Motivated to do well: An examination of the relationships between motivation, effort, and cognitive performance in schizophrenia

Motivated to do well: An examination of the relationships between motivation, effort, and cognitive performance in schizophrenia

SCHRES-06382; No of Pages 7 Schizophrenia Research xxx (2015) xxx–xxx Contents lists available at ScienceDirect Schizophrenia Research journal homep...

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SCHRES-06382; No of Pages 7 Schizophrenia Research xxx (2015) xxx–xxx

Contents lists available at ScienceDirect

Schizophrenia Research journal homepage: www.elsevier.com/locate/schres

Motivated to do well: An examination of the relationships between motivation, effort, and cognitive performance in schizophrenia G. Foussias a,b,d,⁎, I. Siddiqui a,b,d, G. Fervaha a,b,d, S. Mann a,d, K. McDonald a,d, O. Agid a,d, K.K. Zakzanis c, G. Remington a,d a

Campbell Family Research Institute and Schizophrenia Division, Centre for Addiction and Mental Health, 250 College St., Toronto, Ontario M5T 1R8, Canada Institute of Medical Science, Faculty of Medicine, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada Department of Psychology, University of Toronto Scarborough, Toronto, Ontario M1C 1A4, Canada d Department of Psychiatry, University of Toronto, 250 College St., Toronto, Ontario M5T 1R8, Canada b c

a r t i c l e

i n f o

Article history: Received 4 October 2014 Received in revised form 5 May 2015 Accepted 8 May 2015 Available online xxxx Keywords: Motivation Apathy Effort Performance validity Cognition Negative symptoms Schizophrenia

a b s t r a c t The uncertain relationship between negative symptoms, and specifically motivational deficits, with cognitive dysfunction in schizophrenia is in need of further elucidation as it pertains to the interpretation of cognitive test results. Findings to date have suggested a possible mediating role of motivational deficits on cognitive test measures, although findings from formal examinations of effort using performance validity measures have been inconsistent. The aim of this study was to examine the relationships between motivation, effort exerted during cognitive testing, and cognitive performance in schizophrenia. Sixty-nine outpatients with schizophrenia or schizoaffective disorder were evaluated for psychopathology, severity of motivational deficits, effort exerted during cognitive testing, and cognitive performance. Motivation and degree of effort exerted during cognitive testing were significantly related to cognitive performance, specifically verbal fluency, verbal and working memory, attention and processing speed, and reasoning and problem solving. Further, effort accounted for 15% of the variance in cognitive performance, and partially mediated the relationship between motivation and cognitive performance. Examining cognitive performance profiles for individuals exerting normal or reduced effort revealed significant differences in global cognition, as well as attention/processing speed and reasoning and problem solving. These findings suggest that cognitive domains may be differentially affected by impairments in motivation and effort, and highlight the importance of understanding the interplay between motivation and cognitive performance deficits, which may guide the appropriate selection of symptom targets for promoting recovery in patients. © 2015 Elsevier B.V. All rights reserved.

1. Introduction Motivational deficits have long been recognized as a central feature of schizophrenia (Kraepelin, 1919; Bleuler, 1950), and along with diminished expression comprise the two core subdomains of negative symptoms in the illness (Foussias and Remington, 2010; Messinger et al., 2011). Clinically, motivational deficits refer to a diminishment in goal-directed behavior and the associated internal processes (such as interest, curiosity, and drive) that prompt the individual to plan, initiate, and pursue activities (Andreasen, 1982; Marin et al., 1991; Nakagami et al., 2008). These motivational deficits have been shown to play important roles in predicting cross-sectional and longitudinal functional outcomes in schizophrenia (Sayers et al., 1996; Kiang et al., 2003; Faerden et al., 2009a; Foussias et al., 2009; Faerden et al., 2010; Foussias et al., 2011; Konstantakopoulos et al., 2011; Evensen et al., ⁎ Corresponding author at: Centre for Addiction and Mental Health, 250 College St., Toronto, Ontario M5T 1R8, Canada. E-mail address: [email protected] (G. Foussias).

2012; Fervaha et al., 2014a,b). Recent work examining the interaction between negative symptoms and cognitive impairments, and their respective relationships with functional outcomes, has also revealed that negative symptoms, and specifically motivational deficits, mediate the relationship between cognition and functioning (Nakagami et al., 2008; Gard et al., 2009; Ventura et al., 2009; Green et al., 2012). Motivational deficits have also been found to exhibit a direct relationship with cognitive impairments seen in schizophrenia. Early work revealed that motivational deficits seen in individuals with psychotic disorders were linked to poor performance on tests of attention, vigilance, and verbal memory (Schmand et al., 1994). Similarly, clinical measures of motivation have shown significant relationships with cognitive performance, and specifically with verbal fluency, working memory, attention and set-shifting, processing speed, and verbal learning and memory in individuals with schizophrenia (Addington and Addington, 1999; Roth et al., 2004; Nakagami et al., 2008; Faerden et al., 2009b; Gard et al., 2009; Konstantakopoulos et al., 2011; Fervaha et al., 2014c). In addition, a recent examination of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia

http://dx.doi.org/10.1016/j.schres.2015.05.019 0920-9964/© 2015 Elsevier B.V. All rights reserved.

Please cite this article as: Foussias, G., et al., Motivated to do well: An examination of the relationships between motivation, effort, and cognitive performance in schizophrenia, Schizophr. Res. (2015), http://dx.doi.org/10.1016/j.schres.2015.05.019

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G. Foussias et al. / Schizophrenia Research xxx (2015) xxx–xxx

study revealed a significant link between longitudinal change in motivation and change in cognitive test performance (Fervaha et al., 2014c). Furthermore, monetary incentives have been found to improve performance on some cognitive tasks, such as the Wisconsin Card Sorting Task (Heaton, 1981), the Span of Apprehension (Asarnow and Nuechterlein, 1987), and facial emotion recognition tasks (Summerfelt et al., 1991; Kerr and Neale, 1993; Kern et al., 1995; Penn and Combs, 2000). Importantly, this has not been consistent across all studies (Green et al., 1990), suggesting that motivation may differentially impact performance across cognitive domains. Such findings have raised questions of whether some of the cognitive impairment seen in patients with schizophrenia is driven by a lack of motivation to do well on cognitive tasks (Barch, 2005). An alternative approach to investigate the impact of motivational deficits on cognitive performance has been to assess the degree of effort individuals exert during cognitive testing using performance validity tests (PVTs). Such PVTs often employ forced-choice tasks whereby individuals are presented a series of verbal or visual stimuli, followed by presentation of stimulus pairs from which they must identify the one previously presented (Bianchini et al., 2001). While frequently employed in the context of litigation and compensation evaluations whereby an external incentive is present, PVT use has not been without controversy given the absence of a “gold standard” for cognitive effort and their validation based on simulation or known-group designs (Bianchini et al., 2001; Bigler, 2012). Nonetheless, PVTs are essential in the interpretation of neuropsychological test data so as to understand whether participants are providing sufficient effort during testing (Sharland and Gfeller, 2007; McCarter et al., 2009; Fox, 2011). PVTs have also been increasingly used for the assessment of effort in nonlitigation settings, including in children, adolescents, healthy university students, and in neurological disorders (Merten et al., 2007; Locke et al., 2008; Axelrod and Schutte, 2011; Kirk et al., 2011; An et al., 2012; Brooks et al., 2012; Wisdom et al., 2012). Across psychiatric populations, investigations have demonstrated that depression and anxiety disorders do not impact PVT scores (reviewed in Goldberg et al., 2007). In schizophrenia, however, there have been mixed findings. Early studies using PVTs identified 13% to 27% of individuals with schizophrenia as exerting reduced effort (i.e., failing the PVT) (Back et al., 1996; Goldberg et al., 2007). Ensuing work by Egeland et al. (2003), comparing individuals with schizophrenia, depression, and healthy controls found that 5% of individuals with schizophrenia exerted reduced effort, not significantly different from other groups where no individuals exerted reduced effort. Another investigation of individuals with psychotic disorders using the Test of Memory Malingering (TOMM; (Tombaugh, 1996)), one of the most frequently used PVTs (Sharland and Gfeller, 2007; McCarter et al., 2009), found that 8% of participants exerted reduced effort (Duncan, 2005). A subsequent examination by Gorissen et al. (2005) investigated effort and cognitive performance in individuals with schizophrenia using another common PVT, the Word Memory Test (WMT). They found the prevalence of reduced effort to be 72% in the schizophrenia group, compared to 25% in the psychiatric control group, 10% in the neurological control group, and 0% in the healthy control group, with effort accounting for between 14% and 35% of the variance in cognitive test scores (Gorissen et al., 2005). In contrast, another study also using the WMT to assess effort in schizophrenia found much better performance, with average scores on the WMT comparable to the psychiatric control group in Gorissen et al. (2005) (Avery et al., 2009). Similarly, a recent investigation by Strauss et al. (2015) found that 15% of schizophrenia participants exhibited reduced effort on the WMT, with effort being a significant predictor of global cognitive impairment. Finally, an examination of performance across seven PVTs reported that 19% of participants with psychotic disorders exhibited reduced effort determined by failure on a single PVT, although with a lower prevalence of reduced effort (7%) when using more stringent criteria (i.e., failure on two PVTs) (Schroeder and Marshall, 2011).

Given the relationships between motivational and cognitive deficits with functional outcomes in schizophrenia, disentangling the impact of motivation on cognitive functioning is essential as we strive to identify critical treatment targets to improve functional outcomes in this illness. Accordingly, the aim of the present study was to investigate the relationships between motivation, effort exerted on cognitive testing, and cognitive test performance in schizophrenia. In this context, effort assessed through PVT performance served as an objective index of motivation to do well during cognitive testing. We also sought to examine the relationship of effort as measured by the TOMM with cognition both as a continuous and dichotomous construct. This was driven in large part by the recognition that classification of effort as normal or reduced, while useful for forensic evaluations, may not accurately capture the variations in effort that individuals with schizophrenia may exhibit when undertaking cognitive testing. We hypothesized that both clinical measures of motivation and effort exerted on cognitive testing would be significant predictors of cognitive test performance, with effort mediating the relationship between motivation and cognitive test performance. Further, we hypothesized that individuals exhibiting reduced effort on cognitive testing would have significantly lower cognitive test performance. 2. Methods 2.1. Participants Individuals between the ages of 18 and 55 with a DSM-IV diagnosis of Schizophrenia or Schizoaffective Disorder, determined by the Mini International Neuropsychiatric Interview for Schizophrenia and Psychotic Disorders Studies (MINI) (Sheehan et al., 1998), were recruited at the Centre for Addiction and Mental Health, Toronto, Canada. All participants were outpatients on stable doses of antipsychotic medications for at least 4 weeks. Participants were excluded from the study if they: met criteria for substance abuse or dependence within the past 3 months (excepting nicotine), or other DSM-IV Axis I disorders; had a history of neurological disease; were experiencing significant akathisia (a rating of N2 on the Barnes Akathisia Rating Scale Global item (Barnes, 1989)), or significant extrapyramidal symptoms (a rating of N 2 on more than 2 items of the Simpson Angus Rating Scale (SARS) (Simpson and Angus, 1970)). 2.2. Instruments and procedures Positive and negative symptom severity was evaluated with the Scale for the Assessment of Positive Symptoms (SAPS) (Andreasen, 1984), and the Scale for the Assessment of Negative Symptoms (SANS) (Andreasen, 1982), respectively. SAPS total score consisted of the sum of all items excluding global items, while SANS total score consisted of the sum of all items excluding the attention subscale and global items. Further, negative symptoms were separated into their 2 core subdomains: Diminished Expression and Amotivation (reviewed in (Foussias and Remington, 2010)). The SANS Diminished Expression subdomain was comprised of the Affective Flattening subscale and the Poverty of Speech item (excluding inappropriate affect, poverty of content of speech, blocking, response latency, and global items). The SANS Amotivation subdomain was comprised of the Avolition–Apathy and Anhedonia–Asociality subscales (excluding global items). Amotivation was also assessed using the Apathy Evaluation Scale — Clinician version (AES) (Marin et al., 1991), and the Intrinsic Motivation factor score from the Quality of Life Scale (QLS) that consisted of the mean score for QLS items purpose, motivation, and curiosity (Heinrichs et al., 1984; Nakagami et al., 2008). Depressive symptoms were evaluated with the Calgary Depression Scale for Schizophrenia (CDSS) (Addington et al., 1990). Effort exerted during cognitive testing was evaluated using the TOMM, a 50-item forced-choice visual object recognition task that

Please cite this article as: Foussias, G., et al., Motivated to do well: An examination of the relationships between motivation, effort, and cognitive performance in schizophrenia, Schizophr. Res. (2015), http://dx.doi.org/10.1016/j.schres.2015.05.019

G. Foussias et al. / Schizophrenia Research xxx (2015) xxx–xxx

includes two recognition trials and a delayed retention trial. In this study the first recognition trial of the TOMM (TOMM1) was used, with a TOMM1 score b41 (i.e., b82% correct) indicative of failure on the TOMM (i.e., reduced effort). This threshold on the TOMM1 exhibits high levels of sensitivity and specificity in mixed psychiatric populations, and may serve as a better measure of performance validity compared to the original scoring procedure involving the second and retention trials (Hilsabeck et al., 2011; Denning, 2012). Immediately following the TOMM, cognitive functioning was measured with the Brief Assessment of Cognition in Schizophrenia (BACS), which assesses verbal memory (List Learning), working memory (Digit Sequencing Task), motor speed (Token Motor Task), verbal fluency (Category Instances, and Letter Fluency), attention/processing speed (Symbol Coding), and reasoning and problem solving (Tower of London) (Keefe et al., 2004). Participants were evaluated in a single study visit by trained raters (S.M., I.S., K.M., or G.F.), whose interrater agreement was over 80%. The local research ethics board approved this study and all participants provided written informed consent.

2.3. Data analysis Statistical analysis was performed using SPSS v21 (IBM Corp.). All variables were evaluated for violations of the assumptions of parametric statistical analyses, with non-normally distributed variables square root or log-transformed. The BACS subtest and composite scores were transformed into standardized Z-scores based on age and sex normative data. Participant antipsychotic medication dosages were converted to chlorpromazine (CPZ) equivalents (Kane et al., 1998; Kroken et al., 2009; Andreasen et al., 2010; Buchanan et al., 2010). A principal components analysis with varimax rotation was used to create a composite amotivation score from the total scores of the three clinical measures of motivation (i.e., AES, SANS-Amotivation, and QLS Intrinsic Motivation) used in this study. This resulted in a single extracted component with an eigenvalue greater than 1 and accounting for 77.3% of the variance, and with all clinical measures having loadings greater than 0.86. This was used to calculate the regression-weighted composite amotivation score that was subsequently used in all ensuing analyses. Pearson's correlation coefficients were calculated to examine bivariate relationships between effort, motivation, and cognitive performance. Additionally, hierarchical multiple regression was used to evaluate the contributions of effort and clinical measures of psychopathology in predicting cognitive performance. In the hierarchical model, effort was entered first, followed by the amotivation composite score, and finally SANS Diminished Expression, SAPS total score, CDSS total score, CPZ equivalents, and SARS total score, with stepwise selection. A second hierarchical model was also evaluated, whereby amotivation was entered first, followed by effort, in order to evaluate the effect of effort on cognitive performance after controlling for amotivation. In line with the procedure described by Baron and Kenny (1986), we evaluated whether effort mediated the relationship between amotivation and cognitive performance, with significance testing of an indirect effect using the PROCESS Procedure for SPSS (v2.13) (Hayes, 2013) with 95% confidence intervals (CIs) established through bootstrapping with replacement from 10,000 resamples. Finally, t tests were used to evaluate differences in cognitive performance between subjects that passed and failed the TOMM (Normal Effort (NE) and Reduced Effort (RE) groups, respectively). 3. Results 3.1. Participant demographics and clinical characteristics A total of 69 individuals were recruited and evaluated as part of this study. Participant demographic and clinical characteristics are shown in Table 1.

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3.2. The relationship between motivation and cognitive performance in schizophrenia Examination of the relationship between motivation and cognitive performance revealed a significant relationship between the composite measure of amotivation and global cognition (Table 2). In terms of discrete domains of cognition, significant relationships emerged between amotivation and verbal memory; working memory; verbal fluency; attention/processing speed; and reasoning and problem solving. Extrapyramidal symptoms were not correlated with any measure of motivation or cognition except attention/processing speed (r = −.31, p = .009). Partial correlation after controlling for SARS severity led to the relationship between amotivation and attention/processing speed being non-significant. 3.3. The relationships between effort, motivation, and cognition in schizophrenia To evaluate the relationship between effort during cognitive testing and cognitive performance, we first examined bivariate correlations between effort, cognitive performance, and motivation (Table 2). This revealed that effort was significantly correlated with amotivation. Importantly, effort was not correlated with other measures of psychopathology, or SARS severity (all ps N .15). With regard to cognition, effort was significantly correlated with global cognitive performance, as well as with verbal fluency, reasoning and problem solving, attention/processing speed, and working memory (Table 2). Hierarchical multiple regression analysis was used to further investigate the contribution of effort, amotivation, and other measures of psychopathology in predicting global cognitive performance. Effort exerted during cognitive testing was a significant predictor of cognitive performance, accounting for 15% of the variance, with amotivation accounting for an additional 9% of variance (Table 3A). Other measures of motivation, diminished expression, depression, positive symptoms, antipsychotic dose, or extrapyramidal symptoms did not contribute further to the prediction of cognitive performance. A second hierarchical model with effort entering the model after controlling for amotivation revealed that effort significantly contributed to the prediction of cognitive performance after controlling for amotivation, and accounted for an additional 6% of the variance (Table 3B). Amotivation remained a significant predictor of cognitive performance in this model, although with a reduction in the magnitude of its regression coefficient, indicating that effort partially mediates the relationship between amotivation and cognitive performance (Fig. 1). Further, amotivation exhibited a significant indirect effect on cognitive performance through effort (indirect effect Table 1 Participant demographics and clinical characteristics (n = 69). Mean (S.D.) Age Sex (M:F) Diagnosis (schizophrenia:schizoaffective disorder) Duration of illness (years) Antipsychotic medication class (atypical:typical:both) CPZ equivalents (mg) Positive symptom severity (SAPS) Negative symptom severity (SANS) Apathy severity (AES) Intrinsic motivation (QLS) TOMM Trial 1 score Depression score (CDSS) Global cognition composite Z-score (BACS) Extrapyramidal symptom severity (SARS)

38.0 (10.3) 48:21 53:16 14.9 (11.0) 58:8:3 458.2 (258.2) 11.8 (11.8) 24.4 (17.3) 34.1 (8.0) 3.2 (1.5) 45.6 (4.5) 2.5 (3.0) −1.6 (1.2) 0.9 (2.0)

Abbreviations: CPZ — Chlorpromazine; SAPS — Scale for the Assessment of Positive Symptoms; SANS — Scale for the Assessment of Negative Symptoms; AES — Apathy Evaluation Scale; QLS — Quality of Life Scale; TOMM — Test of Memory Malingering; CDSS — Calgary Depression Scale for Schizophrenia; BACS — Brief Assessment of Cognition in Schizophrenia; SARS — Simpson Angus Rating Scale.

Please cite this article as: Foussias, G., et al., Motivated to do well: An examination of the relationships between motivation, effort, and cognitive performance in schizophrenia, Schizophr. Res. (2015), http://dx.doi.org/10.1016/j.schres.2015.05.019

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Table 2 Bivariate correlations between amotivation, effort, and cognitive performance.

Effort (TOMM) BACS composite Verbal memory Working memory Motor speed Verbal fluency Attention/processing speed Reasoning and problem solving

Amotivation composite score (r)

Effort (TOMM) (r)

−.39⁎⁎ −.43⁎⁎⁎ −.30⁎ −.28⁎ ns −.49⁎⁎⁎ −.25⁎ −.25⁎

.39⁎⁎ ns .26⁎ ns .41⁎⁎⁎ .30⁎ .34⁎⁎

Fig. 1. Mediation analysis examining the role of effort exerted during cognitive testing as a potential mediator of the relationship between amotivation and global cognitive test performance. (Values represent standardized regression coefficients; ⁎ p b .05, ⁎⁎ p b .01.)

ns. not significant. ⁎ p b .05. ⁎⁎ p b .01. ⁎⁎⁎ p b .001.

.036, 95% CI: .006, .091; indirect to total effect ratio = .237, 95% CI: .035, .744; kappa-squared = .103, 95% CI: .020, .244). We also conducted analyses of group differences after categorizing participants into NE and RE groups. Of the entire sample, 8 participants (11.6%) comprised the RE group, with 61 participants (88.4%) comprising the NE group. Group comparisons revealed that the RE group had significantly lower global cognitive performance compared to the NE group (t(67) = 2.53, p = .014). Across BACS subtests, the RE group exhibited significantly lower performance on tests of attention/processing speed (t(67) = 2.59, p = .012) and reasoning and problem solving (t(8) = 2.52, p = .037), as well as a trend for verbal fluency (t(67) = 1.73, p = .088) (Fig. 2).

4. Discussion In recognition of the need to further delineate the relationship between motivation and cognitive functioning, as well as between effort and cognition, we sought to investigate the relationships between motivation, effort exerted during cognitive testing, and cognitive performance in schizophrenia. We found that motivation was significantly related to global cognitive performance and, moreover, that this was driven by significant relationships with verbal fluency, verbal memory, working memory, attention/processing speed, and reasoning and problem solving. Further, effort exerted during cognitive testing was significantly related to both motivation and cognitive performance. With regard to cognition, this relationship appeared to be driven by significant relationships with verbal fluency, reasoning and problem solving, attention/processing speed, and working memory. Such effort was a significant predictor of cognitive performance, and partially mediated the relationship between motivation and cognitive performance. Further, individuals exhibiting reduced effort during testing (approximately 12% of our sample) had more severe global cognitive impairments,

Table 3 Predictors of global cognitive performance. A. Step 1 Effort (TOMM) Step 2 Effort (TOMM) Amotivation composite score B. Step 1 Amotivation composite score Step 2 Amotivation composite score Effort (TOMM)

R2

Beta

p

.15

.39

.001

.24

.26 −.33

.028 .007

R2

Beta

p

.18

−.43

b .001

.24

−.33 .26

.007 .028

Abbreviations: TOMM — Test of Memory Malingering.

driven by worse performance on tests of reasoning and problem solving and attention/processing speed. The findings of the present study are congruent with previous findings of a link between negative symptoms, and specifically motivational deficits, and verbal fluency, verbal memory, and working memory (Addington and Addington, 1999; Roth et al., 2004; Nakagami et al., 2008; Faerden et al., 2009b; Gard et al., 2009; Konstantakopoulos et al., 2011). Moreover, our findings are congruent with recent work by Strauss et al.(2015) demonstrating 15% of schizophrenia patients met criteria for reduced effort using the WMT and, further, that reduced effort and negative symptoms accounted for 36% of the variance in global cognitive performance. While they also found the reduced effort group to exhibit significantly worse global cognition, this was driven by worse performance in processing speed, working memory, and visual learning. Similarly, recent investigations of effort–cost computations in schizophrenia found that willingness to exert effort during a decision-making task was correlated with better global cognitive performance, and in particular with processing speed, verbal and visual memory, and reasoning/problem solving domains (Fervaha et al., 2013; Gold et al., 2013). While our findings indicate that effort exerted during cognitive testing partially mediates these relationships between motivation and cognition, there remains a significant direct relationship between motivation and cognitive test performance. It is possible that this persistent relationship reflects the cognitive processes that subserve motivation, including working memory that has been linked to multiple aspects of goal-directed behavior including goal representation and reward learning (Gold et al., 2008), as well as overlapping neural substrates for executive functions and goal-directed action (Barch and Dowd, 2010). While there is some overlap in findings across studies, there are also some discrepancies around particular domains of cognition impacted by reduced effort. Such findings may be a reflection of differential sensitivity across PVTs for detecting reduced effort (Batt et al., 2008; Schroeder and Marshall, 2011), differential demands across cognitive tests, and/or differences in patient characteristics across samples, including differences in the severity of motivational deficits across samples. The prevalence of reduced effort using the TOMM in the current study is consistent with previous findings using both this and other PVTs in schizophrenia (Back et al., 1996; Goldberg et al., 2007). Importantly, no participant in this study scored below chance performance (i.e., 50% correct) on the TOMM, indicating that participants were not exerting effort to intentionally perform poorly. Furthermore, there was no advantage to be gained by performing poorly in this study. This is in keeping with the view that poor PVT performance in schizophrenia is not seen as an intentional attempt to feign impairment, but rather a reflection of motivational deficits inherent to the illness. This is further underscored by the lack of an external incentive to do poorly. There are limitations to the current study that should be noted. First, we did not include a healthy or non-psychotic psychiatric comparison population. This limits our ability to draw conclusions beyond schizophrenia, and does not address the potential impact of a chronic psychiatric illness on reduced effort during cognitive testing. Based on

Please cite this article as: Foussias, G., et al., Motivated to do well: An examination of the relationships between motivation, effort, and cognitive performance in schizophrenia, Schizophr. Res. (2015), http://dx.doi.org/10.1016/j.schres.2015.05.019

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Fig. 2. Cognitive performance profiles for normal effort and reduced effort groups. Global cognition represents mean BACS composite Z-score, while individual cognitive domains represent mean standardized Z-scores for the respective cognitive tests (error bars indicate standard error). Significant group differences are marked (* — p b .05; a — p = .088).

previous studies using the TOMM, however, individuals in our study exhibiting normal effort had equivalent mean scores to healthy controls, traumatic brain injury subjects, and depressed subjects in other studies, while those exhibiting reduced effort had substantially lower mean scores (Tombaugh, 1996; Rees et al., 2001). Further, although PVTs have frequently been used for the examination of effort during cognitive testing, the establishment of the construct validity of these instruments has been limited by the absence of a gold standard. Future studies using alternative strategies to index mental effort, including pupillary responses during cognitive testing (Granholm et al., 2007), may offer additional clarification on the impact of effort and motivation on cognitive performance in schizophrenia. The low proportion of participants in this study exhibiting reduced effort also represents a limitation in that this translates to a small sample size in the RE group, which limits statistical power in the group comparisons. In addition, the use of only trial 1 of the TOMM, although exhibiting good sensitivity and specificity in relation to performance on trial 2 and the retention trial (Hilsabeck et al., 2011; Denning, 2012), represents an abbreviated form of this PVT. Moreover, the use of multiple PVTs, rather than a single PVT would add incremental validity to any conclusions regarding effort per se. Finally, while correlational analysis is valuable to examine interrelationships between variables, it cannot ascribe causation. The relationships in the present study, however, are interpreted in the context of a potential causal pathway whereby change in motivation leads to change in cognitive performance, in line with previous findings with monetary incentives. Overall, the findings of the present examination serve to highlight the complexity of the relationship between motivation and cognitive performance, whereby motivation is differentially related to cognitive domains, with some being more closely linked with amotivation. While the prevalence of reduced effort during cognitive testing in this population is low, such effort is a significant predictor of cognitive performance. As we move towards greater understanding of the impact of cognitive and motivational deficits on the functional outcomes of our patients, this work reinforces the need for appreciating the differential expression of deficits in subgroups of patients, which will serve to guide the appropriate selection of symptom targets for our patients. Those with cognitive deficits in the absence of amotivation may do well with strategies aimed at improving cognitive capacity and performance, while those with co-occurring amotivation may be better served

by initially addressing this loss of motivation that may serve to improve their outcomes and lessen their apparent cognitive deficits. Role of funding source This work has been supported in part by a Centre for Addiction and Mental Health (CAMH) Postdoctoral Research Fellowship, and Canadian Institutes of Health Research (CIHR) Clinician-Scientist Training Awards to G. Foussias. These organizations had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. Contributors Foussias and Remington designed the study and wrote the protocol. Fervaha, Zakzanis, and Agid provided valuable contributions to the study design and data analysis. Foussias, Siddiqui, Mann and McDonald conducted the participant assessments and data collection. Foussias undertook the statistical analysis, and preparation of the first draft of the manuscript. All authors subsequently made meaningful contributions to and have approved the final manuscript. Conflict of interest Dr. Foussias has served as an investigator on research sponsored by Medicure Inc., Neurocrine Bioscience, and Hoffman-La Roche. He has served on advisory boards for Hoffman-La Roche, and received speaker's fees from Hoffman-La Roche, Lundbeck and Novartis. Dr. Agid has received research support from Pfizer Inc. and Janssen-Ortho, consultant fees from Janssen-Ortho, Eli Lilly Inc. US, Eli Lilly Canada, Sepreacor, Sunovion and Lundbeck, and speaker's fees from Janssen-Ortho, Eli Lilly Inc. US, Eli Lilly Canada, Novartis, Sepracor and Sunovion. Dr. Remington has received research support from Novartis, Medicure and Neurocrine Bioscience, as a co-investigator he has received grant support from Pfizer Inc., consultant fees from Laboratorios Farmacéuticos ROVI, Synchroneuron, Novartis, and Roche, and speaker's fees from Novartis. The other authors have no conflicts of interest to disclose. Acknowledgments We thank Ms. Carol Borlido and the psychiatrists at the Centre for Addiction and Mental Health for their assistance with participant recruitment. We also thank the participants that took part in this study.

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Please cite this article as: Foussias, G., et al., Motivated to do well: An examination of the relationships between motivation, effort, and cognitive performance in schizophrenia, Schizophr. Res. (2015), http://dx.doi.org/10.1016/j.schres.2015.05.019

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Please cite this article as: Foussias, G., et al., Motivated to do well: An examination of the relationships between motivation, effort, and cognitive performance in schizophrenia, Schizophr. Res. (2015), http://dx.doi.org/10.1016/j.schres.2015.05.019

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Please cite this article as: Foussias, G., et al., Motivated to do well: An examination of the relationships between motivation, effort, and cognitive performance in schizophrenia, Schizophr. Res. (2015), http://dx.doi.org/10.1016/j.schres.2015.05.019