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 group&#8221;. The at-risk group in this protocol consists of 16 participants who have a first degree relative (parent or sibling) with a diagnosis of MDD, but diagnosed with a psychiatric disorder and are not currently depressed. The control group in this protocol consists of 16 participants who do not have first-degree relatives with depression, have no lifetime diagnosis of a psychiatric disorder and are not currently depressed.
1. Participants Selection
<ol>
	<li>Recruit healthy control and at-risk female participants through the internet and print advertisements in the local community, and through the Department of Psychology, Neuroscience and Behavior at the local university. Recruit depressed participants through the Mood Disorders Clinic at the local hospital. 
	NOTE: Qualifying patients are eligible to participate if they are female and have been diagnosed with a primary mood disorder according to DSM-IV criteria27, and have clinically significant standardized cut-off scores on the Beck Depression Inventory-Version II (BDI-II) and Hamilton Depression Rating Scale (HAM-D) questionnaires, as determined by completion of these measures upon arrival.</li>
	<li>Conduct initial phone or in-person interviews with interested participants to establish eligibility. Exclude participants that do not meet scanner safety requirements, or eligibility criteria for the MDD, at-risk or control groups, and all participants with a current or past history of psychosis, mania or generalized anxiety disorder (GAD). Additionally, exclude participants who have experienced a head injury leading to unconsciousness, or have had previous treatment with electroconvulsive therapy or transcranial magnetic stimulation.</li>
	<li>Invite the selected group of individuals for extensive testing, and a functional magnetic resonance imaging (fMRI) scan using the following parameters [3T, T1-weighted SPGR axial acquisition with: 132 - 160 slices (1 mm thick). fMRI scan, 8-channel head coil, 31 axial slices (4 mm thick, no gap), TR/TE = 2,500/35 msec, FOV = 24 cm, matrix = 64 x 64, flip angle 90&#176;]. 
	NOTE: Exclude participants with GAD as it is anticipated that they might experience higher levels of anxiety during the MRI scanning portion of the study, interfering with concentration and task compliance.</li>
	<li>Scan the participants during the first 12 days of their menstrual cycles (follicular phase) to reduce the potential influences of hormonal fluctuations.</li>
</ol>
2. Build Thought Suppression Task
<ol>
	<li>Build a modified version of the suppression paradigm described by Mitchell and colleagues18, that will be viewed by the participants in the scanner. The paradigm consists of 4 blocks, each marked by a newly presented screen.</li>
	<li>Use psychology paradigm building software to program the paradigm. Using the software, assemble text and image slides to be presented serially, with responses collected with millisecond timing. The first block presents a target statement on the screen for 12.5 sec. Format the paradigm so that a 3-color traffic signal is present on the left hand side of all subsequent screens.</li>
	<li>Configure the paradigm to present a red traffic light signal for 30 sec on the following screen. Program the paradigm to present a green traffic signal for 30 sec on the next screen presented.
	<ol>
		<li>Configure the final screen to present a flashing yellow light. Flash the light four times at pseudorandom intervals between 1,500 - 2,500 msec apart. Repeat this series of screens 12 times.</li>
		<li>Insert the target statements into the paradigm during the participants visit, and therefore construct the paradigm in a way that makes it easily modifiable. During the participants visit, instruct the participants to suppress the target thought when the red light is presented, to free think when the green light is presented, and to press the response button each time the yellow light flashes. Completing this task in the MRI scanner will allow the assessment of neural activity difference during each instructed task.</li>
	</ol>
	</li>
</ol>
3. Participant Visit
<ol>
	<li>Upon arrival, assess depression severity and psychiatric status of all participants with the BDI-II, HAM-D and Mini International Neuropsychiatric Inventory (MINI) questionnaires. Collect information regarding medication status and educational background. 
	NOTE: These questionnaires were completed as part of a larger investigation including other measures not listed here.</li>
	<li>Ask participants to list troubling thoughts or concerns that they have been repeatedly revisiting over the past few weeks and that they have been unable to shake. Record these oral statements while discussing them with the participant. Working with the participant, paraphrase the statement, shortening it to 7 - 10 words in length and identify a key word that is emotionally significant and explicitly conveys the meaning of the target sentence to the participant. &#160;</li>
	<li>Prior to the scan, instruct the participant to observe the traffic signal on the screen throughout the paradigm. Instruct the participant to suppress the presented target statement when the red light is presented. Ask the participant to think freely about anything and let their minds wander when the green light is presented.</li>
	<li>Instruct the participants to press the button on the scanner response box each time the target thought re-emerges during both the thought suppression and free thought periods. Finally, ask the participants to press the response box button each time a flashing yellow light is presented. 
	NOTE: The order of blocks in each functional run is as follows: a) target statement presentation period b) personal or distracter thought suppression period, c) free thought period, and d) motor response period to control for activation of motor areas induced during button presses in the thought suppression and free thought blocks. This pattern repeats 12 times, four times in each of the 3 runs.</li>
	<li>Insert personally relative and distractor target statements and key words into the paradigm. Within each run, ensure the first block consists of two personal thought suppression blocks and two distracter thought suppression blocks (See Figure 1).
	<ol>
		<li>Present the shortened statements and key words in a subsequent order and for 1TR each, followed by the traffic light signal for the rest of the target statement presentation period. Counterbalance the order of personal and distracter thought periods within each of the 3 fMRI scans and across participants. 
		Note: Target statements and key words will consist of both personally relevant negative ruminative thoughts provided by the participant (for example: &#8220;Think about not getting into university&#8221;), and neutral distractor statements taken from a battery prepared by Nolen-Hoeksema (for example: &#8220;Think about a row of shampoo bottles on display&#8221; 2).</li>
	</ol>
	</li>
	<li>Scan each participant with three functional MRI scans.</li>
</ol>
4. Functional Magnetic Resonance Imaging Data Acquisition and Analysis
<ol>
	<li>Conduct imaging on a 3T whole body short bore scanner with an 8-channel parallel receiver head coil. Perform a T1 weighted three-dimensional SPGR axial anatomical scan with 132 - 160 slices (1 mm thick). Acquire three functional MRI runs using a gradient-echo EPI sequence consisting of 31 axial slices (4 mm thick, no gap) beginning at the cerebral vertex and encompassing the entire cerebrum (TR/TE = 2,500/35 msec, FOV = 24 cm, matrix = 64 x 64, flip angle 90&#176;).</li>
	<li>Transfer the acquired images to a work station.
	<ol>
		<li>Transform anatomical MRI data sets into Talairach space28 to perform co-registration on functional data sets and average to generate a composite image.</li>
		<li>Temporally correct the functional data sets29. 3D motion correct the functional data sets29. Realign the functional data sets to the 5th frame of each run29. Smooth using a 6 mm Gaussian kernel and normalize to Talairach space29.</li>
	</ol>
	</li>
	<li>Use an event-related analysis method when analyzing the data. Build an analysis protocol that extracts intervals of time associated with thought suppression, thought re-emergence and successful re-suppression, as outlined below.</li>
	<li>Define a re-emergence event as the interval beginning 500 msec before the button press (re-emergence of thought prior to button press) and continuing for 2,000 msec after the button press, during the thought suppression or free thinking block. The time spanning the thought suppression block with re-emergence events excluded is to define thought suppression in the analysis protocol. 
	NOTE: Define successful re-suppression in the analysis protocol as maintained suppression, without an intrusion event, within one TR following the re-suppression event. Define motor control in the protocol as event times when the yellow light flashed during the motor response period.</li>
	<li>Using the neuroimaging software, contrast activation maps using a general linear model to identify clusters of activity associated with contrasts between and within groups. Conduct a random effects analyses (3 x 2) with a priori hypothesis testing. Conduct between group contrasts for thought suppression vs. motor control and thought re-emergence vs. re-suppression for control/at-risk vs. depressed, control vs. depressed, control vs. at-risk, and at-risk vs. depressed groups.</li>
	<li>Correct contrasts for multiple comparisons using the false discovery rate (FDR, set at p = 0.05) methodology implemented in the neuroimaging software.</li>
</ol>

<ol>
	<li>Gotlib, I. H., Joormann, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cognition+and+depression:+current+status+and+future+directions.">Cognition and depression: current status and future directions.</a> Annu Rev Clin Psychol. 6, 285-332 (2010).</li><li>Nolen-Hoeksema, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Responses+to+depression+and+their+effects+on+the+duration+of+depressive+episodes.">Responses to depression and their effects on the duration of depressive episodes.</a> J Abnorm Psychol. 100, 569-582 (1991).</li><li>McBride, C., Bagby, R. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Rumination+and+interpersonal+dependency:+Explaining+women's+vulnerability+to+depression.">Rumination and interpersonal dependency: Explaining women's vulnerability to depression.</a> Canadian Psychology. 47, 184-194 (2006).</li><li>Thomsen, D. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+association+between+rumination+and+negative+affect:+A+review.">The association between rumination and negative affect: A review.</a> Cognition and Emotion. 20 (8), 1216-1235 (2006).</li><li>Moulds, M. L., Kandris, E., Williams, A. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+impact+of+rumination+on+memory+for+self-referent+material.">The impact of rumination on memory for self-referent material.</a> Memory. 15, 814-821 (2007).</li><li>Nolen-Hoeksema, S., Parker, L. E., Larson, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ruminative+coping+with+depressed+mood+following+loss.">Ruminative coping with depressed mood following loss.</a> J Pers Soc Psychol. 67, 92-104 (1994).</li><li>Just, N., Alloy, L. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+response+styles+theory+of+depression:+Tests+and+an+extension+of+the+theory.">The response styles theory of depression: Tests and an extension of the theory.</a> J Abnorm Psychol. 106, 221-229 (1997).</li><li>Broderick, P. C., Korteland, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+prospective+study+of+rumination+and+depression+in+early+adolescence.">A prospective study of rumination and depression in early adolescence.</a> Clinical Child Psychology and Psychiatry. 9, 383-394 (2004).</li><li>Kuhn, S., Vanderhasselt, M., De Raedt, R., Gallinat, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Why+ruminators+won&#8217;t+stop:+the+structural+and+resting+state+correlates+of+rumination+and+its+relation+to+depression.">Why ruminators won&#8217;t stop: the structural and resting state correlates of rumination and its relation to depression.</a> Journal of Affective Disorders. 141 (2-3), 352-360 (2012).</li><li>Kuyken, W., Watkins, E., Holden, E., Cook, W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Rumination+in+adolescents+at+risk+for+depression.">Rumination in adolescents at risk for depression.</a> J Affect Disord. 96, 39-47 (2006).</li><li>Williams, A. D., Moulds, M. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cognitive+avoidance+of+intrusive+memories:+Recall+vantage+perspective+and+associations+with+depression.">Cognitive avoidance of intrusive memories: Recall vantage perspective and associations with depression.</a> Behav Res Ther. 45, 1141-1153 (2007).</li><li>Wegner, D. M., Schneider, D. J., Carter, S. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=White+TL.+Paradoxical+effects+of+thought+suppression.">White TL. Paradoxical effects of thought suppression.</a> J Pers Soc Psychol. 53, 5-13 (1987).</li><li>Dalgleish, T., Yiend, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+effects+of+suppressing+a+negative+autobiographical+memory+on+concurrent+intrusions+and+subsequent+autobiographical+recall+in+dysphoria.">The effects of suppressing a negative autobiographical memory on concurrent intrusions and subsequent autobiographical recall in dysphoria.</a> J Abnorm Psychol. 115, 467-473 (2006).</li><li>Price, J. L., Drevets, W. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neural+circuits+underlying+the+pathophysiology+of+mood+disorders.">Neural circuits underlying the pathophysiology of mood disorders.</a> Trends in Cognitive Sciences. 16, 61-71 (2012).</li><li>Drevets, W. C., Price, J. L., Furey, M. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Brain+structural+and+functional+abnormalities+in+mood+disorders:+implications+for+neurocircuitry+models+of+depression.">Brain structural and functional abnormalities in mood disorders: implications for neurocircuitry models of depression.</a> Brain Struct Funct. 213, 93-118 (2008).</li><li>Kupfer, D. J., Frank, E., Phillips, M. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Major+depressive+disorder:+new+clinical,+neurobiological+and+treatment+perspectives.">Major depressive disorder: new clinical, neurobiological and treatment perspectives.</a> Lancet. 379, 1045-1055 (2012).</li><li>Matsumoto, K., Tanaka, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Conflict+and+cognitive+control.">Conflict and cognitive control.</a> Science. 303, 969-970 (2004).</li><li>Mitchell, J. P., Heatherton, T. F., Kelley, W. M., Wyland, C. L., Wegner, D. M., Neil Macrae, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Separating+sustained+from+transient+aspects+of+cognitive+control+during+thought+suppression.">Separating sustained from transient aspects of cognitive control during thought suppression.</a> Psychol Sci. 18, 292-297 (2007).</li><li>Goldin, P. R., McRae, K., Ramel, W., Gross, J. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+neural+bases+of+emotion+regulation:+Reappraisal+and+suppression+of+negative+emotion.">The neural bases of emotion regulation: Reappraisal and suppression of negative emotion.</a> Biol Psychiatry. 63, 577-586 (2008).</li><li>Wyland, C. L., Kelley, W. M., Macrae, C. N., Gordon, H. L., Heatherton, T. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neural+correlates+of+thought+suppression.">Neural correlates of thought suppression.</a> Neuropsychologia. 41, 1863-1867 (2003).</li><li>Fossati, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=In+search+of+the+emotional+self:+An+fMRI+study+using+positive+and+negative+emotional+words.">In search of the emotional self: An fMRI study using positive and negative emotional words.</a> Am J Psychiatry. 160, 1938-1945 (2003).</li><li>Disner, S. G., Beevers, C. G., Haigh, E. A. P., Beck, A. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neural+mechanisms+of+the+cognitive+model+of+depression.">Neural mechanisms of the cognitive model of depression.</a> Nature Reviews Neuroscience. 12, 467-477 (2011).</li><li>Nolen-Hoeksema, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+role+of+rumination+in+depressive+disorders+and+mixed+anxiety/depressive+symptoms.">The role of rumination in depressive disorders and mixed anxiety/depressive symptoms.</a> J Abnorm Psychol. 109, 504-511 (2000).</li><li>Sullivan, P. F., Neale, M. C., Kendler, K. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Genetic+epidemiology+of+major+depression:+Review+and+meta-analysis.">Genetic epidemiology of major depression: Review and meta-analysis.</a> Am J Psychiatry. 157, 1552-1562 (2000).</li><li>Drevets, W. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Functional+anatomical+abnormalities+in+limbic+and+prefrontal+cortical+structures+in+major+depression.">Functional anatomical abnormalities in limbic and prefrontal cortical structures in major depression.</a> Prog Brain Res. 126, 413-431 (2000).</li><li>Ray, R. D., Ochsner, K. N., Cooper, J. C., Robertson, E. R., Gabrieli, J. D. E., Gross, J. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Individual+differences+in+trait+rumination+and+the+neural+systems+supporting+cognitive+reappraisal.">Individual differences in trait rumination and the neural systems supporting cognitive reappraisal.</a> Cognitive, Affective, &amp; Behavioral Neuroscience. 5, 156-168 (2005).</li><li>. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Diagnostic and Statistical Manual of Mental Disorders. , (2000).</li><li>Phan, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neural+correlates+of+individual+ratings+of+emotional+salience:+a+trial+related+fMRI+study.">Neural correlates of individual ratings of emotional salience: a trial related fMRI study.</a> NeuroImage. 21, 768-780 (2004).</li><li>Carew, C., Milne, A. M., Tatham, E. L., MacQueen, G. M., Hall, G. B. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neural+Systems+underlying+thought+suppression+in+young+women+with,+and+at-risk,+for+depression.">Neural Systems underlying thought suppression in young women with, and at-risk, for depression.</a> Behavioural Brain Research. 257, 13-24 (2013).</li><li>Jenkins, A. C., Macrae, C. N., Mitchell, J. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Repetition+suppression+of+ventromedial+prefrontal+activity+during+judgment+of+self+and+others.">Repetition suppression of ventromedial prefrontal activity during judgment of self and others.</a> PNAS. 105, 4507-4512 (2008).</li><li>Anderson, M. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neural+systems+underlying+the+suppression+of+unwanted+memories.">Neural systems underlying the suppression of unwanted memories.</a> Science. 303, 232-235 (2004).</li><li>Halari, R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reduced+activation+in+lateral+prefrontal+cortex+and+anterior+cingulate+during+attention+and+cognitive+control+functions+in+medication-naive+adolescents+with+depression+compared+to+controls.">Reduced activation in lateral prefrontal cortex and anterior cingulate during attention and cognitive control functions in medication-naive adolescents with depression compared to controls.</a> J Child Psychol Psychiatry. 50, 307-316 (2009).</li><li>Mannie, Z. N., Norbury, R., Murphy, S. E., Inkster, B., Harmer, C. J., Cowen, P. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Affective+modulation+of+anterior+cingulate+cortex+in+young+people+at+increased+familial+risk+of+depression.">Affective modulation of anterior cingulate cortex in young people at increased familial risk of depression.</a> Br J Psychiatry. 192, 356-361 (2008).</li><li>Koenigs, M., Huey, E. D., Calamia, M., Raymont, V., Tranel, D., Grafman, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Distinct+regions+of+prefrontal+cortex+mediate+resistance+and+vulnerability+to+depression.">Distinct regions of prefrontal cortex mediate resistance and vulnerability to depression.</a> J Neurosci. 28, 12341-12348 (2008).</li></ol>

The authors have nothing to disclose

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" >
	<tbody>
		<tr >
			<td >Magnetic Resonance Imaging Scanner</td>
			<td >General Electric</td>
			<td ></td>
			<td >3T, whole body, short bore scanner, Milwaukee, WI</td>
		</tr>
		<tr >
			<td >Brain Voyageur, QX, V2.1</td>
			<td >Brain Innovation (B.V.)</td>
			<td ></td>
			<td>Maastricht, The Netherlands</td>
		</tr>
		<tr >
			<td >E-prime&#160;</td>
			<td >Psychology Software Tools</td>
			<td ></td>
			<td>Pennsylvania, USA</td>
		</tr>
		<tr >
			<td >Hamilton Depression Rating Scale (HAM-D)</td>
			<td colspan="3">Hamilton M (1967) Development of a rating scale for primary depressive illness. The British journal of social and clinical psychology 6: 278&#8211;296&#160;</td>
		</tr>
		<tr >
			<td >Rosenberg Self-Esteem Questionnaire (RSE)</td>
			<td colspan="3">Rosenberg M (1965). Society and the Adolescent Self-Image. Princeton University Press : Princeton, NJ.</td>
		</tr>
		<tr >
			<td >Childhood Trauma Questionnaire (CTQ)</td>
			<td colspan="3">Bernstein DP, Stein JA, Newcomb M, et al. (2003) Development and validation of a brief screening version of the Childhood Trauma Questionnaire. Child Abuse &#38; Neglect 27: 169&#8211;190.</td>
		</tr>
		<tr >
			<td >NEO-FFI Neuroticism questionnaire</td>
			<td colspan="3">Costa, P. T., &#38; McCrae, R. R. (1992). Revised NEO Personality Inventory (NEO&#8208;PI&#8208;R) and NEO Five&#8208;Factor Inventory (NEO&#8208;FFI) professional manual. Odessa, FL: Psychological Assessment Resources.</td>
		</tr>
		<tr >
			<td >Mini International Neuropsychiatric Inventory (MINI)</td>
			<td colspan="3">Folstein, M. F., Folstein, S. E., &#38; McHugh, P. R. (1975). &#8220;Mini-mental state.&#8221; Journal of Psychiatric Research, 12(3), 189&#8211;198.</td>
		</tr>
		<tr >
			<td >Beck Depression Inventory-Version II (BDI-II)</td>
			<td colspan="3">Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J (1961) An inventory for measuring depression Archives of General Psychiatry 4:561 - 571</td>
		</tr>
	</tbody>
</table>

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 ...

design-implementation-an-fmri-study-examining-thought-suppression

Research

JoVE Journal

Behavior

10.4K Views.  McMaster University. 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.

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

Assessment and Evaluation of the High Risk Neonate: The NICU Network Neurobehavioral Scale

There has been a long-standing interest in the assessment of the neurobehavioral integrity of the newborn infant. The NICU Network Neurobehavioral Scale (NNNS) was developed as an assessment for the at-risk infant. These are infants who are at increased risk for poor developmental outcome because of insults during prenatal development, such as substance exposure or prematurity or factors such as poverty, poor nutrition or lack of prenatal care that can have adverse effects on the intrauterine environment and affect the developing fetus. The NNNS assesses the full range of infant neurobehavioral performance including neurological integrity, behavioral functioning, and signs of stress/abstinence. The NNNS is a noninvasive neonatal assessment tool with demonstrated validity as a predictor, not only of medical outcomes such as cerebral palsy diagnosis, neurological abnormalities, and diseases with risks to the brain, but also of developmental outcomes such as mental and motor functioning, behavior problems, school readiness, and IQ. The NNNS can identify infants at high risk for abnormal developmental outcome and is an important clinical tool that enables medical researchers and health practitioners to identify these infants and develop intervention programs to optimize the development of these infants as early as possible. The video shows the NNNS procedures, shows examples of normal and abnormal performance and the various clinical populations in which the exam can be used.

The NICU Network Neurobehavioral Scale (NNNS) was developed as an assessment for the at-risk infant. The purpose of this article is to describe the NNNS, provide video examples of the NNNS procedures and discuss the ways in which the exam has been used.

There has been a long-standing interest in the assessment of the neurobehavioral integrity of the newborn infant.  The NICU Network Neurobehavioral Scale ...

Transferring Cognitive Tasks Between Brain Imaging Modalities: Implications for Task Design and Results Interpretation in fMRI Studies

As cognitive neuroscience methods develop, established experimental tasks are used with emerging brain imaging modalities. Here transferring a paradigm (the visual oddball task) with a long history of behavioral and electroencephalography (EEG) experiments to a functional magnetic resonance imaging (fMRI) experiment is considered. The aims of this paper are to briefly describe fMRI and when its use is appropriate in cognitive neuroscience; illustrate how task design can influence the results of an fMRI experiment, particularly when that task is borrowed from another imaging modality; explain the practical aspects of performing an fMRI experiment. It is demonstrated that manipulating the task demands in the visual oddball task results in different patterns of blood oxygen level dependent (BOLD) activation. The nature of the fMRI BOLD measure means that many brain regions are found to be active in a particular task. Determining the functions of these areas of activation is very much dependent on task design and analysis. The complex nature of many fMRI tasks means that the details of the task and its requirements need careful consideration when interpreting data. The data show that this is particularly important in those tasks relying on a motor response as well as cognitive elements and that covert and overt responses should be considered where possible. Furthermore, the data show that transferring an EEG paradigm to an fMRI experiment needs careful consideration and it cannot be assumed that the same paradigm will work equally well across imaging modalities. It is therefore recommended that the design of an fMRI study is pilot tested behaviorally to establish the effects of interest and then pilot tested in the fMRI environment to ensure appropriate design, implementation and analysis for the effects of interest.

Transferring a paradigm with a history of use in EEG experiments to an fMRI experiment is considered. It is demonstrated that manipulating the task demands in the visual oddball task resulted in different patterns of BOLD activation and illustrated how task design is crucial in fMRI experiments.

As cognitive neuroscience methods develop, established experimental tasks are used with emerging brain imaging modalities. Here transferring a paradigm ...

A New Method for Inducing a Depression-Like Behavior in Rats

Contagious depression is a phenomenon that is yet to be fully recognized and this stems from insufficient material on the subject. At the moment, there is no existing format for studying the mechanism of action, prevention, containment, and treatment of contagious depression. The purpose of this study, therefore, was to establish the first animal model of contagious depression.
Healthy rats can contract depressive behaviors if exposed to depressed rats. Depression is induced in rats by subjecting them to several manipulations of chronic unpredictable stress (CUS) over 5 weeks, as described in the protocol. A successful sucrose preference test confirmed the development of depression in the rats. The CUS-exposed rats were then caged with na&#239;ve rats from the contagion group (1 na&#239;ve rat/2 depressed rats in a cage) for an additional 5 weeks. 30 social groups were created from the combination of CUS-exposed rats and na&#239;ve rats.
This proposed depression-contagion protocol in animals consists mainly of cohabiting CUS-exposed and healthy rats for 5 weeks. To ensure that this method works, a series of tests are carried out - first, the sucrose preference test upon inducing depression to rats, then, the sucrose preference test, alongside the open field and forced-swim tests at the end of the cohabitation period. Throughout the experiment, rats are given tags and are always returned to their cages after each test.
A few limitations to this method are the weak differences recorded between the experimental and control groups in the sucrose preference test and the irreversible traumatic outcome of the forced swim test. These may be worth considering for suitability before any future application of the protocol. Nonetheless, following the experiment, na&#239;ve rats developed contagion depression after 5 weeks of sharing the same cage with the CUS-exposed rats.

This protocol describes a new model by which healthy rats could contract depression over a given time periodthrough contagion by exposure to chronic unpredictable stressed (CUS) rats.

Contagious depression is a phenomenon that is yet to be fully recognized and this stems from insufficient material on the subject. At the moment, there is ...

Design and Use of an Apparatus for Presenting Graspable Objects in 3D Workspace

Reaching and grasping are highly-coupled movements, and their underlying neural dynamics have been widely studied in the last decade. To distinguish reaching and grasping encodings, it is essential to present different object identities independent of their positions. Presented here is the design of an automatic apparatus that is assembled with a turning table and three-dimensional (3D) translational device to achieve this goal. The turning table switches different objects corresponding to different grip types while the 3D translational device transports the turning table in 3D space. Both are driven independently by motors so that the target position and object are combined arbitrarily. Meanwhile, wrist trajectory and grip types are recorded via the motion capture system and touch sensors, respectively. Furthermore, representative results that demonstrate successfully trained monkey using this system are described. It is expected that this apparatus will facilitate researchers to study kinematics, neural principles, and brain-machine interfaces related to upper limb function.

Presented here is a protocol to build an automatic apparatus that guides a monkey to perform the flexible reach-to-grasp task. The apparatus combines a 3D translational device and turning table to present multiple objects in an arbitrary position in 3D space.

Reaching and grasping are highly-coupled movements, and their underlying neural dynamics have been widely studied in the last decade. To distinguish ...

Assessing the Coherence of Parents' Short Narratives Regarding their Child Using the Five-Minute Speech Sample Procedure

Valid and efficient measures for assessing the quality of parent-child relationships are needed to facilitate research and evidence-based practice with parents. This paper focuses on such a method, namely Five-Minute Speech Sample-Coherence (FMSS-Coherence). In this method, a parent is asked to speak for five uninterrupted minutes about her/his child and their relationship. The resulted narrative is coded for coherence, namely the extent to which the parent provides&#160;in the narrative&#160;a clear, consistent, multidimensional and well-supported portrayal of the child. FMSS-Coherence is based on attachment research that shows that the coherence of parents&#8217; narratives is indicative of the quality of the parent-child relationship and child adjustment. It overcomes the limitations of attachment narrative measures which are typically labor intensive. FMSS-Coherence is less nuanced than extant attachment narrative measures. Yet, studies of families from different cultural backgrounds, across different child ages and in the context of typically developing children as well as children with special needs suggest that coherence can be reliably evaluated using the FMSS procedure. Furthermore, parents&#8217; FMSS-Coherence is associated with parenting quality and children&#8217;s socio-emotional adjustment. Thus, it holds promise for researchers and practitioners who seek a relatively time- and cost-effective method for assessing the coherence of parents&#8217; narratives regarding their child.

Assessing the Coherence of Parents&#039; Short Narratives Regarding their Child Using the Five-Minute Speech Sample Procedure

This paper introduces a method for assessing the coherence of parents' short narratives regarding their child and their relationship using the five-minute speech sample procedure.

Valid and efficient measures for assessing the quality of parent-child relationships are needed to facilitate research and evidence-based practice with ...

Examining Changes in HRV and Emotion Following Artmaking with Three Different Art Materials

This protocol enables the examination of psychological and physiological responses to different types of behavioral engagements. Specifically, in this study example, the emotional response and changes in heart rate variability are examined in response to artmaking with three different art materials that vary in their levels of fluidity. This protocol can be adapted to examine other types of behavior or engagement in artmaking with other materials. There are several benefits to using this protocol. Firstly, the order randomization of the materials improves the probability that the response measured is associated with its qualities and not the order of presentation. Secondly, the continuous measuring of electrocardiogram enables the examination of changes in heart rate variability after engagement with each art material and changes that might occur during the artmaking itself. The advantages of this protocol should be considered with their limitations. The music listening is before each art making session; thus, the return to baseline can only be measured in the first two conditions. The return to baseline provides information on how fast individuals recover after response to working with each of the materials. Furthermore, a more liquid material instead of gouache paint with a brush, such as finger paints, provides more difference between materials. Finally, this protocol can be adapted to specific research needs.

The goal of the protocol is to guide researchers in conducting experiments that are intended to measure changes in self-reported emotional response and heart rate variability following art making with different materials. The protocol can easily be adapted for use in a variety of behavioral conditions and activities.

This protocol enables the examination of psychological and physiological responses to different types of behavioral engagements. Specifically, in this ...

Flypub To Study Ethanol Induced Behavioral Disinhibition and Sensitization

Alcohol use disorder (AUD) remains a serious problem in our society. To develop effective interventions for addiction, it is important to understand the underlying neurobiological mechanisms, for which diverse experimental approaches and model systems are needed. The main ingredient of alcoholic beverages is ethanol, which causes adaptive changes in the central nervous system and behavior upon chronic intake. Behavioral sensitization (i.e., escalated responses) in particular represents a key adaptive change underlying addiction. Most ethanol-induced behavioral sensitization studies in animal models have been conducted on the locomotor activating effect of ethanol. A prominent effect of ethanol is behavioral disinhibition. Behavioral sensitization to the disinhibition effect of ethanol, however, is underrepresented. To address this issue, we developed the Flypub assay that allows measuring the escalated increase in disinhibited courtship activities upon recurring ethanol exposure in Drosophila melanogaster.&#160;Here, we report the step-by-step Flypub assay including assembly of ethanol exposure chambers, setup of the assay station, criteria for fly care and collection, ethanol delivery, quantification of disinhibited courtship activities, data processing and statistical analysis. Also provided are how to troubleshoot critical steps, overcome limitations and expand its utility to assess additional ethanol-induced behaviors. The Flypub assay in combination with powerful genetic tools in Drosophila melanogaster will facilitate the task of discovering the mechanism underlying ethanol-induced behavioral sensitization.

The Flypub assay measures the behaviors that the fruit fly Drosophila melanogaster displays under the influence of ethanol. The assay can be readily mastered by experimenters at all levels and applied to various vaporized stimuli, facilitating substance abuse and addiction studies.

Alcohol use disorder (AUD) remains a serious problem in our society. To develop effective interventions for addiction, it is important to understand the ...

Tactile Vibrating Toolkit and Driving Simulation Platform for Driving-Related Research

Collision warning system plays a key role in the prevention of driving distractions and drowsy driving. Previous studies have proven the advantages of tactile warnings in reducing driver&#8217;s brake response time. At the same time, tactile warnings have been proved effective in take-over request (TOR) for partially autonomous vehicles.
How the performance of tactile warnings can be optimized is an ongoing hot research topic in this field. Thus, the presented low-cost driving simulation software and methods are introduced to attract more researchers to take part in the investigation. The presented protocol has been divided into five sections: 1) participants, 2) driving simulation software configuration, 3) driving simulator preparation, 4) vibrating toolkit configuration and preparation, and 5) conducting the experiment.
In the exemplar study, participants wore the tactile vibrating toolkit and performed an established car-following task using the customized driving simulation software. The front vehicle braked intermittently, and vibrating warnings were delivered whenever the front vehicle was braking. Participants were instructed to respond as quickly as possible to the sudden brakes of the front vehicle. Driving dynamics, such as the brake response time and brake response rate, were recorded by the simulation software for data analysis.
The presented protocol offers insight into the exploration of the effectiveness of tactile warnings on different body locations. In addition to the car-following task that is demonstrated in the exemplar experiment, this protocol also provides options&#160;to apply other paradigms to the driving simulation studies by making simple software configuration without any code development. However, it is important to note that due to its affordable price, the driving simulation software and hardware introduced here may not be able to fully compete with other high-fidelity commercial driving simulators. Nevertheless, this protocol can act as an affordable and user-friendly alternative to the general high-fidelity commercial driving simulators.

This protocol describes a driving simulation platform and a tactile vibrating toolkit for the investigation of driving-related research. An exemplar experiment exploring the effectiveness of tactile warnings is also presented.&#160;

Collision warning system plays a key role in the prevention of driving distractions and drowsy driving. Previous studies have proven the advantages of ...

The Participant-Reported Implementation Update and Score (PRIUS): A Novel Method for Capturing Implementation-Related Data Over Time

"Implementation" of new initiatives in healthcare settings typically encompasses two distinct components: a "clinical intervention" plus accompanying "implementation strategies" that support putting the clinical intervention into day-to-day practice. A novel clinical intervention, for example, might consist of a new medication, a new protocol, a new device, or a new program. As clinical interventions are not self-implementing, however, they nearly always require effective implementation strategies in order to succeed. Implementation strategies set out to engage healthcare providers, staff and patients in ways that increase the likelihood of the new initiative being successfully adopted, a process that often involves behavior change and new ways of thinking by participants. One of the challenges in studying implementation is that it can be difficult to collect data about the status and progress of implementation, including participants' own perspectives and experiences concerning implementation to date. This protocol describes a novel method for collecting and analyzing data related to ongoing implementation called the Participant-Reported Implementation Update and Score, or PRIUS. The PRIUS method allows for the efficient and systematic capture of qualitative and quantitative data that can provide a detailed and nuanced account of implementation over time and from multiple viewpoints. This longitudinal method can enable researchers, as well as implementation leaders and organizational stakeholders, to monitor implementation progress more closely, conduct formative evaluation, identify improvement opportunities, and gauge the effect of any implementation changes on a rolling basis.

The Participant-Reported Implementation Update and Score PRIUS: A Novel Method for Capturing Implementation-Related Data Over Time

This protocol describes a novel method for collecting and analyzing data related to ongoing implementation called the Participant-Reported Implementation Update and Score (PRIUS). The PRIUS method allows for the efficient and systematic capture of data over time and from multiple viewpoints in healthcare settings.

"Implementation" of new initiatives in healthcare settings typically encompasses two distinct components: a "clinical intervention" plus accompanying ...

A Within-Subject Experimental Design using an Object Location Task in Rats

Object place recognition is a prominent method used to investigate spatial memory in rodents. This object place recognition memory forms the basis of the object location task. This paper provides an extensive protocol to guide the establishment of an object location task with the option of up to four repetitions using the same cohort of rats. Both weak and strong encoding protocols can be used to study short- and long-term spatial memories of varying strength and to enable the implementation of relevant memory-inhibiting or -enhancing manipulations. In addition, repetition of the test with the counterbalancing presented here allows the combination of results from two or more tests for within-subject comparison to reduce variability between rats. This method helps to increase statistical power and is strongly recommended, particularly when running experiments that produce high variation in individual behavior. This directly refines the study by increasing the data obtained from each animal and reducing the overall number of animals needed.&#160;Finally, implementation of the repeated object location task increases the efficiency of studies that involve surgical procedures by saving time and labor.

This protocol provides detailed steps for an object location task with four repetitions using the same cohort of rats. Weak and strong encoding can produce short- and long-term memories. The flexibility of the protocol with repetition can be beneficial for studies involving surgical operations by saving time and labor.

Object place recognition is a prominent method used to investigate spatial memory in rodents. This object place recognition memory forms the basis of the ...