Schizophrenia, Schizophrenia Schizoaffective
Conditions
Keywords
schizophrenia, Transcranial magnetic stimulation
Brief summary
Patients with schizophrenia spectrum disorder (SSD) will be exposed to active and sham repetitive transcranial magnetic stimulation (rTMS) in separate sessions. SSD-related biomarkers will be assessed before and after the rTMS administration.
Detailed description
Electrical neural oscillations of the brain can be measured at many levels, ranging from single cell to local field potentials in animals, to large-scale synchronized activities in the human scalp. New evidence suggests that there may be common underlying abnormalities in oscillatory activities that are associated with schizophrenia-related cognitive and functional impairments. There is currently no treatment for these electrical oscillation dysfunctions. Transcranial magnetic stimulation (TMS) provides a non-invasive means for altering brain electrical neural activity. TMS has been approved by FDA for the treatment of depression and many other mental disorders. It has been used in a wide range of clinical research, especially in neurology and psychiatry. The investigators aim to develop TMS paradigms that will modulate brain responses during basic sensory to more complex cognitive performance and determine the parameters in anatomic locations and TMS modalities that may effectively and safely modulate neural activities. If the current experiments successfully identified TMS methods/paradigms that improve neural oscillation and cognitive performances in schizophrenia patients, in the future (not part of the current protocol), the investigators can then develop specific TMS treatment that may correct abnormal brain function and improve cognition and clinical symptoms of schizophrenia.
Interventions
DEVICEactive rTMS first, then sham rTMS
Active rTMS is delivered on the first visit, then sham rTMS is delivered on the second visit.
DEVICEsham rTMS first, then active rTMS
Sham rTMS is delivered on the first visit, then active rTMS is delivered on the second visit.
Sponsors
University of Maryland, Baltimore
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Male and Female between ages 18-65 * Ability to give written informed consent (age 18 or above) * Diagnosed with schizophrenia-spectrum disorder and Evaluation to Sign Consent (ESC) above10.
Exclusion criteria
* Any history of seizures. * Significant alcohol or other drug use (substance dependence within 6 months or substance abuse within 1 month) other than nicotine or marijuana dependence. * Any major medical illnesses that may affect normal brain functioning. Examples of these conditions include, but not limited to, stroke, CNS infection or tumor, other significant brain neurological conditions. * Taking \> 400 mg clozapine/day * Failed TMS screening questionnaire * Cardiac pacemakers, implanted medication pumps, intracardiac lines, or acute, unstable cardiac disease, with intracranial implants (e.g. aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed. * History of head injury with loss of consciousness over 10 minutes; history of brain surgery * Can not refrain from using alcohol and/or marijuana 24 hours or more & cigarette smoking half and hour or more prior to experiments. * Woman who is pregnant (child-bearing potential but not on contraceptive and missing menstrual period; or by self report; or by positive pregnancy test) or has had unprotected sexual intercourse without birth control in the last 4 weeks.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change of Resting-state Functional Connectivity (rsFC) by Active and Sham rTMS | 2 weeks | The strength of rsFC was first defined by correlation coefficient (r). Because the distribution of r values is highly skewed, z scores (normally distributed) were computed via fisher r-to-z transform. The z score central value (i.e., z score of 0) represents no relationship between the two brain regions. A positive (negative) z score indicates a positive (negative) association between the two brain regions. Stronger rsFC (i.e., larger positive z score) was related to stronger connection between the two brain regions. The differences of rsFC between active and sham were reported. A positive (negative) value of rsFC change suggests the rsFC was enhanced (weakened) by active TMS. |
| Change of Mismatch Negativity (MMN) From Electroencephalography (EEG) Signals by Active and Sham rTMS | 2 weeks | TMS effect is explored by comparing MMN changes from active and sham rTMS. MMN is measured by subtracting the averaged EEG response to a set of standard stimuli from the averaged response to rarer deviant stimuli, and taking the amplitude of this difference wave in a given time window. The differences of MMN between active and sham were reported. A negative (positive) value of rsFC change suggests the MMN was enhanced (weakened) by active TMS. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active rTMS First and Sham rTMS Second Participants in this arm will receive active rTMS in one visit first, then receive sham rTMS in another visit.
active rTMS first, then sham rTMS: Active rTMS is delivered on the first visit, then sham rTMS is delivered on the second visit. | 5 |
| Sham rTMS First and Active rTMS Second Participants in this arm will receive sham rTMS in one visit first, then receive active rTMS in another visit.
sham rTMS first, then active rTMS: Sham rTMS is delivered on the first visit, then active rTMS is delivered on the second visit. | 5 |
| Total | 10 |
Baseline characteristics
| Characteristic | Active rTMS First and Sham rTMS Second | Sham rTMS First and Active rTMS Second | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 5 Participants | 10 Participants |
| Age, Continuous | 38.8 years STANDARD_DEVIATION 18.2 | 39.2 years STANDARD_DEVIATION 16.2 | 39.0 years STANDARD_DEVIATION 16.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 5 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 3 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 2 Participants | 3 Participants |
| Region of Enrollment United States | 5 Participants | 5 Participants | 10 Participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 0 / 10 | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 |
Outcome results
Primary
Change of Mismatch Negativity (MMN) From Electroencephalography (EEG) Signals by Active and Sham rTMS
TMS effect is explored by comparing MMN changes from active and sham rTMS. MMN is measured by subtracting the averaged EEG response to a set of standard stimuli from the averaged response to rarer deviant stimuli, and taking the amplitude of this difference wave in a given time window. The differences of MMN between active and sham were reported. A negative (positive) value of rsFC change suggests the MMN was enhanced (weakened) by active TMS.
Time frame: 2 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active rTMS | Change of Mismatch Negativity (MMN) From Electroencephalography (EEG) Signals by Active and Sham rTMS | -0.106 microvolts | Standard Error 0.367 |
| Sham rTMS | Change of Mismatch Negativity (MMN) From Electroencephalography (EEG) Signals by Active and Sham rTMS | 0.044 microvolts | Standard Error 0.217 |
Primary
Change of Resting-state Functional Connectivity (rsFC) by Active and Sham rTMS
The strength of rsFC was first defined by correlation coefficient (r). Because the distribution of r values is highly skewed, z scores (normally distributed) were computed via fisher r-to-z transform. The z score central value (i.e., z score of 0) represents no relationship between the two brain regions. A positive (negative) z score indicates a positive (negative) association between the two brain regions. Stronger rsFC (i.e., larger positive z score) was related to stronger connection between the two brain regions. The differences of rsFC between active and sham were reported. A positive (negative) value of rsFC change suggests the rsFC was enhanced (weakened) by active TMS.
Time frame: 2 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active rTMS | Change of Resting-state Functional Connectivity (rsFC) by Active and Sham rTMS | 0.018 z score of functional connectivity | Standard Error 0.018 |
| Sham rTMS | Change of Resting-state Functional Connectivity (rsFC) by Active and Sham rTMS | 0.007 z score of functional connectivity | Standard Error 0.027 |