Excessive left anterior hippocampal and caudate activation in schizophrenia underlie cognitive underperformance in a virtual navigation task.

We used a virtual navigation paradigm in a city environment to assess neuroanatomical correlates of cognitive deficits in schizophrenia spectrum disorders (SSD). We studied a total of N = 36 subjects: 18 with SSD and 18 matched unaffected controls. Participants completed 10 rapid, single-trial navigation tasks within the virtual city while undergoing functional magnetic resonance imaging (fMRI). All trials tested ability to find different targets seen earlier, during the passive viewing of a path around different city blocks. SSD patients had difficulty finding previously-encountered targets, were less likely to find novel shortcuts to targets, and more likely to attempt retracing of the path observed during passive viewing. Based on a priori region-of-interest analyses, SSD participants had hyperactivation of the left hippocampus when passively viewing turns, hyperactivation of the left caudate when finding targets, and hypoactivation of a focal area of the dorsolateral prefrontal cortex when targets were initially shown during passive viewing. We propose that these brain-behaviour relations may bias or reinforce stimulus-response navigation approaches in SSD and underlie impaired performance when allocentric spatial memory is required, such as when forming efficient shortcuts. This pattern may extend to more general cognitive impairments in SSD that could be used to design remediation strategies.

Characterization and prediction of individual functional outcome trajectories in schizophrenia spectrum disorders (PREDICTS study): Study protocol.

Schizophrenia spectrum disorders (SSDs) are associated with significant functional impairments, disability, and low rates of personal recovery, along with tremendous economic costs linked primarily to lost productivity and premature mortality. Efforts to delineate the contributors to disability in SSDs have highlighted prominent roles for a diverse range of symptoms, physical health conditions, substance use disorders, neurobiological changes, and social factors. These findings have provided valuable advances in knowledge and helped define broad patterns of illness and outcomes across SSDs. Unsurprisingly, there have also been conflicting findings for many of these determinants that reflect the heterogeneous population of individuals with SSDs and the challenges of conceptualizing and treating SSDs as a unitary categorical construct. Presently it is not possible to identify the functional course on an individual level that would enable a personalized approach to treatment to alter the individual's functional trajectory and mitigate the ensuing disability they would otherwise experience. To address this ongoing challenge, this study aims to conduct a longitudinal multimodal investigation of a large cohort of individuals with SSDs in order to establish discrete trajectories of personal recovery, disability, and community functioning, as well as the antecedents and predictors of these trajectories. This investigation will also provide the foundation for the co-design and testing of personalized interventions that alter these functional trajectories and improve outcomes for people with SSDs.

Modeling Effort-Based Decision Making: Individual Differences in Schizophrenia and Major Depressive Disorder.

BACKGROUND: A critical facet of motivation is effort-based decision making, which refers to the mental processes involved in deciding whether a potential reward is worth the effort. To advance understanding of how individuals with schizophrenia and major depressive disorder utilize cost-benefit information to guide choice behavior, this study aimed to characterize individual differences in the computations associated with effort-based decision making. METHODS: One hundred forty-five participants (51 with schizophrenia, 43 with depression, and 51 healthy control participants) completed the Effort Expenditure for Rewards Task, with mixed effects modeling conducted to estimate the predictors of decision making. These model-derived, subject-specific coefficients were then clustered using k-means to test for the presence of discrete transdiagnostic subgroups with different profiles of reward, probability, and cost information utilization during effort-based decision making. RESULTS: An optimal 2-cluster solution was identified, with no significant differences in the distribution of diagnostic groups between clusters. Cluster 1 (n = 76) was characterized by overall lower information utilization during decision making than cluster 2 (n = 61). Participants in this low information utilization cluster were also significantly older and more cognitively impaired, and their utilization of reward, probability, and cost was significantly correlated with clinical amotivation, depressive symptoms, and cognitive functioning. CONCLUSIONS: Our findings revealed meaningful individual differences among participants with schizophrenia, depression, and healthy control participants in their utilization of cost-benefit information in the context of effortful decision making. These findings may provide insight into different processes associated with aberrant choice behavior and may potentially guide the identification of more individualized treatment targets for effort-based motivation deficits across disorders.

Behavioural phenotypes of intrinsic motivation in schizophrenia determined by cluster analysis of objectively quantified real-world performance.

Intrinsic motivation deficits are a prominent feature of schizophrenia that substantially impacts functional outcome. This study used cluster analysis of innate real-world behaviours captured during two open-field tasks to dimensionally examine heterogeneity in intrinsic motivation in schizophrenia patients (SZ) and healthy controls (HC). Wireless motion capture quantified participants' behaviours aligning with distinct aspects of intrinsic motivation: exploratory behaviour and effortful activity in the absence of external incentive. Cluster analysis of task-derived measures identified behaviourally differentiable subgroups, which were compared across standard clinical measures of general amotivation, cognition, and community functioning. Among 45 SZ and 47 HC participants, three clusters with characteristically different behavioural phenotypes emerged: low exploration (20 SZ, 19 HC), low activity (15 SZ, 8 HC), and high exploration/activity (10 SZ, 20 HC). Low performance in either dimension corresponded with similar increased amotivation. Within-cluster discrepancies emerged for amotivation (SZ > HC) within the low exploration and high performance clusters, and for functioning (SZ < HC) within all clusters, increasing from high performance to low activity to low exploration. Objective multidimensional characterization thus revealed divergent behavioural expression of intrinsic motivation deficits that may be conflated by summary clinical measures of motivation and overlooked by unidimensional evaluation. Deficits in either aspect may hinder general motivation and functioning particularly in SZ. Multidimensional phenotyping may help guide personalized remediation by discriminating between intrinsic motivation impairments that require amelioration versus unimpaired tendencies that may facilitate remediation.

Reward-driven decision-making impairments in schizophrenia.

The ability to use feedback to guide optimal decision-making is essential for goal-directed behaviour. While impairments in feedback-driven decision-making have been associated with schizophrenia and depression, this has been examined primarily in the context of binary probabilistic choice paradigms. In real-world decision-making, however, individuals must make choices when there are more than two competing options that vary in the frequency and magnitude of potential rewards and losses. Thus, the current study examined win-stay/lose-shift (WSLS) behaviour on the Iowa Gambling Task (IGT) in order to evaluate the influence of immediate rewards and losses in guiding real-world decision-making in patients with schizophrenia and major depressive disorder. Fifty-one patients with schizophrenia, 43 patients with major depressive disorder, and 51 healthy controls completed the IGT, as well as a series of clinical and cognitive measures. WSLS was assessed by quantifying trial-by-trial behaviour following rewards and losses on the IGT. Multivariate analyses of variance revealed that patients with schizophrenia demonstrated intact lose-shift behaviour, but significantly reduced win-stay rates compared to healthy controls. In contrast, no WSLS impairments emerged in the depressed group. Win-stay impairments in the schizophrenia group were significantly related to deficits in motivation and cognition. Patients with schizophrenia exhibit impaired reward-driven decision-making in the context of multiple choices with concurrent rewards and losses, and this appears to be driven by a reduced propensity for advantageous win-stay behaviour. With the importance of reward learning and decision-making in generating goal-directed behaviour, these findings suggest a potential mechanism contributing to the motivation deficits seen in schizophrenia.

Goal-directed planning and action impairments in schizophrenia evaluated in a virtual environment.

Planning and executing goal-directed behaviours are critical final steps in translating motivation into action. Amotivation is a key feature of schizophrenia, but its impact on goal-directed functioning has not been extensively studied in an objective and ecologically valid manner. To address this, we investigated goal-directed planning and action in schizophrenia using a virtual reality task, the Multitasking in the City Test (MCT). The MCT was administered to 49 outpatients with schizophrenia and 55 healthy controls, and required participants to complete a series of errands in a virtual city. Ability to complete the task as directed was assessed by a performance score based on errands completed and errors committed. Task efficiency was evaluated by the total distance travelled, and an index of path efficiency comparing an optimal route with the traversed route. Schizophrenia participants had lower performance scores, travelled farther, and had reduced path efficiency compared to healthy controls. Greater distance travelled and lower path efficiency in schizophrenia were related to amotivation. Path efficiency in schizophrenia was also related to neurocognition, including planning ability; notably, this relationship appeared to be independent of the relationship with amotivation. Individuals with schizophrenia demonstrated impaired goal-directed planning and action in the context of a simulated everyday errands task, both in terms of reduced capacity to complete errands and reduced efficiency in doing so. The latter may manifest as diminished real-world motivated and functional behaviour in patients with schizophrenia and indicates a specific deficit in the execution of planned behaviour.

Objective investigation of activity preference in schizophrenia: A pilot study.

Amotivation and reduced goal-directed activity engagement are prominent features of schizophrenia. Previous investigations of patients' activities have relied on accounts of daily living activities, rather than objective measures. This study used wireless motion capture to objectively evaluate activity preference when individuals are provided an explicit choice between an active versus passive engagement option. Twenty outpatients with schizophrenia and twenty matched healthy controls completed the Activity Preference Task, in which participants play a motion-based game (active) or watch a film (passive), and were administered clinical and cognitive assessments. Schizophrenia participants' duration, intensity, and persistence of active engagement were associated with apathy and community functioning. No group differences emerged from comparisons of task measures; however, exploratory cluster analysis identified a distinct subgroup of schizophrenia patients with reduced engagement and increased apathy compared to other patients and controls. The Task provides a means of quantifying activity engagement, which may be particularly valuable given the lack of objective measures for intrinsically motivated behaviours. Our initial findings suggest that schizophrenia patients as a group are equally inclined as healthy individuals towards actively engaging activities when presented an explicit choice, but such provision may be insufficient for initiation and maintenance of functional behaviours among amotivated patients.

An Examination of the Multi-Faceted Motivation System in Healthy Young Adults.

Background: Amotivation is a prevalent symptom in schizophrenia (SZ) and depression (MDD), and is linked to poor functional outcomes in affected individuals. Conceptualizations of motivation have outlined a multi-faceted construct comprised of reward responsiveness, reward expectancy, reward valuation, effort valuation, and action selection/preference-based decision making. To date, findings from studies utilizing variable-centered approaches to examining isolated facets of motivation in SZ and MDD have been inconsistent. Thus, the present study adopted a person-centered approach, and comprehensively examined the reward system in a non-clinical sample in an attempt to explore potential subtypes of motivation impairments, while minimizing the effects of illness-related confounds. Methods: Ninety-six healthy undergraduate students were evaluated for amotivation, schizotypal traits, depressive symptoms, and cognition, and administered objective computerized tasks to measure the different facets of motivation. Cluster analysis was performed to explore subgroups of individuals based on similar motivation task performance. Additionally, correlational analyses were conducted in order to examine inter-relationships between motivation facets, and relations between clinical measures and facets of motivation. Results: Cluster analysis identified two subgroups of individuals with differential motivation performance profiles. Correlational analyses revealed that reward responsiveness was associated with amotivation, depressive symptoms, and negative schizotypy. Further, significant inter-correlations were found between reward responsiveness and reward expectancy, as well as between reward valuation and effort valuation. Conclusions: Our results mark important steps forward in understanding motivation in a non-clinical sample, and guide future dimensional and comprehensive analyses of the multi-faceted reward system. It remains to be seen whether these patterns of results will be similar in clinical populations such as SZ and MDD.

Objective assessment of exploratory behaviour in schizophrenia using wireless motion capture.

Motivation deficits are a prominent feature of schizophrenia and have substantial consequences for functional outcome. The impact of amotivation on exploratory behaviour has not been extensively assessed by entirely objective means. This study evaluated deficits in exploratory behaviour in an open-field setting using wireless motion capture. Twenty-one stable adult outpatients with schizophrenia and twenty matched healthy controls completed the Novelty Exploration Task, in which participants explored a novel environment containing familiar and uncommon objects. Objective motion data were used to index participants' locomotor activity and tendency for visual and tactile object exploration. Clinical assessments of positive and negative symptoms, apathy, cognition, depression, medication side-effects, and community functioning were also administered. Relationships between task performance and clinical measures were evaluated using Spearman correlations, and group differences were evaluated using multivariate analysis of covariance tests. Although locomotor activity and tactile exploration were similar between the schizophrenia and healthy control groups, schizophrenia participants exhibited reduced visual object exploration (F(2,35)=3.40, p=0.045). Further, schizophrenia participants' geometric pattern of locomotion, visual exploration, and tactile exploration were correlated with overall negative symptoms (|ρ|=0.46-0.64, p<=0.039) and apathy (|ρ|=0.49-0.62, p<=0.028), and both visual and tactile exploration were also correlated with community functioning (|ρ|=0.46-0.48, p<=0.043). The Novelty Exploration Task may be a valuable tool to quantify exploratory behaviour beyond what is captured through standard clinical instruments and human observer ratings. Findings from this initial study suggest that locomotor activity and object interaction tendencies are impacted by motivation, and reveal deficits specifically in visual exploration in schizophrenia.

Investigating the predictors of happiness, life satisfaction and success in schizophrenia.

BACKGROUND: Previous studies have suggested that, despite marked functional impairments, remitted first episode patients with schizophrenia report levels of well-being that are comparable to healthy controls. The aim of the current study was to specifically evaluate self-reported happiness, life satisfaction and success in individuals with schizophrenia beyond their first-episode of psychosis, and to investigate the impact of symptoms and functioning on these subjective experiences. METHODS: Fifty-one schizophrenia patients and 56 matched healthy controls participated in the study. Factor scores were computed to compare happiness and life satisfaction and success (LSS) between groups. Hierarchical multiple regression analyses were conducted to investigate the predictive value of symptoms and functional impairments on patients' subjective reports of happiness and LSS. RESULTS: Schizophrenia participants endorsed lower levels of LSS compared to healthy controls, with no significant group differences in self-reported happiness. For patients with schizophrenia, motivation deficits and depressive symptoms predicted reductions in both happiness and LSS. CONCLUSIONS: Patients with schizophrenia do not report significant reductions in their subjective experience of happiness, but do endorse lower levels of life satisfaction and success. Further, the absence of a robust link between poor functioning and lower happiness or LSS serves to reaffirm the notion that functional status does not dictate whether an individual with schizophrenia experiences a sense of happiness, satisfaction or success in life.

Investigating consummatory and anticipatory pleasure across motivation deficits in schizophrenia and healthy controls.

Anhedonia has traditionally been considered a characteristic feature of schizophrenia, but the true nature of this deficit remains elusive. This study sought to investigate consummatory and anticipatory pleasure as it relates to motivation deficits. Eighty-four outpatients with schizophrenia and 81 healthy controls were administered the Temporal Experience of Pleasure Scale (TEPS), as well as a battery of clinical and cognitive assessments. Multivariate analyses of variance were used to examine the experience of pleasure as a function of diagnosis, and across levels of motivation deficits (i.e. low vs. moderate. vs. high) in schizophrenia. Hierarchical regression analyses were also conducted to evaluate the predictive value of amotivation in relation to the TEPS. There were no significant differences between schizophrenia and healthy control groups for either consummatory or anticipatory pleasure. Within the schizophrenia patients, only those with high levels of amotivation were significantly impaired in consummatory and anticipatory pleasure compared to low and moderate groups, and compared to healthy controls. Further, our results revealed that amotivation significantly predicts both consummatory and anticipatory pleasure, with no independent contribution of group. Utilizing study samples with a wide range of motivation deficits and incorporating objective paradigms may provide a more comprehensive understanding of hedonic deficits.

Neurocognitive impairment in the deficit subtype of schizophrenia.

Schizophrenia is a heterogeneous disorder characterized by numerous diverse signs and symptoms. Individuals with prominent, persistent, and idiopathic negative symptoms are thought to encompass a distinct subtype of schizophrenia. Previous work, including studies involving neuropsychological evaluations, has supported this position. The present study sought to further examine whether deficit patients are cognitively distinct from non-deficit patients with schizophrenia. A comprehensive neurocognitive battery including tests of verbal memory, vigilance, processing speed, reasoning, and working memory was administered to 657 patients with schizophrenia. Of these, 144 (22 %) patients were classified as deficit patients using a proxy identification method based on severity, persistence over time, and possible secondary sources (e.g., depression) of negative symptoms. Deficit patients with schizophrenia performed worse on all tests of cognition relative to non-deficit patients. These patients were characterized by a generalized cognitive impairment on the order of about 0.4 standard deviations below that of non-deficit patients. However, when comparing deficit patients to non-deficit patients who also present with negative symptoms, albeit not enduring or primary, no group differences in cognitive performance were found. Furthermore, a discriminant function analysis classifying patients into deficit/non-deficit groups based on cognitive scores demonstrated only 62.3 % accuracy, meaning over one-third of individuals were misclassified. The deficit subtype of schizophrenia is not markedly distinct from non-deficit schizophrenia in terms of neurocognitive performance. While deficit patients tend to have poorer performance on cognitive tests, the magnitude of this effect is relatively modest, translating to over 70 % overlap in scores between groups.

Motivation and Social Cognition in Patients with Schizophrenia.

Social cognition, referring to one's ability to perceive and process social cues, is an important domain in schizophrenia. Numerous studies have demonstrated that patients with schizophrenia have poorer performance on tests assessing social cognition relative to healthy comparison participants. However, whether variables such as motivation are related to performance on these tests in patients with schizophrenia is unclear. One thousand three-hundred and seventy-eight patients with schizophrenia completed the Facial Emotion Discrimination Task as a measure of emotional processing, a key facet of social cognition. Level of motivation was also evaluated in these patients using a derived measure from the Quality of Life Scale. The relationship between motivation and task performance was examined using bivariate correlations and logistic regression modeling, controlling for the impact of age and overall severity of psychopathology, the latter evaluated using the Positive and Negative Syndrome Scale. Motivation was positively related to performance on the social cognition test, and this relationship remained significant after controlling for potential confounding variables such as age and illness severity. Social cognition was also related to functioning, and the relationship was mediated by level of motivation. The present study found a significant relationship between motivation and performance on a test of social cognition in a large sample of patients with schizophrenia. These findings suggest that amotivation undermines task performance, or alternatively that poor social cognitive ability impedes motivation. Future studies evaluating social cognition in patients with schizophrenia should concurrently assess for variables such as effort and motivation.

The Effects of Video Games on Cognition and Brain Structure: Potential Implications for Neuropsychiatric Disorders.

Video games are now a ubiquitous form of entertainment that has occasionally attracted negative attention. Video games have also been used to test cognitive function, as therapeutic interventions for neuropsychiatric disorders, and to explore mechanisms of experience-dependent structural brain changes. Here, we review current research on video games published from January 2011 to April 2014 with a focus on studies relating to mental health, cognition, and brain imaging. Overall, there is evidence that specific types of video games can alter brain structure or improve certain aspects of cognitive functioning. Video games can also be useful as neuropsychological assessment tools. While research in this area is still at a very early stage, there are interesting results that encourage further work in this field, and hold promise for utilizing this technology as a powerful therapeutic and experimental tool.

Examination of the validity of the Brief Neurocognitive Assessment (BNA) for schizophrenia.

BACKGROUND: Although many comprehensive batteries exist to evaluate the nature and degree of cognitive impairments in patients with schizophrenia, short batteries hold promise for rapidly screening and estimating deficits in global cognition. Recently, the Brief Neurocognitive Assessment (BNA) was established and has been shown to have similar validity and utility to a more comprehensive battery of cognitive tests in evaluating global cognitive impairments in patients with schizophrenia. The present study sought to further establish the validity of the BNA by comparing it with the MATRICS Consensus Cognitive Battery (MCCB). METHODS: One-hundred seventy-six patients with schizophrenia and 300 healthy volunteers participated in the present study. Global cognition was evaluated using the MCCB composite score and estimated using the BNA. To examine practice effects and test-retest reliability, patients were re-assessed after 4weeks. RESULTS: The BNA was highly correlated with global cognition as evaluated by the MCCB in both the schizophrenia (r=0.82) and healthy control samples (r=0.75). Both instruments were similarly sensitive to deficits in global cognition in patients with schizophrenia relative to healthy controls. The BNA also demonstrated high test-retest reliability in patients with schizophrenia (r=0.87), comparable to the level observed with the MCCB (r=0.91). In addition, both the BNA and MCCB showed a similar level of practice effects (both Cohen's d=0.11), and both instruments demonstrated equivalent sensitivities to longitudinal change. Furthermore, scores from the BNA and MCCB were related to symptom severity and functional capacity to a similar degree. CONCLUSIONS: The BNA provides clinicians and researchers with an efficient and reliable means by which to evaluate global neurocognitive impairments in patients with schizophrenia by allowing estimation of performance on a more comprehensive standardized battery.

Dissecting negative symptoms in schizophrenia: opportunities for translation into new treatments.

Among the constellation of symptoms that characterize schizophrenia, negative symptoms have emerged as a critical feature linked to the functional impairment experienced by affected individuals. Despite advances in our understanding of the role of negative symptoms in the illness, effective treatments for these debilitating symptoms have remained elusive. In this review we explore the contemporary conceptualization of negative symptoms in schizophrenia, including the identification of two key subdomains of diminished expression and amotivation, and clarifications around hedonic capacity. We then explore strategies for clinical assessments of negative symptoms, followed by findings using objective paradigms for evaluating discrete aspects of these negative symptoms in clinical populations and animal models, both for symptoms of diminished expression and within the multifaceted motivation system. We conclude with a consideration of current strategies for drug development for these negative symptoms, the role of heterogeneity in the clinical presentation of symptoms in schizophrenia and opportunities for personalized assessment and treatment approaches, as well as a commentary on current clinical drug trial design and the role of environmental opportunities for novel treatments to effect change and improve outcomes for affected individuals.

Abbreviated quality of life scales for schizophrenia: comparison and utility of two brief community functioning measures.

BACKGROUND: The Heinrichs-Carpenter Quality of Life Scale (QLS) is the most extensively used real-world community functioning scale in schizophrenia research. However, the extensive time required to administer it and the inclusion of items that overlap conceptually with negative symptoms limit its use across studies. The present study examined the validity and utility of two abbreviated QLS measures against the full QLS excluding negative symptom items. METHOD: The sample included 1427 patients with schizophrenia who completed the baseline visit in the CATIE study. The validity of two abbreviated QLS measures (7-item and 4-item) were examined with the full QLS, excluding the intrapsychic foundations subscale, using correlation analysis. The utility of the abbreviated measures was explored by examining associations between the functioning scales and clinical variables and longitudinal change. RESULTS: Both abbreviated QLS measures were highly predictive of the full QLS (both r=0.91, p<0.001), with no difference in predictive value between the abridged measures. Functional status was significantly associated with symptoms and cognition. Importantly, the strength of these associations was similar between the abbreviated and full QLS. Finally, multiple regression models examining the explanatory power of amotivation/apathy in predicting functioning scores after other symptoms and neurocognition had been accounted for were essentially identical irrespective of the QLS instrument used as the dependent measure. Longitudinal change was also similar across the three scales. CONCLUSIONS: The 7-item abbreviated QLS is recommended as a brief measure of community functioning for individuals with schizophrenia, especially when assessment of functional outcome is not the focus.

Is action tremor in Parkinson's disease related to resting tremor?

OBJECTIVE: Action tremor (AT) and resting tremor (RT) have been widely cited in many studies with Parkinson's disease (PD) patients, but studies looking at the association between the two tremor types are few and show inconsistent results. This study will look at the prevalence and association of AT and RT in a large sample of idiopathic PD patients, and will put the results into context with the literature. METHODS: A retrospective chart review analysis of 332 patients with idiopathic PD was performed. Prevalence rates of particular tremor types were noted. The presence of AT was analyzed relative to the presence and severity of RT. RESULTS: Nearly all individuals with AT also had RT. The concurrence of the two tremor types was found to be highly significant by statistical analysis (P < 0.0001). The severity of RT, measured by its laterality, may also be of importance, albeit to a much smaller extent if at all. Neither presence of tremor nor type of tremor present was influenced by patient gender, age, or Hoehn and Yahr stage of PD. CONCLUSIONS: The results indicate that AT has extensive presence in PD. This and its seemingly close relationship to RT suggest that AT may be considered a variant of RT, particularly in PD patients. The degree of association between RT and AT needs to be further analyzed in PD, as well as in essential tremor (ET) and ET-PD.

Simulating real world functioning in schizophrenia using a naturalistic city environment and single-trial, goal-directed navigation.

OBJECTIVE: To develop a virtual reality platform that would serve as a functionally meaningful measure of cognition in schizophrenia and that would also complement standard batteries of cognitive tests during clinical trials for cognitive treatments in schizophrenia, be amenable to human neuroimaging research, yet lend itself to neurobiological comparison with rodent analogs. METHOD: Thirty-three patients with schizophrenia and 33 healthy controls matched for age, sex, video gaming experience, and education completed eight rapid, single-trial virtual navigation tasks within a naturalistic virtual city. Four trials tested their ability to find different targets seen during the passive viewing of a closed path that led them around different city blocks. Four subsequent trials tested their ability to return to four different starting points after viewing a path that took them several blocks away from the starting position. RESULTS: Individuals with schizophrenia had difficulties in way-finding, measured as distance travelled to find targets previously encountered within the virtual city. They were also more likely not to notice the target during passive viewing, less likely to find novel shortcuts to targets, and more likely to become lost and fail completely in finding the target. Total travel distances across all eight trials strongly correlated (negatively) with neurocognitive measures and, for 49 participants who completed the Quality of Life Scale, psychosocial functioning. CONCLUSION: Single-trial, goal-directed navigation in a naturalistic virtual environment is a functionally meaningful measure of cognitive functioning in schizophrenia.

Pain in Parkinson's disease: analysis and literature review.

Pain is a common problem faced by Parkinson's disease (PD) patients. Despite its impact and disabling effects pain is still frequently overlooked. In this study we analyze a representative sample of peer reviewed literature for the prevalence and types of pain in PD, the impact and significance of pain in the quality of life of the PD patient and the challenges inherent in the diagnosis and management of pain in PD patients. We compared and analyzed the findings of articles indexed in the PubMed database which looked at symptoms reported by large cohorts of PD patients. These articles all reported the incidence, nature and quality of pain in these patients and described the effects of pain on quality of life and generally were cross-sectional, retrospective or case-control studies, though a major pharmacoepidemiological design study was also analyzed. Results of our analysis showed that the pain was prevalent in 59.77% of PD patients. Five different types of pain were reported by PD patients--dystonia, musculoskeletal pain, nerve/nerve root pain, primary/central pain and according to some, akathisia. Patients who reported pain symptoms were also significantly more likely to report associated depression and a decreased quality of life. Many PD patients also reported poor management of pain and lower analgesic use than would be expected. We further discuss some of the possible approaches toward the development of a treatment algorithm regarding the management of pain in PD. We conclude that pain in is an under-recognized and under treated symptom in PD patients. Effective management of pain in PD patients would significantly improve their quality of life. Our analysis is in line with current thinking that identifies PD is much more of a multisystem disease with non-motor symptoms than previously thought.