Sara
Back to Psych 204B Projects 2012
Background
Major Depressive Disorder (MDD) is associated with self-focused rumination; people with tendencies to ruminate will focus repetitively on negative emotions and feelings of distress. These negative emotions often co-arise with memories of past experiences; however, many studies of the neural bases of emotional regulation have focused on responses to more immediate aversive stimuli, such as cutaneous shock. Emotion regulation strategies are often a component of cognitive therapies for depression, such as reappraisal in CBT - and yet, interestingly, neuroimaging studies of emotion regulation strategies have not found the measured changes in brain activity to align well with the brain regions considered relevant to depression.
We want to examine the neural bases of emotional regulation in response to negative emotions associated with autobiographical memories in both an MDD and control population, and to compare the use of different strategies in those with MDD relative to non-MDD participants.
Three strategies are are used here to either facilitate or undermine rumination as a response to negative emotional memories. The "feel" strategy asks individuals to focus on the feelings that arise as they recall their experiences; prior research indicates that focusing concretely on feelings tends to increase negative affect and rumination. While the "feel" strategy is intended to increase rumination, the analyze and accept strategies are intended to counteract rumination and promote adaptive self-reflection. The "analyze" strategy asks individuals to objectively analyze the reasons behind their feelings. The "accept" strategy prompts participants to recognize their feelings as transitory mental events that are distinct from the self and exist in a space of constant flux that can be mindfully observed without overwhelm.
Methods
Subjects
Five individuals diagnosed with MDD and five non-depressed control subjects were included in the study. All participants were females between the ages of 18 and 59. The Structured Clinical Interview for the DSM-IV was administered to all participants to assess current and lifetime diagnoses for anxiety, mood, psychotic symptoms, alcohol and substance use, somatoform, and eating disorders. Participants who met DSM-IV criteria for current MDD were included in the MDD group; exclusion criteria included substance abuse within the prior 6 months and co-occurring psychosis and/or mania. Participants with no current or past Axis I disorder, and who were not taking any psychotropic medications, were included in the control (CTL) group. Exclusion criteria for the CTL group included prior substance abuse problems and previous use of psychotropic medications.
Task Design
Participants were trained to associate memory cue words with recall of specific negative autobiographical memories, which they had described in an initial screening session. A computer protocol was used in pre-scan training to ensure participants could quickly recall the associated memory when a cue word appears, i.e. within 10 seconds. Nine memories were used per subject, and memories were matched for ratings of valence and arousal.
Three repetitions of each of the three stimulus blocks (feel, accept, analyze) were presented to subjects in counterbalanced order. Each trial started with a 10-second memory cue phase, prompting the participant to bring to mind the cued autobiographical memory. Next, an instruction cue appeared on the screen, directing the participant to engage in either the feel, analyze, or accept strategy for 30 seconds. Subsequently, participants were prompted to rate how aroused they felt (Rating 1) and how negative they felt (Rating 2) on a 5-point scale. They were given 5 seconds for each question. After this, participants were given a spatial perception task for 30 seconds, in which they saw an arrow pointing right or left and indicated which direction it was pointing. The arrows task was chosen as an active baseline task that would not engage the emotional, regulatory, or memory processes of interest; this task has been used in prior research, and prior work suggests it does not engage these processes.
MR Acquisition
Blood-oxygen level-dependent (BOLD) data were acquired with a 3 Tesla (T) strength General Electric Signa MR scanner (Milwaukee, Wisconsin), using a gradient echo EPI sequence (37 axial slices; field of view [FOV]=224mm, slice thickness=3.2mm, gap=0mm, repetition time [TR]=2000, echo time [TE]=30ms, flip angle [FA]=77°). A structural T1-weighted volume (186 sagittal slices, FOV=240mm, slice thickness=0.9mm, gap=0mm, TR=6200, TE=230, FA=12°) was performed following BOLD scanning runs. Head movement was minimized by using foam cushions.
MR Analysis
The MR data was analyzed using FSL software tools.
Pre-processing
The first 4 volumes (8s) in each functional scan were removed to allow for equilibrium effects. Functional and structural scans were processed with BET (Brain Extraction Tool) to remove the skull and nonbrain tissue. Motion correction was performed using MCFLIRT (part of FSL). Any subjects with motion exceeding 1.5mm were excluded from the analyses (N=1). Functional scans were slice-time corrected. High-pass temporal filtering was used to correct for baseline drifts, and data were spatially smoothed using a 5 mm full-width-half-maximum Gaussian kernel. Functional images were registered to the subjects' structural images using a 6 DOF transformation in FLIRT (FMRIB's Linear Image Registration Tool). Structural images were registered to MNI template space using a 12 DOF transformation in FLIRT, and this transformation was then applied to the functional images.
Statistical Analysis
Statistical analysis of fMRI timecourses was carried out using FEAT (fMRI Expert Analysis Tool) through modeling the following experimental task conditions at the first level: memory cue, instruction cue, rating 1, and rating 2. The arrows epoch was left as the implicit baseline. Analysis used the general linear model (GLM) and a design matrix was generated with a synthetic hemodynamic response function and its first derivative. Motion was included as a variable of no interest, to additionally control for motion. For the voxel-wise analysis of activation within groups, reported regions were thresholded at Z > 2 and a cluster probability of p < 0.05, corrected for whole-brain multiple comparisons using Gaussian random field theory (Worsley, Marrett, Neelin, & Evans, 1992).
To analyze the differences in activation between control and depressed participants, participant-specific maps were carried to higher-level inter-group analyses using FMRIB’s Local Analysis of Mixed Effects (FLAME; Woolrich, Behrens, & Smith, 2004). The resulting statistical images were thresholded at Z > 1.65, corresponding to a one tailed p of 0.05, and corrected for multiple comparisons using Gaussian random field theory.
Results
Accept Task
MDD > CTL for Accept Task: Regions of Increased Activation in the MDD Group
On the accept task (relative to baseline), significantly higher activation is observed in the MDD group relative to the control group in the inferior frontal gyrus, subgenual prefrontal cortex, thalamus, precuneus, and amygdala.
Results are reported thus far only for the mean activation on the accept task for each group and the differences in mean activation on this task between the MDD and CTL groups. More analyses need to be done on the contrasts between strategies in order to determine which areas appear to be selectively activated by the implemented strategy. Also, statistical analyses should be done relating the implemented strategies, levels of activation, and self-ratings of emotional valence and arousal after the instruction block.
Discussion
(TBC)
References
Software