Schizophrenia, Schizoaffective Disorder, Cognitive Impairment, Visual Impairment
Conditions
Keywords
NEURO-COGS, Schizophrenia, Cognitive training, Schizoaffective disorder, BrainHQ, Perceptual discrimination training, Brain metabolism
Brief summary
This study will examine brain metabolic and excitatory/inhibitory mechanisms related to cognitive and visual functioning in adults with schizophrenia and healthy control participants. Participants will complete behavioral assessments, cognitive testing, electroencephalography, magnetic resonance imaging, and magnetic resonance spectroscopy assessments. After baseline assessments, participants will be randomly assigned to one of two computerized cognitive training programs: perceptual discrimination training or cognitive control training. Each training program will include approximately 10 hours of training over 2 to 6 weeks. The study will evaluate changes in cognitive and visual task performance, EEG measures, and brain metabolite concentrations before and after cognitive training. Some participants may also complete optional extended baseline assessments before cognitive training.
Detailed description
Schizophrenia is associated with cognitive and visual impairments that can persist across the lifespan and are not fully addressed by current antipsychotic treatments. These impairments may be related to disruptions in brain metabolism and excitatory/inhibitory balance. This study is designed to better understand neurochemical and neurophysiological mechanisms of cognitive and visual functioning in schizophrenia and to evaluate whether these mechanisms change following cognitive training. The study will enroll adults with schizophrenia or schizoaffective disorder and demographically similar healthy control participants. Participants will complete baseline clinical assessments, cognitive and visual tasks, electroencephalography, structural magnetic resonance imaging, and magnetic resonance spectroscopy. Magnetic resonance spectroscopy will be used to measure brain metabolite concentrations, including metabolites related to brain metabolism and excitatory/inhibitory function. After baseline assessments, participants will be randomly assigned to one of two computerized cognitive training programs: perceptual discrimination training or cognitive control training. Both training programs are delivered through the BrainHQ platform and include approximately 10 hours of training over a 2- to 6-week period. Perceptual discrimination training focuses on visual stimulus discrimination, signal-to-noise resolution, and attentional control. Cognitive control training focuses on maintaining cognitive context in working memory during response selection. After completing cognitive training, participants will return for follow-up assessments, including repeat clinical assessments, cognitive and visual tasks, EEG, MRI, and magnetic resonance spectroscopy. Participants may also choose to complete an optional extended baseline component with additional baseline scanning visits before cognitive training. The primary outcomes include behavioral performance on the DPX task variant, EEG variables related to excitatory/inhibitory balance, and magnetic resonance spectroscopy measures of neurometabolite concentrations. Secondary outcomes include symptom and functioning measures such as the Brief Psychiatric Rating Scale, Scale for the Assessment of Negative Symptoms, Scale for the Assessment of Positive Symptoms, World Health Organization Disability Assessment Schedule, and Global Functioning Social/Role scales.
Interventions
DEVICEPerceptual Discrimination Training
Perceptual discrimination training is a computerized cognitive training program delivered through the BrainHQ platform. Training involves Gabor patch and other visual stimulus discrimination exercises that focus on improving signal-to-noise resolution and attentional control. On each training trial, participants distinguish a target stimulus among distractor stimuli. Training difficulty adapts based on participant performance. Participants complete approximately 10 hours of training over 2 to 6 weeks.
Cognitive control training is a computerized cognitive training program delivered through the BrainHQ platform. Training involves maintaining accurate representations of cognitive context in working memory during response selection. Training difficulty adapts based on participant performance by changing the speed of stimulus presentation or working memory load. Participants complete approximately 10 hours of training over 2 to 6 weeks.
Sponsors
University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Masking description
This is an open-label study. Participants and study staff will know which computerized cognitive training intervention is assigned.
Intervention model description
Participants will be randomly assigned to one of two computerized cognitive training interventions: perceptual discrimination training or cognitive control training. Both training programs include approximately 10 hours of training delivered over a 2- to 6-week period.
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
Yes
Inclusion criteria
All participants (healthy control and SZ): * Age: 18-79 * Have given written informed consent * Be able to read and write in English * General health status: Participants should be in good general physical health (no major neurological disorder or head injury with prolonged unconsciousness, and no current moderate or severe substance use disorder) * Geographic location: Minnesota counties that are approximately within 1 hour driving distance to Twin Cities, including, but not limited to, Hennepin, Ramsey, Washington, Anoka, Wright, Carver, Scott, Dakota, Sherburn * Agree to refrain from using recreational drugs for 1 week prior to each scanning session, including, but not limited to, marijuana For people with schizophrenia (SZ): * Current DSM-5 diagnosis of schizophrenia or schizoaffective disorder. Participants should be in stable psychiatric health, evidenced by no suicide attempt or psychiatric hospitalization within the past 1 month. (Initial diagnosis will be assessed using SCID 5 or MINI-7, and confirmation of ongoing SZ status and symptom changes will be monitored at each major timepoint using BPRS.) * All SZ must have achieved clinical stability, defined as outpatient status for at least one month prior to study participation, plus stable doses of psychiatric medications for at least 1 month prior to study participation (as reported by participants and confirmed via medication list (procured by participants via their own medical or pharmacy records) and/or current pill bottle labels). * All participants should have symptom ratings below a rating of 7 "extremely severe" on a severity scale of 1-7 on the BPRS and/or below grade 3 on longitudinal assessment defined by (as determined by the PI): * Grade 1: Worsening of 1 point on any item within each BPRS factor * Grade 2: Worsening of 2 points on any item within each BPRS factor * Grade 3: Worsening of 3+ points on any item within each BPRS factor, or a change to a rating of extremely severe * Grade 4: Suicide attempt with intent to die
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in DPX Task Performance | Baseline to post-training follow-up, up to 7 months; or baseline to post-training follow-up, up to 42 months for participants completing the optional extended baseline component | Behavioral performance on the DPX task variant will be assessed as a measure of cognitive control. Trial-by-trial behavioral data will be used to derive observed behavioral and computational metrics of cognitive control. The DPX task variant consists of a series of pattern sequences. One pattern is designated the "A" cue followed by the "X" cue, which requires one response (AX, 60-70% of trials, e.g. respond with the left button), while other pattern sequences require a different response (AY or BX, 12-15% of trials each, or BY, 6-10% of trials, e.g. respond with the right button). Given the strong expectation that X's evoke a valid response, BX trials place demands on cognitive control via the fidelity (stability, memory) of the "B" cue representation to overcome this tendency. Unit of Measure: Mean and standard deviation for BX trial error rate |
| Number of participants with pre/post EEG data | Baseline to post-training follow-up, up to 7 months; or baseline to post-training follow-up, up to 42 months for participants completing the optional extended baseline component | The final sample size (participants with resting electroencephalography before and after intervention) will be reported to facilitate future analyses of change in EEG variables, which could include phase synchrony, slope of the spectral power density indexing excitatory/inhibitory balance, and/or prefrontal/parietal theta as a measure of perceptual noise. Units of Measure: Number of participants with pre/post EEG data |
| Number of participants with pre/post Magnetic Resonance Spectroscopy data | Baseline to post-training follow-up, up to 7 months; or baseline to post-training follow-up, up to 42 months for participants completing the optional extended baseline component | Magnetic resonance spectroscopy (MRS) will be used to measure neurometabolite concentrations, including but not limited to glutamate, GABA, glutathione, and glucose. MRS measurements will be collected from prefrontal and occipital cortex. The final sample size (participants with MRS before and after intervention) will be reported to facilitate future analyses of change in MRS variables. Units of Measure: Number of participants with pre/post MRS data |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Brief Psychiatric Rating Scale Score | Baseline to post-training follow-up, up to 7 months; or baseline to post-training follow-up, up to 42 months for participants completing the optional extended baseline component | Psychiatric symptoms will be assessed using the Brief Psychiatric Rating Scale.Brief Psychiatric Rating Scale (BPRS) items are scored between 1-7 with higher scores meaning more severe symptoms (i.e., worse outcomes). The minimum score is 24, and the maximum score is 168. |
| Change in Positive Symptom Scores | Baseline to post-training follow-up, up to 7 months; or baseline to post-training follow-up, up to 42 months for participants completing the optional extended baseline component | Positive symptoms will be assessed using the Scale for the Assessment of Positive Symptoms(SAPS). Items are scored from 0 to 5, with higher scores indicating more severe symptoms and a worse outcome. Total scores range from 0 to 170. |
| Change in Negative Symptom Scores | Baseline to post-training follow-up, up to 7 months; or baseline to post-training follow-up, up to 42 months for participants completing the optional extended baseline component | Negative symptoms will be assessed using the Scale for the Assessment of Negative Symptoms(SANS). Items are scored from 0 to 5, with higher scores indicating more severe symptoms and a worse outcome. Total scores range from 0 to 125. |
| Change in World Health Organization Disability Assessment Schedule Score | Baseline to post-training follow-up, up to 7 months; or baseline to post-training follow-up, up to 42 months for participants completing the optional extended baseline component | Functioning will be assessed using the World Health Organization Disability Assessment Schedule, which assesses domains including cognition, mobility, self-care, social interaction, and social and participatory activities. The World Health Organization Disability Assessment Schedule (WHODAS) is scored so that higher values indicate more severe impacts of disability (i.e., a worse outcome). Each item is scored between 0-4 with a minimum score of zero and a maximum score of 48. |
| Change in Global Functioning Role Scale Score | Baseline to post-training follow-up, up to 7 months; or baseline to post-training follow-up, up to 42 months for participants completing the optional extended baseline component | Real-world role functioning in work or school will be assessed using the Global Functioning Role Scale. This scale is rated from 1 to 10, with higher scores indicating better role functioning. A score of 10 represents superior functioning. |
Countries
United States
Contacts
CONTACTCaroline Demro, PhD, LP
CONTACTClaire McDonald
PRINCIPAL_INVESTIGATORCaroline Demro, PhD, LP
University of Minnesota
Outcome results
None listed