Enhancing Brain Connectivity in Schizophrenia Through Neuromodulation (Study 2)

Overview

Patients with schizophrenia spectrum disorder (SSD) will be exposed to active repetitive transcranial magnetic stimulation (rTMS) from H coil combined with cognitive training for improving white matter integrity.

Detailed description

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.

The patients with schizophrenia will receive active repetitive transcranial magnetic stimulation (rTMS) treatment combined with cognitive training. The 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.

Interventions

• Device Active rTMS
  Active H-coil delivered rTMS sessions will be given three times per treatment visit for up to 10 visits within about 2 weeks. There are about 30 minutes breaks between adjacent TMS sessions. Each TMS session takes about 3 to 4 minutes to complete.
• Behavioral Cognitive Training
  For the cognitive training sessions, patients will be asked to play cognitive computer games involving processing speed tasks for about 15 to 30 minutes.

Primary outcome measures

• Brain microstructural integrity as indicated by white matter fractional anisotropy (FA) values as assessed by magnetic resonance imaging (MRI) [Time frame: baseline, visit 6 (about 1 week after baseline), visit 10 (about 2 weeks after baseline)]
• Brain connectivity as indicated by resting-state functional connectivity (rsFC) values as assessed by functional MRI (fMRI) [Time frame: baseline, visit 6 (about 1 week after baseline), visit 10 (about 2 weeks after baseline)]

Secondary outcome measures (12)

• Electrophysiological response as indicated by mismatch negativity as assessed by electroencephalography (EEG) [Time frame: baseline, visit 6 (about 1 week after baseline), visit 10 (about 2 weeks after baseline)]
• Electrophysiological response as indicated by steady-state auditory evoked responses from electroencephalography recording (EEG) [Time frame: baseline, visit 6 (about 1 week after baseline), visit 10 (about 2 weeks after baseline)]
• Cognitive insight as assessed by the Beck Cognitive Insight Scale [Time frame: baseline, visit 6 (about 1 week after baseline), visit 10 (about 2 weeks after baseline)]
• Depression as assessed by the Depression State and Trait Scale (DST) - state [Time frame: baseline, visit 6 (about 1 week after baseline), visit 10 (about 2 weeks after baseline)]
• Depression as assessed by the Depression State and Trait Scale (DST) - trait [Time frame: baseline, visit 6 (about 1 week after baseline), visit 10 (about 2 weeks after baseline)]
• Depression as assessed by the Calgary Depression Scale [Time frame: baseline, visit 6 (about 1 week after baseline), visit 10 (about 2 weeks after baseline)]
• Depression as assessed by the Beck Depression Inventory [Time frame: baseline, visit 6 (about 1 week after baseline), visit 10 (about 2 weeks after baseline)]
• Perception as assessed by the Perception State and Trait Scale - state [Time frame: baseline, visit 6 (about 1 week after baseline), visit 10 (about 2 weeks after baseline)]
• Perception as assessed by the Perception State and Trait Scale - trait [Time frame: baseline, visit 6 (about 1 week after baseline), visit 10 (about 2 weeks after baseline)]
• Delusion as assessed by the 21-item Peters Delusion Inventory (PDI-21) [Time frame: baseline, visit 6 (about 1 week after baseline), visit 10 (about 2 weeks after baseline)]
• Emotion regulation as assessed by the Profile of Mood States (POMS) [Time frame: day 1 after baseline, day 2 after baseline, day 3 after baseline, day 4 after baseline, day 5 after baseline, day 9 after baseline, day 10 after baseline,]
• Hallucination as assessed by the Revised Hallucinations Scale (RHS) [Time frame: day 1 after baseline, day 2 after baseline, day 3 after baseline, day 4 after baseline, day 5 after baseline, day 9 after baseline, day 10 after baseline]

Eligibility criteria

Inclusion criteria

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

Exclusion criteria

• Inability to sign informed consent.
• Any history of seizures.
• 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).
• Taking > 400 mg clozapine/day and not on anti-seizure medication(s) with sufficient dose.
• Failed TMS screening questionnaire.
• 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.
• A history of thrombosis, family history of thrombosis, or medical conditions that may lead to a hypercoagulable state (increased chance to develop blood clots)
• 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).
• History of head injury with loss of consciousness over 10 minutes; history of brain surgery
• Cannot refrain from using alcohol and/or marijuana 24 hours or more prior to experiments.
• 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).
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• The University of Texas Health Science Center, Houston — Houston

Identifiers

NCT: NCT06961916 · HSC-MS-23-1044 (study 2)

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗