Motivational Deficits In Schizophrenia Research Articles

Learning without contingencies: A loss of synergy between memory and reward circuits in schizophrenia.

Motivational deficits in schizophrenia may interact with foundational cognitive processes including learning and memory to induce impaired cognitive proficiency. If such a loss of synergy exists, it is likely to be underpinned by a loss of synchrony between the brains learning and reward sub-networks. Moreover, this loss should be observed even during tasks devoid of explicit reward contingencies given that such tasks are better models of real world performance than those with artificial contingencies. Here we applied undirected functional connectivity (uFC) analyses to fMRI data acquired while participants engaged in an associative learning task without contingencies or feedback. uFC was estimated and inter-group differences (between schizophrenia patients and controls, n=54 total, n=28 patients) were assessed within and between reward (VTA and NAcc) and learning/memory (Basal Ganglia, DPFC, Hippocampus, Parahippocampus, Occipital Lobe) sub-networks. The task paradigm itself alternated between Encoding, Consolidation, and Retrieval conditions, and uFC differences were quantified for each of the conditions. Significantly reduced uFC dominated the connectivity profiles of patients across all conditions. More pertinent to our motivations, these reductions were observed within and across classes of sub-networks (reward-related and learning/memory related). We suggest that disrupted functional connectivity between reward and learning sub-networks may drive many of the performance deficits that characterize schizophrenia. Thus, cognitive deficits in schizophrenia may in fact be underpinned by a loss of synergy between reward-sensitivity and cognitive processes.

Effortful goal-directed behavior in schizophrenia: Computational subtypes and associations with cognition.

Schizophrenia is associated with amotivation and reduced goal-directed behavior, which have been linked to poor functional outcomes. Motivational deficits in schizophrenia are often measured using effort-based decision-making (EBDM) paradigms, revealing consistent alterations in effort expenditure relative to controls. Although these results have generally been interpreted in terms of decreased motivation, the ability to use trial-by-trial changes in reward magnitude or probability of receipt to guide effort allocation may also be affected by cognitive deficits. To date, it remains unclear whether altered performance in EBDM primarily reflects deficits in motivation, cognitive functioning, or both. We applied a newly developed computational modeling approach to the analysis of EBDM data from two previously collected samples comprising 153 patients and 105 controls to determine the extent to which individuals did or did not use available information about reward and probability to guide effort allocation. Half of the participants with schizophrenia failed to incorporate information about reward and probability when making effort-expenditure decisions. The subset of patients who exhibited difficulties using reward and probability information were characterized by greater impairments across measures of cognitive functioning. Interestingly, even within the subset of patients who successfully used reward and probability information to guide effort expenditure, higher levels of negative symptoms related to motivation and avolition were associated with greater effort aversion during the task. Taken together, these data suggest that prior reports of aberrant EBDM in schizophrenia patients are related to both cognitive function and individual differences in negative symptoms. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Motivational deficits in schizophrenia relate to abnormalities in cortical learning rate signals.

Individuals from across the psychosis spectrum display impairments in reinforcement learning. In some individuals, these deficits may result from aberrations in reward prediction error (RPE) signaling, conveyed by dopaminergic projections to the ventral striatum (VS). However, there is mounting evidence that VS RPE signals are relatively intact in medicated people with schizophrenia (PSZ). We hypothesized that, in PSZ, reinforcement learning deficits often are not related to RPE signaling per se but rather their impact on learning and behavior (i.e., learning rate modulation), due to dysfunction in anterior cingulate and dorsomedial prefrontal cortex (dmPFC). Twenty-six PSZ and 23 healthy volunteers completed a probabilistic reinforcement learning paradigm with occasional, sudden, shifts in contingencies. Using computational modeling, we found evidence of an impairment in trial-wise learning rate modulation (α) in PSZ before and after a reinforcement contingency shift, expressed most in PSZ with more severe motivational deficits. In a subsample of 22 PSZ and 22 healthy volunteers, we found little evidence for between-group differences in VS RPE and dmPFC learning rate signals, as measured with fMRI. However, a follow-up psychophysiological interaction analysis revealed decreased dmPFC-VS connectivity concurrent with learning rate modulation, most prominently in individuals with the most severe motivational deficits. These findings point to an impairment in learning rate modulation in PSZ, leading to a reduced ability to adjust task behavior in response to unexpected outcomes. At the level of the brain, learning rate modulation deficits may be associated with decreased involvement of the dmPFC within a greater RL network.

Motivational Deficits in Schizophrenia Are Associated With Reduced Differentiation Between Gain and Loss-Avoidance Feedback in the Striatum

BackgroundThe current study was designed to test the hypothesis that motivational deficits in schizophrenia (SZ) are tied to a reduced ability to differentially signal gains and instances of loss-avoidance in the brain, leading to reduced ability to form adaptive representations of expected value. MethodsWe administered a reinforcement learning paradigm to 27 medicated SZ patients and 27 control subjects in which participants learned three probabilistic discriminations. In regions of interest in reward networks identified a priori, we examined contrasts between trial types with different expected values (e.g., expected gain–nonmonetary) and between outcomes with the same prediction error valence but different experienced values (e.g., gain–loss-avoidance outcome, miss–loss outcome). ResultsBoth whole-brain and region of interest analyses revealed that SZ patients showed reduced differentiation between gain and loss-avoidance outcomes in the dorsal anterior cingulate cortex and bilateral anterior insula. That is, SZ patients showed reduced contrasts between positive prediction errors of different objective values in these areas. In addition, we observed significant correlations between gain–loss-avoidance outcome contrasts in the ventral striatum and ratings for avolition/anhedonia and between expected gain–nonmonetary contrasts in the ventral striatum and ventromedial prefrontal cortex. ConclusionsThese results provide further evidence for intact prediction error signaling in medicated SZ patients, especially with regard to loss-avoidance. By contrast, components of frontostriatal circuits appear to show reduced sensitivity to the absolute valence of expected and experienced outcomes, suggesting a mechanism by which motivational deficits may emerge.

Achievement motivation in early schizophrenia: Relationship with symptoms, cognition and functional outcome.

Individuals with schizophrenia engage in goal-directed activities significantly less often compared to healthy individuals in the community. There is ample evidence documenting the presence of motivational deficits in schizophrenia using observer-based ratings; however, purely self-reported accounts of patients' motivation are less well understood. This study examined subjective accounts of trait achievement motivation among relatively young, clinically stable, early-course outpatients with schizophrenia. Thirty-nine early-course patients and 39 healthy comparison subjects completed clinical and cognitive assessments in addition to a self-report inventory measuring achievement motivation. Patients were found to endorse significantly lower levels of motivation, a mean difference which translated to a large effect size (Cohen's d = 1.1). Patients' self-reported motivation was significantly related to clinician ratings of motivational deficits which were based on behavioural output, and to vocational functioning. Within the patient sample, 33.3% of individuals were found to experience prominent or clinically significant levels of amotivation based on patients' own self-report. Self-reported achievement motivation was not associated with other clinical variables such as positive symptom severity or expressive negative symptoms. Our results serve to highlight the occurrence and prevalence of motivational deficits in patients with schizophrenia who are in the early stages of their illness. Subjective accounts of motivation in this population were found to be related to important outcomes such as community functioning, highlighting the importance of this domain of illness. Targeting these deficits early in the course of the illness offers the potential to curb potential prospective poor outcomes and sets the stage for recovery.

Negative symptoms are associated with an increased subjective cost of cognitive effort.

Motivational deficits in schizophrenia are proposed to be attributable in part to abnormal effort-cost computations. Inflated subjective cognitive effort costs may explain diminished functioning in schizophrenia to the extent that they drive avoidance of complex decision-making and planning. Although previous data support inflated subjective physical effort costs for individuals with schizophrenia, evidence on cognitive effort is mixed. We exploited the methodological advantages of a recently developed cognitive effort-discounting paradigm (Westbrook, Kester, & Braver, 2013) to examine effort-cost computations in schizophrenia. The paradigm quantifies subjective costs in terms of explicit, continuous discounting of monetary rewards based on parametrically varied demands (levels N of the N-back working memory task), holding objective features of task duration and reward likelihood constant. Both healthy participants (N = 25) and schizophrenia patients (N = 25) showed systematic influences of reward and task demands on choice patterns. Critically, however, participants with schizophrenia discounted rewards more steeply as a function of effort, indicating that effort was more costly for this group. Moreover, discounting varied robustly with symptomatology, such that schizophrenia patients with greater clinically rated negative symptom severity discounted rewards more steeply. These findings extend the current literature on abnormal-effort cost computations in schizophrenia by establishing a clear relationship between the costliness of cognitive effort and negative symptoms. (PsycINFO Database Record

Effort-based decision making as an objective paradigm for the assessment of motivational deficits in schizophrenia

BackgroundNegative symptoms and motivational deficits are prevalent features of schizophrenia, and represent robust predictors of real-world functional outcomes. The standard for assessment of these symptoms is clinical interview and severity ratings on standardized rating scales. In the present study we examined the psychometric properties of a performance-based measure of motivational deficits in patients with schizophrenia. MethodsNinety-seven patients with schizophrenia were included in this investigation. Patients' willingness to expend effort for reward (i.e., motivation) was evaluated using an effort-based decision making paradigm where participants chose over a series of trials whether to expend a greater amount of effort for a larger monetary reward versus less effort for a smaller reward. Effort performance was evaluated twice, separated by a two-week interval. ResultsPatients with schizophrenia opted to expend greater effort for trials with higher reward value and greater likelihood of reward receipt. Patients did not find the task overly difficult and reported being motivated to perform well, underscoring the tolerability of the task for patients. Test–retest consistency was good and there was only minimal change in scores over time. Effort performance was not related to sociodemographic or clinical variables (e.g., positive symptoms); however, deficit syndrome patients exerted effort for reward at a significantly lower rate than nondeficit patients. ConclusionsThe effort-based decision making task used in the present study represents an objective paradigm that can be used to evaluate motivational impairments in patients with schizophrenia. Such performance-based measures of motivation may also serve as viable endpoints in clinical trials.

Effort-Based Decision Making in Schizophrenia: Evaluation of Paradigms to Measure Motivational Deficits.

Effort-based decision making requires one to decide how much effort to expend for a certain amount of reward. As the amount of reward goes up most people are willing to exert more effort. This relationship between reward level and effort expenditure can be measured in specialized performance-based tasks that have only recently been applied to schizophrenia. Such tasks provide a way to measure objectively motivational deficits in schizophrenia, which now are only assessed with clinical interviews of negative symptoms. The articles in this theme provide reviews of the relevant animal and human literatures (first 2 articles), and then a psychometric evaluation of 5 effort-based decision making paradigms (last 2 articles). This theme section is intended to stimulate interest in this emerging area among basic scientists developing paradigms for preclinical studies, human experimentalists trying to disentangle factors that contribute to performance on effort-based tasks, and investigators looking for objective endpoints for clinical trials of negative symptoms in schizophrenia.

Motivational Deficits in Schizophrenia and the Representation of Expected Value.

Motivational deficits (avolition and anhedonia) have historically been considered important negative symptoms of schizophrenia (SZ). Numerous studies have attempted to identify the neural substrates of avolition and anhedonia in schizophrenia , but these studies have not produced much agreement. Deficits in various aspects of reinforcement processing have been observed in individuals with schizophrenia, but it is not exactly clear which of these deficits actually engender motivational impairments in SZ. The purpose of this chapter is to examine how various reinforcement-related behavioral and neural signals could contribute to motivational impairments in both schizophrenia and psychiatric illness, in general. In particular, we describe different aspects of the concept of expected value (EV), such as the distinction between the EV of stimuli and the expected value of actions, the acquisition of value versus the estimation of value, and the discounting of value as a consequence of time or effort required. We conclude that avolition and anhedonia in SZ are most commonly tied to aberrant signals for expected value, in the context of learning. We discuss implications for further research on the neural substrates of motivational impairments in psychiatric illness.

The relevance of motivation in schizophrenia

Lately there is a growing interest in the negative symptoms in schizophrenia and their mechanisms of action, with special focus on the motivation process. The lack of motivation is increasingly recognized to be a very important impediment to positive management in schizophrenic pathology. In this mini-review, we described the current understanding of the nature and causes of the specific motivational deficits in schizophrenia in order to find better management strategies for this heterogeneous disorder. All the data and theories presented here clearly demonstrate that amotivation is a fundamental aspect of the negative symptomatology in schizophrenia and could represent a useful factor in understanding and improving the mechanisms and further management of schizophrenia.

EPA-1456 – Electrophysiological indices of reward anticipation abnormalities in subjects with schizophrenia

Introduction Several factor analytic studies have shown than anhedonia and avolition are included in the same factor, suggesting that motivational deficits in schizophrenia are related to a reduced experience of pleasure; however other studies have not confirmed this hypothesis. More recently, it has been hypothesized that avolition is related to a difficulty in anticipating reward value and\or regulating behavior on the basis of the associations between value and action. Objectives/Aims This study is aimed to verify an impairment of reward anticipation in patients with deficit schizophrenia (DS), but not in those with non-deficit schizophrenia (NDS) and its association with primary negative symptoms, using event-related potentials (ERPs). Methods ERPs were recorded in 11 patients with DS, 23 patients with NDS and 23 healthy controls (HC), during anticipation of five different outcomes, small (SR) or large (LR) reward, small (SP) or large (LP) punishment or no-outcome (NO), and during feedback processing. Results Patients did not differ from HC on indices of anticipatory or consummatory anhedonia, but they showed reduced motivation. During reward anticipation, only patients with primary and persistent avolition showed ERPs abnormalities, with respect to HC, in the early processing stages and a reduced activity of cortical generators in the cingulate, in the temporal-occipital and fronto-parietal regions, that are involved in the attention modulation and visual perceptual processing. Conclusions Our data suggest that anhedonia and avolition are partially independent constructs and that avolition is related to the inability to modulate attention and amplify visual perceptual processing of reward stimuli.

The Roles of Reward, Default, and Executive Control Networks in Set-Shifting Impairments in Schizophrenia

Patients with schizophrenia (SZ) show deficits on tasks of rapid reinforcement learning, like probabilistic reversal learning (PRL), but the neural bases for those impairments are not known. Recent evidence of relatively intact sensitivity to negative outcomes in the ventral striatum (VS) in many SZ patients suggests that PRL deficits may be largely attributable to processes downstream from feedback processing, involving both the activation of executive control task regions and deactivation of default mode network (DMN) components. We analyzed data from 29 chronic SZ patients and 21 matched normal controls (NCs) performing a PRL task in an MRI scanner. Subjects were presented with eight pairs of fractal stimuli, for 50 trials each. For each pair, subjects learned to choose the more frequently-rewarded (better) stimulus. Each time a criterion was reached, the better stimulus became the worse one, and the worse became the better. Responses to feedback events were assessed through whole-brain and regions-of-interest (ROI) analyses in DMN. We also assessed correlations between BOLD signal contrasts and clinical measures in SZs. Relative to NCs, SZ patients showed comparable deactivation of VS in response to negative feedback, but reduced deactivation of DMN components including medial prefrontal cortex (mPFC). The magnitudes of patients' punishment-evoked deactivations in VS and ventromedial PFC correlated significantly with clinical ratings for avolition/anhedonia. These findings suggest that schizophrenia is associated with a reduced ability to deactivate components of default mode networks, following the presentation of informative feedback and that motivational deficits in SZ relate closely to feedback-evoked activity in reward circuit components. These results also confirm a role for ventrolateral and dorsomedial PFC in the execution of response-set shifts.

Ventral striatal activation during attribution of stimulus saliency and reward anticipation is correlated in unmedicated first episode schizophrenia patients

Patients with schizophrenia show deficits in motivation, reward anticipation and salience attribution. Several functional magnetic resonance imaging (fMRI) investigations revealed neurobiological correlates of these deficits, raising the hypothesis of a common basis in midbrain dopaminergic signaling. However, investigations of drug-naïve first-episode patients with comprehensive fMRI tasks are still missing.We recruited unmedicated schizophrenia spectrum patients (N=27) and healthy control subjects (N=27) matched for sex, age and educational levels. An established monetary reward anticipation task in combination with a novel task aiming at implicit salience attribution without the confound of monetary incentive was applied.Patients showed reduced right ventral striatal activation during reward anticipation. Furthermore, patients with a more pronounced hypoactivation attributed more salience to neutral stimuli, had more positive symptoms and better executive functioning. In the patient group, a more differentially active striatum during reward anticipation was correlated positively to differential ventral striatal activation in the implicit salience attribution task.In conclusion, a deficit in ventral striatal activation during reward anticipation can already be seen in drug-naïve, first episode schizophrenia patients. The data suggest that rather a deficit in differential ventral striatal activation than a generally reduced activation underlies motivational deficits in schizophrenia and that this deficit is related to the aberrant salience attribution.

Modeling motivational deficits in mouse models of schizophrenia: Behavior analysis as a guide for neuroscience

In recent years it has become possible to develop animal models of psychiatric disease in genetically modified mice. While great strides have been made in the development of genetic and neurobiological tools with which to model psychiatric disease, elucidation of neural and molecular mechanisms thought to underlie behavioral phenotypes has been hindered by an inadequate analysis of behavior. This is unfortunate given the fact that the experimental analysis of behavior has created powerful methods for isolating and describing the functional properties of behavioral mechanisms that are capable of providing deep understanding of behavioral phenotypes. A better understanding of the biological basis of normal behavior and its disturbance in psychiatric disease will require the application of these rigorous behavior analytic tools to animal models. In this review we provide an example of a merging of genetic and behavioral methods and illustrate its utility in the analysis of a mouse model of the motivational deficits in schizophrenia. The synergy between basic behavior analysis, neuroscience, and animal models of psychiatric disease has great potential for achieving a deeper understanding of behavior and its neurobiological mechanisms as well as for leading to improvements in diagnosis and treatment in clinical settings.

PHENOMENOLOGICAL DIFFERENCES BETWEEN HISPANIC AND CAUCASIAN SCHIZOPHRENIA SUBJECTS

prised of two key symptom subdomains: 1) diminished expression (affective flattening and poverty of speech); and 2) amotivation (apathy and anhedonia), and contribute to functional impairment in this illness. Recent data, including our own work, suggests that motivational deficits serve as a critical determinant to functioning. This study aims to explore the longitudinal relationship between motivational and pleasure deficits, cognitive dysfunction, and functional outcomes in schizophrenia. We hypothesize that motivational deficits are the critical determinant of both current and future functioning in individuals with schizophrenia. Methods: Outpatients between the ages of 18 and 55with a diagnosis of schizophrenia, on stable doses of antipsychotic medication, were evaluated at baseline and 6 months later with the Scales for the Assessment of Positive Symptoms (SAPS) and Negative Symptoms (SANS). Amotivationwas assessed with the Apathy Evaluation Scale – Clinician version (AES-C), anticipatory/consummatory pleasure with the Temporal Experience of Pleasure Scale (TEPS), and cognition with theBriefAssessmentofCognition inSchizophrenia (BACS). TheQuality of Life Scale (QLS) was used to evaluate functional status. Results: Nineteen participants (mean age of 42 years, mean duration of illness of 15 years) were assessed at both baseline and 6 months. Stepwise hierarchical regression revealed that baseline amotivation, as measured by the AES-C, was the strongest predictor of both baseline and future functioning, as measured by the QLS. Specifically, AES-C scores accounted for 75% of the variance in baseline functioning (R2 change=0.749, p<.001), and 73% of the variance in functioning at 6month follow-up (R2 change=0.727, p<.001). After exclusion of the Intrapsychic Foundations subscale of the QLS due to overlap in item content with amotivation measures, the AES-C score continued to be the strongest predictor of functioning at baseline and follow-up, accounting for 65% and64%of the variance in functioning, respectively. Positive symptoms (SAPS total score) explained an additional 7% and 5% of the variance in functioning at baseline and follow-up, respectively. Further, amotivation measured by the SANS amotivation subdomain explained an additional 8% and 10% of the variance in functioning at baseline and follow-up, respectively. Other measures including TEPS anticipatory/consummatory pleasure scores, and BACS composite score did not offer additional predictive value. Discussion: Negative symptoms have been implicated in poor functional outcome, with recent work suggesting that motivational deficits are the central link between negative symptoms and poor functioning. The present data take this issue a step further and examine the longitudinal relationship between the negative symptoms of schizophrenia and functional outcomes. In keeping with the cross-sectional findings, motivational deficits appear to play a pivotal role in predicting longitudinal functional outcomes in schizophrenia, with other symptom domains offering little, if any, additional contribution. These preliminary findings highlight the importance of motivational deficits in schizophrenia, and suggest that it is this loss of drive that links negative symptoms to poor functional outcomes.

Motivation and its Relationship to Neurocognition, Social Cognition, and Functional Outcome in Schizophrenia

Objective A burgeoning area of research has focused on motivational deficits in schizophrenia, producing hypotheses about the role that motivation plays in the well-known relationship between neurocognition and functional outcome. However, little work has examined the role of motivation in more complex models of outcome that include social cognition, despite our increased understanding of the critical role of social cognition in community functioning in schizophrenia, and despite new basic science findings on the association between social cognitive and reward processing in neural systems in humans. Using path analysis, we directly contrasted whether motivation 1) causally influences known social cognitive deficits in schizophrenia, leading to poor outcome or 2) mediates the relationship between social cognitive deficits and outcome in this illness. Method Ninety one patients with schizophrenia or schizoaffective disorder completed interview-based measures of motivation and functional outcome as well as standardized measures of neurocognition and social cognition in a cross-sectional design. Results In line with recent research, motivation appears to mediate the relationship between neurocognition, social cognition and functional outcome. A model with motivation as a causal factor resulted in poor fit indicating that motivation does not appear to precede neurocognition. Conclusions Findings in the present study indicate that motivation plays a significant and mediating role between neurocognition, social cognition, and functional outcome. Potential psychosocial treatment implications are discussed, especially those that emphasize social cognitive and motivational enhancement.

Intrinsic motivation in schizophrenia: Relationships to cognitive function, depression, anxiety, and personality.

The goal of the current project was to assess subjective reports of intrinsic motivation and their relationship to cognitive function, mood, and personality in schizophrenia. The authors used the Motivational Trait Questionnaire to examine 3 components of intrinsic motivation (personal mastery, competitive excellence, motivation related to anxiety). They also examined fluid intelligence, context processing, and working memory, as well as self-reports of mood and personal traits related to motivation. Participants were 66 individuals with schizophrenia or schizoaffective disorder and 44 healthy controls. Self-reports of personal mastery and competitive excellence did not differ between controls and individuals with schizophrenia, though patients did report significantly higher motivation related to anxiety. Among controls, but not patients, self-reports of intrinsic motivation were strongly related to cognitive performance. In contrast, both controls and patients showed similar strong relationships between self-reports of intrinsic motivation and related measures of mood and personality. These results are not consistent with the hypothesis that motivational deficits in schizophrenia reflect impairments in intrinsic motivation. However, they do suggest that the normal relationship between self-reports of intrinsic motivation and cognitive function is disrupted in schizophrenia.

Patients with schizophrenia demonstrate dissociation between affective experience and motivated behavior.

Self-reported emotional experience does not differ between patients with schizophrenia and healthy individuals, suggesting that the anhedonia in schizophrenia instead reflects decoupling of affect from motivated behavior. In 2 behavioral conditions, participants with schizophrenia and healthy participants were able to prolong or decrease exposure to stimuli while stimuli were present or alter the likelihood of future exposure to stimuli on the basis of internal representations. They also provided self-reports of affective experience. Patients showed weaker correspondence between behavior and ratings than did comparison participants. The effect was amplified when patients responded on the basis of internal rather than evoked stimulus representations. These data suggest that the motivational deficits in schizophrenia reflect problems in the ability to translate experience into action.