Development of pro- and antisaccades in children with attention-deficit hyperactivity disorder (ADHD) and healthy controls

To date, the investigation of the antisaccade task, a simple test of "executive functions," in children with ADHD has yielded inconsistent results. The present study aimed at contributing to this issue by (a) the investigation of a large sample of carefully diagnosed ADHD patients aged 7-15 years, and (b) the analyses of differential age effects in patients and controls. Healthy control children were pairwise matched with patients (N = 46; age = 136 +/- 24 months) for age and gender, and did not significantly differ in IQ. Horizontal pro- and antisaccades were elicited under the 200-ms gap and overlap conditions (blocks of 100 trials each). Overall, patients exhibited (a) augmented pro- and antisaccadic reaction times, (b) augmented error rates (antitasks), (c) augmented proportions of early responses (all conditions), and (d) reduced proportions of express saccades under the prosaccadic gap condition. The greater decline in anti- as compared to pro-SRT with increasing age that characterized controls was missing in patients. Confirming Barkley's (1997) neuropsychological theory of ADHD, these results altogether point to alterations in "executive functions" in ADHD patients that are presumably supported by frontal lobe structures, in particular the lateral prefrontal cortex and the frontal eye fields.     

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 influence of stimulus direction and eccentricity on pro- and anti-saccades in humans

We examined the sensory and motor influences of stimulus eccentricity and direction on saccadic reaction times (SRTs), direction-of-movement errors, and saccade amplitude for stimulus-driven (prosaccade) and volitional (antisaccade) oculomotor responses in humans. Stimuli were presented at five eccentricities, ranging from 0.5° to 8°, and in eight radial directions around a central fixation point. At 0.5° eccentricity, participants showed delayed SRT and increased direction-of-movement errors consistent with misidentification of the target and fixation points. For the remaining eccentricities, horizontal saccades had shorter mean SRT than vertical saccades. Stimuli in the upper visual field trigger overt shifts in gaze more easily and faster than in the lower visual field: prosaccades to the upper hemifield had shorter SRT than to the lower hemifield, and more anti-saccade direction-of-movement errors were made into the upper hemifield. With the exception of the 0.5° stimuli, SRT was independent of eccentricity. Saccade amplitude was dependent on target eccentricity for prosaccades, but not for antisaccades within the range we tested. Performance matched behavioral measures described previously for monkeys performing the same tasks, confirming that the monkey is a good model for the human oculomotor function. We conclude that an upper hemifield bias lead to a decrease in SRT and an increase in direction errors.     

Effects of aging on switching the response direction of pro- and antisaccades

The present study investigated effects of task switching between pro- and antisaccades and switching the direction of these saccades (response switching) on performance of younger and older adults. Participants performed single-task blocks, in which only pro- or only antisaccades had to be made as well as mixed-task blocks, in which pro- and antisaccades were required. Analysis of specific task switch effects in the mixed-task blocks showed switch costs for error rates for prosaccades for both groups, suggesting that antisaccade task rules persisted and affected the following prosaccade. The comparison between single- and mixed-task blocks showed that mixing costs were either equal or smaller for older than younger participants, indicating that the older participants were well able to keep task sets in working memory. The most prominent age difference that was observed for response switching was that for the older but not younger group task switching and response switching interacted, resulting in less errors when two consecutive antisaccades were made in the same direction. This finding is best explained with a facilitation of these consecutive antisaccades. The present study clearly demonstrated the impact of response switching and a difference between age groups, underlining the importance of considering this factor when investigating pro- and antisaccades, especially antisaccades, and when investigating task switching and aging.     

Saccade generation and suppression in schizophrenia: effects of response switching and perseveration

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.     

Task-switching in schizophrenia: active switching costs and passive carry-over effects in an antisaccade paradigm

It has been hypothesized that impaired task-switching underlies some of the behavioural deficits in schizophrenia. However, task-switching involves many cognitive operations. In this study our goal was to isolate the effects on latency and accuracy that can be attributed to specific task-switch processes, by studying the inter-trial effects in blocks of randomly mixed prosaccades and antisaccades. By varying the preparatory interval between an instructional cue and the target, we assessed the costs of both (1) an active reconfiguration process that was triggered by the cue, and (2) passive carry-over effects persisting from the prior trial. We tested 15 schizophrenic subjects and 14 matched controls. A very short preparatory interval increased error rates and saccadic latencies in both groups, but more so in schizophrenia, suggesting difficulty in rapidly activating saccadic goals. However, the contrast between repeated and switched trials showed that the costs of task switching in schizophrenia were not significantly different from the controls, at either short or long preparatory intervals, for both antisaccades and prosaccades. These results confirm prior observations that passive carry-over effects are normal in schizophrenia, and show that active reconfiguration is also normal in this disorder. Thus problems with executive control in schizophrenia may not affect specific task-switching operations.     

Age differences in task switching and response monitoring: evidence from ERPs

This study investigates age differences in the flexible adaptation to changing demands on task switching and conflict processing. We applied a cued task-switching version of the Stroop task and manipulated the ratio of conflict trials. During task preparation, the P300 varied as a function of conflict ratio and a later positive component was larger for switch than non-switch trials. Stimulus-related conflict processing as indicated by a negativity for incompatible trials (Ni) was delayed for older adults. Moreover, the Ni varied as a function of conflict ratio and was larger for switch than for non-switch trials. Age differences were also obtained in the correct response negativity (CRN). CRN was larger on incompatible trials and this CRN-compatibility effect was enhanced when incompatible trials were infrequent in younger, but not in older adults. Our findings suggest impairments of older adults primarily in response-related conflict processing and in the flexible adaptation to changing task contexts.     

Task-switching in oculomotor control: Unidirectional switch-cost when alternating between pro- and antisaccades

The antisaccade task requires the suppression of a reflexive prosaccade (i.e., response suppression) and the remapping of a target location to mirror-symmetrical space (i.e., vector inversion). Moreover, antisaccades are associated with increased activation of cortical oculomotor networks: a finding attributed to the top-down requirements of response suppression and vector inversion. The goal of the present study was to determine if the increased cortical activity associated with antisaccades elicits a residual inhibition of oculomotor planning networks. To that end, each trial in this investigation entailed the onset of a single and exogenously presented target (i.e., archetypical antisaccade task) and participants were instructed to alternate between pro- and antisaccades in blocked and random task-switching schedules. In the blocked schedule, the saccade tasks (i.e., pro- and antisaccades) alternated on every second trial (AABB paradigm) whereas in the random schedule the saccade tasks were pseudo-randomly interleaved on a trial-by-trial basis. Reaction times for task-switch prosaccades were longer and more variable than their task-repetition counterparts, whereas antisaccades did not vary as a function of task-switch and task-repetition trials: a finding that was consistent across blocked and random presentation schedules. In other words, results demonstrate a unidirectional switch-cost for prosaccades. As such, we propose that the top-down processes required to complete an antisaccade results in residual inhibition of oculomotor networks supporting a subsequent prosaccade.     

Four-week test-retest stability of individual differences in the saccadic CNV, two saccadic task parameters, and selected neuropsychological tests

The aim of the present study was the comparative assessment of the 4-week test-retest stabilities of the saccadic CNV (sCNV) and saccadic reaction times (SRT) during the execution of pro- and antisaccades, as well as the stability of RT during execution of two neuropsychological tests of alertness and S-R incompatibility. Prosaccades were elicited under the 200-ms gap and overlap conditions, antisaccades under the overlap condition (64 trials each). The EEG was recorded from 25 channels with a DC amplifier (MES, Munich). Data of 20 healthy participants were statistically analyzed. We found high test-retest correlations for all SRT (.76 < or = r(tt) < or = .88) and neuropsychological (.62 < or = r(tt) < or = .88) measures. For the sCNV, coefficients ranging between .58 (pro/gap) and .77 (anti/overlap) were obtained. Whereas SRT were significantly faster during the second than during the first session, group means for the saccadic CNV were stable across the sessions. Our results suggest high 4-week stability of individual differences in SRT, and moderate to good stabilities of saccadic CNV amplitudes. Our results recommend these "traitlike" measures to be used in individual differences research.     

Task confusion after switching revealed by reductions of error-related ERP components

While response delays after task switching have been widely used as an index to investigate the limits of cognitive flexibility, little is known about their counterpart in error rates. It has been hypothesized that at least some postswitching errors are not caused by simple response errors but by task confusion, which refers to the establishment and execution of an incorrect task set. The aim of the current study is to provide evidence for this hypothesis. Using a multitrial paradigm, we firstly dissociated task confusion from simple cue encoding failure, and then measured the error-related negativity (ERN) and the following error positivity (Pe) as indices of the brain's error processing. We predicted that task confusion, if it exists, would cause ambiguity to the criteria of correct response, and therefore attenuate error processing. Results confirmed our prediction, suggesting that task confusion actually occurs after switching.     

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.     

Effects of aging and job demands on cognitive flexibility assessed by task switching

In a cross-sectional, electrophysiological study 91 workers of a big car factory performed a series of switch tasks to assess their cognitive control functions. Four groups of workers participated in the study: 23 young and 23 middle aged assembly line employees and 22 young and 23 middle aged employees with flexible job demands like service and maintenance. Participants performed three digit categorisation tasks. In addition to single task blocks, a cue-based (externally guided) and a memory-based (internally guided) task switch block was administered. Compared to young participants, older ones showed the typical RT-decline. No differences between younger and older participants regarding the local switch costs could be detected despite the source of the current task information. In contrast, whereas the groups did not differ in mixing costs in the cued condition, clear performance decrements in the memory-based mixing block were observed in the group of older employees with repetitive work demands. These findings were corroborated by a number of electrophysiological results showing a reduced CNV suggesting an impairment of task specific preparation, an attenuated P3b suggesting reduced working memory capacity and a decreased Ne suggesting deficits in error monitoring in older participants with repetitive job demands. The results are compatible with the assumption that long lasting, unchallenging job demands may induce several neurocognitive impairments which are already evident in the early fifties. Longitudinal studies are needed to confirm this assumption.     

Caffeine improves anticipatory processes in task switching

We studied the effects of moderate amounts of caffeine on task switching and task maintenance using mixed-task (AABB) blocks, in which participants alternated predictably between two tasks, and single-task (AAAA, BBBB) blocks. Switch costs refer to longer reaction times (RT) on task switch trials (e.g. AB) compared to task-repeat trials (e.g. BB); mixing costs refer to longer RTs in task-repeat trials compared to single-task trials. In a double-blind, within-subjects experiment, two caffeine doses (3 and 5mg/kg body weight) and a placebo were administered to 18 coffee drinkers. Both caffeine doses reduced switch costs compared to placebo. Event-related brain potentials revealed a negative deflection developing within the preparatory interval, which was larger for switch than for repeat trials. Caffeine increased this switch-related difference. These results suggest that coffee consumption improves task-switching performance by enhancing anticipatory processing such as task set updating, presumably through the neurochemical effects of caffeine on the dopamine system.     

Event-related potential correlates of task switching and switch costs

Studies of task switching demonstrate that task switches are associated with response costs and that these costs are reduced when a cue is presented in advance of a switch. The present study examined cortical event-related potential correlates of task switching and switch costs in 39 participants during a cued match/mismatch discrimination task. Compared with non-switch trials, switch trials were associated with a larger cue-related, anticipatory P3b-like waveform. Switch trials were also associated with smaller target-related, stimulus-dependent P2 and P3-like components. Moreover, the switch-related amplitude variability in the P3b to the cue and the P2 to the target were associated with unique components of the residual switch costs. The results support an integrated model of task switching with complementary yet distinct roles for anticipatory and stimulus-dependent processes in task switching and switch costs.     

Influence of stimulus eccentricity and direction on characteristics of pro- and antisaccades in non-human primates

The ability to inhibit reflexes in favor of goal-oriented behaviors is critical for optimal exploration and interaction with our environment. The antisaccade task can be used to investigate the ability of subjects to suppress a reflexive saccade (prosaccade) to a suddenly appearing visual stimulus and instead generate a voluntary saccade (antisaccade) to its mirror location. To understand the neural mechanisms required to perform this task, our lab has developed a non-human primate model. Two monkeys were trained on a task with randomly interleaved pro- and antisaccade trials, with the color of the central fixation point (FP) instructing the monkey to either make a prosaccade (red FP) or an antisaccade (green FP). In half of the trials, the FP disappeared 200 ms before stimulus presentation (gap condition) and in the remaining trials, the FP remained visible (overlap condition) during stimulus presentation. The effect of stimulus eccentricity and direction was examined by presenting the stimulus at one of eight different radial directions (0-360 degrees ) and five eccentricities (2, 4, 8, 10, and 16 degrees ). Antisaccades had longer saccadic reaction times (SRTs), more dysmetria, and lower peak velocities than prosaccades. Direction errors in the antisaccade task were more prevalent in the gap condition. The difference in mean SRT between correct pro- and antisaccades, the anti-effect, was greater in the overlap condition. The difference in mean SRT between the overlap and the gap condition, the gap effect, was larger for antisaccades than for prosaccades. The manipulation of stimulus eccentricity and direction influenced SRT and the proportion of direction errors. These results are comparable to human studies, supporting the use of this animal model for investigating the neural mechanisms subserving the generation of antisaccades.     

Neural correlates of cue retrieval, task set reconfiguration, and rule mapping in the explicit cue task switching paradigm

Event-related brain potentials (ERPs) were used in two experiments to examine the neural correlates of processes underlying task switching in the information-reduction task switching paradigm. Each experiment included 22 participants. The paradigm included two cues for each task. This element of the design allowed us to differentiate the ERP correlates of cue retrieval, task set reconfiguration, and rule mapping. The ERP data revealed a parietal slow wave that was sensitive to processes associated with cue retrieval and task set reconfiguration and a frontal-polar slow wave that was sensitive to processes associated with rule mapping. These findings further the proposal that an endogenous act of control supporting processes related to task set reconfiguration and rule mapping may facilitate performance of the explicit cue task switching paradigm.     

The Met-allele of the BDNF Val66Met polymorphism enhances task switching in elderly

In this study we examined the relevance of the functional brain-derived neurotrophic factor (BDNF) Val66Met polymorphism as a modulator of task-switching performance in healthy elderly by using behavioral and event-related potential (ERP) measures. Task switching was examined in a cue-based and a memory-based paradigm. Val/Val carriers were generally slower, showed enhanced reaction time variability and higher error rates, particularly during memory-based task switching than the Met-allele individuals. On a neurophysiological level these dissociative effects were reflected by variations in the N2 and P3 ERP components. The task switch-related N2 was increased while the P3 was decreased in Met-allele carriers, while the Val/Val genotype group revealed the opposite pattern of results. In cue-based task-switching no behavioral and ERP differences were seen between the genotypes. These data suggest that superior memory-based task-switching performance in elderly Met-allele carriers may emerge due to more efficient response selection processes. The results implicate that under special circumstances the Met-allele renders cognitive processes more efficient than the Val/Val genotype in healthy elderly, corroborating recent findings in young subjects.     

The influence of rTMS over the right dorsolateral prefrontal cortex on intentional set switching

High frequency (HF) repetitive transcranial magnetic stimulation (rTMS) has an excitatory effect on neurons of a specific brain area. The dorsolateral prefrontal cortex (DLPFC) has been associated with executive functions, such as task set switching. One important experimental paradigm for investigating such higher order cognitive control is the task-switching (TS) paradigm. A TS paradigm requires switching between two conditional response tasks with mutually incompatible response–selection rules. In the present study, the influence of HF rTMS over the right DLPFC in healthy female volunteers on a modified TS paradigm was investigated. As expected, reaction time on cued switching trials decreased significant after rTMS, as compared to non-cued switch trials. No changes emerged after the placebo sham condition. Mood remained unchanged after rTMS. These findings demonstrate the role of the right DLPFC in cued intentional set switch initiation.     

Pre-stimulus EEG effects related to response speed, task switching and upcoming response hand

The task-switching paradigm provides an opportunity to study whether oscillatory relations in neuronal activity are involved in switching between and maintaining task sets. The EEG of subjects performing an alternating runs [Rogers, R.D., Monsell, S., 1995. Costs of a predictable switch between simple cognitive tasks. Journal of Experimental Psychology: General 124, 207-231] task-switching task was analyzed using event-related potentials, the lateralized readiness potential, instantaneous amplitude and the phase-locking value [Lachaux, J.P., Rodriguez, E., Martinirie, J., Varela, F.J., 1999. Measuring phase synchrony in brain signals. Human Brain Mapping 8, 194-208]. The two tasks differed in the relevant modality (visual versus auditory) and the hand with which responses were to be given. The mixture model [de Jong, R., 2000. An intention driven account of residual switch costs. In: Monsell, S., Driver, J. (Eds.), Attention and Performance XVII: Cognitive Control. MIT Press, Cambridge] was used to assign pre-stimulus switch probabilities to switch trials based on reaction time; these probabilities were used to create a fast-slow distinction between trials on both switch and hold trials. Results showed both time- and time-frequency-domain effects, during the intervals preceding stimuli, of switching versus maintenance, response speed of the upcoming stimulus, and response hand. Of potential importance for task-switching theory were interactions between reaction time by switch-hold trial type that were found for a frontal slow negative potential and the lateralized readiness potential during the response-stimulus interval, indicating that effective preparation for switch trials involves different anticipatory activity than for hold trials. Theta-band oscillatory activity during the pre-stimulus period was found to be higher when subsequent reaction times were shorter, but this response speed effect did not interact with trial type. The response hand of the upcoming task was associated with lateralization of pre-stimulus mu- and beta-band amplitude and, specifically for switch trials, beta-band phase locking.