Clinical trial NCT02737436
Conditions: Maternal Behavior
Sponsor: Baylor College of Medicine
Start date: 2010-05-01; Completion date: 2019-03-01
Enrollment: 132 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
The investigators plan to conduct functional MRI scanning with a group of mothers who are blindly and randomly assigned either intranasal oxytocin or a placebo. The purpose of this investigation is to explore how oxytocin may modify early maternal brain and behavioral responses to infant cues. This study will examine, for the first time, a potential pharmacological intervention for maternal neglect which targets core neurobiological deficits. This may eventually be used to supplement and augment other psychosocial and behavioral interventions.

In addition, the investigators will examine sex differences in parental brain and behavioral responses to oxytocin by also recruiting fathers to participate in a similar protocol.

Detailed description:
The investigators plan to conduct fMRI scanning with a group of mothers who are blindly and randomly assigned either intranasal oxytocin or a placebo.

Aim 1: To determine whether intranasal oxytocin (IN-OT) affects parental brain responses to infant cues, as measured during functional MRI (fMRI) scanning.

Hypothesis 1 (i): Compared to placebo, mothers who receive intranasal oxytocin will show greater activation of mesocorticolimbic dopamine reward regions in the brain, including the ventral striatum and the medial prefrontal cortex, when viewing their own vs. unknown infant faces during fMRI scanning. Hypothesis 1 (ii): Compared to placebo, fathers will show greater activation of social-cognitive circuits, including the dorsal prefrontal cortex (dPFC).

Aim 2: To determine whether IN-OT affects parental behavioral responses to infant cues, as measured by videotaped parent-infant interaction procedures.

Hypothesis 2 (i): Compared to placebo, parents who receive intranasal oxytocin will score higher on an overall measure of maternal sensitivity, during a free play parent-infant interaction procedure (CARE-Index). Hypothesis 2 (ii): Compared to placebo, mothers who receive intranasal oxytocin will demonstrate more frequent emotionally contingent responses with their infant during the recovery phase of a modified Still-Face procedure.

Aim 3: To determine whether attachment security interacts with the effect of IN-OT on maternal brain and behavioral responses to infant cues.

Hypothesis 3 (i): Compared to secure (Type B) mothers, mothers with insecure/dismissing (Type A) attachment will have a greater brain and behavioral response to IN-OT (as described in Hypotheses 1 and 2), with a 2-way interaction effect seen between treatment and attachment groups. Hypothesis 3 (ii): Compared to Type B mothers, mothers with insecure/preoccupied (Type C) attachment will have a reduced brain and behavioral response to IN-OT (as described in Hypotheses 1 and 2), with a 2-way interaction effect seen between treatment and attachment groups.

Aim 4: To determine whether brain reward activation is associated with other indirect measures of emotional neglect in mothers.

Hypothesis 4 (i): Maternal brain reward system activation, both with and without IN-OT, will be positively correlated with 1) maternal sensitivity (as measured by the CARE-Index), 2) the contingency of maternal responses to infant behavioral cues.

Initial enrollment: Recruitment will occur during the postpartum period. In addition to recruiting from the medical record, the investigators plan to execute other recruiting measures in the form of advertising. Parent(s) will be recruited via newspaper, internet, public postings, and mass mailings. Once eligibility is confirmed, subjects will be scheduled for a study visit where they will be informed of confidentiality and consented before participating in any study activities.

Visit 1: 4 Months Post-Partum - Adult Attachment Interview (AAI). During this visit, each enrolled woman will participate in a modified version of the Adult Attachment Interview (AAI), a semi-structured 1½-2 hour-long interview involving specified questions and follow-up inquiries relating to childhood relationships with attachment figures. The investigators will also collect sociodemographic, breastfeeding data, and screening information for depression. The Edinburgh Postnatal Depression Scale (EPDS) will be repeated during subsequent visits in order to calculate mean scores.

Visits 2A\&B and 3A\&B: Intranasal Oxytocin vs. Placebo Administration In this double-blind cross-over placebo-controlled trial of intranasal oxytocin, maternal brain and behavioral responses to infant cues will be assessed within \& between subjects. Each participant will be administered both the active (oxytocin) and inactive (placebo) nasal spray just prior to separate behavioral or fMRI scanning sessions, with order of administration balanced across subjects and between attachment groups. All involved will be blinded to the identity of the oxytocin or placebo sprays. Before each visit, parent(s) will be asked to abstain from tobacco, food and drink (except water) for at least 2 hours prior to the visit. The investigators will attempt to schedule visits during the latter half of the mother's menstrual cycle, to minimize potential confounding from fluctuations in estrogen levels. Mothers without regular menstrual cycles will be scheduled one month apart. Mothers who are still breastfeeding will be asked to feed their infant at least one hour prior to the visit. For the four visits involving intranasal drug administration (two behavioral testing visits and two fMRI scanning visits), the following protocol will apply: participants will be given a urinary pregnancy test prior to the start of each visit. If a mother tests positive, she will be excluded from the study due to theoretical concern about possible effects of oxytocin on uterine contraction. Due to the fact that the pregnancy test may still not detect an early pregnancy, the mothers will also be asked to abstain from unprotected sexual intercourse during the 2 weeks prior to the visit, and will confirm, in signing the consent form, that there is no substantial chance of a current pregnancy. Just prior to drug administration, the parent(s) will complete the Positive and Negative Affect Scale, to rate her current emotions, for comparison to post-spray. The parent(s) will then self-administer a dose of either oxytocin (3 puffs per nostril \[4 IU per puff\] = 24 IU total) or a placebo spray that contains only the inactive ingredients of the oxytocin solution. Both experimenters and subjects will be blind to the treatment they are receiving. A stopwatch will be started at the moment the subjects begins intranasal administration, so that the behavior assessment or fMRI scanning can begin exactly 50 minutes later. Most other studies of intranasal oxytocin have used a 50 minutes delay time, based on cerebrospinal fluid studies of other intranasally administered neuropeptides, such as the analogous hormone vasopressin. Forty minutes after drug administration, the PANAS will be repeated.

Visits 2A\&B: 5-6 Months Postpartum - Behavioral Response

1. On arrival, the parent(s) and infant will be escorted into a behavioral observation room at the Clinical Nutrition Research Center, where the infant will be introduced to some developmentally appropriate toys. Questionnaires completed at home will be reviewed (Infant Behavior Questionnaire \[IBQ\], Parenting Stress Index \[PSI\] and demographics and breastfeeding questionnaire), and if incomplete will be completed at this time.
2. Each parent will then self-administer the nasal spray, which has been previously randomized by the investigational pharmacy to be either oxytocin or placebo. During the following waiting period, the Bayley Scales of Infant Development screener will be completed with the infant, to exclude developmental delays in areas of fine motor, gross motor, language or social development. This will be performed by a research associate who has been trained in the use of this standardized tool.
3. Fifty minutes after the nasal spray is administered, each parent will rejoin their infant to each participate in a videotaped "free play" interaction on the floor for 3 minutes (described below). The recording will later be coded for dyadic interactions using a 14-point sensitivity scale in the CARE-Index.
4. A modified still-face procedure will then be conducted during the next 3 minutes(as described below).
5. The parent(s) will then be taken to another area of the building, while the infant is videotaped to obtain face images that will be used during the subsequent scanning visits. During the brief separation period, the infant will be secured in a mounted car seat, and videotaped while using age appropriate toys to elicit smiling (and neutral) facial expressions. This should last no more than 10 minutes. Crying faces will also be elicited, if necessary, by briefly leaving the infant alone in the room, secured in the car seat, while the video recorder is running. The infant will be observed at all times from behind a one-way mirror, and only left to cry for around 35-40 seconds. Infant cry will also be recorded at this time.
6. Infant face images with various degrees of affect-happy, neutral and sad-will then be extracted from the digital video recording, for use in the subsequent fMRI procedure (Visit 3). The images will be standardized for size, orientation and background using Adobe Photoshop. All of the face images will be rated on degree of affect using a 5-point adaptation of the Self-Assessment Manikin (SAM), categorizing each image into one of five affect groups: very happy, happy, neutral, sad or very sad. These faces will be matched on age, sex, ethnicity and degree of affect with a large database of "unknown" infant faces.
7. Approximately one month later, at a comparable time in the menstrual cycle, the basic procedure will be repeated for each subject, except that those who received intranasal oxytocin will be given placebo, and vice versa.

Visit 3A\&B: 8-9 Months Postpartum - Brain Response

1. Three months after the first behavioral response session, each parent will attend two scanning sessions at the Human Neuroimaging Laboratory, Baylor College of Medicine. Intranasal oxytocin or placebo will again be administered as described above. Infant face images from Visit 3A will be used in Visit 4A scanning session, and Visit 3B with 4B, to ensure that the repeat scanning session uses comparable but unique face images. The images from both sessions will be matched on degree of facial affect. Prior to intranasal drug administration on the first scanning visit, the parent(s) will complete the Positive and Negative Affect States (PANAS) questionnaire.
2. During the waiting period, the parent(s) will complete questionnaires.
3. Fifty minutes after the administration of the nasal spray, the parent(s) will participate in the functional MRI scanning session, passively viewing a series of unique infant face images and hearing cries of her own infant and of an unknown infant. Using an event-related fMRI design, randomly presented images will be viewed for 2 seconds, with a random inter-stimulus interval of 2, 4 or 6 seconds (Fig 3). The 60 images will be equally divided into 3 affect groups - happy, neutral or sad, with the intensity of happy and sad affect balanced between the "own" and "unknown" faces. The order of the images from each of the 6 groups (Own-Happy \[OH\], Own-Neutral \[ON\], Own-Sad \[OS\], Unknown-Happy \[UH\], Unknown-Neutral \[UN\], Unknown-Sad \[US\]) will be pseudo-randomized within the run, but not between subjects.
4. All imaging will be performed using a 3 Tesla Siemens MRI scanner. Visual images will be generated using a projector, and presented to the parent(s) via an overhead mirror display. Regional brain activation will be assessed by measuring changes in blood-oxygen-level-dependent functional MRI signal (BOLD-fMRI).
5. Subjects will participate in a single whole-brain functional run of around 185 scans each.
6. High-resolution T1-weighted structural images will then be acquired.
7. After the scanning session, each parent will be asked to rate each of the infant face images on how they thought the infant was feeling, as well as their own feelings of pleasure or arousal, using an adaptation of the Self-Assessment Manikin.

b. After the parent(s) has completed the questionnaires, 2 out of 4 randomly selected modules of the Bayley Scales of Infant Development screener will be completed with the infant.

c. The parent(s) will then rejoin their infant to participate in a videotaped "free play" interaction on the floor for 3 minutes. The recording will later be coded for dyadic interactions using a 14-point sensitivity scale in the CARE-Index.

Arms: arm 1: Intranasal oxytocin (24IU) given 50 minutes prior to behavior assessment or scanning arm 2: Intranasal placebo spray given 50 minutes prior to behavior assessment or scanning
Interventions: intervention 1: Intranasal Oxytocin intervention 2: Placebo intervention 3: Functional MRI scanning
Intervention descriptions: intervention 1: Intranasal oxytocin (24IU) given 50 minutes prior to behavior assessment or scanning intervention 2: Intranasal placebo spray given 50 minutes prior to behavior assessment or scanning intervention 3: All study participants underwent two functional MRI scanning visits. On one occasion this was after receiving an intranasal dose of oxytocin; on the other occasions, after receiving intranasal placebo dose.

Protocol documents:
Prot_SAP_000.pdf: 
 
 
 
 
 
 
 
 
 
 
 
 
Intranasal Oxytocin:  
A Neuropharmacological Intervention for Maternal Neglect?  
 
H-26732 
 
December 31, 2024 
 
 
 
 


 
 
Study Protocol 
 
The purpose of this study is to explore how oxytocin may modify early maternal brain and behavioral 
responses to infant cues. This study will examine a potential pharmacological intervention for maternal 
neglect which targets core neurobiological deficits. This may eventually be used to supplement and augment 
other psychosocial and behavioral interventions. 
 
Initial enrollment: Recruitment occurred during the postpartum period using EPIC medical records and  
advertising via newspaper, internet, public postings, etc. Once eligibility was confirmed, subjects were 
scheduled for a study visit where they provided informed consent before participating in any study activities. 
 
Visit 1: 4 Months Postpartum – Adult Attachment Interview (AAI). During this visit, each enrolled woman 
participated in a modified version of the Adult Attachment Interview (AAI), a semi-structured 1½-2 hour-long 
interview involving specified questions and follow-up inquiries relating to childhood relationships with 
attachment figures. The modified version was chosen because of its theoretical links with patterns of 
information processing in the brain. Each digitally recorded interview was transcribed (with personally 
identifying details altered to preserve anonymity), and coded blindly to classify each woman’s adult 
attachment pattern. We also collected sociodemographic and breastfeeding data, and screened for 
postpartum depression using the Edinburgh Postnatal Depression Scale (EPDS).  
 
Visits 2A&B and 3A&B: Intranasal Oxytocin vs. Placebo Administration. In this double-blinded cross-
over placebo-controlled trial of intranasal oxytocin, maternal brain and behavioral responses to infant cues 
were assessed within and between subjects. Each participant was administered both the active (oxytocin) and 
inactive (placebo) nasal spray just prior to separate behavioral or fMRI scanning sessions, with the order of 
administration balanced across subjects. All involved were blinded to the identity of the oxytocin or placebo 
sprays. Before each visit, the mother was asked to abstain from tobacco, food and drink (except water) for at 
least 2 hours prior to the visit. We attempted to schedule visits during the latter half of the mother’s menstrual 
cycle, to minimize potential confounding from fluctuations in estrogen levels. Mothers without regular 
menstrual cycles were attempted to be scheduled one month apart. Mothers who were still breastfeeding were 
asked to feed their infant at least one hour prior to the visit.  
 
For the four visits involving intranasal drug administration (two behavioral testing visits and two fMRI scanning 
visits), the following protocol applied: participants were given a urinary pregnancy test prior to the start of each 
visit. If a mother tested positive, she was excluded from the study due to theoretical concern about possible 
effects of oxytocin on uterine contraction. Just prior to drug administration, the mother completed the Positive 
and Negative Affect Scale (PANAS) to rate her current emotions, for comparison to post-spray. The mother 
then self-administered a dose of either oxytocin (3 puffs per nostril [4 IU per puff] = 24 IU total) or a placebo 
spray containing only the inactive ingredients of the oxytocin solution. Both experimenters and subjects were 
blind to the treatment they are receiving. A stopwatch was started at the moment the subjects began the 
intranasal administration, so that the behavior assessment or fMRI scanning could begin approximately 50 
minutes later. Forty minutes after drug administration, the PANAS was repeated.  
 
Visits 2A&B: 5-6 Months Postpartum – Behavioral Response. On arrival, the mother and infant were 
escorted into a behavioral observation room at the Clinical Nutrition Research Center, where the infant was 
introduced to some developmentally appropriate toys. Questionnaires completed at home were reviewed 
(Infant Behavior Questionnaire [IBQ], Parenting Stress Index [PSI] and demographics and breastfeeding 
questionnaire), and if incomplete, were completed at this time. Each mother then self-administered the nasal 
spray, which had been previously randomized by the investigational pharmacy to be either oxytocin or 
placebo. During the waiting period, the Bayley Scales of Infant Development screener was completed with the 
infant, to exclude developmental delays in areas of fine motor, gross motor, language or social development. 
This was performed by a research associate who has been trained in the use of this standardized tool. Fifty 
minutes after the nasal spray was administered, each mother rejoined her infant to participate in a videotaped 
"free play" interaction on the floor for 3 minutes. The recording was later coded for dyadic interactions using a 


 
 
14-point sensitivity scale in the CARE-Index. A modified still-face procedure was then conducted. The mother 
was then taken to another area of the building, while the infant was videotaped to obtain face images used 
during the subsequent scanning visits. During the brief separation period, the infant was secured in a mounted 
car seat, and videotaped while using age appropriate toys to elicit smiling (and neutral) facial expressions. 
This did not usually last no more than 10 minutes. The mother did not observe the videotaping to ensure that 
each infant face image was novel when presented during the subsequent visits. Crying faces were also 
elicited by briefly leaving the infant alone in the room, if necessary, secured in the car seat, while the video 
recorder was running. The infant was observed at all times from behind a one-way mirror, and only left to cry 
for around 35-40 seconds. Infant cry was also recorded at that time. Infant face images with various degrees 
of affect–happy, neutral and sad–were then extracted from the digital video recording, for use in the 
subsequent fMRI procedure (Visit 3). The images were standardized for size, orientation and background 
using Adobe Photoshop. All of the face images were rated on degree of affect using a 5-point adaptation of 
the Self-Assessment Manikin (SAM), categorizing each image into one of five affect groups: very happy, 
happy, neutral, sad or very sad. These faces were matched on age, sex, ethnicity and degree of affect with a 
large database of “unknown” infant faces, collected during a previous study. Approximately one month later 
the basic procedure was repeated for each subject, except that those who received intranasal oxytocin were 
given placebo, and vice versa.  
 
Visit 3A&B: 8-9 Months Postpartum – Brain Response. Around three months after the first behavioral 
response session, each mother attended two scanning sessions at the Human Neuroimaging Laboratory, 
Baylor College of Medicine. Intranasal oxytocin or placebo was again administered as described above. Infant 
face images from Visit 2A were used in the Visit 3A scanning session, and Visit 2B with 3B, to ensure that the 
repeat scanning session used comparable but unique face images. The images from both sessions were 
matched on degree of facial affect. 
 
Prior to intranasal drug administration on the first scanning visit, the mother completed the Positive and 
Negative Affect States (PANAS) questionnaire. During the waiting period, the mother completed 
questionnaires. Fifty minutes after the administration of the nasal spray, the mother participated in the 
functional MRI scanning session, passively viewing a series of unique infant face images and hearing cries of 
her own infant and of an unknown infant. Each parent was informed that their “brain activity will be monitored 
using functional MRI while you are shown pictures of your own baby”. Using an event-related fMRI design, 
randomly presented images were viewed for 2 seconds, with a random inter-stimulus interval of 2, 4 or 6 
seconds. The 60 images were equally divided into 3 affect groups – happy, neutral or sad, with the intensity 
of happy and sad affect balanced between the “own” and “unknown” faces. The order of the images from 
each of the 6 groups (own-happy [OH], own-sad [OS], unknown-happy [UH], unknown-sad [US]) were 
pseudo-randomized within the run, but not between subjects. All imaging was performed using a 3 Tesla 
Siemens MRI scanner. Visual images were generated using a computer controlled LCD projector, and 
presented to the mother via an overhead mirror display. Regional brain activation was assessed by 
measuring changes in blood-oxygen-level-dependent functional MRI signal (BOLD-fMRI). Subjects 
participated in a single whole-brain functional run of around 185 scans each. High-resolution T1-weighted 
structural images were acquired. After the scanning session, each mother was asked to rate each of the 
infant face images on how they thought the infant was feeling, as well as their own feelings of pleasure or 
arousal, using an adaptation of the Self-Assessment Manikin.  
 
 
 
 
 


 
 
Statistical Analysis Plan 
 
fMRI Data Processing and Analysis:  
Imaging data for each subject was preprocessed and analyzed using the following steps:  
 
Head motion correction was performed by spatial alignment of all brain volumes to the first volume by rigid 
body transformations. Slice scan time correction was performed using sinc interpolation, based on the 
repetition time (TR) and order of slice scanning (ascending interleaved). Following linear trend removal, low 
frequency nonlinear drifts of 3 or less cycles was removed using a temporal high pass filter. Spatial smoothing 
will not performed. The anatomical dataset underwent iso-voxel scaling to 1 x 1 x 1 mm resolution and was 
transformed into sagittal orientation. It was then transformed into AC/PC and MNI standard space. Functional 
runs for each subject were then coregistered with the anatomical 3-dimensional dataset, iso-voxel transformed, 
and then transformed into standard ACPC and MNI coordinate space, resulting in normalized 4-dimensional 
volume-time course data.  
 
For each functional run of the event-related data, a protocol file was created, representing the timing of each 
stimulus event. The four infant face stimulus types in the design matrix included Own-Happy (OH), Own-Sad 
(OS), Unknown-Happy (UH), and Unknown-Sad (US). Each predictor was convolved with a double-gamma 
hemodynamic response function (Friston, Fletcher, Josephs et al. 1998). Using the General Linear Model 
(GLM), group effects was evaluated using a random effects analysis, with a percent time course transformation 
applied to each subject separately. In the random effects analysis, statistical maps was created for each 
individual subject before being subjected to a second level of statistical analysis, allowing generalization to the 
sample population of first-time mothers. Main effects and possible interaction effects of infant “identity” and 
“affect” were explored using 2-factor repeated measure ANOVAs. Group t-maps (2-tailed) were also generated 
after specifying a particular contrast in stimulus types (e.g. OH>UH), and were visualized on an averaged 3D 
anatomical image, which was created from all of the individual subject images. Corrections were made for 
multiple comparisons.  
 
Next, activation patterns were compared between oxytocin treatment groups and attachment groups using a 
mixed-model repeated measures analysis of variance (ANOVA), with fixed effects analyses for 1) “infant face 
category” as a repeated measure within-subjects variable, 2) “oxytocin treatment group” as a within- and 
between-subjects variable, and 3) “attachment group” as a between-subjects variable. Subjects were treated 
as a random effect within each group and were used to test for face affect x treatment group x attachment 
group interaction effects on brain function. Mean beta weights was calculated and compared between the two 
treatment and attachment groups, in a priori regions of interest (VTA, ventral striatum, medial prefrontal 
cortex), using the t-test and the Mann-Whitney U-test for non-parametric data.  
 
Brain/Behavior Analyses:  
The relationship between brain response to the visual infant stimuli described above and interview derived 
measures was examined within the general linear model framework. Measures examined in this manner 
included ratings of the stimuli obtained immediately after scanning, adult attachment classifications, and ratings 
of the parent-infant interaction session (“maternal sensitivity” score). Initially, percent signal change data was 
extracted from regions of interest, including mesocorticolimbic pathway (VTA, ventral striatum, medial 
prefrontal cortex), nigrostriatal pathways (substantia nigra, dorsal striatum, dorsolateral PFC), as well as the 
amygdala, hippocampus, anterior insult and hypothalamus, and was entered into regression models to 
determine whether there was a linear relationship between brain activation in response to the stimuli and 
behavioral scores. We focused on these regions given data from animal and human studies reviewed that 
implicate them in attachment and/or fear neurocircuitry (Leibenluft, Goblin, Harrison et al. 2004a; Lorberbaum, 
Newman, Horwitz et al. 2002a; Nitschke, Nelson, Rusch et al. 2004; Seifritz, Esposito, Neuhoff et al. 2003; 
Strathearn et al., 2008; Swanson, 2000). Regression models also tested for group differences in the 
relationship between brain activation and behavior. Regions of interest were defined using high resolution 3D 


 
 
images normalized to standardized stereotactic space (Collins, Zijdenbos, Kollokian et al. 1998). Measures of 
the striatum included caudate and putamen, outlined on each slice in which these structures were visible. 
Regression analyses were further employed to identify areas that show a continuous linear dose-response 
function.  
 
Analyses by Hypotheses:  
Since the study is a crossover design, the model initially contains terms testing the order of treatment 
(oxytocin/placebo) and the interaction between order and treatment to ensure detection of any unexpected 
carry-over effect from treatment. Since a sufficient washout period was provided and different pictures were 
shown on the two occasions, we expected these terms to be non-significant, in which case they were removed 
from the model.  
 
Hypotheses 1-3 was tested using a generalized estimating equation model (SPSS version 17.0), which 
accounts for repeated measures in the crossover design as well as different types of dependent variables. The 
basic model contains terms for testing each of these hypotheses including treatment, attachment and 
treatment x attachment. Interpretation began with the treatment x attachment interaction. If this interaction was 
not significant, it was omitted from the model. Attachment was initially be treated as a 4-category variable 
(Types A, B, C and A/C), with the main comparisons being between Types A and B, and between Types C and 
B. However, we also combined categories to examine secure (Type B) vs. insecure (Types A, C, A/C) 
attachment. In addition, for the brain-related outcomes, we looked at infant affect as an additional within-
subject factor, and examined possible 3-way interactions – treatment x attachment x affect. If this interaction 
was significant the data was split on attachment group and reanalyzed to assess the treatment x affect 
interaction within attachment groups. If this interaction was not significant, it was removed. A positive finding 
for this interaction would indicate splitting on attachment group and reanalysis is in order to assess treatment 
effect within these groups. Main effects of treatment, attachment, and affect remained in the model. Hypothesis 
2(ii) involving counts showed a Poisson distribution outcome while the others showed a normal distribution.  
 
We will also included in the model stratification variables such as maternal age, ethnicity, breastfeeding status 
and income. Finally, we explored differences between attachment groups on measures of psychopathology, 
such as depression (from BDI), anxiety (from SSTAI) and parenting experience (from the PSI). If differences 
emerged between attachment groups in these measures, we considered including them as covariates in 
analyses.  
 
Hypothesis 4 assessed the correlation between maternal brain reward activation (ventral striatum and medial 
prefrontal cortex) and three indirect measures of maternal neglect using a linear model.