Benjamin M. Robinson

Selective Reinforcement Learning Deficits in Schizophrenia Support Predictions from Computational Models of Striatal-Cortical Dysfunction

BACKGROUND Rewards and punishments may make distinct contributions to learning via separate striatal-cortical pathways. We investigated whether fronto-striatal dysfunction in schizophrenia (SZ) is characterized by selective impairment in either reward- (Go) or punishment-driven (NoGo) learning. METHODS We administered two versions of a probabilistic selection task to 40 schizophrenia patients and 31 control subjects, using difficult to verbalize stimuli (experiment 1) and nameable objects (experiment 2). In an acquisition phase, participants learned to choose between three different stimulus pairs (AB, CD, EF) presented in random order, based on probabilistic feedback (80%, 70%, 60%). We used analyses of variance (ANOVAs) to assess the effects of group and reinforcement probability on two measures of contingency learning. To characterize the preference of subjects for choosing the most rewarded stimulus and avoiding the most punished stimulus, we subsequently tested participants with novel pairs of stimuli involving either A or B, providing no feedback. RESULTS Control subjects demonstrated superior performance during the first 40 acquisition trials in each of the 80% and 70% conditions versus the 60% condition; patients showed similarly impaired (<60%) performance in all three conditions. In novel test pairs, patients showed decreased preference for the most rewarded stimulus (A; t = 2.674; p = .01). Patients were unimpaired at avoiding the most negative stimulus (B; t = .737). CONCLUSIONS The results of these experiments provide additional evidence for the presence of deficits in reinforcement learning in SZ, suggesting that reward-driven learning may be more profoundly impaired than punishment-driven learning.

Delay discounting in schizophrenia

Background. It is well known that individuals with schizophrenia have dopaminergic abnormalities as well as memory-related difficulties, both of which are associated with impulsive decision making. We used a delay discounting measure to test the degree to which patients make future-oriented decisions. Methods. 42 patients with schizophrenia and 29 healthy participants completed a delay discounting measure along with tests of cognitive function and, in patients, symptom ratings. Results. Patients discounted more steeply than did comparison participants. Discounting among patients related to memory capacity and tended to relate inversely to negative symptoms. Conclusions. The impulsive decision making evidenced by patients suggests that they may be prone to choosing immediate over long-term rewards, even when their interests are better served by choosing the latter. Improving cognitive function may enhance their ability to make future-oriented decisions.

Intact Attentional Control of Working Memory Encoding in Schizophrenia

This study reports evidence that individuals with schizophrenia (SC) demonstrate intact attentional selection for visual working memory (WM) storage. A group of 62 participants with SC and 55 control participants without SC were studied in a series of 5 experiments that examined the ability to use top-down and bottom-up cues to guide WM encoding, as well as the ability to spontaneously select a subset of representations for storage. Participants with SC exhibited a consistent and robust ability to use selective attention in the control of WM in all 5 experiments, demonstrating a remarkable island of preserved functioning given the broad spectrum of impairments of attention and WM that have been widely reported in those with SC. These findings indicate that attention is not globally impaired in SC and make it possible to delineate more precisely the nature of the specific impairment of attention in this disorder.

Reduced capacity but spared precision and maintenance of working memory representations in schizophrenia

CONTEXT Working memory deficits are considered a core feature of schizophrenia. Several recent integrative articles have offered mechanistic computational and neurobiological models of the origins of this cognitive deficit. OBJECTIVE To test predictions of these models using a new experimental paradigm from the basic science literature that makes it possible to determine whether patients with schizophrenia show (1) deficits in working memory storage capacity, (2) deficits in the precision of working memory representations, and (3) an amplification of these deficits as the retention interval increases. DESIGN Case-control design. All subjects performed a color working memory test in which they were asked to recall 3 or 4 items after a 1- or 4-second delay. All subjects also received a standard measure of intelligence and the Matrics Consensus Cognitive Battery. SETTING A tertiary care research outpatient clinic. Patients A total of 31 clinically stable patients with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder and 26 healthy volunteers participated. The 2 groups were similar in age, sex, and ethnicity distribution. MAIN OUTCOME MEASURES (1) The number of items stored in working memory and (2) the precision of the working memory representations. RESULTS Patients showed a clear reduction in the number of items stored in working memory. Patients did not differ from controls in the precision of their working memory representations. There was no evidence of delay-related amplification of impairment in either capacity or precision. CONCLUSIONS Patients do not show the type of imprecision or delay-dependent amplification of impairment that is predicted on the basis of current models of the neurobiology of schizophrenia. The models need to be revised to account for a pure reduction in the number of items that patients are able to store in working memory.

The speed of visual attention in schizophrenia: Electrophysiological and behavioral evidence

Schizophrenia is characterized by a substantial slowing of manual response times and by impairments in attention. However, prior research has not investigated whether attention itself is slowed in schizophrenia, and this was the goal of the present study. In Experiment 1, the N2pc component of the event-related potential waveform-an electrophysiological correlate of the focusing of attention-was recorded from 24 schizophrenia spectrum patients and 13 control subjects. Although behavioral response times were delayed by over 100 ms in the patient group, the onset latency of the N2pc component was virtually identical across groups, and no reduction in N2pc amplitude was observed in the patient group. In Experiment 2, a new cueing paradigm was developed to provide a behavioral measure of the speed of attention in 22 schizophrenia spectrum patients and 13 control subjects. We found that the average time required to allocate attention to a cued location was only 19 ms greater for the patient group than for the control group, with most patients within the range of the control subjects. Together, these experiments revealed little or no slowing of the allocation of visual-spatial attention in patients with schizophrenia. Thus, the mechanisms responsible for allocating attention to salient visual targets appear to be largely unaffected by the illness, and the well documented slowing of manual response times in schizophrenia cannot easily be explained by a slowing of attention.

The Relationship Between Working Memory Capacity and Broad Measures of Cognitive Ability in Healthy Adults and People With Schizophrenia

OBJECTIVE Working memory (WM) capacity, typically measured with cognitively complex span tasks, is correlated with higher order cognitive abilities in healthy adults. The goals of this study were to determine whether a more focused measure of visual WM storage capacity would show similar higher order ability correlations in healthy adults and in people with schizophrenia (PSZ), thereby demonstrating the importance of simple storage capacity; determine whether the illness alters the pattern of correlations across cognitive domains; and evaluate whether between-groups differences in WM capacity could account for the generalized cognitive impairment in PSZ. METHOD Ninety-nine PSZ and 77 healthy controls (HCs) completed a visual WM change-localization task, the Wechsler Abbreviated Scale of Intelligence (WASI), and the MATRICS Consensus Cognitive Battery (MCCB). RESULTS PSZ performed more poorly than HCs on all cognitive measures. The between-groups effect size for WM capacity was large (d = 1.11). WM robustly correlated with WASI and MCCB performance, with no significant differences in the magnitude or pattern of correlations across groups. When the groups were pooled, WM capacity correlated at r = .68 with MCCB composite score and at r = .56 with WASI estimated Full Scale IQ. WM capacity accounted for approximately 40% of the between-groups variance across the WASI and MCCB. CONCLUSIONS A simple measure of WM storage capacity is robustly associated with the higher order cognitive abilities assessed by the WASI and MCCB in HCs and PSZ. WM capacity reduction may be a critical determinant of the general cognitive impairment in PSZ.

Impaired control of visual attention in schizophrenia

To investigate attentional impairment in schizophrenia, the authors examined the performance of 22 patients with schizophrenia and 16 healthy control subjects in 4 visual search tasks that varied in perceptual requirements and in the need for precise attentional control. The rate of search was slowed in the patients in all tasks. However, the degree of slowing was largest in tasks requiring precise attentional control and smallest in tasks that were perceptually difficult but required less attentional control. This pattern of results indicates that the primary impairment of attention in schizophrenia lies in the control of attention and not in the selection processes that operate once attention has been directed to an object.

Failure of schizophrenia patients to overcome salient distractors during working memory encoding.

BACKGROUND Prior demonstrations of impaired attentional control in schizophrenia focused on conditions in which top-down control is needed to overcome prepotent response tendencies. Attentional control over stimulus processing has received little investigation. Here, we test whether attentional control is impaired during working memory encoding when salient distractors compete with less salient task-relevant stimuli. METHODS Patients with schizophrenia (n = 28) and healthy control subjects (n = 25) performed a visuospatial working memory paradigm in which half of the to-be-encoded stimuli flickered to increase their salience. After a 2-second delay, stimuli reappeared and participants had to decide whether or not a probed item had shifted location. RESULTS In the unbiased condition where flickering and nonflickering stimuli were equally likely to be probed, both groups displayed a trend toward better memory for the flickering items. In the flicker-bias condition in which the flickering stimuli were likely to be probed, both groups displayed a robust selection advantage for the flickering items. However, in the nonflicker-bias condition in which the nonflickering stimuli were likely to be probed, only healthy control subjects showed selection of the nonflickering items. Patients displayed a trend toward preferential memory for the flickering items, as in the unbiased condition. CONCLUSIONS Both groups were able to select salient over nonsalient stimuli, but patients with schizophrenia were unable to select nonsalient over salient stimuli, consistent with impairment in the effortful control of attention. These findings demonstrate the generality of top-down control failure in schizophrenia in the face of bottom-up competition from salient stimuli as with prepotent response tendencies.

Impaired response selection in schizophrenia: Evidence from the P3 wave and the lateralized readiness potential

Reaction times (RTs) are substantially prolonged in schizophrenia patients, but the latency of the P3 component is not. This suggests that the RT slowing arises from impairments in a late stage of processing. To test this hypothesis, 20 schizophrenia patients and 20 control subjects were tested in a visual oddball paradigm that was modified to allow measurement of the lateralized readiness potential (LRP), an index of stimulus-response translation processes. Difference waves were used to isolate the LRP and the P3 wave. Patients and control subjects exhibited virtually identical P3 difference waves, whereas the LRP difference wave was reduced in amplitude and delayed in latency in the patients. These results indicate that, at least in simple tasks, the delayed RTs observed in schizophrenia are primarily a consequence of impairments in the response selection and preparation processes that follow perception and categorization.

Toward the Neural Mechanisms of Reduced Working Memory Capacity in Schizophrenia

People with schizophrenia (PSZ) demonstrate reliable reductions in working memory (WM) capacity (i.e., the number of objects that can be held in memory). The present study asked whether WM impairments in PSZ can be explained by the same neural mechanisms that underlie individual differences in WM capacity among healthy individuals. Specifically, we examined event-related potentials in PSZ and healthy matched controls during a change detection task that required the storage of multiple objects in WM. The amplitude of contralateral delay activity (CDA), which correlates with WM capacity in healthy individuals, was larger in controls than in PSZ for memory loads of 3 and 5 objects, but larger in PSZ than in controls for a memory load of 1. This same pattern was found in the subgroups of PSZ and controls with an equivalent WM capacity. Moreover, the increase in CDA amplitude was correlated with individual differences in capacity in controls, but not in PSZ. These results demonstrate that WM impairment in PSZ is not associated with the same patterns of neural activity that characterize low WM capacity in healthy individuals. We propose that WM impairment in PSZ instead reflects a specific impairment in the ability to distribute attention broadly.