Evidence for a deficit in volitional action generation in patients with obsessive-compulsive disorder

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.     

Effects of direction on saccadic performance in relation to lateral preferences

A sample of 676 healthy young males performed visually guided saccades and antisaccades and completed the Porac-Coren questionnaire measuring lateral preferences. There was no difference in mean latency between rightward versus leftward saccades or for saccades executed in the left versus right hemispace. There was also no right/left asymmetry for individuals with left or right dominance as assessed by the lateral preferences questionnaire. The same results were observed for the latency of antisaccades and for the error rate in the antisaccade task. Finally, we did not confirm any substantial subpopulation of individuals with idiosyncratic left/right latency asymmetries that persisted both in the saccade and antisaccade task. These results suggest that neither latency nor antisaccade error rate are good indicators of lateral preferences in these tasks. Other oculomotor tasks might be more sensitive to hemifield differences, or cerebral hemispheric asymmetry is not present at the level of cortical organization of saccades and antisaccades.     

Less attention is more in the preparation of antisaccades, but not prosaccades

To make a saccadic eye movement to a target we must first attend to it. It is therefore not surprising that diverting attention increases saccade latency, but is latency increased in all cases? We show that attending to a peripheral discrimination task has a paradoxical effect. If the stimulus to be attended appears shortly (100 to 300 ms) before an eye movement is made in a direction opposite to that of a presented stimulus (an antisaccade), its latency is reduced to well below baseline performance. In contrast, latencies for saccades toward the stimulus (prosaccades) are increased under similar conditions. This paradoxical effect may arise from competition between the processes mediating prosaccades and antisaccades. When the discrimination task is presented at the critical moment, it interferes with a reflexive prosaccade, allowing faster antisaccades. The results suggest that the suppression of sensorimotor reflexes can facilitate volitional motor acts.     

Analysis of volition latency on antisaccadic eye movements

The antisaccadic paradigm can be applied to test the suppression of reflexive saccades and the activation of volitional saccades simultaneously. The impaired frontal cortex has been shown to have difficulty in suppressing reflexive saccade (prosaccade) to make a successful antisaccade. Degraded antisaccade performance can also be observed in patients with Parkinson's disease (PD). The studies of PD based on the prosaccadic and antisaccadic paradigms have shown controversial findings; the latency between patients and age-matched controls could be either with or without significant difference. Even with this inconsistency, our previous study and recent analysis have supported that the latency of both prosaccade and antisaccade increases significantly for patients with PD. The objective of this study is to investigate whether prolonged antisaccade latency is caused by the affected volitional decision process (volition latency) or simply by the delayed initiation of saccade with direction opposite to the cue, by measuring prosaccade and antisaccade latency from the intermingled paradigms. Eleven mildly affected patients with idiopathic PD and eight age-matched normal subjects were tested in this study. As compared to the age-matched control, the results showed that prosaccade, antisaccadic, and volition latency of the patients was significantly elevated (P<0.01). We conclude that antisaccade performance for the PD patients was degraded for both the volition decision process and the initiation of saccade with direction opposite to the cue. Also, volition latency analysis is a more objective method than prosaccade and antisaccade latency analysis, which can be compared among results obtained from different analysis methodologies.     

Event-related potentials associated with correct and incorrect responses in a cued antisaccade task

In an antisaccade task, subjects are instructed to inhibit a reflexive saccade towards a peripheral stimulus flash and to generate a saccade in the opposite direction. It has been shown recently that normal subjects will generate a high number of incorrect prosaccades in an antisaccade task if the fixation point is extinguished 200 ms before the stimulus appears and if a valid cue for the subsequent antisaccade is given during this gap period. In the present study we recorded cerebral event-related potentials from 19 scalp electrodes from normal subjects prior to correct and incorrect responses in a cued antisaccade task to investigate the neural processes associated with correct antisaccades and incorrect prosaccades in this task. Correct antisaccades and incorrect prosaccades were associated with a negative potential with a maximal amplitude around stimulus onset over the dorsomedial frontal cortex. This potential was higher prior to correct antisaccades than prior to incorrect prosaccades. The execution of a correct antisaccade was preceded by a shift of a negative potential from the parietal hemisphere contralateral to the visual stimulus towards the parietal hemisphere ipsilateral to the stimulus. These results support the view that the supplementary eye fields participate in the inhibition of incorrect saccades in a cued antisaccade task and show that the parietal cortex participates in generating a neural representation of the visual stimulus in the hemifield ipsilateral to the stimulus before generating a motor response. Received: 20 December 1996 / Accepted: 18 June 1997     

Volitional saccade performance in a large sample of patients with obsessive‐compulsive disorder and unaffected first‐degree relatives

Recent evidence indicates that patients with obsessive‐compulsive disorder (OCD) as well as their unaffected first‐degree relatives show deficits in the volitional control of saccades, suggesting that volitional saccade performance may constitute an endophenotype of OCD. Here, we aimed to replicate and extend these findings in a large, independent sample. One hundred and fifteen patients with OCD, 103 healthy comparison subjects without a family history of OCD, and 31 unaffected first‐degree relatives of OCD patients were examined using structured clinical interviews and performed a volitional saccade task as well as a prosaccade task. In contrast to previous reports, neither patients nor relatives showed impairments in the performance of volitional saccades compared to healthy controls. Notably, medicated patients did not differ from nonmedicated patients, and there was no effect of depressive comorbidity. Additional analyses investigating correlations between saccade performance and OCD symptom dimensions yielded no significant associations. In conclusion, the present results do not support the notion that volitional saccade execution constitutes an endophenotype of OCD. Possible explanations for inconsistencies with previous studies are discussed.     

Effects of age on latency and error generation in internally mediated saccades

Most studies on the effects of ageing on saccades have examined reflexive saccades; the only commonly studied volitional task has been the antisaccade task, with contradictory results. We examined in both young and elderly normal subjects the latency of anti-, memory-guided, and predictable saccades and the timing of self-paced saccades; we also evaluated errors made on the first two tasks. We expected errors to be correlated between tasks; we also expected antisaccade latencies and errors to be inversely correlated. We also expected antisaccade and memory-guided saccade latencies to be longer in individuals with a high self-paced rate. Except for predictable saccades, mean latencies were significantly higher in the elderly. However, their performance was more variable. Errors were also significantly more frequent on anti- and memory-guided saccade tasks. Most of the hypothesised correlations were not observed. Analysis of error latencies showed that whilst most antisaccade errors were reflexive, for memory-guided saccades both express errors and errors with latencies between 0.4 and 2.5 s were observed. The latter appeared to be a premature release of what would otherwise have been a properly planned response. Age thus impaired all but the predictable saccade task; nevertheless, there were few relationships between measures across tasks. This suggests that a range of processes mediate peoples' performance on these saccade paradigms.     

Shared and distinct oculomotor function deficits in schizophrenia and obsessive compulsive disorder

Detailed analysis of oculomotor function phenotypes in antisaccade, smooth eye pursuit, and active fixation tasks was performed in a sample of 44 patients with schizophrenia, 34 patients with obsessive compulsive disorder (OCD), and 45 matched healthy controls. A common pattern of performance deficits in both schizophrenia and OCD emerged including higher antisaccade error rate, increased latency for corrective antisaccades, as well as higher rates of unwanted saccades in smooth eye pursuit compared to healthy controls. This common pattern could be related to the dysfunction of a network of cognitive control that is present in both disorders, including the dorsolateral prefrontal cortex, the posterior parietal cortex, and the anterior cingulate cortex. In contrast, only patients with schizophrenia showed a specific increase for correct antisaccade mean latency and the intrasubject variability of latency for error prosaccades as well as a decrease in the gain for smooth eye pursuit, suggesting a specific deficit in saccadic motor control and the frontal eye field in schizophrenia that is not present in OCD. A specific deficit in fixation stability (increased frequency of unwanted saccades during active fixation) was observed only for OCD patients pointing to a deficit in the frontostriatal network controlling fixation. This deficit was pronounced for OCD patients receiving additional antipsychotic medication. In conclusion, oculomotor function showed shared and distinct patterns of deviance for schizophrenia and OCD pointing toward shared and specific neurobiological substrates for these psychiatric disorders.     

Event-related potentials before saccades and antisaccades and their relation to reaction time

In the present study, reaction time (RT) was measured in 12 healthy subjects in a saccade and antisaccade task while recording electroencephalographic activity (EEG) from 62 electrodes on the scalp. Event-related potentials averaged both on target appearance and on saccade onset were larger in amplitude (increased negativity) for the antisaccade task compared to the saccade task. The relation of RT variability to EEG amplitude was studied by averaging stimulus-aligned and movement-aligned individual trials for each subject into four RT quartile groups. The analysis showed a relation of EEG amplitude to RT for both saccades and antisaccades. More specifically, the ERP negativity at 100–120 ms after stimulus onset in the saccade task and at 160–200 ms after stimulus onset in the antisaccade task for stimulus-aligned ERPs decreased monotonically with increasing RT as would be expected if this signal would be related to the eye movement preparation processes. This was much more pronounced and wide spread for the antisaccades than for visually triggered saccades. The peak negativity before movement onset for movement-aligned ERPs also covaried with RT suggesting no relation of this activity to movement preparation processes. This study then confirmed that only a particular ERP signal variation was related to the saccadic eye movement preparatory processes while other components of the ERP have no specific relation to the movement preparation. This particular signal was more prominent for antisaccades compared to visually triggered saccades supporting previous evidence for the cortical involvement in the preparation of these voluntary eye movements. In conclusion, this study validates the use of ERPs in the study of the planning and execution of saccadic eye movements.     

Response selection in prosaccades, antisaccades, and other volitional saccades

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.     

The inter-trial effects of stimulus and saccadic direction on prosaccades and antisaccades, in controls and schizophrenia patients

We investigated the influence of the direction of preceding saccadic trials on the latency of current prosaccades and antisaccades, in healthy subjects and patients with schizophrenia. When prosaccades and antisaccades were performed in separate, single-task blocks, we found that only prosaccades were delayed if the saccade in the prior trial was in the same direction, consistent with the expected directional effect from an ‘inhibition of return’-like alternation advantage. However, both types of saccades were executed more quickly when the saccade in the penultimate trial was in the same direction, consistent with previous demonstrations of directional plasticity in monkeys. In blocks of randomly mixed prosaccades and antisaccades, the directional effects in healthy subjects were greatest when a prosaccade was preceded by an antisaccade, consistent with a summation of effects of alternation advantage (from the prior stimulus) and directional plasticity (from the prior saccade). Schizophrenic patients showed an additional phenomenon, a directionally specific inhibition of upcoming saccades by preceding antisaccades. These results suggest that saccades in humans are modulated by inter-trial effects attributable to both an ‘inhibition of return’-like alternation advantage and directional plasticity.     

Prosaccades and antisaccades to onsets and color singletons: evidence that erroneous prosaccades are not reflexive

In the present study participants searched for an onset target or a color singleton target and were required to execute a saccade toward (prosaccade) or away (antisaccade) from the search target. The results showed that participants often made erroneous saccades toward the onset or color singleton when they were the search target in the antisaccade condition, but not when they were presented as task-irrelevant distractors. This suggests that task-relevance plays a critical role in the production of erroneous prosaccades and provides evidence that these saccades are not completely reflexive. Furthermore, it was found that the antisaccade cost (latency difference between prosaccades and antisaccades) was greater for color singleton search targets than for onset search targets. The present findings have implications for our understanding of the processes involved in the programming of antisaccades and the causes of erroneous prosaccades.     

Attentional facilitation of response is impaired for antisaccades but not for saccades in patients with schizophrenia: implications for cortical dysfunction

The facilitation of response known as the gap effect (a decrease of response latency), observed for saccades and antisaccades when attention is modulated prior to such eye movements, was studied in patients with schizophrenia and in controls. The hypothesis tested was whether patients would show a deficient attentional facilitation in response latency. Fifteen patients with schizophrenia and 17 healthy controls performed blocks of saccades and antisaccades in a gap condition and an overlap condition. Saccade and antisaccade response latencies as well as the error rate for antisaccades were measured for each subject. A similar gap effect (decrease in latency for the gap compared to the overlap condition) was present in the saccade task for patients and controls. In contrast the gap effect in the antisaccade task was absent in 50% of patients compared to none of the controls. This finding was interpreted as indicative of deficient preprocessing in antisaccade-specific cortical areas in schizophrenia (such as the prefrontal cortex), while visually guided saccade processing remained intact. Our results, in addition to many other recent findings, could lead to specific hypotheses on cortical dysfunction in schizophrenia.     

Eye movement disorders after frontal eye field lesions in humans

Eye movements were recorded electro-oculographically in three patients with a small ischemic lesion affecting the left frontal eye field (FEF) and in 12 control subjects. Reflexive visually guided saccades (gap and overlap tasks), antisaccades, predictive saccades, memory-guided saccades, smooth pursuit and optokinetic nystagmus (OKN) were studied in the three patients. Staircase saccades and double step saccades were also studied in one of the three patients. For both leftward and rightward saccades, latency in the overlap task (but not in the gap task) and that of correct antisaccades and of memory-guided saccades was significantly increased, compared with the results of controls. There was a significant decrease in the amplitude gain of all rightward saccades programmed using retinotopic coordinates (gap and overlap tasks, predictive and memory-guided saccades), whereas the amplitude gain of corresponding leftward saccades was preserved. Such an asymmetry between leftward and rightward saccades was significant. In the staircase paradigm as well as for the first saccade in the double step paradigm (with the use of retinotopic coordinates in both cases), the amplitude gain of rightward saccades was also significantly lower than that of leftward saccades. Moreover, in the double step paradigm, the amplitude gain of the first rightward saccade was significantly lower than that of the second rightward saccade (programmed using extraretinal signals), which was preserved. The percentage of errors in the antisaccade task did not differ significantly from that of normal subjects. In the predictive saccade paradigm, the percentage of predictive rightward saccades was significantly decreased. The left smooth pursuit gain for all tested velocities, the right smooth pursuit gain for higher velocities, and the left OKN gain were significantly decreased. The results show, for the first time in humans, that the FEF plays an important role in (1) the disengagement from central fixation, (2) the control of contralateral saccades programmed using retinotopic coordinates, (3) saccade prediction and (4) the control of smooth pursuit and OKN, mainly ipsilaterally. In contrast, the left FEF did not appear to be crucial for the control of the only type of saccades programmed using extraretinal signals studied here.     

Control of voluntary and reflexive saccades in Parkinson’s disease

Eight patients with idiopathic Parkinson’s disease (PD) were compared with a group of age-matched controls on both reflexive saccade and antisaccade tasks. While reflexive, visually guided saccades led to equivalent performance in both groups, PD patients were slower, made more errors, and showed reduced gain on antisaccades (AS). This is consistent with previous results showing that PD patients have no difficulty with reflexive saccades but show deficiencies in a number of voluntary saccade paradigms. Moreover, visual information in the form of landmarks improves AS performance more for PD patients than controls, a finding analogous to results seen with other motor acts such as target-directed pointing. Results are discussed in terms of a two-process model of attention and eye movements. Received: 13 October 1998 / Accepted: 11 May 1999     

Effects of switching between leftward and rightward pro- and antisaccades

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).     

Adaptation of reactive and voluntary saccades: different patterns of adaptation revealed in the antisaccade task

Sensorimotor adaptation restores and maintains the accuracy of goal-directed movements. It remains unclear whether these adaptive mechanisms modify actions by controlling peripheral premotor stages that send commands to the effectors and/or earlier processing stages involved in registration of target location. Here, we studied the effect of adaptation of saccadic eye movements, a well-established model of sensorimotor adaptation, in an antisaccade task. This task introduces a clear spatial dissociation between the actual target direction and the requested saccade direction because the correct movement direction is in the opposite direction from the target location. We used this requirement of a vector inversion to assess the level(s) of saccadic adaptation for two different types of adapted saccades. In two different experiments, we tested the transfer to antisaccades of the adaptation in one direction of reactive saccades to jumping targets and of scanning voluntary saccades within a target array. In the first experiment, we found that adaptation of reactive saccades transferred only to antisaccades in the adapted direction. In contrast, in the second experiment, adaptation of scanning voluntary saccades transferred to antisaccades in both the adapted and non-adapted directions. We conclude that adaptation of reactive saccades acts only downstream of the vector inversion required in the antisaccade task, whereas adaptation of voluntary saccades has a distributed influence, acting both upstream and downstream of vector inversion.     

Switch performance in peripherally and centrally triggered saccades

A common hypothesis is that the switch cost measured when switching between prosaccades and antisaccades mainly reflects the inhibition of the saccadic system after the execution of an antisaccade, which requires the inhibition of a gaze response. The present study further tested this hypothesis by comparing switch performance between peripherally triggered saccades and centrally triggered saccades with the latter type of saccades not requiring inhibition of a gaze response. For peripherally triggered saccades, a switch cost was present for prosaccades but not for antisaccades. For centrally triggered saccades, a switch cost was present both for prosaccades and for antisaccades. The difference between both saccade tasks further supports the hypothesis that the switch performance observed for peripherally triggered saccades is related to the inhibition of a gaze response that is required when executing a peripherally triggered antisaccade and the persisting inhibition in the saccadic system this entails. Furthermore, the switch costs observed for centrally triggered saccades indicate that more general processes besides the persisting inhibition in the saccadic system, such as reconfiguration and interference control, also contribute to the switch performance in saccades.     

Event-related fMRI responses in the human frontal eye fields in a randomized pro- and antisaccade task

We examined whether the frontal eye fields (FEF) are involved in the suppression of reflexive saccades. Simultaneous recording of horizontal eye movements and functional magnetic resonance imaging enabled us to perform a randomized pro- and antisaccade task and to sort blood oxygenation level dependent (BOLD) time series on the basis of task performance. Saccadic reaction time distributions were comparable across tasks indicating a similar effort in preprocessing of the saccades. Furthermore, we found similar BOLD activation in FEF during both correctly performed pro- and antisaccades. Frontal eye field activation started prior to target presentation and saccade generation. While we observed only few erroneous antisaccades, these were associated with a decrease in BOLD activity prior to target presentation, and increased BOLD activity after target presentation relative to correctly performed antisaccades. These findings are consistent with a role of the FEF in the suppression of reflexive saccades. The increase in activity after target presentation for antisaccade errors can only be indirectly linked to such a role but may also reflect activity related to the generation of a correction saccade. Frontal eye field BOLD activity may further represent general arousal, preparatory set, short-term memory, or salience-map related activity.     

The relationship of saccadic peak velocity to latency: evidence for a new prosaccadic abnormality in schizophrenia

Antisaccades have not only longer latencies but also lower peak velocities than prosaccades. It is not known whether these latency and velocity differences are related. Studies of non-human primates suggest that prosaccade peak velocity declines as latency from target appearance increases. We examined whether a similar relationship between peak velocity and latency existed in human saccades, whether it accounted for the difference in peak velocity between antisaccades and prosaccades, and whether it was affected by schizophrenia, a condition that affects antisaccade performance. Sixteen control and 21 schizophrenia subjects performed prosaccade and antisaccade trials in the same test session. In both groups antisaccades had lower peak velocities than prosaccades. Latency did not influence the peak velocities of antisaccades in either subject group. At short latencies, the peak velocities of prosaccades were also similar in the two groups. However, while prosaccade peak velocities declined minimally with increasing latency in control subjects, those in the schizophrenia group declined significantly until they reached a value similar to antisaccade peak velocities. We conclude that, in normal subjects, the effect of latency on prosaccade peak velocity is minimal and cannot account for the lower velocity of antisaccades. In schizophrenia, we hypothesize that the latency-related decline in prosaccade peak velocity may reflect either an increased rate of decay of the effect of the transient visual signal at the saccadic goal, or a failure of the continuing presence of the target to sustain neural activity in the saccadic system.