Decision-Making, fMRI, OCD, tDCS
Conditions
Brief summary
People utilize two behavioral strategies, goal-directed and habitual, when engaging in value-based decision-making that involves rewarding or punishing outcomes. Accumulating evidence suggests an imbalance between habitual and goal-directed behavior in favor of habitual control in parallel with exaggerated tendency toward compulsive/harm avoidance behavior in OCD. In healthy subjects, an arbitration mechanism has been proposed recently that controls the balance between those two strategies of action selection. Arbitration regions regulate the goal-directed/habitual decision-making balance by selectively downregulating the activity of the habitual regions. This project aims to explore the neurobehavioral characteristics of arbitration mechanism and its relationship with behaviors and clinical phenotypes in OCD by applying computational cognitive neuroscience, clinical task-based functional magnetic resonance imaging (fMRI) and transcranial direct current stimulation (tDCS) method.
Detailed description
Investigators will recruit 30 male and female adults (age 18-65) with OCD and 30 age-, sex-, and education-matched healthy (medically, neurologically and psychiatrically) controls for this project. Each participant will come for three sessions. There will be 3-4 days interval between sessions: Session 1 that includes initial clinical assessment and obtaining T1 structural image (needed for neuronavigation analysis and electric field modeling). Session 2 and 3 that include performing two separate decision-making and symptom provocation-avoidance tasks by participants with OCD and healthy controls under two conditions: while scanned inside the MRI scanner (no tDCS) or while receiving neuronavigated tDCS neurostimulation outside the scanner (no fMRI imaging). As participates will perform each task twice, there might be an order effect on task performance. For minimizing the impact of such a potential order effect on imaging and tDCS results, participants will be randomly assigned to undergo scanning in the session 2 and then receive tDCS in the session 3 or in the opposite order (tDCS in session 2 and then imaging in session 3) but in each session only one of imaging or tDCS experiments (for both tasks) will be conducted for each participant. OCD-relevant and aversive picture rating (explained below) will be done always in the session 3 as the last experiment.
Interventions
DEVICEtranscranial Direct Current Stimulation (tDCS)
tDCS is a non-invasive brain stimulation method by which constant low direct current can be delivered to the sculpt for changing the excitability of neuronal structure adjunct to the stimulating electrode.
Sponsors
University of California, Los Angeles
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
A) OCD participants inclusion criteria: 1. DSM-5 diagnostic criteria for OCD as primary (most severe) diagnosis (based on the Mini International Neuropsychiatric Interview). 2. Yale-Brown Obsessive-Compulsive Scale (YBOCS) total score is equal or greater than 16. 3. unmediated or being on a stable dose of medication (only SSRIs and clomipramine) for at least 12 weeks prior to the study. 4. fluent English speaker. 5. signed informed consent. B) OCD participants
Exclusion criteria
1. IQ greater than 80 on the Wechsler Abbreviated Scales of Intelligence. 2. lifetime DSM-5 diagnosis of mania, psychotic disorder, or substance dependence (per MINI). 3. current DSM-5 diagnosis of MDD if Montgomery-Asberg Depression Scale (MADRS) scores are equal or greater than 35 (severe), or ADHD. 4. taking any psychotropic medication other than SSRIs or clomipramine. 5. severe psychiatric symptom that requires immediate inpatient psychiatric intervention such as suicidality. 6. presence of any serious psychiatric, psychosocial, or neurological condition requiring immediate treatment. C) Healthy control inclusion criteria: 1-males and females age 18-65 years with signed informed consent and IQ greater than 80 on WASI. D)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Strength of Behaving Model-based (Goal-directed) | On the second or third session when subjects performed the task in the MRI scanner. | Strength of behaving model-based (goal-directed) is measured and quantifiedas a continuous real number between 0 and 1. Here, having a strength's valueof 1 of behaving model-based means that subject in her/his decision-making,exclusively and always utilizes a model-based (goal-directed) strategy fordecision making and having a value of Zero means not utilizing model-based(goal-directed) strategy at all when decising. |
| Reaction Time in Response to Stimuli With OCD Themes | On the second or third session when subjects performed the task in the MRI scanner. | This is a time interval (in seconds) between the start of presentation of visual stimuli with OCD themes and when subjects pushed a bottom to stop the presentation when they could not tolerate those more during symptom provocation and avoidance task. |
| Strength of Frontal Arbitration Modulation of Basal Ganglia Habit Region. | On the second or third session when subjects performed the task in the MRI scanner | Here, by applying Dynamic Causal Modeling (DCM) method, we measured thestrength of frontal arbitration (the interior frontal gyrus (IFG)) modulation ofbasal ganglia habit region (the posterolateral putamen) in terms of the effective(directed) connectivity between the interior frontal gyrus (IFG) andposterolateral putamen. This DCM-based effective connectivity can have avalue between -1 and +1. A value of -1 means a maximum effective connectivitybetween the interior frontal gyrus (IFG) and posterolateral putamen. A value of+1 means maximum excitatory effective connectivity between the interior frontalgyrus (IFG) and posterolateral putamen. And a value of 0 means no effectiveconnectivity between the interior frontal gyrus (IFG) and posterolateralputamen. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Healthy Subjects: fMRI Imaging First, Then tDCS Healthy control subjects who first underwent imaging experiments in which they performed tasks in the MRI scanner on their second visit (no brain stimulation) and on the third session, performed the same tasks when receiving brain stimulation by tDCS (no imaging).
A) Healthy control inclusion criteria:
1-Males and females age 18-65 years fluent English speaker with signed informed consent.
B) Exclusion criteria for control participants:
1. presence of any MR scan contraindications particularly body metal or positive pregnancy test.
2. medical conditions in which cerebral metabolism might be compromised such as thyroid disorders, diabetes or current tobacco smoking (potential effect on imaging endpoints).
3. any history of seizure disorders. | 15 |
| Healthy Subjects: tDCS First, Then fMRI Imaging Healthy control subjects that first performed the two tasks when receiving brain stimulation by tDCS (no imaging) on their second visit and on the third session performed the same tasks in the MRI scanner (no brain stimulation).
A) Healthy control inclusion criteria:
1-Males and females age 18-65 years fluent English speaker with signed informed consent.
B) Exclusion criteria for control participants:
1. presence of any MR scan contraindications particularly body metal or positive pregnancy test.
2. medical conditions in which cerebral metabolism might be compromised such as thyroid disorders, diabetes or current tobacco smoking (potential effect on imaging endpoints).
3. any history of seizure disorders. | 15 |
| OCD Subjects: fMRI Imaging First, Then tDCS OCD subjects who first underwent imaging experiments in which they performed tasks in the MRI scanner on their second visit (no brain stimulation) and on the third session, performed the same tasks when receiving brain stimulation by tDCS (no imaging).
A) OCD participants inclusion criteria:
1. DSM-5 diagnostic criteria for OCD as primary (most severe) diagnosis (based on the Mini International Neuropsychiatric Interview).
2. Yale-Brown Obsessive-Compulsive Scale (YBOCS) total score is equal or greater than 16.
3. unmediated or being on a stable dose of medication (only SSRIs and clomipramine) for at least 12 weeks prior to the study.
4. fluent English speaker.
5. signed informed consent.
B) OCD participants exclusion criteria:
1. IQ greater than 80 on the Wechsler Abbreviated Scales of Intelligence.
2. lifetime DSM-5 diagnosis of mania, psychotic disorder, or substance dependence (per MINI).
3. current DSM-5 diagnosis of MDD if Montgomery-Asberg Depression Scale (MADRS) scores are equal or greater than 35 (severe), or ADHD.
4. taking any psychotropic medication other than SSRIs or clomipramine.
5. severe psychiatric symptom that requires immediate inpatient psychiatric intervention such as suicidality.
6. presence of any serious psychiatric, psychosocial, or neurological condition requiring immediate treatment.
C) Exclusion criteria for OCD participants:
1. presence of any MR scan contraindications particularly body metal or positive pregnancy test.
2. medical conditions in which ce | 15 |
| OCD Subjects: tDCS First, Then fMRI Imaging OCD control subjects that first performed the two tasks when receiving brain stimulation by tDCS (no imaging) on their second visit and on the third session performed the same tasks in the MRI scanner (no brain stimulation).
A) OCD participants inclusion criteria:
1. DSM-5 diagnostic criteria for OCD as primary (most severe) diagnosis (based on the Mini International Neuropsychiatric Interview).
2. Yale-Brown Obsessive-Compulsive Scale (YBOCS) total score is equal or greater than 16.
3. unmediated or being on a stable dose of medication (only SSRIs and clomipramine) for at least 12 weeks prior to the study.
4. fluent English speaker.
5. signed informed consent.
B) OCD participants exclusion criteria:
1. IQ greater than 80 on the Wechsler Abbreviated Scales of Intelligence.
2. lifetime DSM-5 diagnosis of mania, psychotic disorder, or substance dependence (per MINI).
3. current DSM-5 diagnosis of MDD if Montgomery-Asberg Depression Scale (MADRS) scores are equal or greater than 35 (severe), or ADHD.
4. taking any psychotropic medication other than SSRIs or clomipramine.
5. severe psychiatric symptom that requires immediate inpatient psychiatric intervention such as suicidality.
6. presence of any serious psychiatric, psychosocial, or neurological condition requiring immediate treatment.
C) Exclusion criteria for OCD participants:
1. presence of any MR scan contraindications particularly body metal or positive pregnancy test.
2. medical conditions in which cerebral metabolism might be c | 15 |
| Total | 60 |
Baseline characteristics
| Characteristic | Healthy Subjects: fMRI Imaging First, Then tDCS | Healthy Subjects: tDCS First, Then fMRI Imaging | OCD Subjects: fMRI Imaging First, Then tDCS | OCD Subjects: tDCS First, Then fMRI Imaging | 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 | 15 Participants | 15 Participants | 15 Participants | 15 Participants | 60 Participants |
| Age, Continuous | 25 year | 27 year | 27 year | 29 year | 27 year |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 2 Participants | 4 Participants | 3 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 13 Participants | 11 Participants | 12 Participants | 47 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 4 Participants | 3 Participants | 4 Participants | 16 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 11 Participants | 11 Participants | 11 Participants | 40 Participants |
| Region of Enrollment United States | 15 Participants | 15 Participants | 15 Participants | 15 Participants | 60 Participants |
| Sex: Female, Male Female | 10 Participants | 9 Participants | 8 Participants | 8 Participants | 35 Participants |
| Sex: Female, Male Male | 5 Participants | 6 Participants | 7 Participants | 7 Participants | 25 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 / 30 | 0 / 30 | 0 / 30 | 0 / 30 |
| other Total, other adverse events | 0 / 30 | 0 / 30 | 0 / 30 | 0 / 30 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 | 0 / 30 | 0 / 30 |
Outcome results
Primary
Reaction Time in Response to Stimuli With OCD Themes
This is a time interval (in seconds) between the start of presentation of visual stimuli with OCD themes and when subjects pushed a bottom to stop the presentation when they could not tolerate those more during symptom provocation and avoidance task.
Time frame: On the second or third session when subjects performed the task in the MRI scanner.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy Subjects: fMRI Imaging First, Then tDCS | Reaction Time in Response to Stimuli With OCD Themes | 5.6 seconds | Standard Deviation 2.18 |
| Healthy Subjects: tDCS First, Then fMRI Imaging | Reaction Time in Response to Stimuli With OCD Themes | 5.5 seconds | Standard Deviation 2.91 |
| OCD Subjects: fMRI Imaging First, Then tDCS | Reaction Time in Response to Stimuli With OCD Themes | 4.3 seconds | Standard Deviation 2.01 |
| OCD Subjects: tDCS First, Then fMRI Imaging | Reaction Time in Response to Stimuli With OCD Themes | 4.8 seconds | Standard Deviation 2.93 |
Primary
Strength of Behaving Model-based (Goal-directed)
Strength of behaving model-based (goal-directed) is measured and quantifiedas a continuous real number between 0 and 1. Here, having a strength's valueof 1 of behaving model-based means that subject in her/his decision-making,exclusively and always utilizes a model-based (goal-directed) strategy fordecision making and having a value of Zero means not utilizing model-based(goal-directed) strategy at all when decising.
Time frame: On the second or third session when subjects performed the task in the MRI scanner.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy Subjects: fMRI Imaging First, Then tDCS | Strength of Behaving Model-based (Goal-directed) | 0.09 units on a scale | Standard Deviation 0.132 |
| Healthy Subjects: tDCS First, Then fMRI Imaging | Strength of Behaving Model-based (Goal-directed) | 0.07 units on a scale | Standard Deviation 0.14 |
| OCD Subjects: fMRI Imaging First, Then tDCS | Strength of Behaving Model-based (Goal-directed) | -0.08 units on a scale | Standard Deviation 0.082 |
| OCD Subjects: tDCS First, Then fMRI Imaging | Strength of Behaving Model-based (Goal-directed) | 0.06 units on a scale | Standard Deviation 0.091 |
Primary
Strength of Frontal Arbitration Modulation of Basal Ganglia Habit Region.
Here, by applying Dynamic Causal Modeling (DCM) method, we measured thestrength of frontal arbitration (the interior frontal gyrus (IFG)) modulation ofbasal ganglia habit region (the posterolateral putamen) in terms of the effective(directed) connectivity between the interior frontal gyrus (IFG) andposterolateral putamen. This DCM-based effective connectivity can have avalue between -1 and +1. A value of -1 means a maximum effective connectivitybetween the interior frontal gyrus (IFG) and posterolateral putamen. A value of+1 means maximum excitatory effective connectivity between the interior frontalgyrus (IFG) and posterolateral putamen. And a value of 0 means no effectiveconnectivity between the interior frontal gyrus (IFG) and posterolateralputamen.
Time frame: On the second or third session when subjects performed the task in the MRI scanner
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy Subjects: fMRI Imaging First, Then tDCS | Strength of Frontal Arbitration Modulation of Basal Ganglia Habit Region. | -0.07 units on ascale | Standard Deviation 0.121 |
| Healthy Subjects: tDCS First, Then fMRI Imaging | Strength of Frontal Arbitration Modulation of Basal Ganglia Habit Region. | -0.06 units on ascale | Standard Deviation 0.131 |
| OCD Subjects: fMRI Imaging First, Then tDCS | Strength of Frontal Arbitration Modulation of Basal Ganglia Habit Region. | -0.003 units on ascale | Standard Deviation 0.161 |
| OCD Subjects: tDCS First, Then fMRI Imaging | Strength of Frontal Arbitration Modulation of Basal Ganglia Habit Region. | -0.004 units on ascale | Standard Deviation 0.132 |