Schizophrenia
Conditions
Brief summary
The major goal is to determine if Transcranial magnetic stimulation (TMS) enhances visual plasticity in schizophrenia. TMS sessions (sham/placebo and real TMS) will be conducted before two MRI scans with two weeks in-between to assess whether TMS stimulation to the visual cortex will enhance visual plasticity in patients with schizophrenia-spectrum disorders. This project may provide a better understanding of the underlying neurobiological mechanisms responsible for learning and memory deficits in schizophrenia.
Detailed description
Learning and memory impairments are commonly observed in schizophrenia spectrum disorders. Alterations in long-term potentiation (LTP), a basic mechanism underlying learning and memory, may explain this impairment. This project will assess fMRI visual plasticity, thought to reflect LTP, in participants with and without schizophrenia spectrum disorders. Previous studies have shown that visual plasticity is impaired in schizophrenia. The major goal is to determine if Transcranial magnetic stimulation (TMS) enhances visual plasticity in schizophrenia. Transcranial magnetic stimulation (TMS) provides a non-invasive means for altering brain electrical neural activity. TMS sessions (sham/placebo and real TMS) will be conducted before two MRI scans with two weeks in-between to assess whether TMS stimulation to the visual cortex will enhance visual plasticity in patients with schizophrenia-spectrum disorders. This project may provide a better understanding of the underlying neurobiological mechanisms responsible for learning and memory deficits in schizophrenia.
Interventions
DEVICETranscranial Magnetic Stimulation
Transcranial Magnetic Stimulation
Sponsors
University of Maryland, Baltimore
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. age: 18-65, 2. no neurological illness, head trauma, or major medical illness, 3. not pregnant or nursing, 4. no contraindication for TMS or MRI scanning, 5. no current substance abuse/dependence. Healthy controls will have no DSM-5 diagnosis and no first-degree relatives with a psychotic disorder. Inclusion criteria for patients includes: 1. DSM-5 diagnosis of schizophreniform, schizophrenia or schizoaffective and competent to sign an informed consent, 2. not currently taking other medications that affects brain structure (e.g. steroids), 3. less than 12 months antipsychotic exposure and on the same psychotropic medications for 4 weeks prior to study, 4. not be taking clozapine (due to its effects on NMDA receptors and increase of seizure threshold), 5. clinically stable (i.e. no change in psychotic symptoms for at least 4 weeks).
Exclusion criteria
1. age outside of 18-65, 2. neurological illness, head trauma, or major medical illness, 3. pregnant or nursing, 4. contraindication for TMS or MRI scanning, 5. current substance abuse/dependence, 6. currently taking medications that affects brain structure (e.g. steroids). Healthy controls with a DSM-5 diagnosis and/or a first-degree relative with a psychotic disorder. Participants with schizophrenia that are not competent to sign an informed consent, have more than 12 months antipsychotic exposure, not on the same psychotropic medications for 4 weeks prior to study, taking clozapine, and not clinically stable (i.e.a change in psychotic symptoms for at least 4 weeks).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| fMRI Blood Oxygenation Level Dependent (BOLD) Response of Visual Plasticity | ~1 hour | fMRI BOLD response in visual cortex, during visual stimulation (0.9 Hz) before and after high frequency visual stimulation (9 Hz). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Magnetic Resonance Spectroscopy (MRS) Assessment of Glutamate | ~1 hour | MRS was used to obtain occipital cortical glutamate levels (active, sham). Levels reflect institutional units, as is standard for the field. |
Countries
United States
Participant flow
Pre-assignment details
17 adults provided informed consent. 2 screen failures and 1 lost to follow-up before screening.
Participants by arm
| Arm | Count |
|---|---|
| TMS (Active Then Sham) Participants first received active rTMS 10Hz to the occipital cortex and then 2 weeks later received sham (A sham coil was used to control for the auditory artifacts induced by rTMS) | 3 |
| TMS (Sham Then Active) Participants first received sham (A sham coil was used to control for the auditory artifacts induced by rTMS) and then 2 weeks later received active rTMS 10Hz to the occipital cortex | 0 |
| iTBS (Active Then Sham) Participants first received active iTBS 5 Hz to the occipital cortex and then 2 weeks later received sham (a sham coil was used to control for the auditory artifacts induced by iTBS). | 6 |
| iTBS (Sham Then Active) Participants first received sham (a sham coil was used to control for the auditory artifacts induced by iTBS) and then 2 weeks later received active iTBS 5 Hz to the occipital cortex | 5 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | iTBS (Sham Then Active) | iTBS (Active Then Sham) | TMS (Active Then Sham) | TMS (Sham Then Active) | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 6 Participants | 3 Participants | 0 Participants | 14 Participants |
| Age, Continuous | 33 years STANDARD_DEVIATION 13.2 | 32.5 years STANDARD_DEVIATION 10.6 | 33 years STANDARD_DEVIATION 1 | — | 32.77 years STANDARD_DEVIATION 10.26 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 1 Participants | — | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 6 Participants | 2 Participants | — | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | — | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | — | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants | — | 2 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 3 Participants | 1 Participants | — | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | — | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | — | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | — | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 2 Participants | 1 Participants | — | 5 Participants |
| Region of Enrollment United States | 5 participants | 6 participants | 3 participants | — | 14 participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 0 Participants | — | 4 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 3 Participants | — | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 0 / 3 | 0 / 3 | 0 / 10 | 0 / 10 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 0 / 10 | 0 / 10 |
Outcome results
Primary
fMRI Blood Oxygenation Level Dependent (BOLD) Response of Visual Plasticity
fMRI BOLD response in visual cortex, during visual stimulation (0.9 Hz) before and after high frequency visual stimulation (9 Hz).
Time frame: ~1 hour
Population: 13 participants completed active and/or sham conditions for either TMS or iTBS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patient: Active TMS 10 Hz | fMRI Blood Oxygenation Level Dependent (BOLD) Response of Visual Plasticity | -2.95 Beta values | Standard Deviation 0 |
| Patient: Sham TMS | fMRI Blood Oxygenation Level Dependent (BOLD) Response of Visual Plasticity | -0.66 Beta values | Standard Deviation 0 |
| Patient: Active iTBS | fMRI Blood Oxygenation Level Dependent (BOLD) Response of Visual Plasticity | -0.29 Beta values | Standard Deviation 2.55 |
| Patient: Sham iTBS | fMRI Blood Oxygenation Level Dependent (BOLD) Response of Visual Plasticity | 2.57 Beta values | Standard Deviation 4.17 |
| Control: Active TMS 10 Hz | fMRI Blood Oxygenation Level Dependent (BOLD) Response of Visual Plasticity | -0.7 Beta values | Standard Deviation 4.33 |
| Control: Sham TMS | fMRI Blood Oxygenation Level Dependent (BOLD) Response of Visual Plasticity | 0.86 Beta values | Standard Deviation 2.33 |
| Control: Active iTBS | fMRI Blood Oxygenation Level Dependent (BOLD) Response of Visual Plasticity | -2.44 Beta values | Standard Deviation 3.27 |
| Control: Sham iTBS | fMRI Blood Oxygenation Level Dependent (BOLD) Response of Visual Plasticity | 2.47 Beta values | Standard Deviation 1.36 |
Secondary
Magnetic Resonance Spectroscopy (MRS) Assessment of Glutamate
MRS was used to obtain occipital cortical glutamate levels (active, sham). Levels reflect institutional units, as is standard for the field.
Time frame: ~1 hour
Population: 2 participants had missing data; 11 participants completed active and sham conditions for either TMS or iTBS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patient: Active TMS 10 Hz | Magnetic Resonance Spectroscopy (MRS) Assessment of Glutamate | 8.96 spectroscopy institutional units | — |
| Patient: Sham TMS | Magnetic Resonance Spectroscopy (MRS) Assessment of Glutamate | 9.23 spectroscopy institutional units | — |
| Patient: Active iTBS | Magnetic Resonance Spectroscopy (MRS) Assessment of Glutamate | 9.34 spectroscopy institutional units | Standard Deviation 1.19 |
| Patient: Sham iTBS | Magnetic Resonance Spectroscopy (MRS) Assessment of Glutamate | 9.16 spectroscopy institutional units | Standard Deviation 1.15 |
| Control: Active TMS 10 Hz | Magnetic Resonance Spectroscopy (MRS) Assessment of Glutamate | 10.61 spectroscopy institutional units | Standard Deviation 0.49 |
| Control: Sham TMS | Magnetic Resonance Spectroscopy (MRS) Assessment of Glutamate | 9.97 spectroscopy institutional units | Standard Deviation 0.07 |
| Control: Active iTBS | Magnetic Resonance Spectroscopy (MRS) Assessment of Glutamate | 12.04 spectroscopy institutional units | — |
| Control: Sham iTBS | Magnetic Resonance Spectroscopy (MRS) Assessment of Glutamate | 11.91 spectroscopy institutional units | — |