Name: design and implementation of an fmri study examining thought suppression in young women with, and at-risk, for depression
Uploaded: 2015-05-19T13:00:00
Description: Watch this Scientific Journal Video about Design and Implementation of an fMRI Study Examining Thought Suppression in Young Women with, and At-risk, for Depression at JoVE.com

We would like to thank Richie Davidson, Waisman Center, University of Wisconsin-Madison, for his guidance and support.

All participants were briefed about the procedures and signed a consent form prior to study initiation. The McMaster University Health Sciences and St. Joseph&#8217;s Healthcare Research Ethics Boards approved all procedures. 
Note: In this protocol, 47 right-handed females between the ages of 16 and 24 years are used. Of which, 15 participants suffer from MDD (physician-confirmed diagnosis) and are experiencing a depressive episode at the time of the study. This group of individuals is denoted as the &#8220;MDD gro...

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Elements of the neural circuitry disrupted in depression15,16,25 are also associated with the regulation of conscious thought17,18. By examining suppression-related neural processing in at-risk and depressed participants we were able to examine whether there are alterations in brain activation patterns that are common in both individuals with a genetic predisposition to depression and a current depressive episode.
In keeping with our hypotheses and the existing literature...

A common trait in individuals with major depressive disorder (MDD) is the tendency to engage in ruminative thought1. This coping mechanism is considered maladaptive as it involves passive fixation on negative thoughts and events with no attempt at resolution2-5. Rumination is associated with increased risk of developing depression1,6-9 and increased length and severity of depressive episodes10.
Individuals who regularly ruminate will often try to reduce the frequency of these negative thoughts by actively suppressing them11. However, engaging in thought suppression can make such thoughts more accessible and likely to quickly re-emerge in the individual&#8217;s thoughts12. This may be seen more often in depressed individuals as their ability to actively suppress thoughts may be compromised. Additionally, thought suppression has been shown to increase the likelihood of other negative thoughts in dysphoric individuals13. Therefore, for depressed individuals the suppression of ruminative thoughts may lead to an exacerbation of symptoms; a product of increased cycling of ruminative intrusions and heightened negative thinking.
Neuropathological models of depression posit a dysregulation of the limbic, striatal, thalamic, and cortical brain circuits14. Resting disruptions of regional metabolism and blood flow are consistently reported in MDD, with heightened basal levels observed in the amygdala, orbital frontal cortex, ventral medial prefrontal cortex and medial thalamus. In addition, reduced levels are found in the dorsolateral prefrontal cortex, and subgenual and dorsal anterior cingulate cortex compared to healthy controls15,16. These observations have led to the notion that MDD involves a reduction in the activity of dorsal regions and heightened emotional limbic activity in more ventral brain regions.
Cognitive theories regarding the regulation of thought have identified a role for two separate mechanisms in thought suppression. It is suggested that the first mechanism of control is constantly engaged in order to maintain a baseline level of thought suppression and the second mechanism is transiently activated to re-suppress any unwanted thoughts that manage to intrude above this baseline17. Functional MRI data implicate a number of brain regions in these processes including the dorsolateral and ventrolateral prefrontal cortices18,19, the insula19,20, anterior cingulate cortex20, and dorsomedial prefrontal cortex19,21 during maintenance of thought suppression. Additionally, the re-emergence of a suppressed thought has been specifically associated with engagement of the anterior cingulate cortex18. Thus, there appears to be considerable overlap between the brain regions shown to be dysregulated in depression including the dorsolateral prefrontal cortex, insula, anterior cingulate cortex, dorsomedial prefrontal cortex22 and those involved in thought suppression. This suggests that a neurophysiological, and not just a behavioral link, between thought suppression and depression exists.
Young women who engage in ruminative thought are at greater risk for developing depression23. Risk for depression is also conferred genetically; individuals with a parent or sibling with depression are much more likely to develop depression than individuals with no family history of the disorder24. This study was carried out to explore the neural systems involved in thought suppression in a group of young women with a familial risk for depression, a group of young women currently experiencing depression, and a group of healthy controls. We developed a novel ruminative thought suppression paradigm to examine the changes in neural activity associated with sustained and transient thought suppression of both neutral and personally relevant thoughts. This design allowed us to investigate whether there were differences in neural activity for the suppression of personally relevant thoughts relative to neutral thoughts. Moreover, testing the at-risk group provided an opportunity to explore potential vulnerability markers of depression by determining whether risk for depression is associated with the magnitude of the blood oxygen level dependant (BOLD) signal in regions implicated in depression.
Based on the literature surrounding neural activity in depression15,16, and the studies on rumination and thought suppression25,26 it was predicted that the suppression of thoughts would be associated with reduced engagement of the dorsolateral prefrontal cortex in participants with MDD compared to controls. It was expected that the greater vulnerability to depression in the at-risk group would be reflected in levels of dorsolateral cortical activity that fall between that of the control and depressed groups. Furthermore, it was expected that the re-emergence of suppressed thoughts would be associated with activation of the anterior cingulate cortex, and that this activation would be greater in controls than in the at-risk group. Additionally, it was expected to observe significantly less anterior cingulate cortex activation in depressed participants as compared to both the control and at-risk participants during re-emergence of suppressed thoughts.

<table border="0" cellpadding="0" cellspacing="0" >
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			<td >Brain Voyageur, QX, V2.1</td>
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			<td>Maastricht, The Netherlands</td>
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			<td >Psychology Software Tools</td>
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design and implementation of an fmri study examining thought suppression in young women with, and at-risk, for depression

Ruminative brooding is associated with increased vulnerability to major depression. Individuals who regularly ruminate will often try to reduce the frequency of their negative thoughts by actively suppressing them. We aim to identify the neural correlates underlying thought suppression in at-risk and depressed individuals. Three groups of women were studied; a major depressive disorder group, an at-risk group (having a first degree relative with depression) and controls. Participants performed a mixed block-event fMRI paradigm involving thought suppression, free thought and motor control periods. Participants identified the re-emergence of &#8220;to-be-suppressed&#8221; thoughts (&#8220;popping&#8221; back into conscious awareness) with a button press. During thought suppression the control group showed the greatest activation of the dorsolateral prefrontal cortex, followed by the at-risk, then depressed group. During the re-emergence of intrusive thoughts compared to successful re-suppression of those thoughts, the control group showed the greatest activation of the anterior cingulate cortices, followed by the at-risk, then depressed group. At-risk participants displayed anomalies in the neural regulation of thought suppression resembling the dysregulation found in depressed individuals. The predictive value of these changes in the onset of depression remains to be determined.

Block Condition Analyses: Thought Suppression versus Motor Control
ANOVA analyses were used to determine the brain activation associated with block periods of thought suppression (with intrusions removed) relative to a motor control. Contrast results for control and at-risk versus MDD, control versus MDD, control versus at-risk, and at-risk versus MDD are detailed in Table 1. There were no between or within group differences in activity associated with suppression of personally r...

Watch this Scientific Journal Video about Design and Implementation of an fMRI Study Examining Thought Suppression in Young Women with, and At-risk, for Depression at JoVE.com

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

We aim to identify the neural correlates underlying sustained and transient thought suppression, and thought re-emergence in controls, at-risk and depressed individuals. Activation was greatest for controls compared to the at-risk and the depressed group in the dorsolateral prefrontal cortex during thought suppression and anterior cingulate cortex during thought re-emergence.

Ruminative brooding is associated with increased vulnerability to major depression. Individuals who regularly ruminate will often try to reduce the ...

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