Perinatal Depression, Post Partum Depression, Depression, Postpartum, Depression
Conditions
Keywords
Irritability, Estrogen, Progesterone, Lupron Depot, Mood Disorders, Perinatal Depression, Postpartum, Hormones, Physiological effects of drugs, Reproductive Control Agents, Mental Disorders, Hormone Intervention, Functional Magnetic Resonance Imaging
Brief summary
The proposed study involves experimentally manipulating reproductive hormones in nonpregnant, euthymic women to create a scaled down version of the changes that occur during pregnancy and the postpartum period. This endocrine manipulation paradigm, which the investigators have shown provokes irritability in past studies, will be used to examine the neurocircuitry underlying irritability under baseline and hormone challenge conditions among women who are hormone sensitive (HS+; n=15) and non-hormone sensitive (HS-; n=15). The long-term goal of this research is to advance understanding of the neural systems underlying both the triggering of and susceptibility to irritability in women. The objective of the current project is to examine whether HS+ show differences in the behavioral activation system relative to HS- under baseline and hormone challenge conditions using functional magnetic resonance imaging (fMRI) and behavioral tests.
Detailed description
Irritability, defined as a predisposition to exhibit anger, is a prominent, defining symptom of perinatal depression (PND) and many other neuropsychiatric disorders. Despite the near ubiquity of irritability across disorders, the neural dysfunction underlying the vulnerability to, onset of, and exacerbation of irritability is understudied and poorly understood. The proposed study involves experimentally manipulating reproductive hormones in nonpregnant, euthymic women to create a scaled down version of the changes that occur during pregnancy and the postpartum period. This endocrine manipulation paradigm, which the investigators have shown provokes irritability in past studies, will be used to examine the neurocircuitry underlying irritability under baseline and hormone challenge conditions among women who are hormone sensitive (HS+; n=15) and non-hormone sensitive (HS-; n=15). The long-term goal of this research is to advance understanding of the neural systems underlying both the triggering of and susceptibility to irritability in women. The objective of the current project is to examine whether HS+ show differences in the behavioral activation system relative to HS- under baseline and hormone challenge conditions using functional magnetic resonance imaging (fMRI) and behavioral tests. The investigator's central hypothesis is that reproductive hormone changes are associated with dysregulated threat and reward processing and consequent irritability in HS+. The rationale for the proposed study is that employing a scaled down model of puerperal hormonal events permits the identification of a group of individuals homogeneous for hormone sensitivity (HS+), hence creating the best opportunity for disentangling the specific changes in brain function due to reproductive hormones (i.e., HS-) from those accompanying reproductive hormone-precipitated affective dysfunction (i.e., HS+). Because women will act as their own controls across time, this study design also allows for a powerful evaluation of state and trait variables that may contribute to irritability, including both threat and reward processing. Identifying both state and trait markers of irritability, and disentangling them from the effects of reproductive hormones on brain and behavior, will allow for the identification of neural substrates of irritability susceptibility that can be investigated across neuropsychiatric disorders. The expected outcome of this research is the identification of neural circuits underlying both the susceptibility to and mediation of irritability.
Interventions
3.75 mg/month leuprolide acetate intramuscular injection
DRUGEstradiol 2 Mg tablet
2 mg estradiol tablet
DRUGMicronized progesterone
200 mg micronized progesterone tablets
Sponsors
National Institute of Mental Health (NIMH)
University of North Carolina, Chapel Hill
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
22 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
Participants will include healthy, euthymic 22-45 year old women with a history of postpartum depression (n=15) and women without such a history (n=15). Thus, only participants capable of giving informed consent will be enrolled. Participants will be compensated upon completion of the study. Inclusion Criteria. Group 1: Women with a history of perinatal depression * A history of a the Diagnostic Statistic Manual of Mental Disorders - fifth edition (DSM-V) major depression episode that occurred within 6 weeks of childbirth (as determined by a SCID interview) and remitted at least one year prior to enrollment in the study; * has been well for a minimum of one year; * a regular menstrual cycle for at least three months; * age 22-45; * medication free (including birth control pills);. Group 2: Healthy Controls * Controls will meet all inclusion criteria specified above except they must not have any past or present Axis I diagnosis or evidence of menstrually related mood disorders. A structured clinical interview for DSM-V (SCID) will be administered to all women prior to study entry. Any woman with a current axis I psychiatric diagnosis will be excluded from participating in this protocol.
Exclusion criteria
Patients will not be permitted to enter this protocol if they have important clinical or laboratory abnormalities including any of the following: * current axis I psychiatric diagnosis (based on a structured clinical interview for DSM-V (SCID); * endometriosis; * undiagnosed enlargement of the ovaries; * liver disease; * breast cancer; * a history of blood clots in the legs or lungs; * undiagnosed vaginal bleeding; * porphyria; * diabetes mellitus; * malignant melanoma; * gallbladder or pancreatic disease; * heart or kidney disease; * cerebrovascular disease (stroke); * cigarette smoking; * a history of suicide attempts or psychotic episodes requiring hospitalization; * recurrent migraine with aura; * pregnancy-related medical conditions such as hyperemesis gravidarum, preeclampsia and toxemia, deep vein thrombosis (DVT) and bleeding diathesis; * Any woman with a first degree relative (immediate family) with premenopausal breast cancer or breast cancer presenting in both breasts or any woman who has multiple family members (greater than three relatives) with postmenopausal breast cancer will also be excluded from participating in this protocol; Any woman meeting the Stages of Reproductive Aging Workshop Criteria (STRAW) for perimenopause will be excluded from participation. Specifically, the investigators will exclude any woman with an elevated plasma follicle stimulating hormone (FSH) level (\> 14 IU/L) and with menstrual cycle variability of \> 7 days different from their normal cycle length. Pregnant women will be excluded from participation (patients will be warned not to become pregnant during the study and will be advised to employ barrier contraceptive methods), and women who become pregnant (although unlikely because of the hormone manipulation) will be withdrawn. The use of leuprolide acetate is not recommended during pregnancy. Prior to treatment, a complete physical, including a serum β-human chorionic gonadotropin (HCG) test for pregnancy. Participants will be seen at the outpatient clinic on a regular biweekly basis. All participants will be required to use non-hormonal forms of birth control (e.g., barrier methods) to avoid pregnancy during this study. Participants will also undergo urine toxicology and pregnancy tests on the day of each of the two fMRI scans. If a woman becomes pregnant during the study, she will not complete the fMRI scan, and the hormone protocol will be discontinued.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean BOLD Activation of the Left Nucleus Accumbens During the Affective Posner Task Over Time | up to 6 weeks | This outcome measure determines the extent to which HS+ is characterized by BOLD activation of the left nucleus accumbens in response to frustrative non-reward (FNR) in the Affective Posner Task during hormone addback relative to baseline in the target population. The Affective Posner Task tests whether HS+ is characterized by reduced subcortical activation in response to frustration. This task is divided into 3 runs: during Run 1 (practice run), participants receive accurate feedback about their performance on the task and do not win or lose money; during Run 2, participants receive accurate feedback about their performance and win or lose 50 cents per trial; and during Run 3 (frustration), participants are told they must respond accurately to win money, but participants are given feedback that they responded too slowly on 60% of accurate trials, regardless of their performance. |
| Mean BOLD Activation of the Right Caudate During the Affective Posner Task Over Time | up to 6 weeks | This outcome measure determines the extent to which HS+ is characterized by BOLD activation of the right caudate in response to frustrative non-reward (FNR) in the Affective Posner Task during hormone addback relative to baseline in the target population. The Affective Posner Task tests whether HS+ is characterized by reduced subcortical activation in response to frustration. This task is divided into 3 runs: during Run 1 (practice run), participants receive accurate feedback about their performance on the task and do not win or lose money; during Run 2, participants receive accurate feedback about their performance and win or lose 50 cents per trial; and during Run 3 (frustration), participants are told they must respond accurately to win money, but participants are given feedback that they responded too slowly on 60% of accurate trials, regardless of their performance. |
| Mean BOLD Activation of the Left Caudate During the Affective Posner Task Over Time | up to 6 weeks | This outcome measure determines the extent to which HS+ is characterized by BOLD activation of the left caudate in response to frustrative non-reward (FNR) in the Affective Posner Task during hormone addback relative to baseline in the target population. The Affective Posner Task tests whether HS+ is characterized by reduced subcortical activation in response to frustration. This task is divided into 3 runs: during Run 1 (practice run), participants receive accurate feedback about their performance on the task and do not win or lose money; during Run 2, participants receive accurate feedback about their performance and win or lose 50 cents per trial; and during Run 3 (frustration), participants are told they must respond accurately to win money, but participants are given feedback that they responded too slowly on 60% of accurate trials, regardless of their performance. |
| Mean BOLD Activation of the Right Putamen During the Affective Posner Task Over Time | up to 6 weeks | This outcome measure determines the extent to which HS+ is characterized by BOLD activation of the right putamen in response to frustrative non-reward (FNR) in the Affective Posner Task during hormone addback relative to baseline in the target population. The Affective Posner Task tests whether HS+ is characterized by reduced subcortical activation in response to frustration. This task is divided into 3 runs: during Run 1 (practice run), participants receive accurate feedback about their performance on the task and do not win or lose money; during Run 2, participants receive accurate feedback about their performance and win or lose 50 cents per trial; and during Run 3 (frustration), participants are told they must respond accurately to win money, but participants are given feedback that they responded too slowly on 60% of accurate trials, regardless of their performance. |
| Mean BOLD Activation of the Left Putamen During the Affective Posner Task Over Time | up to 6 weeks | This outcome measure determines the extent to which HS+ is characterized by BOLD activation of the left putamen in response to frustrative non-reward (FNR) in the Affective Posner Task during hormone addback relative to baseline in the target population. The Affective Posner Task tests whether HS+ is characterized by reduced subcortical activation in response to frustration. This task is divided into 3 runs: during Run 1 (practice run), participants receive accurate feedback about their performance on the task and do not win or lose money; during Run 2, participants receive accurate feedback about their performance and win or lose 50 cents per trial; and during Run 3 (frustration), participants are told they must respond accurately to win money, but participants are given feedback that they responded too slowly on 60% of accurate trials, regardless of their performance. |
| Mean BOLD Activation of the Right Nucleus Accumbens During the Affective Posner Task Over Time | up to 6 weeks | This outcome measure determines the extent to which HS+ is characterized by BOLD activation of the right nucleus accumbens in response to frustrative non-reward (FNR) in the Affective Posner Task during hormone addback relative to baseline in the target population. The Affective Posner Task tests whether HS+ is characterized by reduced subcortical activation in response to frustration. This task is divided into 3 runs: during Run 1 (practice run), participants receive accurate feedback about their performance on the task and do not win or lose money; during Run 2, participants receive accurate feedback about their performance and win or lose 50 cents per trial; and during Run 3 (frustration), participants are told they must respond accurately to win money, but participants are given feedback that they responded too slowly on 60% of accurate trials, regardless of their performance. |
| Mean Threat Processing Bias During Visual Dot-probe Paradigm Over Time | up to 6 weeks | This outcome measure determines the extent to which irritability is characterized by dysfunctional threat processing during reproductive hormone challenge relative to baseline in HS+ and HS- by examining threat attention bias assessed during the visual dot-probe paradigm. The Visual Dot-Probe Paradigm asks participants to detect a target stimulus that is embedded in a matrix of distracting stimuli (e.g., a target stimulus, an angry face, might be embedded in a matrix of neutral distractor faces). Attention biases are inferred from faster response times to detect a threatening stimulus in a matrix of neutral stimuli relative to response time to detect neutral stimuli in neutral matrices. Thus, positive times reflect attention bias toward threat, whereas negative times reflect attention bias away from threat. |
| Mean Right Amygdala-medial Prefrontal Cortex BOLD Connectivity During Implicit Emotion Face Processing Task Over Time | up to 6 weeks | This outcome measure determines the extent to which irritability is characterized by dysfunctional threat processing during reproductive hormone challenge relative to baseline in HS+ and HS-. By examining amygdala-medial prefrontal cortex (PFC) Blood-oxygen-level-dependent (BOLD) connectivity in response to threatening faces on the implicit emotion face processing fMRI task in HS+ (compared with HS-) during hormone challenge relative to baseline. The implicit emotion face processing task asks participants to identify the gender of angry, happy, and fearful faces at 50%, 100% and 150% emotion intensity presented in random order for 2000 milliseconds followed by jittered fixation. Trials appear in 3 blocks, generating 30 trials of each emotion at each intensity and 90 neutral face emotion trials. |
| Mean Left Amygdala-medial Prefrontal Cortex BOLD Connectivity During Implicit Emotion Face Processing Task Over Time | up to 6 weeks | This outcome measure determines the extent to which irritability is characterized by dysfunctional threat processing during reproductive hormone challenge relative to baseline in HS+ and HS-. By examining amygdala-medial prefrontal cortex (PFC) connectivity in response to threatening faces on the implicit emotion face processing fMRI task in HS+ (compared with HS-) during hormone challenge relative to baseline. The implicit emotion face processing task asks participants to identify the gender of angry, happy, and fearful faces at 50%, 100% and 150% emotion intensity presented in random order for 2000 milliseconds followed by jittered fixation. Trials appear in 3 blocks, generating 30 trials of each emotion at each intensity and 90 neutral face emotion trials. |
| Mean Reactive Aggression During Hormone Addback Over Time | up to 6 weeks | This outcome measure determines the extent to which HS+ is characterized by reactive aggression during hormone addback relative to baseline in the target population. Reactive aggression will be defined as the number of point subtractions the participant makes during the Point Subtraction Aggression Paradigm. Point Subtraction Aggression Paradigm measures relational aggression (approach behavior) in response to frustration. In the task, participants are asked to press a button to accrue money or press another button to subtract money from a (fictional) partner at no direct gain to themselves. Frustration is induced by periodic subtractions of their own money, which is attributed to the partner. |
| Mean BOLD Activation of the Right Amygdala During the Affective Posner Task Over Time | up to 6 weeks | This outcome measure determines the extent to which HS+ is characterized by BOLD activation of the right amygdala in response to frustrative non-reward (FNR) in the Affective Posner Task during hormone addback relative to baseline in the target population. The Affective Posner Task tests whether HS+ is characterized by reduced subcortical activation in response to frustration. This task is divided into 3 runs: during Run 1 (practice run), participants receive accurate feedback about their performance on the task and do not win or lose money; during Run 2, participants receive accurate feedback about their performance and win or lose 50 cents per trial; and during Run 3 (frustration), participants are told they must respond accurately to win money, but participants are given feedback that they responded too slowly on 60% of accurate trials, regardless of their performance. |
| Mean BOLD Activation of the Left Amygdala During the Affective Posner Task Over Time | up to 6 weeks | This outcome measure determines the extent to which HS+ is characterized by BOLD activation of the left amygdala in response to frustrative non-reward (FNR) in the Affective Posner Task during hormone addback relative to baseline in the target population. The Affective Posner Task tests whether HS+ is characterized by reduced subcortical activation in response to frustration. This task is divided into 3 runs: during Run 1 (practice run), participants receive accurate feedback about their performance on the task and do not win or lose money; during Run 2, participants receive accurate feedback about their performance and win or lose 50 cents per trial; and during Run 3 (frustration), participants are told they must respond accurately to win money, but participants are given feedback that they responded too slowly on 60% of accurate trials, regardless of their performance. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlation Between the Inventory of Depressive and Anxiety Symptoms (IDAS) Ill Temper Scale and Right Amygdala-medial Prefrontal Cortex (PFC) BOLD Connectivity. | Endpoint (week 6) | This outcome measure determines the extent to which irritability is characterized by dysfunctional reward processing during reproductive hormone challenge in HS+ and HS- by examining the correlation between the IDAS Ill Temper (i.e., irritability) Scale and amygdala-medial PFC connectivity in HS+. |
| Correlation Between the Inventory of Depressive and Anxiety Symptoms (IDAS) Ill Temper Scale and Left Amygdala-medial Prefrontal Cortex (PFC) BOLD Connectivity. | Endpoint (week 6) | This outcome measure determines the extent to which irritability is characterized by dysfunctional reward processing during reproductive hormone challenge in HS+ and HS- by examining the correlation between the IDAS Ill Temper (i.e., irritability) Scale and amygdala-medial PFC connectivity in HS+. |
| Correlation Between Irritability and Reactive Aggression During Hormone Addback | Endpoint (week 6) | This outcome measure determines the degree of irritability and reactive aggression in HS+ during hormone addback and its relationship to the target population. Irritability will be defined as score on the IDAS Ill Temper Scale. Reactive aggression will be defined as the number of point subtractions the participant makes during the Point Subtraction Aggression Paradigm. The Point Subtraction Aggression Paradigm measures relational aggression (approach behavior) in response to frustration. In the task, participants are asked to press a button to ac |
| Correlation Between Irritability Subcortical Activation in HS+ During Hormone Addback | Endpoint (week 6) | This outcome measure determines the degree of subcortical (amygdala, caudate, putamen, and nucleus accumbens) activation in HS+ during hormone addback and it's relationship to the target population. The activation in amygdala and ventral striatum (caudate, putamen, nucleus accumbens) regions of interest (ROIs) will be assessed during the Affective Posner Task. The Affective Posner Task tests whether HS+ is characterized by reduced subcortical activation in response to frustration. This task is divided into 3 runs: during Run 1 (practice run), participants receive accurate feedback about their performance on the task and do not win or lose money; during Run 2, participants receive accurate feedback about their performance and win or lose 50 cents per trial; and during Run 3 (frustration), participants are told they must respond accurately to win money, but participants are given feedback that they responded too slowly on 60% of accurate trials, regardless of their performance. |
| Correlation Between the Inventory of Depressive and Anxiety Symptoms (IDAS) Ill -0.8Scale and Threat Attention Bias | Endpoint (week 6) | This outcome measure determines the extent to which irritability is characterized by dysfunctional reward processing during reproductive hormone challenge in HS+ and HS- by examining the correlation between the Inventory of Depressive and Anxiety Symptoms (IDAS) Ill Temper (i.e., irritability) Scale and threat attention bias. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Hormone Sensitive Women (HS+) Participants will take leuprolide acetate (lupron) via intramuscular injection, for 2 months. Participants will take 2 mg of estradiol twice daily and 200 mg of progesterone twice daily for 2 weeks.
Leuprolide Acetate 3.75 MG/ML: 3.75 mg/month leuprolide acetate intramuscular injection
Estradiol 2 Mg tablet: 2 mg estradiol tablet
Micronized progesterone: 200 mg micronized progesterone tablets | 13 |
| Hormone Insensitive Women (HS-) Participants will take leuprolide acetate (lupron) via intramuscular injection, for 2 months. Participants will take 2 mg of estradiol twice daily and 200 mg of progesterone twice daily for 2 weeks.
Leuprolide Acetate 3.75 MG/ML: 3.75 mg/month leuprolide acetate intramuscular injection
Estradiol 2 Mg tablet: 2 mg estradiol tablet
Micronized progesterone: 200 mg micronized progesterone tablets | 10 |
| Total | 23 |
Baseline characteristics
| Characteristic | Hormone Sensitive Women (HS+) | Total | Hormone Insensitive Women (HS-) |
|---|---|---|---|
| Age, Continuous | 34.81 years STANDARD_DEVIATION 6.46 | 35.77 years STANDARD_DEVIATION 5.31 | 37.15 years STANDARD_DEVIATION 2.82 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 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 | 10 Participants | 20 Participants | 10 Participants |
| Region of Enrollment United States | 13 Participants | 23 Participants | 10 Participants |
| Sex: Female, Male Female | 13 Participants | 23 Participants | 10 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 10 |
| other Total, other adverse events | 12 / 13 | 9 / 10 |
| serious Total, serious adverse events | 0 / 13 | 0 / 10 |
Outcome results
Primary
Mean BOLD Activation of the Left Amygdala During the Affective Posner Task Over Time
This outcome measure determines the extent to which HS+ is characterized by BOLD activation of the left amygdala in response to frustrative non-reward (FNR) in the Affective Posner Task during hormone addback relative to baseline in the target population. The Affective Posner Task tests whether HS+ is characterized by reduced subcortical activation in response to frustration. This task is divided into 3 runs: during Run 1 (practice run), participants receive accurate feedback about their performance on the task and do not win or lose money; during Run 2, participants receive accurate feedback about their performance and win or lose 50 cents per trial; and during Run 3 (frustration), participants are told they must respond accurately to win money, but participants are given feedback that they responded too slowly on 60% of accurate trials, regardless of their performance.
Time frame: up to 6 weeks
Population: Participants exceeding the motion threshold were excluded.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hormone Sensitive Women (HS+) | Mean BOLD Activation of the Left Amygdala During the Affective Posner Task Over Time | Baseline (Visit 3) | 0.005316917 Arbitrary Units | Standard Deviation 0.10109272 |
| Hormone Sensitive Women (HS+) | Mean BOLD Activation of the Left Amygdala During the Affective Posner Task Over Time | Hormone Addback (Visit 6) | -0.047401917 Arbitrary Units | Standard Deviation 0.19032614 |
| Hormone Insensitive Women (HS-) | Mean BOLD Activation of the Left Amygdala During the Affective Posner Task Over Time | Baseline (Visit 3) | -0.009866667 Arbitrary Units | Standard Deviation 0.12208237 |
| Hormone Insensitive Women (HS-) | Mean BOLD Activation of the Left Amygdala During the Affective Posner Task Over Time | Hormone Addback (Visit 6) | -0.086876444 Arbitrary Units | Standard Deviation 0.11792679 |
p-value: 0.791ANOVA
Primary
Mean BOLD Activation of the Left Caudate During the Affective Posner Task Over Time
This outcome measure determines the extent to which HS+ is characterized by BOLD activation of the left caudate in response to frustrative non-reward (FNR) in the Affective Posner Task during hormone addback relative to baseline in the target population. The Affective Posner Task tests whether HS+ is characterized by reduced subcortical activation in response to frustration. This task is divided into 3 runs: during Run 1 (practice run), participants receive accurate feedback about their performance on the task and do not win or lose money; during Run 2, participants receive accurate feedback about their performance and win or lose 50 cents per trial; and during Run 3 (frustration), participants are told they must respond accurately to win money, but participants are given feedback that they responded too slowly on 60% of accurate trials, regardless of their performance.
Time frame: up to 6 weeks
Population: Participants with signal loss were excluded.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hormone Sensitive Women (HS+) | Mean BOLD Activation of the Left Caudate During the Affective Posner Task Over Time | Baseline (Visit 3) | -0.043943333 Arbitrary Units | Standard Deviation 0.19455199 |
| Hormone Sensitive Women (HS+) | Mean BOLD Activation of the Left Caudate During the Affective Posner Task Over Time | Hormone Addback (Visit 6) | 0.059099917 Arbitrary Units | Standard Deviation 0.09144575 |
| Hormone Insensitive Women (HS-) | Mean BOLD Activation of the Left Caudate During the Affective Posner Task Over Time | Baseline (Visit 3) | 0.0077258 Arbitrary Units | Standard Deviation 0.18794868 |
| Hormone Insensitive Women (HS-) | Mean BOLD Activation of the Left Caudate During the Affective Posner Task Over Time | Hormone Addback (Visit 6) | -0.049988 Arbitrary Units | Standard Deviation 0.17179757 |
p-value: 0.0861ANOVA
Primary
Mean BOLD Activation of the Left Nucleus Accumbens During the Affective Posner Task Over Time
This outcome measure determines the extent to which HS+ is characterized by BOLD activation of the left nucleus accumbens in response to frustrative non-reward (FNR) in the Affective Posner Task during hormone addback relative to baseline in the target population. The Affective Posner Task tests whether HS+ is characterized by reduced subcortical activation in response to frustration. This task is divided into 3 runs: during Run 1 (practice run), participants receive accurate feedback about their performance on the task and do not win or lose money; during Run 2, participants receive accurate feedback about their performance and win or lose 50 cents per trial; and during Run 3 (frustration), participants are told they must respond accurately to win money, but participants are given feedback that they responded too slowly on 60% of accurate trials, regardless of their performance.
Time frame: up to 6 weeks
Population: Participants with signal loss were excluded.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hormone Sensitive Women (HS+) | Mean BOLD Activation of the Left Nucleus Accumbens During the Affective Posner Task Over Time | Baseline (Visit 3) | -0.028451818 Arbitrary Units | Standard Deviation 0.13242342 |
| Hormone Sensitive Women (HS+) | Mean BOLD Activation of the Left Nucleus Accumbens During the Affective Posner Task Over Time | Hormone Addback (Visit 6) | 0.031632727 Arbitrary Units | Standard Deviation 0.25999277 |
| Hormone Insensitive Women (HS-) | Mean BOLD Activation of the Left Nucleus Accumbens During the Affective Posner Task Over Time | Baseline (Visit 3) | 0.0691907 Arbitrary Units | Standard Deviation 0.24951478 |
| Hormone Insensitive Women (HS-) | Mean BOLD Activation of the Left Nucleus Accumbens During the Affective Posner Task Over Time | Hormone Addback (Visit 6) | -0.072512 Arbitrary Units | Standard Deviation 0.16302971 |
p-value: 0.0449ANOVA
Primary
Mean BOLD Activation of the Left Putamen During the Affective Posner Task Over Time
This outcome measure determines the extent to which HS+ is characterized by BOLD activation of the left putamen in response to frustrative non-reward (FNR) in the Affective Posner Task during hormone addback relative to baseline in the target population. The Affective Posner Task tests whether HS+ is characterized by reduced subcortical activation in response to frustration. This task is divided into 3 runs: during Run 1 (practice run), participants receive accurate feedback about their performance on the task and do not win or lose money; during Run 2, participants receive accurate feedback about their performance and win or lose 50 cents per trial; and during Run 3 (frustration), participants are told they must respond accurately to win money, but participants are given feedback that they responded too slowly on 60% of accurate trials, regardless of their performance.
Time frame: up to 6 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hormone Sensitive Women (HS+) | Mean BOLD Activation of the Left Putamen During the Affective Posner Task Over Time | Baseline (Visit 3) | -0.001223462 Arbitrary Units | Standard Deviation 0.11938667 |
| Hormone Sensitive Women (HS+) | Mean BOLD Activation of the Left Putamen During the Affective Posner Task Over Time | Hormone Addback (Visit 6) | 0.048155385 Arbitrary Units | Standard Deviation 0.13830948 |
| Hormone Insensitive Women (HS-) | Mean BOLD Activation of the Left Putamen During the Affective Posner Task Over Time | Baseline (Visit 3) | 0.0383029 Arbitrary Units | Standard Deviation 0.2004158 |
| Hormone Insensitive Women (HS-) | Mean BOLD Activation of the Left Putamen During the Affective Posner Task Over Time | Hormone Addback (Visit 6) | -0.021029 Arbitrary Units | Standard Deviation 0.17785651 |
p-value: 0.237ANOVA
Primary
Mean BOLD Activation of the Right Amygdala During the Affective Posner Task Over Time
This outcome measure determines the extent to which HS+ is characterized by BOLD activation of the right amygdala in response to frustrative non-reward (FNR) in the Affective Posner Task during hormone addback relative to baseline in the target population. The Affective Posner Task tests whether HS+ is characterized by reduced subcortical activation in response to frustration. This task is divided into 3 runs: during Run 1 (practice run), participants receive accurate feedback about their performance on the task and do not win or lose money; during Run 2, participants receive accurate feedback about their performance and win or lose 50 cents per trial; and during Run 3 (frustration), participants are told they must respond accurately to win money, but participants are given feedback that they responded too slowly on 60% of accurate trials, regardless of their performance.
Time frame: up to 6 weeks
Population: Participants exceeding the motion threshold were excluded as were those with signal loss.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hormone Sensitive Women (HS+) | Mean BOLD Activation of the Right Amygdala During the Affective Posner Task Over Time | Baseline (Visit 3) | -0.04544 Arbitrary Units | Standard Deviation 0.100148 |
| Hormone Sensitive Women (HS+) | Mean BOLD Activation of the Right Amygdala During the Affective Posner Task Over Time | Hormone Addback (Visit 6) | 0.022654 Arbitrary Units | Standard Deviation 0.071363 |
| Hormone Insensitive Women (HS-) | Mean BOLD Activation of the Right Amygdala During the Affective Posner Task Over Time | Baseline (Visit 3) | 0.037334 Arbitrary Units | Standard Deviation 0.137479 |
| Hormone Insensitive Women (HS-) | Mean BOLD Activation of the Right Amygdala During the Affective Posner Task Over Time | Hormone Addback (Visit 6) | -0.15643 Arbitrary Units | Standard Deviation 0.089792 |
p-value: 0.000723ANOVA
Primary
Mean BOLD Activation of the Right Caudate During the Affective Posner Task Over Time
This outcome measure determines the extent to which HS+ is characterized by BOLD activation of the right caudate in response to frustrative non-reward (FNR) in the Affective Posner Task during hormone addback relative to baseline in the target population. The Affective Posner Task tests whether HS+ is characterized by reduced subcortical activation in response to frustration. This task is divided into 3 runs: during Run 1 (practice run), participants receive accurate feedback about their performance on the task and do not win or lose money; during Run 2, participants receive accurate feedback about their performance and win or lose 50 cents per trial; and during Run 3 (frustration), participants are told they must respond accurately to win money, but participants are given feedback that they responded too slowly on 60% of accurate trials, regardless of their performance.
Time frame: up to 6 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hormone Sensitive Women (HS+) | Mean BOLD Activation of the Right Caudate During the Affective Posner Task Over Time | Baseline (Visit 3) | -0.069919077 Arbitrary Units | Standard Deviation 0.11155759 |
| Hormone Sensitive Women (HS+) | Mean BOLD Activation of the Right Caudate During the Affective Posner Task Over Time | Hormone Addback (Visit 6) | 0.045146154 Arbitrary Units | Standard Deviation 0.1320315 |
| Hormone Insensitive Women (HS-) | Mean BOLD Activation of the Right Caudate During the Affective Posner Task Over Time | Baseline (Visit 3) | 0.061407 Arbitrary Units | Standard Deviation 0.15720728 |
| Hormone Insensitive Women (HS-) | Mean BOLD Activation of the Right Caudate During the Affective Posner Task Over Time | Hormone Addback (Visit 6) | 0.0058011 Arbitrary Units | Standard Deviation 0.15927022 |
p-value: 0.0372ANOVA
Primary
Mean BOLD Activation of the Right Nucleus Accumbens During the Affective Posner Task Over Time
This outcome measure determines the extent to which HS+ is characterized by BOLD activation of the right nucleus accumbens in response to frustrative non-reward (FNR) in the Affective Posner Task during hormone addback relative to baseline in the target population. The Affective Posner Task tests whether HS+ is characterized by reduced subcortical activation in response to frustration. This task is divided into 3 runs: during Run 1 (practice run), participants receive accurate feedback about their performance on the task and do not win or lose money; during Run 2, participants receive accurate feedback about their performance and win or lose 50 cents per trial; and during Run 3 (frustration), participants are told they must respond accurately to win money, but participants are given feedback that they responded too slowly on 60% of accurate trials, regardless of their performance.
Time frame: up to 6 weeks
Population: Participants with signal loss were excluded.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hormone Sensitive Women (HS+) | Mean BOLD Activation of the Right Nucleus Accumbens During the Affective Posner Task Over Time | Baseline (Visit 3) | 0.044384167 Arbitrary Units | Standard Deviation 0.17318851 |
| Hormone Sensitive Women (HS+) | Mean BOLD Activation of the Right Nucleus Accumbens During the Affective Posner Task Over Time | Hormone Addback (Visit 6) | -0.005181667 Arbitrary Units | Standard Deviation 0.16825616 |
| Hormone Insensitive Women (HS-) | Mean BOLD Activation of the Right Nucleus Accumbens During the Affective Posner Task Over Time | Baseline (Visit 3) | 0.052685333 Arbitrary Units | Standard Deviation 0.13130308 |
| Hormone Insensitive Women (HS-) | Mean BOLD Activation of the Right Nucleus Accumbens During the Affective Posner Task Over Time | Hormone Addback (Visit 6) | -0.006394444 Arbitrary Units | Standard Deviation 0.21780392 |
p-value: 0.91ANOVA
Primary
Mean BOLD Activation of the Right Putamen During the Affective Posner Task Over Time
This outcome measure determines the extent to which HS+ is characterized by BOLD activation of the right putamen in response to frustrative non-reward (FNR) in the Affective Posner Task during hormone addback relative to baseline in the target population. The Affective Posner Task tests whether HS+ is characterized by reduced subcortical activation in response to frustration. This task is divided into 3 runs: during Run 1 (practice run), participants receive accurate feedback about their performance on the task and do not win or lose money; during Run 2, participants receive accurate feedback about their performance and win or lose 50 cents per trial; and during Run 3 (frustration), participants are told they must respond accurately to win money, but participants are given feedback that they responded too slowly on 60% of accurate trials, regardless of their performance.
Time frame: up to 6 weeks
Population: Participants with signal loss were excluded.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hormone Sensitive Women (HS+) | Mean BOLD Activation of the Right Putamen During the Affective Posner Task Over Time | Baseline (Visit 3) | -0.007560692 Arbitrary Units | Standard Deviation 0.09339182 |
| Hormone Sensitive Women (HS+) | Mean BOLD Activation of the Right Putamen During the Affective Posner Task Over Time | Hormone Addback (Visit 6) | 0.036225385 Arbitrary Units | Standard Deviation 0.1357793 |
| Hormone Insensitive Women (HS-) | Mean BOLD Activation of the Right Putamen During the Affective Posner Task Over Time | Baseline (Visit 3) | 0.002542222 Arbitrary Units | Standard Deviation 0.17117375 |
| Hormone Insensitive Women (HS-) | Mean BOLD Activation of the Right Putamen During the Affective Posner Task Over Time | Hormone Addback (Visit 6) | -0.080736333 Arbitrary Units | Standard Deviation 0.08070693 |
p-value: 0.139ANOVA
Primary
Mean Left Amygdala-medial Prefrontal Cortex BOLD Connectivity During Implicit Emotion Face Processing Task Over Time
This outcome measure determines the extent to which irritability is characterized by dysfunctional threat processing during reproductive hormone challenge relative to baseline in HS+ and HS-. By examining amygdala-medial prefrontal cortex (PFC) connectivity in response to threatening faces on the implicit emotion face processing fMRI task in HS+ (compared with HS-) during hormone challenge relative to baseline. The implicit emotion face processing task asks participants to identify the gender of angry, happy, and fearful faces at 50%, 100% and 150% emotion intensity presented in random order for 2000 milliseconds followed by jittered fixation. Trials appear in 3 blocks, generating 30 trials of each emotion at each intensity and 90 neutral face emotion trials.
Time frame: up to 6 weeks
Population: Participants exceeding the motion threshold and those completing the task incorrectly were excluded.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hormone Sensitive Women (HS+) | Mean Left Amygdala-medial Prefrontal Cortex BOLD Connectivity During Implicit Emotion Face Processing Task Over Time | Baseline (Visit 3) | 0.0247 arbitrary units | Standard Deviation 0.0653 |
| Hormone Sensitive Women (HS+) | Mean Left Amygdala-medial Prefrontal Cortex BOLD Connectivity During Implicit Emotion Face Processing Task Over Time | Hormone Addback (Visit 6) | -0.0192 arbitrary units | Standard Deviation 0.0893 |
| Hormone Insensitive Women (HS-) | Mean Left Amygdala-medial Prefrontal Cortex BOLD Connectivity During Implicit Emotion Face Processing Task Over Time | Baseline (Visit 3) | 0.0213 arbitrary units | Standard Deviation 0.0374 |
| Hormone Insensitive Women (HS-) | Mean Left Amygdala-medial Prefrontal Cortex BOLD Connectivity During Implicit Emotion Face Processing Task Over Time | Hormone Addback (Visit 6) | 0.00111 arbitrary units | Standard Deviation 0.0884 |
p-value: 0.368ANOVA
Primary
Mean Reactive Aggression During Hormone Addback Over Time
This outcome measure determines the extent to which HS+ is characterized by reactive aggression during hormone addback relative to baseline in the target population. Reactive aggression will be defined as the number of point subtractions the participant makes during the Point Subtraction Aggression Paradigm. Point Subtraction Aggression Paradigm measures relational aggression (approach behavior) in response to frustration. In the task, participants are asked to press a button to accrue money or press another button to subtract money from a (fictional) partner at no direct gain to themselves. Frustration is induced by periodic subtractions of their own money, which is attributed to the partner.
Time frame: up to 6 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hormone Sensitive Women (HS+) | Mean Reactive Aggression During Hormone Addback Over Time | Baseline (Visit 3) | 103.08 Number of subtraction responses | Standard Deviation 121.68 |
| Hormone Sensitive Women (HS+) | Mean Reactive Aggression During Hormone Addback Over Time | Hormone Addback (Visit 6) | 34.62 Number of subtraction responses | Standard Deviation 44.84 |
| Hormone Insensitive Women (HS-) | Mean Reactive Aggression During Hormone Addback Over Time | Baseline (Visit 3) | 129.20 Number of subtraction responses | Standard Deviation 105.76 |
| Hormone Insensitive Women (HS-) | Mean Reactive Aggression During Hormone Addback Over Time | Hormone Addback (Visit 6) | 54.90 Number of subtraction responses | Standard Deviation 71.85 |
p-value: 0.881ANOVA
Primary
Mean Right Amygdala-medial Prefrontal Cortex BOLD Connectivity During Implicit Emotion Face Processing Task Over Time
This outcome measure determines the extent to which irritability is characterized by dysfunctional threat processing during reproductive hormone challenge relative to baseline in HS+ and HS-. By examining amygdala-medial prefrontal cortex (PFC) Blood-oxygen-level-dependent (BOLD) connectivity in response to threatening faces on the implicit emotion face processing fMRI task in HS+ (compared with HS-) during hormone challenge relative to baseline. The implicit emotion face processing task asks participants to identify the gender of angry, happy, and fearful faces at 50%, 100% and 150% emotion intensity presented in random order for 2000 milliseconds followed by jittered fixation. Trials appear in 3 blocks, generating 30 trials of each emotion at each intensity and 90 neutral face emotion trials.
Time frame: up to 6 weeks
Population: Participants exceeding the motion threshold and those completing the task incorrectly were excluded.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hormone Sensitive Women (HS+) | Mean Right Amygdala-medial Prefrontal Cortex BOLD Connectivity During Implicit Emotion Face Processing Task Over Time | Baseline (Visit 3) | 0.0174 arbitrary units | Standard Deviation 0.0606 |
| Hormone Sensitive Women (HS+) | Mean Right Amygdala-medial Prefrontal Cortex BOLD Connectivity During Implicit Emotion Face Processing Task Over Time | Hormone Addback (Visit 6) | -0.0114 arbitrary units | Standard Deviation 0.0751 |
| Hormone Insensitive Women (HS-) | Mean Right Amygdala-medial Prefrontal Cortex BOLD Connectivity During Implicit Emotion Face Processing Task Over Time | Baseline (Visit 3) | 0.0533 arbitrary units | Standard Deviation 0.0338 |
| Hormone Insensitive Women (HS-) | Mean Right Amygdala-medial Prefrontal Cortex BOLD Connectivity During Implicit Emotion Face Processing Task Over Time | Hormone Addback (Visit 6) | 0.00804 arbitrary units | Standard Deviation 0.0943 |
p-value: 0.1922ANOVA
Primary
Mean Threat Processing Bias During Visual Dot-probe Paradigm Over Time
This outcome measure determines the extent to which irritability is characterized by dysfunctional threat processing during reproductive hormone challenge relative to baseline in HS+ and HS- by examining threat attention bias assessed during the visual dot-probe paradigm. The Visual Dot-Probe Paradigm asks participants to detect a target stimulus that is embedded in a matrix of distracting stimuli (e.g., a target stimulus, an angry face, might be embedded in a matrix of neutral distractor faces). Attention biases are inferred from faster response times to detect a threatening stimulus in a matrix of neutral stimuli relative to response time to detect neutral stimuli in neutral matrices. Thus, positive times reflect attention bias toward threat, whereas negative times reflect attention bias away from threat.
Time frame: up to 6 weeks
Population: All available data are reported. Data are missing for participants who had insufficient time to complete the task or due to computer malfunction.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hormone Sensitive Women (HS+) | Mean Threat Processing Bias During Visual Dot-probe Paradigm Over Time | Baseline (Visit 3) | -0.57 attention bias in milliseconds | Standard Deviation 18.92 |
| Hormone Sensitive Women (HS+) | Mean Threat Processing Bias During Visual Dot-probe Paradigm Over Time | Hormone Addback (Visit 6) | -9.04 attention bias in milliseconds | Standard Deviation 31.57 |
| Hormone Insensitive Women (HS-) | Mean Threat Processing Bias During Visual Dot-probe Paradigm Over Time | Baseline (Visit 3) | 36.92 attention bias in milliseconds | Standard Deviation 110.98 |
| Hormone Insensitive Women (HS-) | Mean Threat Processing Bias During Visual Dot-probe Paradigm Over Time | Hormone Addback (Visit 6) | -42.35 attention bias in milliseconds | Standard Deviation 102.99 |
p-value: 0.16repeated measures ANOVA
Secondary
Correlation Between Irritability and Reactive Aggression During Hormone Addback
This outcome measure determines the degree of irritability and reactive aggression in HS+ during hormone addback and its relationship to the target population. Irritability will be defined as score on the IDAS Ill Temper Scale. Reactive aggression will be defined as the number of point subtractions the participant makes during the Point Subtraction Aggression Paradigm. The Point Subtraction Aggression Paradigm measures relational aggression (approach behavior) in response to frustration. In the task, participants are asked to press a button to ac
Time frame: Endpoint (week 6)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Hormone Sensitive Women (HS+) | Correlation Between Irritability and Reactive Aggression During Hormone Addback | 0.18 correlation coefficient |
| Hormone Insensitive Women (HS-) | Correlation Between Irritability and Reactive Aggression During Hormone Addback | 0.03 correlation coefficient |
p-value: 0.568Pearson's Correlation Coefficient
p-value: 0.944Pearson's Correlation Coefficient
Secondary
Correlation Between Irritability Subcortical Activation in HS+ During Hormone Addback
This outcome measure determines the degree of subcortical (amygdala, caudate, putamen, and nucleus accumbens) activation in HS+ during hormone addback and it's relationship to the target population. The activation in amygdala and ventral striatum (caudate, putamen, nucleus accumbens) regions of interest (ROIs) will be assessed during the Affective Posner Task. The Affective Posner Task tests whether HS+ is characterized by reduced subcortical activation in response to frustration. This task is divided into 3 runs: during Run 1 (practice run), participants receive accurate feedback about their performance on the task and do not win or lose money; during Run 2, participants receive accurate feedback about their performance and win or lose 50 cents per trial; and during Run 3 (frustration), participants are told they must respond accurately to win money, but participants are given feedback that they responded too slowly on 60% of accurate trials, regardless of their performance.
Time frame: Endpoint (week 6)
Population: The a priori hypothesis focused on the HS+ group only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Hormone Sensitive Women (HS+) | Correlation Between Irritability Subcortical Activation in HS+ During Hormone Addback | 0.47 correlation coefficient |
p-value: 0.103Pearson's Correlation Coefficient
Secondary
Correlation Between the Inventory of Depressive and Anxiety Symptoms (IDAS) Ill -0.8Scale and Threat Attention Bias
This outcome measure determines the extent to which irritability is characterized by dysfunctional reward processing during reproductive hormone challenge in HS+ and HS- by examining the correlation between the Inventory of Depressive and Anxiety Symptoms (IDAS) Ill Temper (i.e., irritability) Scale and threat attention bias.
Time frame: Endpoint (week 6)
Population: All available data are reported. Data are missing for participants who had insufficient time to complete the task or due to computer malfunction.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Hormone Sensitive Women (HS+) | Correlation Between the Inventory of Depressive and Anxiety Symptoms (IDAS) Ill -0.8Scale and Threat Attention Bias | -0.35 correlation coefficient |
| Hormone Insensitive Women (HS-) | Correlation Between the Inventory of Depressive and Anxiety Symptoms (IDAS) Ill -0.8Scale and Threat Attention Bias | 0.11 correlation coefficient |
p-value: 0.322Pearson's Correlation Coefficient
p-value: 0.772Pearson's Correlation Coefficient
Secondary
Correlation Between the Inventory of Depressive and Anxiety Symptoms (IDAS) Ill Temper Scale and Left Amygdala-medial Prefrontal Cortex (PFC) BOLD Connectivity.
This outcome measure determines the extent to which irritability is characterized by dysfunctional reward processing during reproductive hormone challenge in HS+ and HS- by examining the correlation between the IDAS Ill Temper (i.e., irritability) Scale and amygdala-medial PFC connectivity in HS+.
Time frame: Endpoint (week 6)
Population: Participants exceeding the motion threshold and those completing the task incorrectly were excluded.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Hormone Sensitive Women (HS+) | Correlation Between the Inventory of Depressive and Anxiety Symptoms (IDAS) Ill Temper Scale and Left Amygdala-medial Prefrontal Cortex (PFC) BOLD Connectivity. | -0.13 correlation coefficient |
| Hormone Insensitive Women (HS-) | Correlation Between the Inventory of Depressive and Anxiety Symptoms (IDAS) Ill Temper Scale and Left Amygdala-medial Prefrontal Cortex (PFC) BOLD Connectivity. | 0.49 correlation coefficient |
p-value: 0.70859639Pearson correlation
p-value: 0.2617744Pearson correlation
Secondary
Correlation Between the Inventory of Depressive and Anxiety Symptoms (IDAS) Ill Temper Scale and Right Amygdala-medial Prefrontal Cortex (PFC) BOLD Connectivity.
This outcome measure determines the extent to which irritability is characterized by dysfunctional reward processing during reproductive hormone challenge in HS+ and HS- by examining the correlation between the IDAS Ill Temper (i.e., irritability) Scale and amygdala-medial PFC connectivity in HS+.
Time frame: Endpoint (week 6)
Population: Participants exceeding the motion threshold and those completing the task incorrectly were excluded.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Hormone Sensitive Women (HS+) | Correlation Between the Inventory of Depressive and Anxiety Symptoms (IDAS) Ill Temper Scale and Right Amygdala-medial Prefrontal Cortex (PFC) BOLD Connectivity. | -0.57 correlation coefficient |
| Hormone Insensitive Women (HS-) | Correlation Between the Inventory of Depressive and Anxiety Symptoms (IDAS) Ill Temper Scale and Right Amygdala-medial Prefrontal Cortex (PFC) BOLD Connectivity. | -0.08 correlation coefficient |
p-value: 0.068Pearson correlation
p-value: 0.8759289Pearson correlation