Effects of the egg protein hydrolysate NWT-03 on cognitive function in men and women with the metabolic syndrome: a randomized, double-blind, placebo-controlled study.

Objectives: The metabolic syndrome is associated with cardiovascular diseases and cognitive decline. The egg protein hydrolysate NWT-03 has shown to improve cardiovascular risk factors in humans. This study investigated whether NWT-03 also has an effect on cognitive function.Methods: Men and women with the metabolic syndrome (n = 76) with a mean age of 60 ± 10 years participated in this randomized, double-blind, placebo-controlled, cross-over trial with an intervention (5 g/day NWT-03) and control period (5 g/day maltodextrin) of 4 weeks separated by a wash-out period of 2-8 weeks. Cognitive function was assessed with the anti-cue reaction time test (impulse control) and psychomotor vigilance test (sustained attention) at day 0, 2, and 27 of both periods. Serum brain-derived neurotrophic factor (BDNF) concentrations were measured at the start and end of both periods.Results: NWT-03 consumption significantly improved the change (day 27 - day 0) in response times of the anti-cue reaction time test compared with the control period (P < 0.001), but not of the psychomotor vigilance test (P = 0.487). Serum BDNF concentrations of all subjects did not significantly change (P = 0.241).Conclusion: NWT-03 has the ability to improve cognitive function within the executive function domain. The underlying mechanism warrants further research and could either be indirect via inhibition of dipeptidyl peptidase 4 (DPP4) or direct via passage of small peptides over the blood-brain barrier inducing local effects.Trial registration: ClinicalTrials.gov identifier: NCT02561663.

Proactive motor control within and between hands: Effects of age, motor set, and cue type.

Several studies have reported that proactive motor control in a cued four-finger choice reaction task proceeds more efficiently with a 2-hands motor set (two fingers on each hand) than with a 1-hand motor set (four fingers on one hand). According to the Grouping Model, this is because the 2-hands motor set recruits distinct left and right hand representations located in separate cerebral hemispheres, whereas the 1-hand motor set recruits partially overlapping neural areas grouped together in one hemisphere. The latter neural organization increases neuromotor noise, thereby complicating proactive motor selection. The present study examined the effect of older age on the 2-hands motor selection advantage. A group of young and a group of older adults performed two proactive motor tasks-the procue task and the anticue task-with two motor sets: a 2-hands and 1-hand set. Predictive cues preceded the target signal at five different time intervals (100-850 ms), allowing advance selection of 2 out of 4 fingers. Older adults showed longer reaction times and smaller cueing benefits compared to younger adults. Overall, cueing benefits were greater, and accrued faster, with the 2-hands than with the 1-hand motor set, reflecting the beneficial impact of the neuroanatomical hand distinction. Importantly, the 2-hands advantage was substantially greater in the older age group, suggesting that the hand distinction might abate age-related neural dedifferentiation. These findings highlight the impact of cortical representational distinctiveness in proactive motor control, especially in older age.

Aerobic Exercise Training Improves Cerebral Blood Flow and Executive Function: A Randomized, Controlled Cross-Over Trial in Sedentary Older Men.

BACKGROUND: Physical activity may attenuate age-related cognitive decline by improving cerebrovascular function. The aim of this study was therefore to investigate effects of aerobic exercise training on cerebral blood flow (CBF), which is a sensitive physiological marker of cerebrovascular function, in sedentary older men. METHODS: Seventeen apparently healthy men, aged 60-70 years and with a BMI between 25 and 35 kg/m2, were included in a randomized, controlled cross-over trial. Study participants were randomly allocated to a fully-supervised, progressive, aerobic exercise training or no-exercise control period for 8 weeks, separated by a 12-week wash-out period. Measurements at the end of each period included aerobic fitness evaluated using peak oxygen consumption during incremental exercise (VO2 peak), CBF measured with pseudo-continuous arterial spin labeling magnetic resonance imaging, and post-load glucose responses determined using an oral glucose tolerance test (OGTT). Furthermore, cognitive performance was assessed in the domains of executive function, memory, and psychomotor speed. RESULTS: VO2 peak significantly increased following aerobic exercise training compared to no-exercise control by 262 ± 236 mL (P < 0.001). CBF was increased by 27% bilaterally in the frontal lobe, particularly the subcallosal and anterior cingulate gyrus (cluster volume: 1008 mm3; P < 0.05), while CBF was reduced by 19% in the right medial temporal lobe, mainly temporal fusiform gyrus (cluster volume: 408 mm3; P < 0.05). Mean post-load glucose concentrations determined using an OGTT decreased by 0.33 ± 0.63 mmol/L (P = 0.049). Furthermore, executive function improved as the latency of response was reduced by 5% (P = 0.034), but no changes were observed in memory or psychomotor speed. CONCLUSION: Aerobic exercise training improves regional CBF in sedentary older men. These changes in CBF may underlie exercise-induced beneficial effects on executive function, which could be partly mediated by improvements in glucose metabolism. This clinical trial is registered on ClinicalTrials.gov as NCT03272061.

Both facilitatory and inhibitory impairments underlie age-related differences of proactive cognitive control across the adult lifespan.

We investigated two components of proactive cognitive control, response facilitation and response inhibition, in an adult lifespan sample (N=544, age range=18-91years) by administering two response-preparation tasks: a procue task, primarily involving facilitation, and an anticue task, involving both facilitation and inhibition. Cues in both tasks corresponded with the index and middle fingers of either the left or right hand. After a random preparation interval (PI) of 100-850ms following the onset of the cue signal, a single-target stimulus indicated the required response. Where procues were spatially aligned with the two fingers of the responding hand, anticues consistently indicated the two fingers of the opposite hand, requiring a remapping of cue location and response hand. This remapping requires inhibition to suppress the automatic activation of the ipsilateral responses. Previous research revealed typical reaction time (RT) profiles for procues and anticues as a function of PI. Whereas procues generate RT benefits (relative to a neutral-cue condition) already at short PIs, which increase with longer PIs, anticues generate RT costs at short PIs and RT benefits at longer PIs. Our results showed that, in the anticue task, older participants needed more preparation time to turn RT costs into RT benefits than younger participants, revealing an age-related deficit of response inhibition. Moreover, in both tasks, older participants were less able to increase RT benefits with longer PIs, revealing a deficit of response facilitation. We conclude that both facilitatory and inhibitory impairments contribute to age-related deficiencies in proactive cognitive control.

Benefits of Substituting Sitting with Standing and Walking in Free-Living Conditions for Cardiometabolic Risk Markers, Cognition and Mood in Overweight Adults.

Background: We investigated whether substituting sitting with standing and self-perceived light walking in free-living conditions would improve cardiometabolic risk factors, mood, and cognition in overweight/obese adults. Methods: In a randomized, cross-over study, 24 (m/f: 13/11) sedentary overweight/obese participants (64 ± 7 years, BMI 29 ± 2 kg/m2) followed two activity regimens of each 4 days in free-living conditions: "Sit": sitting 13.5 h/day, standing 1.4 h/day, self-perceived light-intensity walking 0.7 h/day; for "SitLess" these activities lasted 7.6, 4.0, and 4.3 h/day, respectively. Meals were standardized and physical activity was assessed by accelerometry (activPAL). Insulin sensitivity (expressed as Matsuda-index based on an oral glucose tolerance test), circulating lipids, blood pressure, mood (pleasantness and arousal), and cognition were assessed on the morning after the activity regimens. Quality of life and sleep were assessed on the last day of the activity regimens. Results: We observed that AUC (0-190 min) for insulin decreased by 20% after SitLess vs. Sit [10,125 (656) vs. 12,633 (818); p = 0.006]. Insulin sensitivity improved by 16% after SitLess vs. Sit [Matsuda-index, mean (SEM): 6.45 (0.25) vs. 5.58 (0.25) respectively; p = 0.007]. Fasting triglycerides, non-HDL-cholesterol, and apolipoprotein B decreased by 32, 7, and 4% respectively, whereas HDL-cholesterol increased by 7% after SitLess vs. Sit (all p < 0.01). Diastolic blood pressure was lower after SitLess vs. Sit (p < 0.05). Pleasantness (as one marker of mood status) after the oral glucose tolerance test was higher after SitLess vs. Sit (p < 0.05). There was no significant difference between regimens for cognition, quality of life and sleep. Conclusions: Reducing sitting time in free-living conditions markedly improved insulin sensitivity, circulating lipids, and diastolic blood pressure. Substituting sitting with standing and self-perceived light walking is an effective strategy to improve cardiometabolic risk factors in overweight/obese subjects.

Foresight beats hindsight: The neural correlates underlying motor preparation in the pro-/anti-cue paradigm.

BACKGROUND: Human motor behaviors are characterized by both, reactive and proactive mechanisms. Yet, studies investigating the neural correlates of motor behavior almost exclusively focused on reactive motor processes. Here, we employed the pro-/anti-cue motor preparation paradigm to systematically study proactive motor control in an imaging environment. In this paradigm, either pro- or anti-cues are presented in a blocked design. Four fingers (two from each hand) are mapped onto four visual target locations. Visual targets require a speeded response by one corresponding finger, but, most importantly, they are preceded by visual cues that are congruent ("pro-cue"), incongruent ("anti-cue"), or neutral with respect to the responding hand. With short cue-target intervals, congruence effects are based on automatic motor priming of the correct hand (in case of pro-cues) or incorrect hand (in case of anti-cues), generating, respectively, reaction time benefits or reaction time costs relative to the neutral-cue. With longer cue-target intervals, slower top-down processes become effective, transforming early anti-cue interference into late anti-cue facilitation. METHODS: We adapted this paradigm to be compatible with neuroimaging, tested and validated it behaviorally-both inside and outside the imaging environment-and implemented it in a whole-brain functional magnetic resonance imaging study. RESULTS AND CONCLUSION: Our imaging results indicate that pro-cues elicited much less neural activation than did anti-cues, the latter recruiting well-known cognitive top-down networks related to attention, response inhibition, and error monitoring/signaling, thereby revealing high-level influences on proactive motor processes.

Switch hands! Mapping proactive and reactive cognitive control across the life span.

We investigated the effects of age on proactive and reactive cognitive control in a large population sample of 809 individuals, ranging in age between 5 and 97 years. For that purpose, we used an anticue paradigm, which required a consistent remapping of cue location and response hand: Left-sided cues required right-hand responses and vice versa. After a random preparation interval of 100-850 ms, these anticues were followed by a target stimulus, which prompted a response with the index or middle finger of 1 of 2 hands. A neutral control condition involved uninformative cues, indicating all 4 possible response locations. The primary outcome measure was the difference between neutral and anticue reaction time (RT). Negative values indicated RT costs of the anticue, relative to the neutral condition, reflecting reactive cognitive control. Positive values indicated RT benefits, reflecting proactive cognitive control. Results were twofold. First, the switch from RT costs to benefits took place at longer preparation intervals in the youngest and oldest age groups than in the intermediate age groups. Second, irrespective of preparation interval, anticue performance followed an inverted U-shaped trajectory as a function of age, with a relatively steep improvement during childhood and adolescence, relative stability between 26 and 60 years, and a slightly accelerating decline into old age. Both patterns of results suggest an age-related transition from a primarily reactive, to a primarily proactive mode of cognitive control in early life and back again from a primarily proactive, to a primarily reactive mode of control in later life. (PsycINFO Database Record

The integration of sequential aiming movements: Switching hand and direction at the first target.

Movement times to a single target are typically shorter compared to when movement to a second target is required. This one target movement time advantage has been shown to emerge when participants use a single hand throughout the target sequence and when there is a switch between hands at the first target. Our goal was to investigate the lacuna in the movement integration literature surrounding the interactive effects between switching hands and changing movement direction at the first target. Participants performed rapid hand movements in five conditions; movements to a single target; two target movements with a single hand in which the second target required an extension or reversal in direction; and movements to two targets where the hands were switched at the first target and the second target required an extension or reversal in direction. The significance of including these latter two (multiple hand-multiple direction) movements meant that for the first time research could differentiate between peripheral and central processes within movement integration strategies. Reaction times were significantly shorter in the single task compared to the two target tasks. More importantly, movement times to the first target were significantly shorter in the single target task compared to all two target tasks (reflecting the so-called one target advantage), except when the second movement was a reversal movement with the same hand. These findings demonstrate for the first time the contrasting effects of movement integration at central and peripheral levels.

Switch hands! Mapping temporal dynamics of proactive manual control with anticues.

This study uses a novel behavioral paradigm-the anticue task-to investigate the temporal dynamics of proactive control aimed at the resolution of response conflict in the manual motor system. The anticue task is a 4-choice reaction time (RT) task, with left and right anticues indicating mirror-symmetrical response hands. In particular, anticues require participants to prepare fingers on the hand opposite to the side of the cue (counter-corresponding mapping), which contrasts with the more standard procues that prompt participants to prepare fingers on the hand spatially in line with the cue (corresponding mapping). In Experiment 1, we examined the effects of anticues and procues as a function of cue-target interval (range: 100-850ms). Results showed that procues produced RT benefits (relative to neutral cues), which increased with longer cue-target intervals. Anticues, however, produced RT costs with short cue-target intervals and RT benefits with longer cue-target intervals. These findings support the view that anticues are mediated by a time-consuming, proactive control process that, using inhibition and activation, redirects the initial but wrong activation of the ipsilateral hand to the correct contralateral hand. In Experiment 2, we used a simple detection response to test, and reject, an alternative (attentional) account of these findings. Theoretical and practical implications are discussed in the context of dual-route models of response selection, the activation-suppression model, and related experimental protocols such as antisaccade, Simon, Stroop, Eriksen flanker, and task switching paradigms.

Sequential aiming with one and two limbs: effects of target size.

It is well reported that movement times to the first target in a two-target sequence are slower than when a single target response is required. This one-target advantage has been shown to emerge when the two-target sequence is performed with the same limb and when the first and second segments within the sequence are performed with different limbs (i.e., when there is a switch between limbs at the first target). The present study examined the functional dependency between response segments in both single and two limb sequential aiming by varying the accuracy demands at the first and second target. Results revealed that, for both one and two limb conditions, the one-target advantage was present with large first targets but not with small first targets. Additionally, when the first target was large and the second target was small, spatial variability at the first target was significantly less (or constrained more) in both one and two limb conditions compared to conditions requiring only a single target response. These findings suggest that similar principles underlie the one-target advantage in both single and two limb sequential movements.

Aging and response interference across sensory modalities.

Advancing age is associated with decrements in selective attention. It was recently hypothesized that age-related differences in selective attention depend on sensory modality. The goal of the present study was to investigate the role of sensory modality in age-related vulnerability to distraction, using a response interference task. To this end, 16 younger (mean age = 23.1 years) and 24 older (mean age = 65.3 years) adults performed four response interference tasks, involving all combinations of visual and auditory targets and distractors. The results showed that response interference effects differ across sensory modalities, but not across age groups. These results indicate that sensory modality plays an important role in vulnerability to distraction, but not in age-related distractibility by irrelevant spatial information.

Effect of resistance-type exercise training with or without protein supplementation on cognitive functioning in frail and pre-frail elderly: secondary analysis of a randomized, double-blind, placebo-controlled trial.

Physical activity has been proposed as one of the most effective strategies to prevent cognitive decline. Protein supplementation may exert an additive effect. The effect of resistance-type exercise training with or without protein supplementation on cognitive functioning in frail and pre-frail elderly people was assessed in a secondary analysis. Two 24-week, double-blind, randomized, placebo-controlled intervention studies were carried out in parallel. Subjects performed a resistance-type exercise program of two sessions per week (n=62) or no exercise program (n=65). In both studies, subjects were randomly allocated to either a protein (2×15 g daily) or a placebo drink. Cognitive functioning was assessed with a neuropsychological test battery focusing on the cognitive domains episodic memory, attention and working memory, information processing speed, and executive functioning. In frail and pre-frail elderly, resistance-type exercise training in combination with protein supplementation improved information processing speed (changes in domain score 0.08±0.51 versus -0.23±0.19 in the non-exercise group, p=0.04). Exercise training without protein supplementation was beneficial for attention and working memory (changes in domain scores 0.35±0.70 versus -0.12±0.69 in the non-exercise group, p=0.02). There were no significant differences among the intervention groups on the other cognitive tests or domain scores.

Response-repetition effects depend on motor set: evidence for anatomical coding in response selection.

Successful motor performance requires a process of response selection that chooses the correct response out of a set of possible ones. Most theories of response selection assume that this selection process operates on spatial codes, which define the location of stimuli and responses in environmental coordinates, with little or no role for the anatomical codes of the effectors involved. In this study, we tested this assumption by investigating response-repetition effects in a response-cuing paradigm using two motor sets (fingers on one hand vs. fingers on two hands). Reaction time results demonstrated a robust response-repetition benefit that was greater for the one-hand set than for the two-hands set. Furthermore, with the one-hand set the repetition benefit was independent of cue type and cue-stimulus interval on the previous trial, whereas with the two-hands set it was strongly modulated by these two factors. These differential response-repetition effects for one- and two-hands motor sets demonstrate the important role of the neuro-anatomical hand distinction in response selection, thereby supporting multiple coding notions.

The impact of protein supplementation on cognitive performance in frail elderly.

PURPOSE: Maintenance of cognitive abilities is important for elderly to stay independent. With the aging of the population, the call for modifiable factors is emerging. Dietary protein might improve cognitive performance; however, this has hardly been studied. Therefore, we studied the impact of 24-week dietary protein supplementation on cognitive performance in pre-frail and frail elderly people. METHODS: Pre-frail and frail elderly subjects, according to the Fried criteria, randomly received a protein drink containing 15 g protein or a placebo drink twice a day. Cognitive performance was measured at baseline and after 24 weeks by means of a sensitive neuropsychological test battery. In addition, reaction time was assessed after both 12 and 24 weeks of intervention. Domain scores were calculated for the domains episodic memory, attention and working memory, information processing speed, and executive functioning. Analyses of covariance were used to determine differences between groups. Linear mixed models were used to determine differences in reaction time over time and per treatment. RESULTS: In total, 65 subjects (79 ± 8 years) with a median Mini-Mental State Examination score of 28 (interquartile range 26-30) were included. Reaction time improved more in the protein group (68 ms) than in the placebo group (18 ms, P = 0.03). Dietary protein had no significant effect on any of the cognitive domain scores. CONCLUSIONS: Protein supplementation might improve reaction time performance in pre-frail and frail elderly, but did not improve other cognitive functions.

Both hand position and movement direction modulate visual attention.

The current study explored effects of continuous hand motion on the allocation of visual attention. A concurrent paradigm was used to combine visually concealed continuous hand movements with an attentionally demanding letter discrimination task. The letter probe appeared contingent upon the moving right hand passing through one of six positions. Discrimination responses were then collected via a keyboard press with the static left hand. Both the right hand's position and its movement direction systematically contributed to participants' visual sensitivity. Discrimination performance increased substantially when the right hand was distant from, but moving toward the visual probe location (replicating the far-hand effect, Festman et al., 2013). However, this effect disappeared when the probe appeared close to the static left hand, supporting the view that static and dynamic features of both hands combine in modulating pragmatic maps of attention.

Serum 25-hydroxyvitamin D is associated with cognitive executive function in Dutch prefrail and frail elderly: a cross-sectional study exploring the associations of 25-hydroxyvitamin D with glucose metabolism, cognitive performance and depression.

OBJECTIVES: The primary objective was to explore the possible association of serum 25-hydroxyvitamin D (25[OH]D) and vitamin D intake with markers of glucose metabolism, depression, and cognitive performance. In addition, we examined to what extent the associations between vitamin D and cognitive performance were modified or mediated by fasting plasma glucose (FPG) levels. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study using data of 127 frail or prefrail Dutch elderly, aged 65 years or older. Frailty was defined according to the criteria of Fried and colleagues. A participant was classified prefrail when 1 to 2 criteria were met; frailty was classified as the presence of 3 or more criteria. MEASUREMENTS: Associations of 25(OH)D and vitamin D intake with markers of glucose metabolism and domain-specific cognitive performance were examined by multivariable regression analyses. The possible association of vitamin D with depression and global cognitive performance was explored by Poisson regression. RESULTS: No associations were observed for 25(OH)D with FPG, fasting plasma insulin (FPI), Homeostasis Model Assessment-estimated Insulin Resistance (HOMA-IR), or depression. In contrast, serum 25(OH)D was positively associated with executive functioning (ß 0.007, P = .01) and tended to be associated with information-processing speed (ß 0.006, P = .06). FPG did not modify or mediate these associations. Vitamin D intake was not associated with cognitive performance, glucose metabolism, or depression. CONCLUSION: This cross-sectional study suggests an association of serum 25(OH)D with domain-specific cognitive performance, in particular executive functioning and possibly information-processing speed, but not with FPG, FPI, HOMA-IR, or depression. Whether these associations are causal is yet to be demonstrated.

Patients with type 2 diabetes show a greater decline in muscle mass, muscle strength, and functional capacity with aging.

BACKGROUND: The loss of muscle mass with aging reduces muscle strength, impairs functional capacity, and increases the risk of developing chronic metabolic disease. It has been suggested that the development of type 2 diabetes results in a more rapid decline in muscle mass, strength, and functional capacity. OBJECTIVE: To investigate the impact of type 2 diabetes on muscle mass, strength, and functional capacity in an older population. METHODS: Muscle mass (DXA and muscle biopsies), strength (1-repetition maximum), functional capacity (sit-to-stand test and handgrip strength), and reaction time performance (computer task) were compared between 60 older men with type 2 diabetes (71 ± 1 years) and 32 age-matched normoglycemic controls (70 ± 1 years). Data were analyzed using ANCOVA to adjust for several potential confounders. RESULTS: Leg lean mass and appendicular skeletal muscle mass were significantly lower in older men with type 2 diabetes (19.1 ± 0.3 and 25.9 ± 0.4 kg, respectively) compared with normoglycemic controls (19.7 ± 0.3 and 26.7 ± 0.5 kg, respectively). Additionally, leg extension strength was significantly lower in the group with type 2 diabetes (84 ± 2 vs 91 ± 2 kg, respectively). In agreement, functional performance was impaired in the men with type 2 diabetes, with longer sit-to-stand time (9.1 ± 0.4 vs 7.8 ± 0.3 seconds) and lower handgrip strength (39.5 ± 5.8 vs 44.6 ± 6.1 kg) when compared with normoglycemic controls. However, muscle fiber size and reaction time performance did not differ between groups. CONCLUSION: Older patients with type 2 diabetes show an accelerated decline in leg lean mass, muscle strength, and functional capacity when compared with normoglycemic controls. Exercise intervention programs should be individualized to specifically target muscle mass, strength, and functional capacity in the older population with type 2 diabetes.

Continuous hand movement induces a far-hand bias in attentional priority.

Previous research on the interaction between manual action and visual perception has focused on discrete movements or static postures and discovered better performance near the hands (the near-hand effect). However, in everyday behaviors, the hands are usually moving continuously between possible targets. Therefore, the current study explored the effects of continuous hand motion on the allocation of visual attention. Eleven healthy adults performed a visual discrimination task during cyclical concealed hand movements underneath a display. Both the current hand position and its movement direction systematically contributed to participants' visual sensitivity. Discrimination performance increased substantially when the hand was distant from but moving toward the visual probe location (a far-hand effect). Implications of this novel observation are discussed.

The closer the better: Hand proximity dynamically affects letter recognition accuracy.

A growing literature has suggested that processing of visual information presented near the hands is facilitated. In this study, we investigated whether the near-hands superiority effect also occurs with the hands moving. In two experiments, participants performed a cyclical bimanual movement task requiring concurrent visual identification of briefly presented letters. For both the static and dynamic hand conditions, the results showed improved letter recognition performance with the hands closer to the stimuli. The finding that the encoding advantage for near-hand stimuli also occurred with the hands moving suggests that the effect is regulated in real time, in accordance with the concept of a bimodal neural system that dynamically updates hand position in external space.

Coordinated flexibility: how initial gaze position modulates eye-hand coordination and reaching.

Reaching to targets in space requires the coordination of eye and hand movements. In two experiments, we recorded eye and hand kinematics to examine the role of gaze position at target onset on eye-hand coordination and reaching performance. Experiment 1 showed that with eyes and hand aligned on the same peripheral start location, time lags between eye and hand onsets were small and initiation times were substantially correlated, suggesting simultaneous control and tight eye-hand coupling. With eyes and hand departing from different start locations (gaze aligned with the center of the range of possible target positions), time lags between eye and hand onsets were large and initiation times were largely uncorrelated, suggesting independent control and decoupling of eye and hand movements. Furthermore, initial gaze position strongly mediated manual reaching performance indexed by increments in movement time as a function of target distance. Experiment 2 confirmed the impact of target foveation in modulating the effect of target distance on movement time. Our findings reveal the operation of an overarching, flexible neural control system that tunes the operation and cooperation of saccadic and manual control systems depending on where the eyes look at target onset.