Theta-burst rTMS in Schizophrenia to Ameliorate Negative and Cognitive Symptoms

Theta-burst rTMS in Schizophrenia to Ameliorate Negative and Cognitive Symptoms: a Double-blind, Randomized Clinical Trial

The major target of the study is to confirm the safety and efficacy of our augmented protocol of theta-burst TMS in schizophrenia. Our aim is to confirm the beneficial effects of rTMS treatment on multiple aspects of the disorder such as (1) clinical aspect in terms of PANSS, (2) cognitive aspect such as emotion recognition (ER) and working memory (WM) / distractor filtering (DF) performance, and (3) neurobiology in terms of electrophysiology correlates of ER, WM and DF such as ERPs, event related theta synchronization, resting state theta power, and network connectivity. Response prediction to (theta-burst) TB-rTMS will be the exploratory part of the study.

Response prediction will be based on spectral slope, individual alpha peak, and frontal alpha asymmetry, calculated from baseline resting-state EEG in the closed-eye condition (the open-eye condition may also be used). Baseline resting-state fMRI will also be used to predict responses.

Inclusion Criteria:

1. diagnosis of schizophrenia or schizoaffective disorder;
2. clinically stabilized on antipsychotic: a stable dose of antipsychotic medication for >4 weeks;
3. age 18-60 years, and
4. presence of negative symptoms (based on PANSS): a negative subscore ≥16 points and [one of items N1-N7 scoring ≥4 or two items N1-N7 scoring ≥3]

Exclusion Criteria:

1. any significant neurological illness;
2. mental retardation
3. history of head injury with loss of consciousness for more than 1 hour
4. history of epileptic seizures or epileptic activity on the baseline EEG (evaluated by an expert in clinical EEG and epilepsy),
5. alcohol or drug abuse within the past 3 months, and
6. depressive episode or antidepressant treatment in the past 4 weeks.
7. Severe positive symptoms inferfere with cognitive tests
8. Implanted pacemaker, implanted drug pump, cochlear implant, implanted defibrillator, implanted neurostimulator or any other TMS incompatible implanted metal device
9. Skin surface is severly injured in the stimulated region of the skull
10. Sclerosis multiplex
11. Pregnancy
12. Severe sleep deprivation
13. Severe heart failure
14. Increased intracranial pressure
15. Untreated migrain