Schizo Affective Disorder, SCHIZOPHRENIA 1 (Disorder)
Conditions
Keywords
social cognition, fMRI, event-related potentials, motion detection, face emotion recognition, transcranial direct current stimulation
Brief summary
This study investigates the ability of transcranial direct current stimulation (tDCS) applied over the motion processing area of the brain (area MT) to improve face emotion recognition (FER) ability. tDCS is a type of non-invasive brain stimulation in which low level currents are applied over the scalp to influence underlying brain function. In schizophrenia, impaired ability to detect facial motion has been shown to contribute to impaired FER, which, in turn, leads to difficulties in social cognition and poor social outcome. The study will use both fMRI and EEG to measure brain function while participants view moving dot and dynamic face stimuli. Analyses will compare changes in fMRI and EEG activity in individuals receiving active vs. sham stimulation.
Detailed description
The studey involves a randomized, parallel group comparison of personalized, MR-guided, cathodal HD-tDCS vs. sham targeting the middle temporal motion-sensitive region (HCP MMP1.0-atlas area MT+ complex) for the reversal of physiological impairments in Sz related to motion processing and social cognitive dysfunction. RDoC constructs to be tested include face emotion recognition (FER) and Understanding Mental State (UMS), which has also been termed Theory of Mind (ToM) or mentalizing. The overall goals of the study are to determine whether tDCS applied over MT+ can ameliorate 1) motion-processing deficits in Sz and 2) deficits in activation of other TVP regions. Key outcome measures include 1) activation of MT+, pSTS and mSTS regions to motion and dynamic FER stimuli and 2) fractional occupancy (FO) of the CAP state corresponding to the TVP structure. Behavioral outcomes will include scores on motion discrimination, FER to dynamic faces, and TASIT sarcasm (UMS). Participants will include 120 individuals with Sz and 30 healthy controls (HC). Sz individuals will be evaluated both cross-sectionally and during blinded, randomized active (cathodal) or sham pHD-tDCS targeted to MTC. HC will be evaluated cross-sectionally only. All participants will first undergo baseline assessment (Visit 1) and baseline physiological assessments (Visit 2). Each Sz participant will then be assigned to blinded intervention with either active or sham tDCS and will participate in one ERP (Visit 3) and one fMRI session (Visit 4) involving up to 40-min stimulation each. The two tDCS sessions will be conducted at least 1 week apart and may occur in either order. For each participant, the same randomized treatment (active vs. sham tDCS) will be used in both the ERP and fMRI sessions (Visits 3 and 4). Behavior is obtained during the ERP session (Visit 3). Comparisons will focus on correlations among the fMRI, ERP and behavioral outcome measures within participants as well as the effects of active vs. sham tDCS across participants.
Interventions
DEVICEtranscranial direct current stimulation
tDCS will be applied over cortical region MT+
DEVICESham stimulation
Ramp up/ramp down to simulate scalp sensation associated with tDCS. No sustained current flow
Sponsors
Nathan Kline Institute for Psychiatric Research
National Institute of Mental Health (NIMH)
Columbia University
Research Foundation for Mental Hygiene, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female subject, age 18-55 2. Competent and willing to sign informed consent 3. No more than moderately ill 4. SCID DSM-5 diagnosis of Sz/SzAff 5. WAIS IQ \>70 6. Does not meet current criteria for DSM-5 defined substance abuse or dependence or have a history of diagnosis within past 6 months 7. On medication within clinically approved range 8. Does not meet criteria for another DSM-5 disorder other than those judged to be minor (e.g. simple phobia)
Exclusion criteria
1. Significant neurological illness or history of significant head trauma 2. Unstable physical illness or significant auditory/visual deficits that might interfer 3. Contraindication to MRI (e.g. metal implants, claustrophobia, pregnancy) 4. Contraindications to tDCS including metal implant, pacemaker, history of seizure, traumatic brain injury or stroke 5. Significant risk for suicide 6. Has a history of an illness, disease, condition injury, or disability which, in the opinion of the principal investigator, may interfere with the completion of all study requirements per protocol, impact the quality of the data, or the validity of the study results, including unstable physical illness, significant neurological illness, significant head trauma 7. Moderate or greater DSM-5 current substance use disorder, defined based on the presence of 4 or more of 11 substance use criteria within the past 12 months. In addition, individuals for whom substance use leads to not being able to perform work, home or school activities
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| MT+ activation as determined using fMRI | Simultaneously with the administration of the active or sham tDCS intervention during study day 10 | Magnitude of activation in area MT+ during random dot kinematogram (RDK) stimulation measured by the beta weight of the BOLD fMRI signal, expressed in units of percentage signal change |
| MT+ activation as determined using event-related potentials (ERP) | Simultaneously with the administration of the active or sham tDCS intervention during study day 3 | Amplitude of the ERP response to random dot kinematogram (RDK) stimulation, measured in microvolts |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Activation of the third visual pathway (regions pSTS/mSTS) during a dynamic face emotion recognition (FER) task, as measured using fMRI | Simultaneously with the administration of the active or sham tDCS intervention during study day 10 | Magnitude of activation in areas pSTS and mSTS during the dynamic FER task as measured by the beta weight of the BOLD fMRI signal, expressed in units of percentage signal change |
| Fractional occupancy (FO) of the TVP CAP state | Simultaneously with the administration of the active or sham tDCS intervention during study day 10 | Fractional occupancy of the TVP CAP state during the NV-fMRI stimuli (Despicable me, Sherlock), as measured in percentage units |
| Activation of the third visual pathway (regions pSTS/mSTS) during a dynamic face emotion recognition (FER) task, as measured using ERP | Simultaneously with the administration of the active or sham tDCS intervention during study day 3 | Amplitude of the ERP response to dynamic emotional face stimuli, measured in microvolts |
| Motion discrimination threshold | Simultaneously with the administration of the active or sham tDCS intervention during study day 3 | % motion of the random dot kinetamatogram (RDK) stimuli needed for detection of motion, measured in percent |
| Face emotion recognition (FER) accuracy | Simultaneously with the administration of the active or sham tDCS intervention during study day 3 | % correct responses on the dynamic face emotion recognition task, measured as percent correct |
| Understanding mental states (UMS) accuracy | Simultaneously with the administration of the active or sham tDCS intervention during study day 3 | Percentage correct performance on the TASIT sarcasm task, measured as percent correct |
Countries
United States
Contacts
CONTACTOdeta Beggel, MA
PRINCIPAL_INVESTIGATORDaniel C Javitt, MD, PhD
Nathan Kline Institute
PRINCIPAL_INVESTIGATORAntigona Martinez, PhD
Nathan Kline Institute
Outcome results
None listed