Design and Implementation of an fMRI Study Examining Thought Suppression in Young Women with, and At-risk, for Depression

The overall goal of this procedure is to identify alterations in brain activation associated with depression and risk for depression in teenage and young adult women. This is accomplished by first programming, a mixed block and event related thought suppression paradigm for use in the FMRI. The second step is to interview participants upon arrival and identify a subject specific set of ruminative statements.

Next, the ruminative statements should be entered into the ePrime FMRI paradigm prior to scanning. The final step is to scan the participant while they use an MRI compatible response box to signal the moments when suppressed thoughts reemerge and enter conscious awareness. Ultimately, the thought suppression paradigm can be used to show changes in brain activation associated with a suppression of personally significant or troubling ruminative thoughts in young women at risk for major depression.

This technique can provide us with a better understanding of the underlying neural mechanisms in major depressive disorder, and it may offer us a potential biomarker for future research. For this protocol start by building a modifiable thought suppression paradigm that will be viewed by participants inside the MRI scanner. ePrime can be used to program the text and image slides and assure that button press responses are collected with millisecond timing.

The paradigm should consist of four blocks each marked by a newly presented screen. The first block is a target statement period, and should present either a subject specific statement or distractor text for 12.5 seconds alongside a keyword. The three blocks following the text should then display a three color traffic signal on the left hand side of the screen.

The first of these blocks with the red traffic signal is a 32nd thought suppression period. Then the signal should turn green for 30 seconds to indicate a free thought period. The last screen in the block should then present a flashing yellow light to signify a motor response period.

Configure the light to flash four times at pseudorandom intervals between 1, 520 500 milliseconds apart. Then repeat this series of blocks 12 times so that blocks are presented four times in each of three imaging runs. Be sure to construct this paradigm in a way that makes it easily modifiable so that the target statements for each participant can be inserted into the paradigm during the experimental visit.

The target statements and keywords will consist of both personally relevant negative ruminative thoughts provided by the participant, as well as neutral distractor statements and keywords as seen on screen here upon the subject's arrival. First, obtain written and informed consent and screen for MRI safety. Then assess depression severity and psychiatric status with the Beck Depression Inventory, the Hamilton Depression Rating Scale, and the mini International Neuropsychiatric inventory.

Also collect information regarding medication status and education background. Next, ask the participant to list troubling thoughts or concerns that they have been repeatedly revisiting over the past few weeks and have been unable to shake. Discuss this with the participant and record their oral statement.

Then work with the participant to paraphrase this statement, shortening it to seven to 10 words. Also, identify a keyword that is emotionally significant and explicitly conveys the meaning of this target statement to the participant. Insert these personally related statements as well as neutral distractor statements and keywords into the previously prepared paradigm within each run.

The first block should consist of two personal thought suppression blocks and two distractor thought suppression blocks. Counterbalance the order of personal and distractor thought periods within each of the three FMRI scans within and across participants prior to scanning. Provide the participant with task instructions.

Inform them that they should observe the traffic signal on the screen throughout the paradigm and suppress thoughts during the target statement. When they see the red light, then think freely when they see the green light. The response box button should be pressed every time the target thought reemerges during both the thought suppression and free thought periods.

Also, ask the participant to press the response box button each time they see the flashing yellow light. Conduct all imaging on a three T whole body short bore scanner equipped with an eight channel parallel receiver head coil. Begin by acquiring a T one weighted three dimensional SPGR axial anatomical scan with 132 to 161 millimeter thick slices.

Next set up for functional MRI with slices, beginning at the cerebral vertex and encompassing the entire cerebral. Acquire three functional runs using a gradient echo EPI sequence while the participant performs the paradigm. Once scanning is complete, transfer the acquired images to an analysis workstation.

Begin analysis by transforming the anatomical MRI data into TX space. Then perform co-registration to functional data sets and average all anatomic scans across all subjects to yield a composite image. Then temporally correct the functional data sets.

Apply 3D motion correction and realign to the fifth frame of each run. Also smooth using a six millimeter Gaussian kernel and normalize the functional data to TX space. Next, use an event related analysis method by building an analysis protocol that extracts intervals associated with thought suppression, thought reemergence, and successful repression during either the thought suppression or free thinking blocks.

Define a reemergence event as an interval that begins 500 milliseconds. Before a button press up to 2000 milliseconds after the button press, then the periods within the thought suppression block without any reemergence should define successful thought suppression. Also, define motor control as event times when the yellow light flashed during the motor response period.

Next, use the general linear model to identify clusters of activity associated with contrast between and within groups. Also conduct a random effects analysis with a priori hypothesis. Finally, conduct between group contrasts for thought suppression using the contrast and groups seen on screen here.

Be sure to correct contrast for multiple comparisons using a false discovery rate. Here we can see activation maps representing thought suppression compared to motor control in a control subjects versus individuals with major depressive disorder. B, at risk individuals versus major depressive disorder individuals and C control subjects versus at risk individuals.

These maps show areas involved in reemergence of target thoughts compared to successful thought suppression in a control versus major depressive disorder individuals, B control subjects versus at risk individuals and C at risk versus major depressive disorder individuals. Finally, this figure shows bold signal change in the anterior cingulate cortex for reemergence and repression of thought conditions. Greatest bold differences between the two conditions were elicited by the controls then at risk, and finally by major depressive disorder participants Following this procedure.

Other methods like functional connectivity analyses can allow us to look at differences in the brain connectivity between major depressive disorder and individuals at risk.