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Pavlovian learning mechanisms are of great importance both for models of psychiatric disorders and treatment approaches, but understudied in obsessive-compulsive disorder (OCD). Using an established Pavlovian fear conditioning and reversal procedure, we studied skin conductance responses in 41 patients with OCD and in 32 matched healthy control participants. Within both groups, fear acquisition and reversal effects were evident. When comparing groups, patients showed impaired differential learning of threatening and safe stimuli, consistent with previous research. In contrast to prior findings, differential learning impairments were restricted to fear acquisition, and not observed in the reversal stage of the experiment. As previous and present fear reversal experiments in OCD differed in the use of color coding to facilitate stimulus discrimination, the studies converge to suggest that differential learning of threatening versus safe stimuli is impaired in OCD, but manifests itself differently depending on the difficulty of the association to be learned. When supported by the addition of color, patients with OCD previously appeared to acquire an association early but failed to reverse it according to changed contingencies. In absence of such color coding of stimuli, our data suggest that patients with OCD already show differential learning impairments during fear acquisition, which may relate to findings of altered coping with uncertainty previously observed in OCD. Impaired differential learning of threatening versus safe stimuli should be studied further in OCD, in order to determine whether impairments in differential learning predict treatment outcomes in patients, and whether they are etiologically relevant for OCD.

Previous research using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) suggests that the heterogeneous symptoms of obsessive-compulsive disorder (OCD) may reflect four underlying dimensions. However, past results vary substantially, which may be due to (a) the reliance on aggregated scores, (b) the common use of exploratory factor analyses, and (c) the exclusion of several symptoms. The present study tested the homogeneity of the original Y-BOCS categories using confirmatory factor analysis and modified categories where necessary. To test multidimensional models, data were further analyzed with Bayesian structural equation models, which better capture item heterogeneity in contrast to ordinary factor analysis. All analyses were run with two samples of patients with OCD allowing for cross-validation. Only a minority of the original Y-BOCS categories proved to be homogeneous. Modification yielded 10 homogeneous first-order factors, which can be reduced to four second-order factors: Incompleteness, Taboo Thoughts, Responsibility, and Contamination. This two-level factor model outperformed competing factor structures. The results corroborate the notion of four broader symptom dimensions in OCD, although the specific factor structure deviates from previous research. Differences presumably derive from using the full range of OCD symptoms and the combined exploratory and confirmatory approach with BSEM as a theoretically more appropriate analytical framework.

This study explores whether self-disorders occur and can be assessed reliably in a non-clinical sample, and whether the prevalence of these anomalies depends upon the degree of psychometrically defined schizotypy. Participants with either high (n=30) or low (n=20) schizotypy scores were interviewed using a modified version of the Examination of Anomalous Self-Experience (EASE). The degree to which interviewees experienced self-disorder symptoms was rated by the interviewer and an independent rater. Inter-rater reliability was calculated for each item, domain scores and the total score. For the total, sample most items (=66) showed substantial or perfect agreement (κ>0.61), with a few (=6) showing moderate agreement (κ>0.41). Reliability scores were only slightly lower when just the more homogeneous group of individuals with high Schizotypal Personality Questionnaire (SPQ) scores were examined. As expected, high SPQ scores were associated with a high level of self-disorders. In sum, the results suggest that self-disorders can be measured reliably in non-clinical samples and are particularly frequent in individuals with pronounced schizotypical traits.

Saccades made to the opposite side of a visual stimulus (antisaccades) and to central cues (simple volitional saccades) both require active response selection but whether the mechanisms of response selection differ between these tasks is unclear. Response selection can be assessed by increasing the number of response alternatives: this leads to increased reaction times when response selection is more demanding. We compared the reaction times of prosaccades, antisaccades, saccades cued by a central arrow, and saccades cued by a central number, in blocks of either two or six possible responses. In the two-response blocks, reaction times were fastest for prosaccades and antisaccades, and slowest for arrow-cued and number-cued saccades. Increasing response alternatives from two to six caused a paradoxical reduction in reaction times of prosaccades, had no effect on arrow-cued saccades, and led to a large increase in reaction times of number-cued saccades. For antisaccade reaction times, the effect of increasing response alternatives was intermediate, greater than that for arrow-cued saccades but less than that for number-cued saccades. We suggest that this pattern of results may reflect two components of saccadic processing: (a) response triggering, which is more rapid with a peripheral stimulus as in the prosaccade and antisaccade tasks and (b) response selection, which is more demanding for the antisaccade and number-cued saccade tasks, and more automatic when there is direct stimulus-response mapping as with prosaccades, or over-learned symbols as with arrow-cued saccades.

Schizophrenia patients show impaired saccadic response switching, pointing to action control deficits at the level of response selection. Previous studies on healthy subjects suggested that response switch effects might decrease if the prior response is longer ago, reflecting a slow dissipation of the response program persisting from the previous trial. The present study aimed at directly investigating whether response switch effects in schizophrenia patients and healthy subjects depend on the inter-response interval (IRI). Effects of response switching on pro- and antisaccade performance were analyzed in 19 schizophrenia patients and 19 healthy controls at 3 different IRIs (2,500, 3,000, 4,000 ms). Response switch effects of healthy subjects did not vary with the IRI, suggesting that the previous response program persists as long as no contrary response program is activated. In schizophrenia, response switch deficits were replicated at an IRI of 3,000 ms, whereas at IRIs of 2,500 and 4,000 ms, effects of response switching did not significantly differ from healthy subjects. This might suggest that there is a specific IRI range particularly sensitive to response switch deficits in schizophrenia. However, effects of response switching at different IRIs remain to be consolidated.

Action control deficits of schizophrenia patients result from frontostriatal brain abnormalities and presumably reflect an impairment of selective cognitive processes. This study aimed at dissociating two different levels of action control in saccades toward and away from visual stimuli (pro- and antisaccades). Results of previous studies suggested that task switch effects (between pro- and antisaccades) reflect the persistence of a task-specific production rule and refer to the level of task selection, whereas response switch effects (between leftward and rightward saccades) point to the persistence of a specific response program, referring to the level of response selection. In the present study, task switching and response switching were investigated in 20 schizophrenia patients and 20 control subjects. Groups did not differ concerning task switch effects. In contrast, response switching entailed a stronger enhancement of error rates in patients, suggesting a specific deficit on the level of response selection in schizophrenia. The deficit was associated with spatial working memory capacities, confirming and specifying existing hypotheses on a relationship between working memory and action control.

The antisaccade task is a model of the conflict between an unwanted reflexive response (which must be inhibited) and a complex volitional response (which must be generated). The present experiment aimed to investigate separately the neural correlates of these cognitive components using a delayed saccade paradigm to dissociate saccade inhibition from generation. Seventeen healthy volunteers completed event-related functional magnetic resonance imaging at 1.5 T during saccades to and away from a peripheral visual target (prosaccades and antisaccades, respectively). Saccades were requested in response to an auditory go signal on average 12 s after peripheral target appearance. It was found that the right supramarginal gyrus showed significantly greater activation during the inhibition phase than the generation phase of the paradigm for both antisaccade and prosaccade trials, suggesting a role in saccade inhibition or stimulus detection. On the other hand, the right lateral frontal eye field and bilateral intraparietal sulcus showed evidence of selective involvement in antisaccade generation. Ventrolateral and dorsolateral prefrontal cortices showed comparable levels of activation in both phases of the task. These areas likely fulfill a more general supervisory role in the volitional control of eye movements, such as stimulus appraisal, task set, and decision making.

Schizophrenia patients show prefrontal cortex dysfunctions of neurodevelopmental origin, but the cognitive implications of these dysfunctions are not yet understood. This study used experimental variations of oculomotor tasks to evaluate the relative roles of volitional action initiation and the inhibition of reflexive behavior. Thirty schizophrenia patients and 30 control participants performed standard prosaccades (SP), standard antisaccades (SA), delayed prosaccades (DP), and delayed antisaccades (DA). The delayed tasks allowed separating the inhibition of erroneous prosaccades and the initiation of volitional saccades, which coincide in the SA task. Arrow-cued (AC) saccades were used to evaluate initiation without any inhibitory component. Erroneous prosaccades were less frequent in the delayed tasks than in the SA task. Error rates were generally larger in schizophrenia patients than in control participants, but the deficit was smaller in the delayed tasks than in the SA task. Correct saccade latencies of schizophrenia patients were normal in the SP task, but not on conditions of volitional saccade initiation (all other tasks). Volitional saccade latencies were positively correlated with error rates in the schizophrenia group. These results confirm that schizophrenia patients have a specific deficit in initiating volitional action, which may also contribute to the increased error rates.

Clinical and theoretical models suggest deficient volitional initiation of action in schizophrenia patients. Recent research provided an experimental model of testing this assumption using saccade tasks. However, inconsistent findings necessitate a specification of conditions on which the deficit may occur. The present study sought to detect mechanisms that may contribute to poor performance. Sixteen schizophrenia patients and 16 healthy control participants performed visually guided and two types of volitional saccade tasks. All tasks varied as to whether the initial fixation stimulus disappeared (fixation stimulus offset) or continued during saccade initiation, and whether a direction cue allowed motor preparation of the specific saccade. Saccade latencies of the two groups were differentially affected by task type, fixation stimulus offset, and cueing, suggesting abnormal volitional saccade generation, fixation release, and motor preparation in schizophrenia. However, substantial performance deficits may only occur if all affected processes are required in a task.

Previous studies suggested that random switching between pro- and antisaccades increases errors in both tasks. However, little is known about the effects of switching between leftward and rightward saccades (response switching). The present study investigated task and response switching using an alternating runs procedure. Tasks (i.e., prosaccades versus antisaccades) were switched every second trial. Response switches (i.e., leftward saccades versus rightward saccades) were counterbalanced across tasks and task-switching conditions. Task switching increased errors in both tasks. Response switching increased errors when antisaccades were preceded by antisaccades but not when antisaccades were preceded by prosaccades or for prosaccades regardless of the preceding saccade type. The task-switch effects suggest that both pro- and antisaccade trials activate specific production rules that can persist in a subsequent trial. The differential response-switch effects may reflect different modes of response activation in pro- and antisaccades (sensorimotor transformation of visual information versus selection of motor programs).

Although externally as well as internally-guided eye movements allow us to flexibly explore the visual environment, their differential neural mechanisms remain elusive. A better understanding of these neural mechanisms will help us to understand the control of action and to elucidate the nature of cognitive deficits in certain psychiatric populations (e.g., schizophrenia) that show increased latencies in volitional but not visually-guided saccades. Both the superior precentral sulcus (sPCS) and the intraparietal sulcus (IPS) are implicated in the control of eye movements. However, it remains unknown what differential contributions the two areas make to the programming of visually-guided and internally-guided saccades. In this study we tested the hypotheses that sPCS and IPS distinctly encode internally-guided saccades and visually-guided saccades. We scanned subjects with fMRI while they generated visually-guided and internally-guided delayed saccades. We used multi-voxel pattern analysis to test whether patterns of cue related, preparatory and saccade related activation could be used to predict the direction of the planned eye movement. Results indicate that patterns in the human sPCS predicted internally-guided saccades but not visually-guided saccades in all trial periods and patterns in the IPS predicted internally-guided saccades and visually-guided saccades equally well. The results support the hypothesis that the human sPCS and IPS make distinct contributions to the control of volitional eye movements.

Recent research suggests that patients with obsessive–compulsive disorder (OCD) have deficits in the volitional control of saccades. Specific evidence comes from increased latencies of saccadic eye movements when they were volitionally executed but not when they were visually guided. The present study sought to test whether this deviance represents a cognitive endophenotype. To this end, first-degree relatives of OCD patients as genetic risk carriers were compared with OCD patients and healthy controls without a family history of OCD. Furthermore, as volitional response generation comprises selection and initiation of the required response, the study also sought to specify the cognitive mechanisms underlying impaired volitional response generation. Twenty-two unaffected first-degree relatives of OCD patients, 22 unmedicated OCD patients, and 22 healthy comparison subjects performed two types of volitional saccade tasks measuring response selection or only response initiation, respectively. Visually guided saccades were used as a control condition. Our results showed that unaffected first-degree relatives and OCD patients were significantly slowed compared to healthy comparison subjects in volitional response selection. Patients and relatives did not differ from each other. There was no group difference in the visually guided control condition. Taken together, the study provides first evidence that dysfunctional volitional response selection is a candidate endophenotype for OCD.

Schizophrenia (SZ) patients showed increased volitional saccade latencies, suggesting deficient volitional initiation of action. Yet increased volitional saccade latencies may also result from deficits in attention shifts. To dissociate attention shifting and saccade initiation, we asked 25 SZ patients and 25 healthy subjects to make saccades toward newly appearing (onset) targets and toward the loci of disappearing (offset) targets. Similar onsets and offsets were also used as attention cues in a Posner-type manual task. As expected, onsets and offsets had similar effects on attention. In contrast, saccade latencies were considerably longer with offset compared to onset targets, reflecting additional time for volitional saccade initiation. Unexpectedly, SZ patients had normal saccade latencies. Presumably, the expected deficit was compensated by decreased fixation-related neural activity, which was induced by the disappearance of fixation stimuli.

Obsessive-compulsive disorder (OCD) patients show deficits in tasks of executive functioning like the antisaccade (AS) task. These deficits suggest problems in response inhibition or volitional saccade generation. Thirty patients (15 nonmedicated) and 30 healthy subjects performed antisaccades and simple volitional saccades (SVS), that is, centrally cued saccades. In SVS, two aspects of volitional saccade generation were disentangled: response selection and initiation. Latencies of OCD patients were increased in volitional saccades independent of response selection demands. AS performance did not differ. Across groups, latencies in AS were faster than in SVS. Medicated patients did not differ from nonmedicated patients. In sum, response initiation is deficient in OCD patients, which may reflect a general problem in volitional action generation. This deficit did not affect antisaccade performance, possibly due to a lower volitional demand in that task.

The antisaccade task has proven highly useful in basic and clinical neuroscience, and the neural structures involved are well documented. However, the cognitive and neural mechanisms that mediate task performance are not yet understood. An event-related fMRI study was designed to dissociate the neural correlates of two putative key functions, volitional saccade generation and inhibition of reflexive saccades, and to investigate their interaction. Nineteen healthy volunteers performed a task that required (a) to initiate saccades volitionally, either with or without a simultaneous demand to inhibit a reflexive saccade; and (b) to inhibit a reflexive saccade, either with or without a simultaneous demand to initiate a saccade volitionally. Analysis of blood oxygen level-dependent signal changes confirmed a major role of the frontal eye fields and the supplementary eye fields in volitional saccade generation. Inhibition-related activation of a specific fronto-parietal network was highly consistent with previous evidence involved in inhibitory processes. Unexpectedly, there was little evidence of specific brain activation during combined generation and inhibition demands, suggesting that the neural processing of generation and inhibition in antisaccades is independent to a large extent.

Poor antisaccade performance is a reliable index of action control deficits in schizophrenia. To further elucidate the underlying cognitive impairments, the current study aimed to confirm effects of switching the response direction on saccadic performance and to investigate whether response switch effects relate to perseveration. Fourteen schizophrenia patients and 14 healthy controls performed sequences of 1 to 3 simple volitional saccades to one direction and a subsequent volitional saccade with distractor to the same or the opposite direction. Response switches increased error rates in schizophrenia if they followed 3 saccades to the opposite side, suggesting that response switching affects performance on conditions of strong persisting response programs. The increase of response switch error rates with multiple repetitions of the prior response points to a relationship between perseveration and response selection.

Event-related potential (ERP) studies identified the error-related negativity (Ne/ERN) and the error positivity (Pe) to be associated with performance errors. However, the functional significance of these components is not yet resolved. With the present study we intended to further investigate to what extent these components are related to error awareness. ERPs were recorded during an antisaccade task, and error awareness was obtained from accuracy ratings on each trial. In accordance with earlier findings, aware and unaware errors did not differ in Ne/ERN amplitude. Whereas the late Pe (400-600 ms) shows an increased parietal positivity for aware compared with unaware errors, the early Pe (200-300 ms) shows no dissociation between aware and unaware errors. These data lend further support to the view that the Ne/ERN and the (late) Pe reflect different processes in performance monitoring. In fact the present results provide a clear replication of [S. Nieuwenhuis et al. (2001) Psychophysiology, 38, 752-760], showing that the Pe is associated with error awareness and remedial action. Furthermore, it has been shown that this is only true for the late Pe, whereas the early Pe like the Ne/ERN is not modulated by error awareness.

The antisaccade task appears to be particularly suitable for analyzing processes involved in executive control of action. Schizophrenic patients show enhanced rates of erroneous reflexive saccades in this task. This is commonly interpreted as a failure of inhibitory mechanisms. The role of volitional saccade generation is largely neglected in these accounts. In this study, experimental variations of the antisaccade task were applied to manipulate the contribution of volitional processes on antisaccade performance. Fifteen patients with a diagnosis of schizophrenia and 15 healthy control participants performed antisaccade tasks requiring them to look to the mirror location of a peripheral visual stimulus at the onset of this stimulus (standard antisaccade task) or after a brief delay (delayed antisaccade task). As expected, schizophrenic patients showed more reflexive saccade errors than controls. In the delay conditions, reflexive errors decreased, and this effect was significantly stronger in schizophrenic patients. Latencies of correct antisaccades tended to be longer in patients than in control participants. The results suggest that the generation of voluntary saccades is at least in part responsible for the antisaccade deficit in schizophrenic patients. More comprehensive models to account for executive deficits in the antisaccade task must be considered.