2005 LUPIEN Montreal Imaging Stress Task

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J Psychiatry Neurosci 2005;30(5)

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Objective:

We developed a protocol for inducing moderate psychologic stress in a functional imaging setting and evaluated the effectsof stress on physiology and brain activation.

Methods:

The Montreal Imaging Stress Task (MIST), derived from the Trier Mental Chal-lenge Test, consists of a series of computerized mental arithmetic challenges, along with social evaluative threat components that arebuilt into the program or presented by the investigator. To allow the effects of stress and mental arithmetic to be investigated separately,the MIST has 3 test conditions (rest, control and experimental), which can be presented in either a block or an event-related design, foruse with functional magnetic resonance imaging (fMRI) or positron emission tomography (PET). In the rest condition, subjects look at astatic computer screen on which no tasks are shown. In the control condition, a series of mental arithmetic tasks are displayed on thecomputer screen, and subjects submit their answers by means of a response interface. In the experimental condition, the difficulty andtime limit of the tasks are manipulated to be just beyond the individual’s mental capacity. In addition, in this condition the presentation ofthe mental arithmetic tasks is supplemented by a display of information on individual and average performance, as well as expected per-formance. Upon completion of each task, the program presents a performance evaluation to further increase the social evaluative threatof the situation.

Results:

In 2 independent studies using PET and a third independent study using fMRI, with a total of 42 subjects, levelsof salivary free cortisol for the whole group were significantly increased under the experimental condition, relative to the control and restconditions. Performing mental arithmetic was linked to activation of motor and visual association cortices, as well as brain structures in-volved in the performance of these tasks (e.g., the angular gyrus).

Conclusions:

We propose the MIST as a tool for investigating the ef-fects of perceiving and processing psychosocial stress in functional imaging studies.

Objectif:

Nous avons mis au point un protocole afin de provoquer un stress psychologique moyen en contexte d’imagerie fonctionnelleet nous en avons évalué l’effet sur la physiologie et l’activation cérébrale.

Méthodes:

Dérivée de l’épreuve de provocation mentale Trier,la tâche du stress d’imagerie de Montréal (MIST) consiste en une série de provocations sous forme de calcul mental informatisé com-portant des éléments de menace d’évaluation par la société et intégrées dans le programme ou présentées par le chercheur. Pour pou-voir étudier séparément les effets du stress et du calcul mental, l’épreuve MIST comporte trois conditions d’essai (repos, contrôle, con-texte expérimental) qu’il est possible de présenter en bloc ou selon un concept relié aux événements et d’utiliser avec l’imagerie parrésonnance magnétique fonctionnelle (IRMf) ou la tomographie par émission de positrons (TEP). Au repos, les sujets regardent unécran d’ordinateur statique sur lequel aucune tâche n’apparaît. En condition contrôlée, on affiche à l’écran de l’ordinateur une série detâches de calcul mental et les sujets soumettent leurs réponses au moyen d’une interface de réponse. En contexte expérimental, on ma-nipule la difficulté des tâches et le temps qui y est consacré pour qu’elles dépassent à peine la capacité mentale du sujet. Dans cettecondition, on complète la présentation des tâches de calcul mental en affichant de l’information sur le sujet et son rendement moyen,ainsi que sur le rendement attendu. Lorsque chaque tâche est terminée, le programme présente une évaluation du rendement afin d’ac-croître encore davantage la menace d’évaluation par la société que présente la situation.

Résultats:

Au cours de deux études indépen-dantes pendant lesquelles on a utilisé la TEP et d’une troisième où l’on a utilisé l’IRMf, pour un total de 42sujets, les concentrations de

Douglas Hospital Research Centre SymposiumSymposium du Centre de recherche de l’Hôpital Douglas

The Montreal Imaging Stress Task: using functionalimaging to investigate the effects of perceiving andprocessing psychosocial stress in the human brain

Katarina Dedovic, BSc; Robert Renwick, BSc; Najmeh Khalili Mahani, MSc;Veronika Engert, MSc; Sonia J. Lupien, PhD; Jens C. Pruessner, PhD

Dedovic, Khalili Mahani, Engert, Lupien, Pruessner — Douglas Hospital Research Centre, Borough of Verdun, and Depart-ment of Psychiatry, McGill University, Montréal, Que.; Renwick — Faculty of Medicine, University of Toronto, Toronto, Ont.

Correspondence to: Dr. Jens C. Pruessner, FBC 1133, Douglas Hospital Research Centre, 6875 LaSalle Blvd., Borough of Verdun,Montréal QC H4H 1R3; fax 514 888-4099; jens@bic.mni.mcgill.ca

Medical subject headings: cognition; perception; psychophysiology; stress, psychological; pituitary–adrenal system; cortisol.Submitted Apr. 22, 2005; Revised July 21, 2005; Accepted July 25, 2005

© 2005 CMA Media Inc.

Introduction

Associated with adverse effects on cardiovascular, immune,metabolic and psychological variables, stress is considered tohave a significant impact on population health.

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Investigatingsituations and variables that are perceived as stressful mighttherefore allow researchers to uncover some of the mecha-nisms that link stress to adverse health. In humans, one of thekey physiologic markers of stress is activation of the hypo-thalamic–pituitary–adrenal (HPA) axis, with the accompany-ing secretion of corticotropin-releasing hormone from the hy-pothalamus, adrenocorticotropic hormone (ACTH) from thepituitary and cortisol from the adrenal cortex. Psychosocialstress has been identified as among the most powerful typeof stress in activating the HPA axis.

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In a recent review, socialevaluative threat was identified as one of the key compo-nents of psychosocial stress.

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To investigate stress in the laboratory, paradigms that have been used effectively in the past include the Trier SocialStress Test,

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consisting of public speaking and oral mentalarithmetic, and the Trier Mental Challenge Test,

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consistingof computerized mental arithmetic with negative feedback.Dependent measures obtained in conjunction with these testsusually include physiologic or endocrinologic markers ofstress, e.g., changes in heart rate or in ACTH and cortisol lev-els. Direct assessment of changes in brain activation in re-sponse to stress has so far been impossible because of a lackof appropriate protocols to induce and measure stress infunctional imaging environments. To overcome this limita-tion, we have developed the Montreal Imaging Stress Task(MIST). Based on the Trier Mental Challenge Test, the MISTcomprises a series of computerized mental arithmetic taskswith an induced failure component. The protocol was devel-oped to fit the constraints of the imaging environment interms of stimulus content and duration of presentation andto incorporate social evaluative threat components, which are built into the program and brought on by the investigator.In this article, we describe the MIST protocol and summa-rize its effects on physiologic and brain activation changespreviously investigated in 3 independent studies usingpositron emission tomography (PET) and functional mag-netic resonance imaging (fMRI).

Methods

Subjects

For all studies, subjects were recruited by posting flyers at lo-cal university buildings and through advertisement in localnewspapers. Upon initial contact, a telephone interview wasconducted to establish demographic information and medicalhistory. Exclusion criteria consisted of past or current depres-sion, past head injuries with subsequent loss of consciousnessand any known past occurrences of dysregulation of theHPA, the hypothalamic–pituitary–gonadal axis or the hypo-thalamic–pituitary–thyroid axis.In study 1, 10 healthy young individuals (1 woman and 9men, 21–30 years of age) were invited to participate in a PETstudy to investigate dopamine release as indicated by[

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C]raclopride receptor binding in the ventral striatum. Instudy 2, 10 healthy male college students (20–25 years of age)were recruited to participate in a PET study to investigate theeffects of acute stress perception and processing in the human brain on cerebral blood flow using [

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O]H

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O. Finally, in study3, we recruited 22 healthy young men (20–24 years of age) toinvestigate the effects of acute stress perception using fMRI.

Montreal Imaging Stress Task

The MIST protocol consists of a training session, conductedoutside the imaging unit, and a test session, during which thefunctional images are acquired. Depending on the imagingmethod used, up to 3 different conditions (rest, control andexperimental) are implemented.The principal component of the MIST is a computer programthat displays a mental arithmetic task, a rotary dial for submis-sion of a response, a text field that provides feedback on thesubmitted response (“correct,” “incorrect” or “timeout”) and 2performance indicators, one for the individual subject’s perfor-mance and one for average performance of all subjects (Fig. 1).In the experimental condition, a time limit is enforced for eachtask; the elapsed time is displayed by a progress bar movingfrom left to right on the computer screen, with the exact time al-lowed for each task depending on the subject’s previous perfor-mance (Fig. 1).The program was developed using the SuperCard applica-tion for Mac OS X (Solutions Etcetera, Pollock Pines, Calif.).The basic algorithm of the program creates mental arithmetictasks using up to 4 numbers ranging from 0 to 99 and up to 4operands (+ for addition, – for subtraction, * for multiplicationand / for division). The algorithm has been designed to auto-matically create tasks for which the solution will be an integer between 0 and 9, such that a single keystroke is needed for theresponse. A difficulty gradient for the mental arithmetic is built into the algorithm, with 5 different categories. In the 2easiest categories, only tasks with 2 or 3 one-digit integers arecreated, and the operands are limited to + or – (example: 2 + 9– 7). In the medium-difficulty categories, tasks with up to 4 in-tegers are created, with up to 2 of these integers in the 2-digitrange, and the * operand is also allowed (example: 3 * 12 – 29).Finally, in the fifth and most difficult category, tasks with 4 in-tegers are created, the * and / operands are used, and all

Dedovic et al

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Rev Psychiatr Neurosci 2005;30(5)

cortisol libre dans la salive pour tout le groupe étaient beaucoup plus élevées en contexte expérimental qu’en contexte de contrôle et aurepos. On a établi un lien entre le calcul mental et l’activation des cortex moteur et d’association visuelle, ainsi que des structurescérébrales qui interviennent dans l’exécution de ces tâches (p.ex., le gyrus angulaire).

Conclusions:

Nous proposons l’épreuve MIST

Montreal Imaging Stress Task

J Psychiatry Neurosci 2005;30(5)

321

numbers may be in the 2-digit range (example: 12 * 12 / 8 – 9).A subject selects a number on the rotary dial either by press-ing the left or right arrow keys on the keyboard (during thetraining session, outside of the imaging unit) or by pressingthe left or right mouse buttons on a scanner-compatible USBkeyboard response box (when inside the scanner). Pressing theleft arrow or left mouse button moves the highlighted numberon the rotary dial of the program’s user interface counter-clockwise, whereas pressing the right arrow key or mouse but-ton moves the highlighted number on the rotary dial of theprogram’s user interface clockwise (see Fig. 1). Pressing thedown arrow key or the middle mouse button submits thehighlighted number on the rotary dial as the subject’s responseto the arithmetic task. This response is then compared with thecorrect answer for the task, and the appropriate feedback(“correct” or “incorrect”) is presented in the feedback field ofthe computer screen. If no response is recorded within the timelimit, the response “timeout” is displayed.In the training session (outside the imaging unit), the subject’s ability to perform mental arithmetic is assessed byrecording the average time needed to solve problems at vari-ous difficulty levels. For this purpose, no time limit is en-forced, and no time progress bar is shown on the screen. Inaddition, no performance indicators (for the subject’s ownperformance or the average performance of all subjects) aredisplayed. However, the recorded time is used to set a defaulttime limit for the experimental condition. The testing sessionmust be at least 2 minutes long for the program to determinethe average time the subject takes to perform mental arith-metic in the different categories; usually, the subject is given 5minutes to practise the program before the imaging session.During each experimental session (inside the imaging unit),the program is set to a time limit that is 10% less than the subject’s average response time; this approach induces a high fail-ure rate. In addition, the program continuously records thesubject’s average response time and the number of correct re-sponses. If the subject answers a series of 3 consecutive mentalarithmetic tasks correctly, the program reduces the time limitto 10% less than the average time for the 3 correctly solvedtasks. Conversely, if the subject answers a series of 3 consecu-tive tasks incorrectly, the program increases the time limit forthe following tasks by 10%. As such, under experimental con-ditions, a range of about 20% to 45% correct answers is en-forced. Individual runs last between 2 and 6 minutes, depend-ing on the scanning method (PET or fMRI) and the paradigm(receptor-binding or cerebral blood flow for PET scanning,event-related or block design for fMRI). During the experi-mental sessions, the colour bar at the top of the screen shows2 performance indicators, for the subject’s own performanceand average performance of all subjects. The average perfor-mance arrow appears in the green area, at the right of thescreen, while the subject’s individual performance usually ap-pears in the red area, to the left of the screen. Between experi-mental runs, the investigator informs the subject about his orher performance, reminding him or her that the average per-formance is about 80%–90% correct answers. The subject isthen reminded that there is a required minimum performanceand that his or her individual performance must be close orequal to the average performance of all subjects if his or herdata are to be used in the study. The subject is told about theneed for standard performance across users to allow the datato be grouped and is reminded about the correct use of the re-sponse box for submitting responses. Finally, the subject istold that all of the people in the scanner room (investigator,assistants, MR technicians) are following the subject’s perfor-mance on a second monitor in the control room of the scan-ning environment. The investigator then leaves the room, andthe next run of mental arithmetic is initiated.During the control condition, the program tries to matchfor any cerebral activation caused by the mental arithmeticaspects of the task, but without the stress components. Forthat purpose, mental arithmetic is presented with the samelevel of difficulty and at the same frequency as during the ex-perimental sessions, but no time restriction is enforced, andindividual performance and average users’ performance arenot displayed. To match the frequency of mental arithmetictasks, the time between tasks is varied as a function of thetime limit imposed during the experimental condition, sothat the total number of tasks presented per condition isidentical. Feedback (“correct” or “incorrect”) is still shown af-ter each task, but because of the absence of a time limit, aver-age performance increases to about 90%. In between runs,which last between 2 and 6 minutes (i.e., the same as in theexperimental condition; see above), the investigator tells thesubject to try and perform the task as quickly and accuratelyas possible, but also states that his or her performance is not being evaluated because this is a control condition.Finally, during the rest condition, which records a baselinestate of cerebral activation, the interface of the computer pro-gram remains on the screen, but no tasks are shown. Subjectsare told not to move the mouse until the next mental arithmetictask appears. The rest condition varies between 1 and 3 min-utes, depending on the imaging method and paradigm used.

Fig. 1:

Graphical user interface of the Montreal Imaging StressTask (MIST). From top to bottom, the figure shows the perfor-mance indicators (top arrow = average performance, bottom arrow= individual subject’s performance), the mental arithmetic task, theprogress bar reflecting the imposed time limit, the text field forfeedback, and the rotary dial for the response submission.

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