Case Report Top-Down Computerized Cognitive Remediation in ...downloads.hindawi.com/journals/crips/2015/242364.pdf · schizophrenia were recruited and consented to participate. ey

Case ReportTop-Down Computerized Cognitive Remediation inSchizophrenia A Case Study of an Individual with Impairmentin Verbal Fluency

Marjolaine Masson1 Til Wykes2 Michel Maziade34 Clare Reeder2 Marie-Anne Garieacutepy1

Marc-Andreacute Roy34 Hans Ivers1 and Caroline Cellard13

1 Ecole de Psychologie Universite Laval Quebec QC Canada G1V 0A62Institute of Psychiatry Kingrsquos College London London SE5 8AF UK3Centre de Recherche de lrsquoInstitut Universitaire en Sante Mentale de Quebec Quebec QC Canada G1J 2G34Departement de Psychiatrie Faculte de Medecine Universite Laval Quebec QC Canada G1V 0A6

Correspondence should be addressed to Marjolaine Masson marjolainemassongmailcom

Received 18 January 2015 Accepted 29 March 2015

Academic Editor Toshiya Inada

Copyright copy 2015 Marjolaine Masson et al This is an open access article distributed under the Creative Commons AttributionLicense which permits unrestricted use distribution and reproduction in any medium provided the original work is properlycited

The objective of this case studywas to assess the specific effect of cognitive remediation for schizophrenia on the pattern of cognitiveimpairments Case A is a 33-year-old man with a schizophrenia diagnosis and impairments in visual memory inhibition problemsolving and verbal fluency He was provided with a therapist delivered cognitive remediation program involving practice andstrategy which was designed to train attention memory executive functioning visual-perceptual processing and metacognitiveskills Neuropsychological and clinical assessments were administered at baseline and after three months of treatment At posttestassessment Case A had improved significantly on targeted (visual memory and problem solving) and nontargeted (verbal fluency)cognitive processes The results of the current case study suggest that (1) it is possible to improve specific cognitive processes withtargeted exercises as seen by the improvement in visual memory due to training exercises targeting this cognitive domain (2)cognitive remediation can produce improvements in cognitive processes not targeted during remediation since verbal fluencywas improved while there was no training exercise on this specific cognitive process and (3) including learning strategies incognitive remediation increases the value of the approach and enhances participant improvement possibly because strategies usingverbalization can lead to improvement in verbal fluency even if it was not practiced

1 Introduction

Cognitive impairments are a core feature of schizophreniawith impairments in nearly every cognitive domain [1 2]A recent meta-analysis [2] demonstrated that patients withschizophrenia scored significantly lower than did controlsacross all cognitive tests and domains with largest impair-ments in processing speed and episodicmemory [2 3]While70ndash80 of individuals with schizophrenia demonstratecognitive impairments one standard deviation below themean of healthy comparison subjects (ie 16th percentile)[3 4] relative to the general population nearly 100 demon-strate decreased performance relative to their own premorbid

cognitive status [5 6] Cognitive impairments in attentionverbal memory and executive functioning have demon-strable prognostic value that is the degree of impairmentpredicts ability to achieve functional goals through treatment[7ndash9]

In considering the improvement of functioning it isimportant to take account of any specific cognitive difficultiesthat are related to functioning outcomes Episodic memoryis one of the cognitive domains usually associated with poorsocial functioning [10] However one overlooked cognitivedeficit that can negatively impact social life is verbal fluency[10] Verbal fluency is generally considered as a measureof executive functions To assess verbal fluency participants

Hindawi Publishing CorporationCase Reports in PsychiatryVolume 2015 Article ID 242364 10 pageshttpdxdoiorg1011552015242364

2 Case Reports in Psychiatry

are asked to name as many items as possible from a givencategory in a given time period The category may besemantic such as animals or types of fruit or phonemic suchas words that begin with the letter 119901 [11] Some studies havedemonstrated that patients with schizophrenia produce feweritems and do not use recall strategies (eg farm animals andwild animals) during letter and semantic fluency tests [12]Impairment in verbal fluency was more severe for semanticfluency (effect size = 121) than for letter fluency (effect size =098) [2 13]

Considering the generalized cognitive impairments sev-eral psychological treatment strategies have therefore beendeveloped to improve cognitive functioning in this pop-ulation and they are referred to as cognitive remediationstrategies As defined at the Cognitive Remediation ExpertsWorkshop (Florence Italy April 2010) cognitive remediationfor schizophrenia refers to ldquoa behavioral training based inter-vention that aims to improve cognitive processes ( ) withthe goal of durability and generalizationrdquo Two recent meta-analyses [14 15] demonstrated that cognitive remediationfor individuals with schizophrenia has a positive moderateeffect on overall cognition psychosocial functioning andsymptoms Moreover greater effects on psychosocial func-tioning were observed when cognitive remediation was com-bined with psychiatric rehabilitation [14] However transferof gains from the research context to everyday life is ofmoderate effect size across cognitive rehabilitation studiesthat included measures of psychosocial functioning [14 15]Cognitive remediation tasks are typically quite structuredand are therefore significantly different from the situationsthat individuals with schizophrenia encounter in everydaylife [16] Currently cognitive remediation with schizophreniapatients includes two primary approaches ldquodrill and practicerdquoand ldquodrill practice and strategyrdquo [14] The first is a bottom-up approach that trains cognitive processes by repetitionusing exercises that focus on specific impaired processes [17]The second is a top-down approach that also trains cog-nitive processes by repetition However this approach alsoprovides patients with strategies for applying the practicedprocesses in daily life [18 19] That is the ldquodrill practice andstrategyrdquo remediation approach provides cues for managingreal-life situations Cognitive remediation programs thatincorporate strategies andmethods for addressing beliefs andmotivation rather than relying solely on drill and practiceare associated with more positive psychosocial outcomes[20] Moreover in developing interventions for improvingsocial functioning in this population it has been useful toconceptualize communication behavior in terms of socialskills and constituent elements of social skills [21] Onesuch cognitive remediation program for individuals withschizophrenia is the Computerized Interactive Remediationof Cognition Training for Schizophrenia CIRCuiTS [22]TheCIRCuiTS program targets difficulties with goal-directedbehavior in daily life The objectives of the program are todevelop a list of individualized goals to create an action planfor cognitive training and to implement strategies designedto facilitate the transfer of skills into everyday life

Patients with schizophrenia have heterogeneous cogni-tive profiles The CIRCuiTS program software addresses

multiple cognitive processes and allows therapists to removeor adjust exercises to adapt therapy sessions as needed Tohighlight specific cognitive deficits that are less visible ina larger sample the present paper presents a case study ofcognitive remediation in a patient with schizophrenia Thepatient (Case A) demonstrated global cognitive impairmentwith specific impairment in verbal fluency He participatedin a three-month general top-down cognitive remediationprogram We hypothesized that Case A would improve per-formance in the cognitive domains observed to be impairedat neuropsychological baseline and targeted by the CIRCuiTSprogram Moreover as verbalization is one of the primarystrategies in the CIRCuiTS program we anticipated that thismay have a beneficial effect on verbal fluency even though itis not directly targeted by specific exercises

2 Case Report

This research project was approved by the appropriate ethicscommittee at Centre de Recherche de lrsquoInstitut Universitaireen Sante Mentale in Quebec City Canada Participants withschizophrenia were recruited and consented to participateThey were informed that they could withdraw participationat any time The current paper presents a case study drawnfrom the larger sample recruited for this project Case A wasa young participant with recent-onset schizophrenia

The inclusion criteria for the larger study were (1) con-firmed DSM-IV-TR [23] schizophrenia diagnosis within thelast ten years (2) clinical status permitting reliable cognitiveassessment and (3) cognitive difficulties in visual episodicmemory immediate recall or delayed recall below the 16thpercentile as measured by the Rey complex figure test(RCFT) Exclusion criteria were (1) brain and metabolicdisorders known to cause neuropsychological impairments(2) substance dependence within the past six months and (3)Intelligent Quotient below 70

Case A was a 33-year-old man who lived alone Hehad completed 13 years of education and had obtained aprofessional certificate in institutional plumbing He wasdiagnosed with depression at age 28 and with schizophrenia(DSM-IV) at age 30 He had a past history of amphetaminedependence His pharmacological treatment which didnot change throughout the intervention included met-formin (2 times 850mg) for diabetes modafinil (100mg) todecrease sleepiness atorvastatin (10mg) for hypercholes-terolemia atenolol (12mg) for recurrentmigraines clozapine(200mg hs) desvenlafaxine (50mg) for musical obsessionsmeeting criteria for obsessional compulsive disorder (incomplete remission throughout the intervention) and twodrops of atropine (1 hs) for hypersialorrhea The patientmet with his psychiatrist approximately once per month andwith his psychologist and occupational therapist twice permonth Socially Case A saw only members of his family onceor twice a week he has worked as a plumber until 2008 andhas been unemployed since 2008

21 Cognitive Complaints At the first therapy session CaseArsquos therapist presented the cognitive remediation programand explained the study procedure in detail Difficulties in

Case Reports in Psychiatry 3

Table 1 Neuropsychological and clinical assessments

Cognitive processes Tests VariablesNeuropsychological assessment

Intelligence Wechsler Adult Intelligence Scale thirdedition (WAIS-III) [43] Global intelligence

Verbal episodic memory The California verbal learning test-II(CVLT-II) [44]

Immediate recall delayed recall andrecognition

Visual episodic memory Rey complex figure test (RCFT) [45] Immediate recall delayed recall andrecognition

Sustained attention Continuous performance test-II (CPT-II)[46]

Hit reaction time block change (change inperformance over time)Hit standard error block change (accuracy)

Selective attentionInhibitory processes

CPT-IIInhibition score of the Stroop test from theDelis-Kaplan Executive Function System(D-KEFS) [47]

Omissions commissions and detectability

Working memory Span [48] Total spatial span forward and backwardand total digit span forward and backward

Problem solving Wisconsin card sorting test-128 cards(WCST CV4) [49]

Trials to complete the first category andfailure to maintain set

Initiationstrategic search Verbal fluency test (French-Canadianversion)

Semantic (ie animals) and phonemic (iewords starting with the letter ldquofrdquo) categories

Planning Tower of London (TOLDX) [50] Number of problems solved in minimummoves rule violation and time violation

Clinical assessment

Psychiatric symptoms Positive and Negative Syndrome Scale(PANSS) [51]

This instrument includes 30 items rated on ascale from 1 (absent) to 7 (extreme)

Social and occupational functioning Global assessment of functioning (GAF)[52]

This instrument measures on a scale from 1to 100 higher scores reflecting betterfunctioning It is divided into ranges of 10points (ie 1ndash10 11ndash20 etc up to 91ndash100)

daily life were also discussed Case A reported the follow-ing cognitive complaints difficulty retaining informationconcentration and comprehension problems and memoryloss The set of goals of cognitive remediation treatmentwas jointly agreed by both therapist and patient Case Arsquosobjectives derived directly from his complaints and includedthe following read a newspaper article and understand thetext read an entire book and retain the thread of the plotand watch a movie without the use of the ldquopauserdquo or ldquorewindrdquobuttons

3 Materials and Methods

31 Neuropsychological and Clinical Assessments Nine neu-ropsychological tests and two clinical tests were used to assessCase A before the cognitive remediation (Table 1) When ascore below the 16th percentile was observed in at least onevariable of a cognitive domain then the cognitive domainwasconsidered as impaired

32 Procedure The experimental design included threesteps baseline assessment a three-month cognitive reme-diation (CIRCuiTS) and posttest assessment Baseline andposttest assessments both consisted of neuropsychologicaland clinical assessments neuropsychological assessment was

conducted by a research assistant and clinical assessment wasconducted by Case Arsquos treating psychiatrist who had treatedhim since the beginning of treatment

321 Baseline Assessment At baseline Case A demon-strated pathological scores (lt5th percentile) or impair-mentsdifficulties (lt16th percentile) in four of the ninecognitive domains assessed with neuropsychological tests(Table 2) visual episodic memory (immediate and delayedrecalls) selective attention (inhibition variable) initia-tionstrategic search (phonemic and semantic categories)and problem solving (high trial number of first category ina card sorting test) Poor verbal fluency was also qualitativelyobserved during the baseline evaluation session (ie povertyof speech) Case Arsquos scores were within the normal range(from 21st to 97th percentiles) for all of the remaining cog-nitive processes assessed (verbal episodic memory workingmemory sustained attention and planning) Finally Case Aseemed to have good metacognitive skills because his cog-nitive deficits were congruent with his cognitive complaints(retaining information concentration and comprehensionproblems and memory loss)

322 Cognitive Remediation The cognitive remediationprogram used is named CIRCuiTS [22] Several cognitive


Table 2 Case Arsquos results on neuropsychological and clinical assessments

Baseline PosttestScore PR Score PR

Cognitive TestsIntelligence

Global IQa 88 21 95 37Verbal episodic memory

CVLT-II total recall 55 55 50 50CVLT-II delayed recall 14 84 14 70CVLT-II recognition 16 70 14 70

Visual episodic memoryRCFT immediate recall 12 1 235 50RCFT delayed recall 20 1 43 24RCFT recognition 23 86 19 8

Sustained attentionCPT-hit reaction timeb 005 9712 002 7466CPT-hit standard errorb 003 6212 000 47

Selective attentionCPT omissionsb 0 208 1 3041CPT commissionsb 11 3724 14 5237CPT detectability 1198891015840b 062 5692 052 653Stroop D-KEFS inhibition 66 16 64 16

Working MemoryTotal spatial span 20 84 18 63Total digit span 16 37 18 50

Executive functionproblem solvingWCST total errors 20 42 17 50WCST number of categories completed 6 gt16 6 gt16WCST trials 1st category 13 11ndash16 11 gt16

WCST failure to maintain set 0 gt16 0 gt16WCST learning to learn 28 gt16 minus152 gt16

Executive functioninitiationLetter fluency test 6 2 12 25Category fluency test 12 3 21 44

Executive functionplanningTotal number of problems solved with minimal movements 4 40 1 9Total time violations 0 66 0 66Total rules violations 0 55 0 55

Clinical TestsGAF 48 na 48 naPANSS 85 na 74 na

Positive Symptoms Scale 14 na 14 naNegative Symptoms Scale 23 na 21 naGeneral Psychopathological Scale 48 na 39 na

aGlobal IQ was reported in standardized scorebThe PR of CPT scale is reversed Higher PR indicates more severe impairmentPercentile rankPR The scores correspond to the raw score obtained for each variable California verbal learning test-II CVLT-II Rey complex figure testRCFT global IQ as measured with the WAIS-III continuous performance test-II CPT-II Wisconsin card sorting test-128 cards WCST global assessment offunctioning GAF Positive and Negative Syndrome Scale PANSS not applicable (na)Deficit at baseline improved to normal at posttest scores


remediation programs existThe originality of CIRCuiTS canbe summarized in key points First CIRCuiTS is theory-driven based on a metacognitive model of the relationshipbetween cognitive and functional change Using a strategy-based approach CIRCuiTS has an integrated focus on thetransfer of cognitive skills to daily activities It aims todevelop metacognitive regulation and metacognitive knowl-edge which are hypothesized to be important for the appro-priate generalization of cognitive skills to daily living [24]The focus on transfer also comes from its use of real-worldgoals homework to facilitate in vivo use of new strategiesand a formulation-based approach in which the impact ofcognitive strengths and difficulties on daily living skills isconsidered All of these factors are known to be associatedwith increased motivation [25 26] Second CIRCuiTS hashigh feasibility and acceptability among both service usersand therapists as seen in a series of quantitative and quali-tative studies designed to inform and test the developmentof CIRCuiTS [27] Third CIRCuiTS has high adaptabilityto individual differences because it is based on a flexiblemodular system [28]

CIRCuiTS is a computerized psychological therapy pro-gram although patients can use the program independentlyit is ideally administered by a therapist Various cognitivetraining techniques and strategies are employed includingsimplification and errorless learning Those techniques havebeen proven to be effective in improving cognitive perfor-mance in empirical studies [24] CIRCuiTS was designed tobe completed in forty therapy sessions at aminimumof threesessions per week Therapy sessions last up to one hour buttherapists can adjust time according to the patient

A therapy session consists of multiple (approximately 4ndash8) activities covering a wide range of cognitive functionsattention memory executive functions visual-perceptualprocessing and metacognitive skills The activities are de-signed to target verbal skills nonverbal skills or bothTasks are rotated to be diverse interesting and engagingfor participants The CIRCuiTS program includes two typesof tasks (1) abstract tasks which are designed to improvecognitive functions in an abstract context (eg rememberinga list of words) and (2) exercises that is complex tasksdesigned to reflect everyday activities (eg make a dailyschedule and read a letter) Whereas abstract tasks areperformed throughout the CIRCuiTS program exercises areintroduced gradually across sessions the final sessions of theprogram consist primarily of exercises The rationale is thatpatients learn new cognitive skills in an abstract context andsubsequently gradually transfer the skills to everyday lifeThat overall objective of the program is for participants toeventually apply cognitive skills and new strategies developedin therapy in daily life

33 Therapist Strategies Verbalization of cues prompts andstrategies for completing a given task are key therapiststrategies During a task the therapist verbalizes hints forthe participant in order to facilitate mentalization of relevantstrategies Verbalized prompts are often used repetitivelyparticipants becomes increasingly independent as therapyprogresses with the therapist verbalising key instructions at

first and the participant gradually taking over the verbalisa-tion process which occurs first overtly (out loud) and latercovertly (mentally) For example in the ldquolearning a listrdquo taskthe therapist may encourage the participant to repeat the listof words to him or herself

34 Clinical Hypotheses Given a program that specificallyaddressed and targeted many of Case Arsquos particular deficitswe expected improvement in each of his impaired scoresImprovements were expected in visual episodic memory (asmeasured by the RCFT) selective attentioninhibition (asmeasured by the Stroop inhibition test) and problem solving(as measured by the WCST) The underlying skills of verbalfluency were not directly practiced in CIRCuiTS Howeververbalization is one of the primary strategies used by thetherapist and the patient during the therapy Improvementin verbal fluency was therefore expected No baseline deficitswere observed in verbal episodic memory working memoryor sustained attention and planning and therefore no signif-icant improvements were expected

35 Statistical Analysis Two approaches were adopted toestimate changes on main outcomes after cognitive remedi-ation First the Reliable Change Index (RCI) [29] was calcu-lated to determine whether posttherapy change observed foreach variable for each participant reaches significance levelRCI similar to a Z-change score (a) allows estimating theextent by which a patient distance themselves from a distri-bution of similar symptomatic patients whowere not exposedto the intervention while (b) controlling for the instrumentreliability and (c) allowing a conclusion about the ldquostatisticalsignificancerdquo of the change RCI larger than 196 are seen asstatistically significant at a two-tailed 5 alpha level It can benoted that this statistical approach is quite conservative [30] aminimum change of two standard deviations is required to beconsidered significantThe conservative thresholdmeans thatan observed change is unlikely to be attributable to simplemeasurement unreliability or practice effect within pre- andposttests [31]

The RCI were computed with these variables The stan-dard deviations for the neuropsychological variables weregathered from our laboratory (M Maziade) The resultshave been published previously in Schizophrenia BulletinHowever to have a greater sample size we used unpublishedstandard deviations collected from our laboratory since thepublication of the paper in Schizophrenia Bulletin Only oneneuropsychological variable the Stroop from the D-KEFSbattery was gathered from a paper in the literature [32] Thestandard deviations for the clinical variables were obtainedfrom published research Positive and Negative SyndromeScale (PANSS) [33] and global assessment of functioning(GAF) [32]We fixed the same test-retest to 080 as a standardfor each testThe reliability of 080 to 090 is considered as theminimum acceptable for internal consistency and 070 is theminimum for the test-retest reliability [34]

The second approach (less conservative) was to considerthe movement of scores from below to above the 16thpercentile on instruments with available clinical normativedata In clinical practice a score above the 16th percentile


is considered as normal performance As a consequencechanges in status from ldquodeficitrdquo to ldquonormalrdquo performancewere considered to be a clinical improvement

4 Results

41 Neuropsychological Assessment Difference between base-line and posttest assessment scores was calculated and RCIare reported in Table 3

The conservative method revealed that Case A signifi-cantly improved on RCFT immediate recall (RCI = 268) andRCFT delayed recall (RCI = 186)The expected improvementin verbal fluency was observed for both categories (phonemicfluency RCI = 220 categorical fluency RCI = 251) Howeverthe expected improvement in selective attention betweenbaseline and posttest assessments was not observed Case Arsquosscore on the Stroop inhibition test remained unchanged atthe threshold of deficit (percentile = 16)

Finally the less conservative method revealed that diffi-culties observed at baseline in problem solving (percentile =11ndash16) disappeared at posttest assessment (percentile gt 16)however RCI was not significant

42 Clinical Assessment No significant change was observedin clinical symptoms (as assessedwith the PANSS) or in socialfunctioning (assessed with the GAF) (Table 3)

43 Clinical Change during Cognitive Remediation TherapyThe clinical case formulation (see Table 1 in the supplemen-tal material see Supplementary Material available onlineat httpdxdoiorg1011552015242364) pointed out severedifficulties in verbal fluency but important strengths withgood comprehension and high motivation Verbal fluencywas not practiced with specific exercise during cognitiveremediation with CIRCuiTS At the beginning of therapyCase A was unable to identify examples where the strategieslearned in CIRCuiTS might be useful in his daily life Bymidtreatment it was expected that Case A would be ableto identify applications in his daily life independently butthis was not the case Case Arsquos deficit in verbal fluency couldprevent him from verbally generating a list of applicationsduring the therapy session His therapist therefore asked himto make a list of the areas of his life in which he experiencedcognitive difficulties (eg work friends or medication) ashomework for the following session The task was verydifficult for him but after several drafts the final versionwas exhaustive with concrete examples that reflected hisdaily life In the following session Case Arsquos therapist askedhim to use a CIRCuiTS strategy to organize his list CaseA successfully categorized each of the identified situations(eg food interests and social situations) and the list wasused for the remainder of therapy By asking participantsto verbalize strategies during and after training exercisesthe CIRCuiTS program helps participants gain awareness ofstrategies and generate new strategies if application efforts arenot successful The list was an interactive document open tomodification and enhancement it served to keep track of theobjectives set at the beginning of therapy As mentioned inthe clinical case formulation (see Table 1 in the supplemental

Table 3 Reliable Change Index (RCI) for the neuropsychologicalvariables

RCI

Cognitive TestsIntelligenceGlobal IQ 0919

Verbal episodic memoryCVLT-II total recall minus0799

CVLT-II delayed recall 0000

CVLT-II recognition minus0930

Visual episodic memoryRCFT Immediate Recall 2682

RCFT delayed recall 1863

RCFT recognition minus3194

Sustained attentionCPT-hit reaction time minus1581

CPT-hit standard error minus0565

Selective attentionCPT omissions 0166

CPT commissions 0569

CPT detectability 1198891015840 minus0386

Stroop D-KEFS inhibition minus0167

Working MemoryTotal spatial span minus1068

Total digit span 0811

Executive functionproblem-solvingWCST total errors minus0188

WCST number of categories completed 0000

WCST trials 1st category minus0083

WCST failure to maintain set 0000

WCST learning to learn minus1016

Executive functioninitiationLetter fluency test 2196

Category fluency test 2514

Executive functionplanningTotal number of problems solved with minimalmovements

minus1890

Total time violations 0000

Total rules violations 0000

Clinical TestsGAF 0000

PANSS minus1214

Positive Symptoms Scale 0000

Negative Symptoms Scale minus0497

General Psychopathological Scale minus0180Abbreviations RCI Reliable Change Index GAF Global Assessment ofFunctioning PANSS Positive and Negative Syndrome ScaleSignificant with unilateral criteria (cut off = 164) Significant with bilateralcriteria (cut-off = 196)


material) Case Arsquos goals were very concrete and directlylinked to his daily life (eg read a book) The ldquolistrdquo strategywas used because Case A demonstrated deficits in verbalfluency This deficit made him a unique and interesting casestudy however the strategy is likely to be applicable anduseful for other participants even in the absence of verbalfluency problems

Case Arsquos problem in verbal fluency also included slowingdown during reading and difficulties to synthesize instruc-tions which led to a decrease in the number of exercisesperformed during a session This synthesis problem couldbe due to Case Arsquos cognitive behavioral style (see Table 1in the supplemental material) Effectively the clinical caseformulation reported some difficulties such as sensitivity tointerference or trouble to stay focusconcentrate for a longtimeThus the first task of Case Awas to learn to concentrateby buying the newspaper choosing an article reading it aloneand trying to summarize it by writing taking his time Thestrategy chosen by the patient was to highlight importantinformation in the text to bring out the essentialmeaningThefirst summary of Case A looked like a ldquocopy and pasterdquo of theoriginal text but it became more and more accurate At thenext session Case A had to read aloud the summary he hadpreviously prepared at home in order to learn to take breaksduring his reading time Then Case A had to do it againwithout looking at his paper The first attempts were quitelaborious with too much detail without understanding themain message of the text The same homework was repeateduntil Case A was able to summarize a text briefly and tounderstand its meaning

Overall the main strategies that Case A used in therapyand at home were to highlight a text (eg in the newspaper)to buy and use a notebook to categorize the information(eg shopping list) to say the information out loud the self-repetition to take break during reading to check his answerbefore validating it and to plan before beginning a task thesestrategies allowed him to reach two of the three expectedgoals mentioned in the formulation case plus four others notexpected read the newspaper cook watch movie play boardgame and remember birthdays and phone numbers

5 Discussion

We hypothesized that Case Arsquos performance would improvein each of the cognitive domains identified as impairedat baseline and targeted by CIRCuiTS including visualmemory inhibition and problem solvingThehypothesis waspartially validated Case A improved significantly in visualmemory (conservative method) and in problem solving (lessconservativemethod) Since verbalization is a strategy widelyused in CIRCuiTS cognitive remediation improvement inverbal fluency was expected even though it was not directlypracticed by specific exercise This second hypothesis wasvalidatedThe effects of cognitive remediation were observedonly on the neuropsychological measures in this case studyNo significant changes were observed in global functioningor in positivenegative symptoms

Where visual memory was concerned Case Arsquos improve-ment was clear his scores were normal at posttest assessment

Exercises used to train visual memory in the CIRCuiTS pro-gramprimarily involved copying and recalling images as wellas practicing memory for faces and places Case Arsquos therapisttaught him several strategies for visual memory includingusing a grid for visual cues focusing on one attribute at a time(eg face body and name) taking notes and visual scanning(leftright and updown) Case A seemed to integrate thesestrategies by the end of therapy as demonstrated by hisimprovement in visual memory at posttest assessment Thisobservation is consistent with recent literature demonstratingimprovement in visual memory after basic visual processingtraining via computer [35]

We expected an improvement in inhibition processesbut none was observed Case Arsquos impairment remained nearthe deficit threshold at posttest assessment According toLecardeur et al [36] improvement is rarely observed inindividuals with small tomoderate deficits (05 to 15 standarddeviation from the norm) and the usefulness of cognitiveremediation in such cases is not certain In the present casestudy baseline score was on the edge between deficit andnormality (percentile 16 one standard deviation from thenorm) and the opportunity for improvement was thereforelimited

Case A demonstrated improvement (with less conser-vative method) in problem solving at posttest assessmentCognitive remediation included several exercises designed totrain problem solving including ldquoseating planrdquo and ldquoplan-a-dayrdquo In the first type of exercise Case Arsquos task was to seatindividuals at a table while respecting instructions about whoshould not be seated together In the second type of exercisehis taskwas to organize and schedule a list of activities and to-do items in a diary respecting the instructions given Duringthe two exercises Case A used the following strategiesprioritize and follow the simplest rule place tasks with a fixedtime into the schedule first He learned to dissect instructionsbefore initiating a task and to write down the steps to solve aproblem These strategies appear to have been effective CaseArsquos problem solving score improved from impaired to withinthe normal range at posttest assessment A similar study[37] demonstrated that at least in the planningproblemsolving domains patients with impaired performance arelikely to benefit from interventions with very specific tar-gets The authors compared the impact of two types ofcognitive remediation specific problem solving training andbasic cognition training The results demonstrated that onlyspecific training (ie ldquoplan-a-dayrdquo task) resulted in improvedproblem solving

Finally we expected that the verbalization strategyapplied in therapy would result in observable improvementsin Case Arsquos verbal fluency This hypothesis was supported forboth semantic fluency and phonemic fluency improvementsin verbal fluency were observed during the remediationsessions and Case A also reported improvements in everydaylife That verbal fluency improved despite lack of directtraining demonstrates that cognitive remediation had a non-specific effectThis finding is corroborated by ameta-analysis[38] where computer-assisted cognitive remediation yieldedcomparable effects in targeted and nontargeted cognitivedomains


In the current case study one possible explanation for theobserved nonspecific improvement is the type of cognitiveremediation used in the CIRCuiTS program namely theldquodrill practice and strategyrdquo approach ldquoDrill and practicerdquoremediation does not focus on strategies (eg verbalization)Therefore if it does not focus on verbal fluency exercisesmaking improvement in verbal fluency is unlikely In con-trast the ldquodrill practice and strategyrdquo approach is likely tohave awidespread effect and to generate nonspecific improve-ments [39] Vianin et al [40] demonstrated this effect Theymeasured brain activity during a verbal fluency task in eightpatients with schizophrenia (experimental group) before andafter participation in a cognitive remediation program thatdid not target verbal fluency They compared the results withthose of a control group of individuals who did not receiveremediation Following cognitive remediation neuroimagingresults revealed greater activation of Brocarsquos area duringverbal fluency tasks in the experimental group comparedto in the control group The authors hypothesized that theobserved brain changes were attributable to verbal mediationtechniques such as verbalization Finally the current casestudy corroborates the fact that cognitive remediation ther-apy benefits more to patients with schizophrenia with lowinitial memory performances [41] Effectively Case Arsquos base-line performancewas very low in visual episodicmemory andthis impairment could allow him to have general benefit ofcognitive remediation by obtaining specific and nonspecificimprovements

There are several limitations to the present study Firstthe case study presented here did not assess the long-termeffect of cognitive remediation It would be interesting toconduct a follow-up assessment of cognitive performancesuch an assessment would permit observation of change insocial functioning (ongoing project) Second the case studydesign is often considered to be less valid than are groupdesigns because of threats to internal and external validityHowever many authors have argued that single-case studiesplay an important role in evidence-based clinical practice ofcognitive remediation [42] Finally the administration of thesame neuropsychological battery at baseline and at posttestassessment may have positively influenced posttest scoresTherefore the problem solvingrsquos improvement observed withthe less conservative method must be interpreted with cau-tion because it could be due to the practice effect

6 Conclusions

This case study highlights several important points Firstcognitive processes improved when the participantrsquos trainingfocused on specific targets such as visual memory and prob-lem solving Second when cognitive remediation includeslearning strategies cognitive processes such as verbal fluencymay improve even though they are not practiced by specificexercisesThat is learning strategies can produce generalizedimprovements and enhance the positive impact of cognitiveremediation In the light of this case study cognitive reme-diation appears to be an interesting avenue workable andadvantageous for patients with schizophrenia Therefore theuse of cognitive remediation in clinical practice represents an

obvious interest and could lead to positive impact on socialfunctioning

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper

References

[1] R W Heinrichs and K K Zakzanis ldquoNeurocognitive deficit inschizophrenia a quantitative review of the evidencerdquoNeuropsy-chology vol 12 no 3 pp 426ndash445 1998

[2] J Schaefer E Giangrande D RWeinberger and D DickinsonldquoThe global cognitive impairment in schizophrenia consistentover decades and around the worldrdquo Schizophrenia Researchvol 150 no 1 pp 42ndash50 2013

[3] D Dickinson M E Ramsey and J M Gold ldquoOverlooking theobvious a meta-analytic comparison of digit symbol codingtasks and other cognitive measures in schizophreniardquo Archivesof General Psychiatry vol 64 no 5 pp 532ndash542 2007

[4] B W Palmer S E Dawes and R K Heaton ldquoWhat dowe know about neuropsychological aspects of schizophreniardquoNeuropsychology Review vol 19 no 3 pp 365ndash384 2009

[5] J M Gold ldquoIs cognitive impairment in schizophrenia ready fordiagnostic prime timerdquoWorld Psychiatry vol 7 no 1 pp 32ndash332008

[6] C M Wilk J M Gold K Humber F Dickerson W S Fen-ton and R W Buchanan ldquoBrief cognitive assessment inschizophrenia Normative data for the Repeatable Battery forthe Assessment of Neuropsychological Statusrdquo SchizophreniaResearch vol 70 no 2-3 pp 175ndash186 2004

[7] M F Green R S Kern and R K Heaton ldquoLongitudinalstudies of cognition and functional outcome in schizophreniaImplications forMATRICSrdquo Schizophrenia Research vol 72 no1 pp 41ndash51 2004

[8] K H Nuechterlein K L Subotnik M F Green et alldquoNeurocognitive predictors of work outcome in recent-onsetschizophreniardquo Schizophrenia Bulletin vol 37 supplement 2 ppS33ndashS40 2011

[9] C R Bowie C Depp J A McGrath et al ldquoPrediction ofreal-world functional disability in chronic mental disordersa comparison of schizophrenia and bipolar disorderrdquo TheAmerican Journal of Psychiatry vol 167 no 9 pp 1116ndash11242010

[10] M F Green R S Kern D L Braff and J Mintz ldquoNeurocog-nitive deficits and functional outcome in schizophrenia are wemeasuring the lsquoright stuff rsquordquo Schizophrenia Bulletin vol 26 no1 pp 119ndash136 2000

[11] M D Lezak Neuropsychological Assessment Oxford UniversityPress Oxford UK 1995

[12] E M Joyce S L Collinson and P Crichton ldquoVerbal fluency inschizophrenia relationship with executive function semanticmemory and clinical alogiardquo Psychological Medicine vol 26 no1 pp 39ndash49 1996

[13] C E Bokat and T E Goldberg ldquoLetter and category flu-ency in schizophrenic patients a meta-analysisrdquo SchizophreniaResearch vol 64 no 1 pp 73ndash78 2003

[14] T Wykes V Huddy C Cellard S R McGurk and P CzoborldquoA meta-analysis of cognitive remediation for schizophrenia


methodology and effect sizesrdquoThe American Journal of Psychi-atry vol 168 no 5 pp 472ndash485 2011

[15] S R McGurk E W Twamley D I Sitzer G J McHugo andK T Mueser ldquoA meta-analysis of cognitive remediation inschizophreniardquoTheAmerican Journal of Psychiatry vol 164 no12 pp 1791ndash1802 2007

[16] M N Levaux F Laroslashi M Malmedier I Offerlin-Meyer JDanion and M Van der Linden ldquoRehabilitation of executivefunctions in a real-life setting goal management training ap-plied to a person with schizophrenirdquoCase Reports in Psychiatryvol 2012 Article ID 503023 15 pages 2012

[17] S Barlati G Deste L de Peri C Ariu and A Vita ldquoCog-nitive remediation in schizophrenia current status and futureperspectiverdquo Schizophrenia Research and Treatment vol 2013Article ID 156084 12 pages 2013

[18] A Medalia and J Choi ldquoCognitive remediation in schizophre-niardquo Neuropsychology Review vol 19 no 3 pp 353ndash364 2009

[19] TWykes C Reeder J Corner CWilliams and B Everitt ldquoTheeffects of neurocognitive remediation on executive processingin patients with schizophreniardquo Schizophrenia Bulletin vol 25no 2 pp 291ndash307 1999

[20] A Medalia and A M Saperstein ldquoDoes cognitive remedia-tion for schizophrenia improve functional outcomesrdquo CurrentOpinion in Psychiatry vol 26 no 2 pp 151ndash157 2013

[21] A S Bellack K T Mueser S Gingerich and J Agresta SocialSkills Training for Schizophrenia A Step-by-Step Guide GuilfordPress New York NY USA 2nd edition 2004

[22] C Reeder and T Wykes Computerised Interactive Remedia-tion of CognitionmdashInteractive Training for Schizophrenia (CIR-CUITS) Kings College London UK 2010

[23] American Psychiatric Association Diagnostic and StatisticalManual ofMental Disorders DSM-IV-TR American PsychiatricAssociation Washington DC USA 2000

[24] T Wykes and C Reeder Cognitive Remediation Therapy forSchizophrenia Theory and Practice Routledge 2005

[25] R M Ryan and E L Deci ldquoIntrinsic and extrinsic motivationsclassic definitions and new directionsrdquo Contemporary Educa-tional Psychology vol 25 no 1 pp 54ndash67 2000

[26] J Choi T Mogami and A Medalia ldquoIntrinsic motivation in-ventory an adaptedmeasure for schizophrenia researchrdquo Schiz-ophrenia Bulletin vol 36 no 5 pp 966ndash976 2010

[27] C Reeder V Harris A Pickles A Patel M Cella and TWykes ldquoDoes change in cognitive function predict change incosts of care for peoplewith a schizophrenia diagnosis followingcognitive remediation therapyrdquo Schizophrenia Bulletin vol 40no 6 pp 1472ndash1481 2014

[28] C J Press R J Drake and N Husain ldquoSouth Asiansrsquo attitudestowards cognitive remediation after first episodes of psychosisrdquoSchizophrenia Research vol 117 no 2-3 p 512 2010

[29] N S Jacobson and P Truax ldquoClinical significance a statisticalapproach to defining meaningful change in psychotherapyresearchrdquo Journal of Consulting and Clinical Psychology vol 59no 1 pp 12ndash19 1991

[30] J Marsden B Eastwood CWright C Bradbury J Knight andP Hammond ldquoHow best to measure change in evaluations oftreatment for substance use disorderrdquo Addiction vol 106 no 2pp 294ndash302 2011

[31] R K Heaton N Temkin S Dikmen et al ldquoDetecting changea comparison of three neuropsychological methods using nor-mal and clinical samplesrdquo Archives of Clinical Neuropsychologyvol 16 no 1 pp 75ndash91 2001

[32] C Simonsen K Sundet A Vaskinn et al ldquoNeurocognitivedysfunction in bipolar and schizophrenia spectrum disordersdepends on history of psychosis rather than diagnostic grouprdquoSchizophrenia Bulletin vol 37 no 1 pp 73ndash83 2011

[33] S Bayard D Capdevielle J-P Boulenger and S Raffard ldquoDis-sociating self-reported cognitive complaint from clinical insightin schizophreniardquo European Psychiatry vol 24 no 4 pp 251ndash258 2009

[34] E H Strauss E M Sherman and O Spreen A Compendium ofNeuropsychological Tests Administration Norms and Commen-tary Oxford University Press New York NY USA 3rd edition2006

[35] T S Surti S Corbera M D Bell and B E Wexler ldquoSuccess-ful computer-based visual training specifically predicts visualmemory enhancement over verbal memory improvement inschizophreniardquo Schizophrenia Research vol 132 no 2-3 pp 131ndash134 2011

[36] L Lecardeur S Meunier-Cussac and S Dollfus ldquoCognitivedeficits in first episode psychosis patients and people at riskfor psychosis from diagnosis to treatmentrdquo Encephale vol 39supplement 1 pp S64ndashS71 2013

[37] K Rodewald D V Holt M Rentrop et al ldquoPredictors forimprovement of problem-solving during cognitive remediationfor patients with schizophreniardquo Journal of the InternationalNeuropsychological Society vol 20 no 4 pp 455ndash460 2014

[38] O Grynszpan S Perbal A Pelissolo et al ldquoEfficacy and speci-ficity of computer-assisted cognitive remediation in schizophre-nia a meta-analytical studyrdquo Psychological Medicine vol 41 no1 pp 163ndash173 2011

[39] X Seron ldquoLevaluation de lrsquoefficacite des traitementsrdquo in Traitede Neuropsychologie Clinique X Seron and M van der LindenEds vol 2 pp 39ndash62 Solal Marseille France 2000

[40] P Vianin S Urben P Magistretti P Marquet E Fornari andL Jaugey ldquoIncreased activation in Brocarsquos area after cognitiveremediation in schizophreniardquo Psychiatry Research vol 221 no3 pp 204ndash209 2014

[41] B Pillet Y Morvan A Todd et al ldquoCognitive remediationtherapy (CRT) benefits more to patients with schizophreniawith low initial memory performancesrdquoDisability and Rehabil-itation pp 1ndash8 2014

[42] M Perdices and R L Tate ldquoSingle-subject designs as a toolfor evidence-based clinical practice are they unrecognised andundervaluedrdquo Neuropsychological Rehabilitation vol 19 no 6pp 904ndash927 2009

[43] DWechslerWechsler Adult Intelligence ScaleThePsychologicalCorporation San Antonio Tex USA 3rd edition 2005

[44] D Delis J Kramer E Kaplan and B Ober ldquoCalifornia verballearning testmanualrdquo USAPatent SanAntonio Tex USA 1987

[45] J Meyers and K Meyers Rey Complex Figure Test andRecognition Trial (RCFT) Psychological Assessment ResourcesOdessa Fla USA 1995

[46] K Conners ldquoContinuous Performance Test IIrdquo PsychologicalAssessment Resources 1999

[47] D C Delis E Kaplan and J H KramerDelis-Kaplan ExecutiveFunction System (D-KEFS) Psychological Corporation 2001

[48] DWechslerWMS-III ManualThe Psychological CorporationNew York NY USA 1997

[49] R K Heaton G J Chelune J L Talley G G Kay and G Cur-tissWisconsin Card Sorting Test Manual Revised and Expand-ed Research Edition (WCST-CV4) 128 Cards PsychologicalAssessment Resources Odessa Fla USA 1993


[50] W Culbertson and E Zillmer The Tower of London DX(TOLDX) Manual Multi-Health Systems North TonawandaNY USA 2001

[51] S R Kay L A Opler and J-P Lindenmayer ldquoThe Positive andNegative Syndrome Scale (PANSS) rationale and standardisa-tionrdquoBritish Journal of Psychiatry vol 155 no 7 pp 59ndash65 1989

[52] American Psychiatric Association Diagnostic Criteria fromDSM-IV American Psychiatric Association 1994

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014


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Disease Markers


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PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

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Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom


are asked to name as many items as possible from a givencategory in a given time period The category may besemantic such as animals or types of fruit or phonemic suchas words that begin with the letter 119901 [11] Some studies havedemonstrated that patients with schizophrenia produce feweritems and do not use recall strategies (eg farm animals andwild animals) during letter and semantic fluency tests [12]Impairment in verbal fluency was more severe for semanticfluency (effect size = 121) than for letter fluency (effect size =098) [2 13]

Considering the generalized cognitive impairments sev-eral psychological treatment strategies have therefore beendeveloped to improve cognitive functioning in this pop-ulation and they are referred to as cognitive remediationstrategies As defined at the Cognitive Remediation ExpertsWorkshop (Florence Italy April 2010) cognitive remediationfor schizophrenia refers to ldquoa behavioral training based inter-vention that aims to improve cognitive processes ( ) withthe goal of durability and generalizationrdquo Two recent meta-analyses [14 15] demonstrated that cognitive remediationfor individuals with schizophrenia has a positive moderateeffect on overall cognition psychosocial functioning andsymptoms Moreover greater effects on psychosocial func-tioning were observed when cognitive remediation was com-bined with psychiatric rehabilitation [14] However transferof gains from the research context to everyday life is ofmoderate effect size across cognitive rehabilitation studiesthat included measures of psychosocial functioning [14 15]Cognitive remediation tasks are typically quite structuredand are therefore significantly different from the situationsthat individuals with schizophrenia encounter in everydaylife [16] Currently cognitive remediation with schizophreniapatients includes two primary approaches ldquodrill and practicerdquoand ldquodrill practice and strategyrdquo [14] The first is a bottom-up approach that trains cognitive processes by repetitionusing exercises that focus on specific impaired processes [17]The second is a top-down approach that also trains cog-nitive processes by repetition However this approach alsoprovides patients with strategies for applying the practicedprocesses in daily life [18 19] That is the ldquodrill practice andstrategyrdquo remediation approach provides cues for managingreal-life situations Cognitive remediation programs thatincorporate strategies andmethods for addressing beliefs andmotivation rather than relying solely on drill and practiceare associated with more positive psychosocial outcomes[20] Moreover in developing interventions for improvingsocial functioning in this population it has been useful toconceptualize communication behavior in terms of socialskills and constituent elements of social skills [21] Onesuch cognitive remediation program for individuals withschizophrenia is the Computerized Interactive Remediationof Cognition Training for Schizophrenia CIRCuiTS [22]TheCIRCuiTS program targets difficulties with goal-directedbehavior in daily life The objectives of the program are todevelop a list of individualized goals to create an action planfor cognitive training and to implement strategies designedto facilitate the transfer of skills into everyday life

Patients with schizophrenia have heterogeneous cogni-tive profiles The CIRCuiTS program software addresses

multiple cognitive processes and allows therapists to removeor adjust exercises to adapt therapy sessions as needed Tohighlight specific cognitive deficits that are less visible ina larger sample the present paper presents a case study ofcognitive remediation in a patient with schizophrenia Thepatient (Case A) demonstrated global cognitive impairmentwith specific impairment in verbal fluency He participatedin a three-month general top-down cognitive remediationprogram We hypothesized that Case A would improve per-formance in the cognitive domains observed to be impairedat neuropsychological baseline and targeted by the CIRCuiTSprogram Moreover as verbalization is one of the primarystrategies in the CIRCuiTS program we anticipated that thismay have a beneficial effect on verbal fluency even though itis not directly targeted by specific exercises

2 Case Report

This research project was approved by the appropriate ethicscommittee at Centre de Recherche de lrsquoInstitut Universitaireen Sante Mentale in Quebec City Canada Participants withschizophrenia were recruited and consented to participateThey were informed that they could withdraw participationat any time The current paper presents a case study drawnfrom the larger sample recruited for this project Case A wasa young participant with recent-onset schizophrenia

The inclusion criteria for the larger study were (1) con-firmed DSM-IV-TR [23] schizophrenia diagnosis within thelast ten years (2) clinical status permitting reliable cognitiveassessment and (3) cognitive difficulties in visual episodicmemory immediate recall or delayed recall below the 16thpercentile as measured by the Rey complex figure test(RCFT) Exclusion criteria were (1) brain and metabolicdisorders known to cause neuropsychological impairments(2) substance dependence within the past six months and (3)Intelligent Quotient below 70

Case A was a 33-year-old man who lived alone Hehad completed 13 years of education and had obtained aprofessional certificate in institutional plumbing He wasdiagnosed with depression at age 28 and with schizophrenia(DSM-IV) at age 30 He had a past history of amphetaminedependence His pharmacological treatment which didnot change throughout the intervention included met-formin (2 times 850mg) for diabetes modafinil (100mg) todecrease sleepiness atorvastatin (10mg) for hypercholes-terolemia atenolol (12mg) for recurrentmigraines clozapine(200mg hs) desvenlafaxine (50mg) for musical obsessionsmeeting criteria for obsessional compulsive disorder (incomplete remission throughout the intervention) and twodrops of atropine (1 hs) for hypersialorrhea The patientmet with his psychiatrist approximately once per month andwith his psychologist and occupational therapist twice permonth Socially Case A saw only members of his family onceor twice a week he has worked as a plumber until 2008 andhas been unemployed since 2008

21 Cognitive Complaints At the first therapy session CaseArsquos therapist presented the cognitive remediation programand explained the study procedure in detail Difficulties in



















Clinical assessment









































4 Results







RCI
























minus1890




PANSS minus1214








5 Discussion










6 Conclusions





References





























































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of


































Clinical assessment









































4 Results







RCI
























minus1890




PANSS minus1214








5 Discussion










6 Conclusions





References





























































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of













































4 Results







RCI
























minus1890




PANSS minus1214








5 Discussion










6 Conclusions





References





























































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of




























4 Results







RCI
























minus1890




PANSS minus1214








5 Discussion










6 Conclusions





References





























































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of


















4 Results







RCI
























minus1890




PANSS minus1214








5 Discussion










6 Conclusions





References





























































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of




















5 Discussion










6 Conclusions





References





























































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of



















6 Conclusions





References





























































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of






























































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

























of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of





















of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















Documents

Case Report Top-Down Computerized Cognitive Remediation in ...downloads.hindawi.com/journals/crips/2015/242364.pdf · schizophrenia were recruited and consented to participate. ey