Schizophrenia Research xxx (2017) xxx–xxx

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Schizophrenia Research

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Abnormal prefrontal and parietal activity linked to deficient activebinding in working memory in schizophrenia

Stéphanie Grot a,b, Virginie Petel Légaré a,c, Olivier Lipp b, Isabelle Soulières a,d, Florin Dolcos e, David Luck a,b,c,⁎a Centre de recherche, Institut universitaire en santé mentale de Montréal, Montreal, Canadab Department of Psychiatry, Faculty of Medicine, Université de Montréal, Montreal, Canadac Department of Neurosciences, Faculty of Medicine, Université de Montréal, Montreal, Canadad Department of Psychology, Université du Québec à Montréal, Montréal, Canada.e Department of Psychology, Neuroscience Program, and Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, IL, USA

⁎ Corresponding author at: Centre de recherche, Institude Montréal, 7401, rue Hochelaga, Montréal, Québec H1N

E-mail address: david.luck@umontreal.ca (D. Luck).

http://dx.doi.org/10.1016/j.schres.2017.01.0210920-9964/© 2017 Elsevier B.V. All rights reserved.

Please cite this article as: Grot, S., et al., Abschizophrenia, Schizophr. Res. (2017), http:/

a b s t r a c t

a r t i c l e i n f o

Article history:Received 3 November 2016Received in revised form 6 January 2017Accepted 9 January 2017Available online xxxx

Working memory deficits have been widely reported in schizophrenia, and may result from inefficient bindingprocesses. These processes, and their neural correlates, remain understudied in schizophrenia. Thus,we designedan FMRI study aimed at investigating the neural correlates of both passive and active binding inworkingmemoryin schizophrenia. Nineteen patients with schizophrenia and 23 matched controls were recruited to perform aworking memory binding task, in which they were instructed to memorize three letters and three spatial loca-tions. In the passive binding condition, letters and spatial locationswere directly presented as bound. Conversely,in the active binding condition, words and spatial locations were presented as separated, and participants wereinstructed to intentionally create associations between them. Patients exhibited a similar performance to thecontrols for the passive binding condition, but a significantly lower performance for the active binding. FMRIanalyses revealed that this active binding deficit was related to aberrant activity in the posterior parietal cortexand the ventrolateral prefrontal cortex. This study provides initial evidence of a specific deficit for actively bind-ing information in schizophrenia, which is linked to dysfunctions in the neural networks underlying attention,manipulation of information, and encoding strategies. Together, our results suggest that all these dysfunctionsmay be targets for neuromodulation interventions known to improve cognitive deficits in schizophrenia.

© 2017 Elsevier B.V. All rights reserved.

Keywords:SchizophreniaFMRIWorking memoryMemory binding

1. Introduction

Schizophrenia (SZ) is associated with severe cognitive deficits, suchas attention, memory and executive function (Heinrichs and Zakzanis,1998; Saykin et al., 1991), which are among the most critical determi-nants of quality of life and level of function in patients (Green, 2006;Sharma and Antonova, 2003). Impairments of working memory(WM) – the system that transiently holds andmanipulates informationin the mind – are particularly prominent in SZ (Park and Gooding,2014), and are considered as a cardinal feature of the illness (Barchand Ceaser, 2012; Goldman-Rakic, 1994). Researches revealedWMdef-icits across different tasks, stimuli modalities, or temporal componentsof events (Park and Gooding, 2014). One aspect of WM dysfunctionthat has received limited attention is the complexity of informationprocessed, dissociating discrete (or unimodal) from bound (or multi-modal) stimuli. For instance, it has been suggested that patients withSZ have more difficulties memorizing the association between

t Universitaire en SantéMentale3M5, Canada.

normal prefrontal and pariet/dx.doi.org/10.1016/j.schres.2

information (multimodal) than the information itself (unimodal)(Burglen et al., 2004). This associative process, usually referred to asbinding, may be of great importance in SZ, as its disturbance might in-duce incomplete or inaccurate representations (Mitchell and Johnson,2009). Recently, we investigated WM binding in SZ in a set of comple-mentary studies (Luck et al., 2008, 2009, 2010), in which participantswere instructed tomaintain items composed of letters and spatial loca-tions, presented either bound or separated. We established that, whencontrolling for memory load and for spatial WM performance, patientsperformed equally well as controls for the binding condition, thus sug-gesting preserved binding capacities in patients (Giersch et al., 2011;Luck et al., 2008, 2009, 2010). This was recently confirmed by a meta-analysis on data from 301 patients with SZ and 237 healthy controls(Grot et al., 2014).

Noteworthy,most experimental assessments in SZ are based on pas-sive binding, as information is presented as already bound, and henceless is known about active binding and its neural correlates in thesepatients. In everyday life, information processing also occurs withconscious efforts to associate things (e.g. stimuli, events and thoughts),in order to create a unified and coherent representation in memory.Consequently, the assessment of such active binding could provide a

al activity linked to deficient active binding in working memory in017.01.021

2 S. Grot et al. / Schizophrenia Research xxx (2017) xxx–xxx

crucialmissing part for a complete portrait ofWM functioning in SZ. Ac-tive binding requires different cognitive operations, such as selective at-tention (Luck and Gold, 2008; Nuechterlein et al., 2015), manipulationof information (Gooding and Tallent, 2004; Kim et al., 2004), andencoding strategies (Bonner-Jackson and Barch, 2011; Bonner-Jacksonet al., 2005), which are attributed to prefrontal and parietal functioning(Prabhakaran et al., 2000; Shafritz et al., 2002;Wendelken et al., 2008).

To the best of our knowledge, active binding and its neural correlateshave not been investigated so far in SZ. Thus, we designed an experi-mental protocol that examined both passive and active forms of bindingin WM in SZ. To identify possible finer cerebral dysfunctions in SZ,we used an event-related FMRI design that allowed assessment ofencoding, maintenance, and retrieval processes. Based on our previousfindings, we hypothesized that patients with SZ would exhibit pre-served performance for passive binding, but altered performance foractive binding. At the neural level, we anticipated that the specific activebinding deficit would be linked to aberrant activity in prefrontal andparietal cortices that support cognitive processes required for activebinding, such as attention, manipulation of information, and encodingstrategies.

2. Material and methods

2.1. Participants

Demographic and clinical data are summarized in Table 1. Nineteenoutpatients and 23 healthy controls participated in the study. All pa-tients met the DSM-IV-TR criteria for schizophrenia (APA, 2000),based on the Structured Clinical Interview for DSM-IV (First et al.,2002). Symptom severity was determined using the Positive and Nega-tive Syndrome Scale (PANSS) (Kay et al., 1987). Patients were clinicallystable for at least one month at the time of testing. Seventeen patientswere taking 2nd generation antipsychotic medication, one patient wastaking 1st generation antipsychotic medication, and one patient wastaking both types of medication. The healthy controls were recruitedby means of advertisements placed in local newspapers. Controls wereexcluded if they reported current or past history of any Axis I disorders,neurological diseases, head trauma causing loss of consciousness, or if afirst-degree family member had sought help for mental health issues or

Table 1Sociodemographic and clinical data in patientswith schizophrenia (SZ) and in controls. Alldata are presented as means and SEMs.

Characteristic Patients with SZN = 19

ControlsN = 23

Analysis(P)

Sociodemographic characteristicsAge (years) 36.30

(1.70)32.78(2.52)

0.20

Gender (M/F) 14/5 15/8 0.55Handednessa 0.84

(0.05)0.78(0.11)

0.63

Parental SES scoreb 51.88(3.31)

45.83(4.60)

0.28

IQc 96.21(2.93)

105.18(2.29)

0.02

Clinical characteristicsAntipsychotic dosed 349.76

(47.26)PANSS Positive 16.16

(1.18)PANSS Negative 15.89

(0.90)PANSS General 34.38

(2.04)

a Edinburgh Handedness Inventory.b Hollingshead Parental Socio-Economic Status.c Evaluated with the WAIS-III.d Expressed in CPZ equivalent.

Please cite this article as: Grot, S., et al., Abnormal prefrontal and parieschizophrenia, Schizophr. Res. (2017), http://dx.doi.org/10.1016/j.schres.2

received a psychiatric diagnosis. The patient and control groups werematched on age, gender, handedness, parental socio-economic status,but had significantly different IQ1 (see Table 1). The RegroupementNeuroimagerie/Québec Ethical Review Board approved the study. Allparticipants signed an informed consent form prior to the experimentand received financial compensation for their participation.

2.2. Procedure

Prior to scanning, participants were provided with a detailed de-scription of the task, followed by a short practice session administeredin order to familiarize them with the experimental task.

The experimental task is illustrated in Fig. 1. It was divided into sixblocks of 15 trials (five consecutive trials per condition). Each trialstarted with the presentation of a central fixation cross (1 s), followedby a target display of items (3 s). This period was defined as theencoding phase. The target display consisted of three words and threespatial locations defined by an ellipse. The words were selected fromthe French Lexicon Project (Ferrand et al., 2010).Within a target display,the threewordswere semantically unrelated. Five naive raters validatedthe absence of semantic links between the three words of each targetdisplay.

The presentation of verbal and spatial information differed depend-ing on the experimental condition. In the “active binding” condition, thethree words were central, and separated from the three ellipses. In thiscondition, participants had to mentally link the verbal and spatial infor-mation sharing the same color (e.g. the word in red must be associatedwith the position defined by a red ellipse). In the “passive binding” con-dition, words were already included within ellipses. Binding here wasdeemed “passive”, as verbal and spatial information was presented asalready integrated. Then, a probe composed of aword and a spatial loca-tion was presented (3 s). This period was defined as the retrieval phase.In both binding conditions, a word within an ellipse was presented.Participants had to decide whether their pairing was identical to theencoding phase or not (i.e., the word was associated with a locationthat was previously paired with another word). Thus, making correctresponses in spite of re-pairings presented as distractors required accu-rate memory not only for verbal and spatial information, but also fortheir pairing (Mitchell et al., 2000). After a blank screen of 10 s, a newtrial began. This long inter-trial interval was used to avoid elevatedbaseline activity prior to the onset of the next display (Yamasaki et al.,2002). A third condition, in which memory for isolated letters and spa-tial locations was assessed, was also included. However, this conditionwas not presented here, considering that the paper focuses on the dif-ferences between active and passive binding. Exclusion of this conditiondoes not influence the conclusion of the manuscript.

2.3. FMRI scanning protocol

The scanning sessions were carried out at the Institut Universitairede Gériatrie de Montréal (IUGM) on a 3 T scanner (Siemens MagnetonTRIO). The scanning sessions began with the acquisition of functionalimages over the entire brain using a T2* BOLD EPI sequence along theAC-PC axis (TR = 2.25 s/TE = 30 ms/Flip angle = 90°/37slices/resolu-tion = 3 × 3 × 3 mm3). The first three scans were removed to obtaina steady-state T1 partial saturation effect. Finally, an anatomical MRIusing a 3D T1-weighted (TR = 22 ms/TE = 9.2 ms/flip angle = 30°/FOV=256mm/176 slices/resolution=1×1× 1mm3)was performed.

1 SZ is usually associatedwith intellectual deficits, as reflected by a lower IQ score in pa-tients relative to controls. However, patients' IQ score did not differ significantly frommean 100 (t18 = −−1.29; p = 0.21). In addition, the parental socio-economic statuswas used as a measure of premorbid functioning.

tal activity linked to deficient active binding in working memory in017.01.021

Fig. 1. Procedure and timeline for experimental conditions. In the “active binding” condition, participants have to intentionally and mentally link the words and ellipses sharing the samecolor (e.g. the word in red must be associated with the position defined by a red ellipse). In the “passive binding” condition, words and ellipses are presented as bound together. (Forinterpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

3S. Grot et al. / Schizophrenia Research xxx (2017) xxx–xxx

2.4. Data analysis

2.4.1. Behavioral analysesBehavioral performance was analyzed using Statistica 6.0 (Statsoft).

Accuracy was estimated using the Pr index (Hits–False Alarms), toprovide an objective measure of sensitivity that is independent ofparticipant response bias (Snodgrass and Corwin, 1988). A repeated-measure analysis of variance (ANOVA) was performed with the group(patients vs. controls) entered as between-group factor and bindingconditions (passive binding vs. active binding) as within-group factor.When needed, Duncan test comparisons were performed for post-hocanalyses. In all behavioral analyses, the alpha level was set at 0.05.

2.4.2. Neuroimaging analysesAnalyses were performed with SPM8 (http://www.fil.ion.ucl.ac.uk/

spm/spm8). First, for preprocessing, functional images were realignedto the first volume in their respective run, and then normalized to theMontreal Neurological Institute (MNI) template. Then, data werespatially smoothed using a 3D 8-mm Gaussian filter. High-pass andlow-pass filters were applied to filter out physiological artifacts. Priorto individual analyses, the movement correction logs were examinedto ensure that none of the participants presented movements N5 mmor 5°. In addition, head translation and head rotation were extractedduring the preprocessing realignment and included as covariates inthe first-level models. Four event types were modeled in each bindingcondition: encoding, early period ofmaintenance, late period ofmainte-nance, and retrieval. Themaintenance phasewas split into two separateregressors, as different processes are associated with the early and thelate maintenance (Naveh-Benjamin and Jonides, 1984). The cut offwas set at 3 s in accordance with previous studies (Bergmann et al.,2013; Khader et al., 2007). For each of the four phases, an individual [ac-tive – passive] contrast was generated. These individual activationmapswere then pooled into a second-level analysis to perform a random-ef-fect group analysis (two-sample t-test) for each group (Friston et al.,2002). To address the issue of multiple comparisons, a cluster-extent

Please cite this article as: Grot, S., et al., Abnormal prefrontal and parietschizophrenia, Schizophr. Res. (2017), http://dx.doi.org/10.1016/j.schres.2

based correction, determined through Monte-Carlo simulation, withtheMatlab script developed by Slotnick et al. (2003). Results of our sim-ulation indicated that, given a voxel-wise intensity threshold ofp b 0.005 and the whole-brain search space, a cluster extent thresholdof 51 contiguous voxels would be necessary to achieve an overall typeI error rate of p b 0.05, corrected for multiple comparisons. This combi-nation of intensity and extent thresholds has been deemed appropriatein yielding a good balance between Type I and II error rates (Liebermanand Cunningham, 2009).

2.4.3. Additional analysesPearson correlations were also performed to examine the potential

impact of medication and symptoms on both behavioral performanceand BOLD signals. B\\Ymethod FDR correctionswere applied to controlfor multiple comparisons (Narum, 2006).

3. Results

3.1. Behavioral results

Pr scores are illustrated in Fig. 2, and summarized in Table 2. Thegroup X binding conditions ANOVA showed a significant effect ofgroup (F(1,40) = 6.56; p = 0.02) with patients' overall performancebeing lower than that of controls. There was also a significant effect ofconditions (F(1,40) = 23.27; p b 0.001), with greater performance inthe passive than active binding task. Finally there was a significantgroup X conditions interaction (F(1,40) = 4.56; p = 0.04). Post-hocanalyses revealed that patients exhibited significantly lower perfor-mance for active binding relative to controls (p b 0.02), but performedequally well as controls for passive binding (p = 0.31).

3.2. FMRI results

For concision purpose, only between-group differences are present-ed in the following sections; intra-group activations are reported in theSupplementary material.

al activity linked to deficient active binding in working memory in017.01.021

Fig. 2. Behavioral performance. Mean Pr (hits – false alarms) scores for both bindingconditions are shown for controls and patients with schizophrenia (SZ). Errors barsrepresent SEM. ⁎p b 0.05.

4 S. Grot et al. / Schizophrenia Research xxx (2017) xxx–xxx

3.2.1. EncodingBetween-group contrasts showed greater activation in controls rela-

tive to patientswith SZ in the superior and inferior parietal lobules bilat-erally, the lingual gyrus bilaterally, the left fusiformgyrus, theprecentralgyrus bilaterally, the left superior frontal gyrus, the right postcentralgyrus and the right cerebellum (Fig. 3 and Table S1). In contrast, patientsexhibited no greater activation than controls.

3.2.2. Early maintenanceAnalyses revealed that controls showed greater activations than

patients in the left ventrolateral prefrontal cortex (VLPFC) (Fig. 4 andTable S2). Conversely, patients with SZ exhibited greater activationthan controls in the left thalamus, and the left postcentral gyrus.

3.2.3. Late maintenanceBetween-group differences showed greater activations in controls

relative to patients in the left inferior parietal lobule and the leftprecentral gyrus. In contrast, patients exhibited no greater activationsthan controls (Table S3).

3.2.4. RetrievalFinally, patients with SZ showed a lower activation in the left cere-

bellum and left fusiform gyrus relative to controls. Conversely, patientsexhibited no greater activations than controls (Table S4).

Table 2Mean and SEM proportions of Pr index (hits, H – false alarms, FA), as a function of experiment

Passive binding

H FA P

Patients with SZ 0.81(0.02)

0.08(0.06)

0(

Controls 0.85(0.01)

0.02(0.01)

0(

Please cite this article as: Grot, S., et al., Abnormal prefrontal and parieschizophrenia, Schizophr. Res. (2017), http://dx.doi.org/10.1016/j.schres.2

3.3. Additional analyses

Correlations between antipsychotic dosages (expressed in chlor-promazine equivalent), and both Pr scores and BOLD signals wereassessed. None of the analyses showed any significant correlations (allp's N 0.05 after correction), indicating that the overall level of patientperformance and BOLD activation were unlikely influenced by thedose of their current antipsychotic medication. Another set of analysesrevealed no significant correlations between symptom severity andbrain activation or behavioral performance (all p's N 0.05 aftercorrection).

4. Discussion

4.1. A specific deficit of active binding in SZ

This FMRI study aimed to investigate the neural basis of active andpassive binding inWM in SZ. At the behavioral level, our study revealedthat patientswith SZwere able to correctlymemorize already bound in-formation. Such results are in line with our previous works on passivebinding inWM (Luck et al., 2008, 2009, 2010), and with our meta-anal-ysis conclusions (Grot et al., 2014). The novelty is that patients exhibiteda specific deficit in voluntarily binding information. This deficit may notresult from a reduced memory span (Barch and Ceaser, 2012), or diffi-culties to simultaneously process different types of information, sinceboth experimental conditions were composed of the same amount ofinformation (i.e. three letters and three spatial positions), and the pa-tients exhibited similar performance to that of controls for the passivebinding condition. Instead, the specific deficit of active binding in pa-tients with SZ can be explained by three notmutually exclusive hypoth-eses linked to the differences identified in brain activity, as discussedbelow.

4.2. Evidence for abnormal posterior parietal cortex and VLPFC functioningin SZ

1. Does posterior parietal activity reflect patients' attentional difficul-ties? It has been suggested that maintaining bound information inWM requires additional attentional resources thanmaintaining discreteinformation (Allen et al., 2006; Wheeler and Treisman, 2002), and thisespecially for active/intentionally bound information (Morey, 2011).Active processes require additional attentional resources. Specifically,during encoding, active binding requires focusing and switching atten-tion to all the displayed information (Corbetta et al., 1995), involving in-ferior (Nee et al., 2013; Nee and Jonides, 2008) and superior parietalcortex activity (Chiu and Yantis, 2009; Wager et al., 2004; Wang et al.,2015), respectively. Thus, the deficit for active binding observed in pa-tients may result from their inability to switch andmaintain focused at-tention on the link between verbal and spatial information. However,this attention-deficit hypothesis hardly explains the deficit specificityfor active binding, since other studies have found contradictory resultssuggesting thatmaintaining bound information inWMdoes not requiremore attentional resources than maintaining discrete information(Allen et al., 2006; Vogel et al., 2001). Consequently, lower performancein patients relative to controls should have been observed in both bind-ing conditions. Additionally, the observed posterior parietal cortex

al conditions for patients with schizophrenia (SZ) and controls.

Active binding

r H FA Pr

.730.04)

0.74(0.03)

0.23(0.05)

0.51(0.08)

.830.04)

0.85(0.03)

0.10(0.02)

0.75(0.06)

tal activity linked to deficient active binding in working memory in017.01.021

Fig. 3. FMRI results for the encoding. Section A illustrates between-group comparisons during the encoding period. Greater activations in controls relative to patientswith SZ are showed inwarm colors. Section B illustrates beta values in the left SPL, and IPL bilaterally in controls and in patients with SZ. PG, Postcentral Gyrus; PcG, Precentral Gyrus; IPL, Inferior Parietal Lobule;SPL, Superior Parietal Lobule; IOG, Inferior Occipital Gyrus; LG, Lingual Gyrus; FG, Fusiform Gyrus.

5S. Grot et al. / Schizophrenia Research xxx (2017) xxx–xxx

hypoactivation during encodingwould have been observed during bothearly and late maintenance as well. To sum up, the explanation that theactive binding deficit may result from limited attentional resources isonly partially supported by our results.

2. Does posterior parietal activity reflect patients' failure to manipulateinformation? Another hypothesis relies on a deficit of informationmanipulation. Unlike the passive binding condition, the active bindingcondition required the manipulation of verbal and spatial informationto voluntarily and consciously create a link between them. Behavioralstudies in WM have shown that patients with SZ have marked

Fig. 4. FMRI results for the early maintenance. Section A illustrates between-group comparisonwith SZ are showed in warm colors, whereas greater activations in SZ patients relative to conVentro-Lateral Prefrontal Cortex; PG, Postcentral Gyrus; Th, Thalamus.

Please cite this article as: Grot, S., et al., Abnormal prefrontal and parietschizophrenia, Schizophr. Res. (2017), http://dx.doi.org/10.1016/j.schres.2

difficulties in manipulating information in WM (Barch, 2005; Park andGooding, 2014), to a greater extent than for its encoding and mainte-nance. This hypothesis is strengthened by our results of hypoactivationof the posterior parietal cortex during encoding, a cerebral regioninvolved in the manipulation of information in WM (Champod andPetrides, 2007; Koenigs et al., 2009; Owen et al., 2005). Such ahypoactivation may indicate that patients, unlike controls, failed to ma-nipulate or reorganize verbal and spatial information efficiently duringtheir initial presentation, and were thereby unable to create unifiedrepresentations.

s during the early maintenance period. Greater activations in controls relative to patientstrols are showed in cold colors. Section B illustrates beta values in the left VPLFC. VLPFC,

al activity linked to deficient active binding in working memory in017.01.021

6 S. Grot et al. / Schizophrenia Research xxx (2017) xxx–xxx

3. Does VLPFC mediates binding or encoding strategies failure in pa-tients? Beside increased activity in the posterior parietal cortex duringearly maintenance, patients also exhibited reduced activity in theVLPFC. This region is considered to be involved in articulatory rehearsal,which is essential for maintaining discrete verbal information (Gruberet al., 2006; Rottschy et al., 2012), aswell as bound verbal and spatial in-formation (Campo et al., 2010). Thus, hypoactivation of the VLPFC mayreflect the patients' difficulties tomaintain integrated representations inWM, as they did not create such representations during encoding.Another explanation is that patients, unlike controls, did not useeffective strategies to maintain bound information in our task. Aspinpointed by Bor et al. (2003), the VLPFC is involved in the generationof cognitive strategies to maintain complex information in memory.Thus, lower VLPFC activity in patientsmay reflect their inability to spon-taneously use efficient strategies to maintain information in WM(Bonner-Jackson and Barch, 2011; Bonner-Jackson et al., 2005), leadingto poorer performance for the active binding condition.

4.3. Caveats

The effect of psychotropic drugs may constitute a limitation to thisstudy. As all patients were taking antipsychotic medication during ourstudy, their effect cannot be ruled out completely, and the possibilitythat thismay have had an influence on our results cannot be discounted.However, there was no significant correlation between behavioralperformance or BOLD signal and the mean dose of antipsychoticmedication. This suggests that the dose of the medication did not havea significant impact on the results. Another limitation is that we didnot strictly control for literacy, which is associated with poor cognitivefunctioning in patients (Clegg et al., 2005; Dickson et al., 2014). Al-though all participants reported having completed their high schooltraining, ensuring a minimum level of literacy, we consider that furtherinvestigations are required to examine more in detail the impact of lit-eracy on active binding deficits in patients with SZ.

5. Conclusion

Our study disentangled preserved from altered processes of WM inSZ, arguing against a generalized deficit. More precisely, our resultsshowed that patientswith SZmay suffer froma lack of attention,manip-ulation and the use of strategies which are required for correctly mem-orizing actively bound information in WM. This results from theabnormal functioning of the posterior parietal cortex and the VLPFC.Such a dysfunction may constitute the target for new therapeutic inter-ventions, such as neuromodulation techniques, known to improvedifferent aspects of cognition (Brunoni and Vanderhasselt, 2014;Demirtas-Tatlidede et al., 2013; Lett et al., 2014).

Role of the funding source

This study was supported by the Brain and Behavior Research Foun-dation (#18917) and the Quebec BioImaging Network (#5.06). Dr. Luckis supported by a salary award from the Fonds de recherche en santé duQuébec (FRSQ) (#27178). Dr. Dolcos was supported by a Helen CorleyPetit Endowed Scholarship and an Emanuel Donchin ProfessorialScholarship from the University of Illinois.

Conflict of interestAll authors declare that they have no conflicts of interest.

ContributorsAuthor SG acquired and analyzed the data, interpreted results, and wrote the first

draft of themanuscript. Author VPL and FD collaborated in the writing of the final versionof the manuscript. Authors OL and IS supervised clinical and neuropsychological assess-ments. Author DL conceptualized the study, supervised the study, provided laboratoryspace and resources for data analyses. All authors contributed to and have approved thefinal manuscript.

Please cite this article as: Grot, S., et al., Abnormal prefrontal and parieschizophrenia, Schizophr. Res. (2017), http://dx.doi.org/10.1016/j.schres.2

AcknowledgementsThe authors thank Drs Jean-Pierre Melun and Luigi de Benedictis for their help in re-

cruitment. This study was supported by the Brain and Behavior Research Foundation(#18917) and the Quebec BioImaging Network (#5.06). Dr. Luck is supported by a salaryaward from the Fonds de recherche en santé du Québec (FRSQ) (#27178). Dr. Dolcos wassupported by a Helen Corley Petit Endowed Scholarship and an Emanuel Donchin Profes-sorial Scholarship from the University of Illinois.

Appendix A. Supplementary data

Supplementary data to this article can be found online at http://dx.doi.org/10.1016/j.schres.2017.01.021.

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Please cite this article as: Grot, S., et al., Abnormal prefrontal and parietschizophrenia, Schizophr. Res. (2017), http://dx.doi.org/10.1016/j.schres.2

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