing, consistent with evidence that the most common hallucinated utterances are abusive terms,contributing in up to 25% of the cases to a serious suicide attempt.The neuroanatomical basis of auditory hallucinations is thought to involve increasing blood flow of the speech perception areas of the brain, such as the superior temporal cortex of the dominant hemisphere as well as right and left superior temporal cortex.Brain imaging studies of patients with auditory hallucinations have revealed an active area in the right and left superior temporal cortex, Broca's area, and the left temporoparietal cortex. Shergill et al. reported the presence of active areas in the anterior cingulate cortex, right thalamus, left hippocampus, and parahippocampal cortex when subjects were experiencing auditory hallucinations.

Magnetic Stimulation of Left Temporoparietal Cortex suggest that the mechanism of auditory hallucinations involves activation of the left temporoparietal cortex.Reasons to believe that right frontotemporal TMS stimulation cortex can ameliorate auditory hallucinations include evidence that right temporoparietal stimulation achieved significant changes in the frequency of auditory hallucinations,in the patients with auditory hallucinations an increase in blood flow is noted in the right superior temporal gyrus,right temporal lobe activation during auditory hallucination,effect of rTMS can spread to the opposite hemisphere through interhemispheric connections,some evidence that brain circuits involved in the production of auditory hallucinations and symptoms of schizophrenia are widespread and not confined in the left temporoparietal cortex.Deep TMS can reach brain structures as deep as 5 cm whereas non-deep TMS can reach structures less than half that distance. As deep brain structures such as thalamic, limbic and paralimbic regions have been shown to be activated during auditory hallucinations and suspected to play a role in the pathogenesis of auditory hallucinations, their stimulation may attenuate auditory hallucinations. Non-deep TMS can stimulate the cortex but not the neuronal pathways connecting it to deeper brain structures and which stimulation may be additive.


Options:
A: Inclusion Criteria:

* Patients will fulfill DSM-IV-TR diagnostic criteria for schizophrenia
* Patients reporting auditory hallucinations on average at least 5 times per day based on prospective assessment using a diary or handheld counter.
* Patients are maintained on their psychotropic medication at steady dosages for at least 4 weeks before study entry and for the duration of the trial.

Exclusion Criteria:

* Cardiac pacemaker implant, or a history of epilepsy, neurosurgery, or brain trauma patients suffering from chronic medical conditions of any sort
* History of current hypertension
* 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 intra-cardiac lines
* Implanted neuro-stimulators
* Surgical clips or any medical pumps
* History of frequent or severe headaches
* History of migraine
* History of hearing loss
* Known history of cochlear implants
* History of drug abuse or alcoholism
* Pregnancy or not using a reliable method of birth control (non-pregnancy will be proved by beta-HCG test)
* Systemic and metabolic disorders
* Inadequate communication skills or under custodial care.
B: Inclusion Criteria for Schizophrenia Subjects:

* Voluntary and competent to consent
* SCID-IV Diagnosis of Schizophrenia or Schizoaffective Disorder
* Between the ages of 18 and 85

Inclusion Criteria for Healthy Subjects:

* voluntary and competent to consent
* between the ages of 18-85
* considered a healthy individual free of psychopathology based on the Personality Assessment Inventory
* right-handed determined by the TMS screening and demographic form
* self-reported non-smoker
* do not have a self-reported concomitant major medical or neurologic illness
* if a woman of childbearing potential, must be on an effective means of birth control determined through completion of the TMS screening and demographic form.

Exclusion Criteria for both Healthy Controls and Schizophrenia Subjects:

* Have a DSM-IV history of substance abuse or dependence in the last 6 months
* Have a concomitant major and unstable medical or neurologic illness
* Have a history of seizures
* Have a first degree relative with a history of a seizure disorder
* Are pregnant
* Have any clinically significant EEG activity indicating an increased risk of seizure, as confirmed by a neurologist.
C: Inclusion Criteria:

* Male or female in-patients and out-patients, 18 - 60 years of age
* Diagnostic criteria for schizophrenia according to ICD-10/DSM IV
* PANSS negative sum score \> 20 points, 1 of items N1 - N7 (range 1 to 7) ≥ 4 (at least moderate)
* Improvement in PANSS negative sum score less than 10 % in the last 2 weeks prior to study entry, stable antipsychotic medication
* Informed Consent

Exclusion Criteria:

* Clinically relevant psychiatric comorbidity, verbal IQ \< 85
* History of epileptic seizures, organic brain disease
* Instable medical comorbidity or condition
* Previous treatment by rTMS
* Factors not compatible with the use of TMS, e.g. cardiac pace makers or other metallic implants, pregnancy
D: Inclusion Criteria:

* voluntary and capable to consent based on the subject's ability to provide a spontaneous narrative description of the key elements of the study
* have a diagnosis of Schizophrenia or Schizoaffective Disorder as confirmed by the Structured Clinical Interview for the DSM-IV (SCID-IV)
* between the ages of 18 and 65
* meet criteria for AH of at least moderate severity based on the Positive and Negative Symptom Scale (PANSS)
* willing to keep the dose of antipsychotic stable for the duration of the study
* meet criteria for medication resistance, defined as daily AH despite 2 adequate 6-week trials of at least 2 antipsychotic medications and including 1 atypical antipsychotic medication. An adequate trial is defined as a daily dose of 1000 chlorpromazine equivalents for typical antipsychotics medications and the following dosages for atypical antipsychotic medications: risperidone 6 mg, olanzapine 15 mg, quetiapine 500 mg, clozapine 300 mg.

Exclusion Criteria:

* DSM-IV history of alcohol and/or substance abuse in past month, or alcohol and/or substance dependence in the last 6 months
* presence of concomitant major, unstable medical or neurologic illness, or a history of seizures
* are pregnant
* have received rTMS for any reason in the past
* have had a dose change of usual psychotropic medications in the 4 weeks preceding study entry.

Answer: A