Enhancing Brain Connectivity in Schizophrenia Through Neuromodulation (Study 3)

Enhancing Brain Connectivity in Schizophrenia Through Neuromodulation (Study 3)

The aim of the study is to assess the treatment effects of deep active repetitive transcranial magnetic stimulation (rTMS) with H4 coil combined with cognitive training for improving frontal white matter microstructural integrity in patients with schizophrenia spectrum disorder (SSD).

Schizophrenia is a severe mental illness that affects about 1% of the population but a major source of disability. Information processing between brain regions occurs due to transfer of electrical impulses among them. This process is determined by the existing neuronal/fiber connections, which may be altered and or modified in the presence of neuronal stimulation or cognitive intervention. The frontal lobe information flow is critical for higher cognitive functions, thought processes, and proper emotional and behavioral responses. Improving the myelination in the frontal lobe may increase cognitive functions and reduce risks to develop symptoms of schizophrenia. The investigators propose that increasing electrical signaling in the frontal white matter in patients with schizophrenia may also enhance myelination and improve the white matter integrity.

rTMS with H coil is FDA-cleared for short-term smoking cessation in the general population. The efficacy of its combination with cognitive training in myelination modulation has not been evaluated.

Inclusion Criteria:

1. Male and female ages between ages 18-60 years
2. Ability to give written informed consent (age 18 or above)
3. Diagnosed with schizophrenia-spectrum disorder and Evaluation to Sign Consent (ESC) above 10.

Exclusion Criteria:

1. Inability to sign informed consent.
2. Any history of seizures.
3. Any acute and unstable major medical illnesses that may affect normal brain functioning. Examples of these conditions include, but not limited to, recent stroke, seizure, history of significant head trauma, CNS infection or tumor, other significant brain neurological conditions (As this is a study of medical comorbidity, most medical conditions, once stable, are not exclusion criteria).
4. Taking > 400 mg clozapine/day and not on anti-seizure medication(s) with sufficient dose.
5. Failed TMS screening questionnaire.
6. Significant alcohol or other drug use (substance abuse within 1 month or substance dependence history within 6 months and having substance usage within 1 month) other than nicotine or marijuana dependence.
7. A history of thrombosis, family history of thrombosis, or medical conditions that may lead to a hypercoagulable state (increased chance to develop blood clots)
8. Woman who is pregnant (child-bearing potential but not on contraceptive and missing menstrual period; or by self-report; or by positive urine pregnancy test).
9. History of head injury with loss of consciousness over 10 minutes; history of brain surgery
10. Cannot refrain from using alcohol and/or marijuana 24 hours or more prior to experiments.
11. Students and employees currently involved with our lab (lab employees and personnel will be excluded from the study to avoid possible coercion or possible appearance of coercion, or chance of breach of privacy and confidentiality).
12. For MRI, unable to undergo MRI scanning due to metallic devices or objects (cardiac pacemaker or neurostimulator, some artificial joints, metal pins, surgical clips, or other implanted metal parts) or claustrophobic to the scanner.