Antisaccade Reaction Times Research Articles

Anti-saccade can be used as a screening tool for early cognitive impairment: a correlation study based on anti-saccade parameters and cognitive function.

Eye movement tasks, especially anti-saccade tasks, have been used to assess cognitive function in patients with neuropsychiatric disorders. Although it has been shown that individuals with cognitive impairment perform worse on anti-saccades tasks, there is a lack of systematic evaluation of the sensitivity of parameters of anti-saccades to assess different subtypes of cognitive impairment. A total of 158 participants were enrolled in this study, consisting of 66 men and 92 women, with an average age of 50.2 ± 10 years. The comparison of pro-saccade reaction time, anti-saccade reaction time, and error rates in the saccade task between individuals with cognitive impairments and a normal group was conducted. Furthermore, we systematically analyzed the correlations between the performance in neurological function tests (Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Stroop) and these anti-saccade parameters. Especially, the correlation between these parameters and cognitive function in different domains of the MoCA task were also evaluated. The pro-saccade reaction time, anti-saccade reaction time and error rate were negatively correlated with the MMSE and MoCA scores (P < 0.001), and positively correlated with the time used in Stroop tasks. Among them, the error rate had the strongest correlation with the performance of MMSE, MoCA and Stroop tasks (MoCA: P < 0.0001, r2 = -0.608; MMSE: P < 0.0001, r2 = -0.344; Stroop: P < 0.0001, r2 = 0.455). Among the seven cognitive domains examined by the MoCA task, error rates had relatively high correlations with visuospatial/executive (P < 0.0001, r2 = -0.4660) and delayed recall (P < 0.0001, r2 = -0.4228) compared to naming, language (P = 0.0004, r2 = -0.0788), attention (P = 0.0004, r2 = -0.0780), abstraction (P < 0.0001, r2 = -0.1515), orientation (P < 0.0001, r2 = -0.1075). Moreover, pro-saccade reaction time, anti-saccade reaction time and error rate of people with high MoCA scores were significantly higher than those of people with low MoCA scores, which can be used to identify people with mild cognitive impairment. Our study's results provide valuable clinical evidence supporting the effectiveness of anti-saccades in assessing cognitive impairment, which is beneficial for screening and timely clinical intervention in individuals with specific cognitive impairment.

Menstrual cycle status does not impact exercise-based changes in cerebral blood flow or executive function benefits

ABSTRACT A single bout of exercise enhances executive function (EF) and may relate to an increase in cerebral blood flow (CBF). A limitation in the current literature is that biologically female participants are underrepresented given some evidence that changes in hormone levels across the menstrual cycle impact physiological and psychological variables. Here, biologically female participants completed separate single bouts of moderate intensity exercise (80% of estimated lactate threshold) during the follicular (FOL) and luteal (LUT) phases of their menstrual cycle. In addition, biologically male participants completed a same duration/intensity exercise session. Middle cerebral artery velocity (MCAv) was used to estimate CBF and pre- and postexercise EF was assessed via the antisaccade task. Results showed that resting MCAv was larger in the LUT than FOL phase; however, the exercise-mediated increase in MCAv was equivalent between menstrual cycle phases, and between female and male participants. Antisaccade reaction times reliably decreased from pre- to postexercise and frequentist and non-frequentist statistics demonstrated that the magnitude of the decrease was equivalent across FOL and LUT phases, and between female and male participants. Thus, results evince that menstrual cycle status should not serve as a basis limiting biologically female participants’ inclusion in research examining exercise and EF.

10-min exposure to a 2.5% hypercapnic environment increases cerebral blood blow but does not impact executive function

Space travel and exploration are associated with increased ambient CO2 (i.e., a hypercapnic environment). Some work reported that the physiological changes (e.g., increased cerebral blood flow [CBF]) associated with a chronic hypercapnic environment contributes to a “space fog” that adversely impacts cognition and psychomotor performance, whereas other work reported no change or a positive change. Here, we employed the antisaccade task to evaluate whether transient exposure to a hypercapnic environment influences top-down executive function (EF). Antisaccades require a goal-directed eye movement mirror-symmetrical to a target and are an ideal tool for identifying subtle EF changes. Healthy young adults (aged 19–25 years) performed blocks of antisaccade trials prior to (i.e., pre-intervention), during (i.e., concurrent) and after (i.e., post-intervention) 10-min of breathing factional inspired CO2 (FiCO2) of 2.5% (i.e., hypercapnic condition) and during a normocapnic (i.e., control) condition. In both conditions, CBF, ventilatory and cardiorespiratory responses were measured. Results showed that the hypercapnic condition increased CBF, ventilation and end-tidal CO2 and thus demonstrated an expected physiological adaptation to increased FiCO2. Notably, however, null hypothesis and equivalence tests indicated that concurrent and post-intervention antisaccade reaction times were refractory to the hypercapnic environment; that is, transient exposure to a FiCO2 of 2.5% did not produce a real-time or lingering influence on an oculomotor-based measure of EF. Accordingly, results provide a framework that – in part – establishes the FiCO2 percentage and timeline by which high-level EF can be maintained. Future work will explore CBF and EF dynamics during chronic hypercapnic exposure as more direct proxy for the challenges of space flight and exploration.

Passive exercise increases cerebral blood flow velocity and supports a postexercise executive function benefit.

Executive function entails high-level cognitive control supporting activities of daily living. Literature has shown that a single-bout of exercise involving volitional muscle activation (i.e., active exercise) improves executive function and that an increase in cerebral blood flow (CBF) may contribute to this benefit. It is, however, unknown whether non-volitional exercise (i.e., passive exercise) wherein an individual's limbs are moved via an external force elicits a similar executive function benefit. This is a salient question given that proprioceptive and feedforward drive from passive exercise increases CBF independent of the metabolic demands of active exercise. Here, in a procedural validation participants (n=2) used a cycle ergometer to complete separate 20-min active and passive (via mechanically driven flywheel) exercise conditions and a non-exercise control condition. Electromyography showed that passive exercise did not increase agonist muscle activation or increase ventilation or gas exchange variables (i.e., V̇O2 and V̇CO2 ). In a main experiment participants (n=28) completed the same exercise and control conditions and transcranial Doppler ultrasound showed that active and passive exercise (but not the control condition) increased CBF through the middle cerebral artery (ps <.001); albeit the magnitude was less during passive exercise. Notably, antisaccade reaction times prior to and immediately after each condition showed that active (p < .001) and passive (p=.034) exercise improved an oculomotor-based measure of executive function, whereas no benefit was observed in the control condition (p=.85). Accordingly, results evince that passive exercise 'boosts' an oculomotor-based measure of executive function and supports convergent evidence that increased CBF mediates this benefit.

Exercise intensity-specific changes to cerebral blood velocity do not modulate a postexercise executive function benefit

Executive function is transiently improved (i.e., <60-min) following a single bout of aerobic exercise. A candidate mechanism for this improvement is an exercise-mediated increase in cerebral blood flow (CBF). Further, it has been proposed that an increase in CBF across the continuum of increasing exercise intensities improves the magnitude of a postexercise executive function benefit (i.e., drive theory); however, this proposal has not been empirically tested. Here, participants completed four experimental sessions: a V̇O2peak test to determine cardiorespiratory fitness and estimated lactate threshold (LT), followed by separate 10-min sessions of light- (i.e., 25 W), moderate- (i.e., 80% estimated LT), and heavy-intensity (i.e., 15% of the difference between LT and V̇O2peak) aerobic exercise. An estimate of CBF during exercise was achieved via transcranial Doppler ultrasound and near-infrared spectroscopy to quantify blood velocity (BV) through the middle cerebral artery and deoxygenated hemoglobin (HHb), respectively. Executive function was assessed before and after each session via the executive-mediated antisaccade task (i.e., saccade mirror-symmetrical to a target). Results demonstrated that BV increased in relation to increasing exercise intensity, whereas HHb decreased by a comparable magnitude independent of intensity. In terms of executive function, null hypothesis and equivalence tests indicated a comparable magnitude postexercise reduction in antisaccade reaction time across exercise intensities. Accordingly, the magnitude of CBF change during exercise does not impact the magnitude of a postexercise executive function benefit.

Pupillometry Reveals the Role of Arousal in a Postexercise Benefit to Executive Function.

A single bout of aerobic exercise improves executive function; however, the mechanism(s) underlying this improvement remains unclear. Here, we employed a 20-min bout of aerobic exercise, and at pre- and immediate post-exercise sessions examined executive function via pro- (i.e., saccade to veridical target location) and anti-saccade (i.e., saccade mirror symmetrical to a target) performance and pupillometry metrics. Notably, tonic and phasic pupillometry responses in oculomotor control provided a framework to determine the degree that arousal and/or executive resource recruitment influence behavior. Results demonstrated a pre- to post-exercise decrease in pro- and anti-saccade reaction times (p = 0.01) concurrent with a decrease and increase in tonic baseline pupil size and task-evoked pupil dilations, respectively (ps < 0.03). Such results demonstrate that an exercise-induced improvement in saccade performance is related to an executive-mediated “shift” in physiological and/or psychological arousal, supported by the locus coeruleus norepinephrine system to optimize task engagement.

Exercise and Executive Function during Follicular and Luteal Menstrual Cycle Phases.

A single bout of aerobic or resistance exercise improves executive function. We sought to determine whether menstrual cycle variations in ovarian hormone concentrations differentially influence the expression and/or magnitude of a postexercise executive benefit. Eumenorrheic female participants completed 20-min single bouts of aerobic exercise (via cycle ergometer) at a moderate intensity (i.e., 80% of estimated lactate threshold) during the early follicular and midluteal phases of their menstrual cycle. Pre- and postexercise executive function was examined via antisaccades-an executive task requiring a saccade mirror-symmetrical to a visual stimulus. Antisaccades are an ideal tool for examining postexercise executive changes because the task is mediated via the same frontoparietal networks as modified following single-bout and chronic exercise. Antisaccade reaction times decreased from the pre- to postexercise assessments by an average of 22 ms (P = 0.003), and this benefit was independent of changes in directional errors or end point accuracy (P's > 0.26). In other words, participants did not decrease their postexercise reaction times at the cost of increased planning times or execution errors. Most notably, the postexercise antisaccade benefit did not vary in magnitude across follicular or luteal phases (P = 0.33) and a two one-sided test statistic (i.e., equivalence testing) provided support for the null hypothesis (P = 0.008). A postexercise executive benefit is independent of hormonal variations in the menstrual cycle. Further, our results evince that the phase of a female participant's menstrual cycle should not be a limiting factor in determining their inclusion in exercise neuroscience research.

Older adults elicit a single-bout post-exercise executive benefit across a continuum of aerobically supported metabolic intensities

Ten minutes of aerobic or resistance training can ‘boost’ executive function in older adults. Here, we examined whether the magnitude of the exercise benefit is influenced by exercise intensity. Older adults (N = 17: mean age = 73 years) completed a volitional test to exhaustion (VO2peak) via treadmill to determine participant-specific moderate (80% of lactate threshold (LT)), heavy (15% of the difference between LT and VO2peak) and very-heavy (50% of the difference between LT and VO2peak) exercise intensities. Subsequently, in separate sessions all participants completed 10-min constant load single-bouts of exercise at each intensity. Pre- and post-exercise executive function were examined via the antisaccade task. Antisaccades require a saccade mirror-symmetrical to a target and extensive evidence has shown that antisaccades are supported via frontoparietal networks that demonstrate task-dependent changes following single-bout and chronic exercise. We also included a non-executive task (saccade to veridical target location; i.e., prosaccade) to determine whether a putative post-exercise benefit is specific to executive-related oculomotor control. Results showed that VO2 and psychological ratings of perceived exertion concurrently increased with increasing exercise intensity. As well, antisaccade reaction times showed a 24 ms (i.e., 8%) reduction from pre- to post-exercise assessments (p < .001), whereas prosaccade values did not (p = .19). Most notably, the post-exercise change in antisaccade RTs did not reliably vary with exercise intensity. Further, for each exercise intensity participants’ cardiorespiratory fitness level was unrelated to the magnitude of the post-exercise executive benefit (ps > .13). Accordingly, an exercise duration as brief as 10-min provides a selective benefit to executive function in older adults across the continuum of moderate to very-heavy intensities.

A Comparison of Cognitive Load and Emotional Arousal on Liar's Pupil Diameter Changes

Pupil size is an easy-to-measure, non-invasive method to index various cognitive processes. Although a growing number of studies have incorporated measures of pupil size into clinical investigation, there have only been limited studies in Parkinson's disease (PD). Convergent evidence has suggested PD patients exhibit cognitive impairment at or soon after diagnosis. Here, we used an interleaved pro- and anti-saccade paradigm while monitoring pupil size with saccadic eye movements to examine the relationship between executive function deficits and pupil size in PD patients. Subjects initially fixated a central cue, the color of which instructed them to either look at a peripheral stimulus automatically (pro-saccade) or suppress the automatic response and voluntarily look in the opposite direction of the stimulus (anti-saccade). We hypothesized that deficits of voluntary control should be revealed not only on saccadic but also on pupil responses because of the recently suggested link between the saccade and pupil control circuits. In elderly controls, pupil size was modulated by task preparation, showing larger dilation prior to stimulus appearance in preparation for correct anti-saccades, compared to correct pro-saccades, or erroneous pro-saccades made in the anti-saccade condition. Moreover, the size of pupil dilation correlated negatively with anti-saccade reaction times. However, this profile of pupil size modulation was significantly blunted in PD patients, reflecting dysfunctional circuits for anti-saccade preparation. Our results demonstrate disruptions of modulated pupil responses by voluntary movement preparation in PD patients, highlighting the potential of using low-cost pupil size measurement to examine executive function deficits in early PD.

A six-month study of antisaccade reaction time in elderly adults with cognitive impairment in a retirement living home: A Mind Fun sub-study.: Antisaccade reaction time in elderly adults

Background: Oculomotor control assessed via the antisaccade task has shown to be sensitive to change following exercise programs in older adult populations. The antisaccade task has been shown to be associated with executive function. However, this task has not been assessed in adults over 80 years of age. Purpose:The purpose of this investigation was to determine the feasibility of the antisaccade task in octogenarians over a 6-month period and determine if any change in reaction time (RT) occurs. Methods: The subjects participated in a 12-week Square-stepping exercise (SSE) program (over a 6-month period). The feasibility and change of an executive-related oculomotor task required participants to look mirror-symmetrical to a target (i.e., antisaccades), which were assessed at baseline and post-intervention. Results: Seven adults (85.4 years old, SD=3.2; Montreal Cognitive Assessment score of 22.6, SD=3.5) out of a larger cluster of 71 completed assessments at baseline and post-intervention. Results showed no reliable change in antisaccade RT from baseline (360 ms, SD=37) to post-intervention (361 ms, SD=40); however, a decrease in RT variability was observed during this time frame (i.e., baseline: 23 ms, SD=12; post-intervention: 15 ms, SD=13). Conclusions: Oculomotor assessments have limited feasibility in elderly adults with cognitive impairment due to age-related eye disease. Furthermore, our results demonstrated maintenance of executive control and improved post-intervention planning stability in an elderly population at risk for further cognitive decline; further investigation with a control group is required.

Results From a Feasibility Study of Square-Stepping Exercise in Older Adults With Type 2 Diabetes and Self-Reported Cognitive Complaints to Improve Global Cognitive Functioning.

Adults with type 2 diabetes mellitus have an increased risk for dementia. Therefore, we proposed an intervention called the Square-stepping exercise (SSE) program to mitigate this risk. Our primary aim was to determine the feasibility of SSE in adults with type 2 diabetes and self-reported cognitive complaints. Our secondary aim was to determine whether 24 weeks of SSE improved cognition. Our tertiary aim was to determine whether SSE improved antisaccade reaction time, which is a measure of executive-related oculomotor control. Adults >49 years with type 2 diabetes and self-reported cognitive complaints were randomized to an SSE group (2×/week for 24 weeks of SSE) or a control group. Feasibility was assessed by recruitment and attendance. Participants were assessed at baseline, after 12 weeks and after 24 weeks for global cognitive function, memory, planning, reasoning and concentration via a computer-based cognitive battery (Cambridge Brain Sciences) and antisaccade reaction time (at baseline and 24 weeks). Participants in the SSE group were (mean [SD]): 65.9 (5.2) years old; 33% female; body mass index 33.3 kg/m2 (4.8) (n=12). Participants in the control group were 71.2 (6.9) years old; 31% female; body mass index 31.9 kg/m2 (4.6) (n=13). Over 24 weeks, attendance was 70.2% (SD 17.2) for 4/12 participants. There were 4 withdrawals and 1 adverse event. There were no differences in global cognitive functioning. The SSE group improved in planning domain change scores between 12 and 24 weeks (F=5.8, p=0.03, ηp2=0.28) compared to controls. In the SSE group, we found a nonsignificant improvement in antisaccade reaction time of 38 ms (SD 16), n=2, compared to 9 ms (SD 45) in the control group, n=8. SSE should be evaluated further to improve its feasibility in older adults with type 2 diabetes. This study provides preliminary evidence that SSE improves executive function in adults with type 2 diabetes and self-reported cognitive complaints.

Executive-related oculomotor control is improved following a 10-min single-bout of aerobic exercise: Evidence from the antisaccade task

Previous work has shown that a single-bout of moderate-to-vigorous intensity exercise improves task-specific activity within frontoparietal networks and produces a short-term ‘boost’ to executive-related cognitive control – an effect in healthy young adults that is reported to be selective to exercise durations of 20min or greater. The present study sought to determine whether such a ‘boost’ extends to an exercise duration as brief as 10min. Healthy young adults performed a 10-min single-bout of moderate-to-vigorous intensity aerobic exercise (i.e., via a cycle ergometer) and pre- and post-exercise executive control was examined via the antisaccade task. Antisaccades are an executive task requiring a goal-directed eye movement (i.e., a saccade) mirror-symmetrical to a visual stimulus. The hands- and language-free nature of antisaccades coupled with the temporal precision of eye-tracking technology make it an ideal tool for identifying executive performance changes. Moreover, an extensive literature has shown that antisaccades are mediated via frontoparietal networks that are modulated following single-bout and chronic exercise training. Results showed that antisaccade reaction time (RT) reliably decreased by 27ms from pre- to post-exercise assessments. Further, the percentage of antisaccade directional errors did not reliably vary from the pre- (13%) to post-exercise (9%) assessments – a result indicating that the RT improvement was unrelated to a speed-accuracy trade-off. A follow-up experiment involving antisaccade sessions separated by a non-exercise interval did not show a similar RT modulation. Thus, a 10-min bout of moderate-to-vigorous intensity aerobic exercise benefits executive-related oculomotor control, and is a finding we attribute to an exercise-based increase in attention/arousal and/or improved task-specific activity within the frontoparietal networks supporting antisaccades.

Oculomotor Executive Dysfunction during the Early and Later Stages of Sport-Related Concussion Recovery.

Executive dysfunction represents the most persistent sequela of mild traumatic brain injury. It is, however, largely unclear whether a sport-related concussion similarly contributes to a persistent executive dysfunction even when an athlete has been cleared medically for return to play. Here, individuals with a diagnosis of a sport-related concussion-and their age- and sex-matched controls-completed an oculomotor assessment during the acute and later stages of injury recovery. Prosaccades (i.e., saccade to a target) and executive-related antisaccades (i.e., saccade mirror-symmetrical to a target) were completed: (1) 2-6 days after a concussive event (initial assessment), and (2) 14-20 days after the initial oculomotor assessment when individuals were cleared for return to play (follow-up assessment). At the initial assessment, the concussed group produced antisaccade reaction times (RT) that were 93 ms longer than the control group (p < 0.001), whereas prosaccade RTs did not differ between groups (p = 0.25). At the follow-up assessment, concussed and control groups produced comparable pro- and antisaccade RTs (ps >0.31); however, the former group exhibited a continued increase in directional errors (p < 0.05). That initial assessment antisaccades-but not prosaccades-differed between groups indicates that the acute recovery of a concussion is associated with a selective executive-related oculomotor deficit, and the continued increase in directional errors at the follow-up assessment suggests that such a deficit persists even when an athlete has been cleared medically for return to play. The antisaccade task may therefore serve to assess subtle executive deficits and determine when an athlete may return to play safely.

Age related prefrontal compensatory mechanisms for inhibitory control in the antisaccade task

Cognitive decline during aging includes impairments in frontal executive functions like reduced inhibitory control. However, decline is not uniform across the population, suggesting individual brain response variability to the aging process. Here we tested the hypothesis, within the oculomotor system, that older adults compensate for age-related neural alterations by changing neural activation levels of the oculomotor areas, or even by recruiting additional areas to assist with cognitive performance. We established that the observed changes had to be related to better cognitive performance to be considered as compensatory. To probe this hypothesis we used the antisaccade paradigm and analyzed the effect of aging on brain activations during the inhibition of prepotent responses to visual stimuli. While undergoing a fMRI scan with concurrent eye tracking, 25 young adults (21.7 y/o ± 1.9 SDM) and 25 cognitively normal older adults (66.2 y/o ± 9.8 SDM) performed an interleaved pro/antisaccade task consisting of a preparatory stage and an execution stage. Compared to young adults, older participants showed a larger increase in antisaccade reaction times, while also generating more antisaccade direction errors. BOLD signal analyses during the preparatory stage, when response inhibition processes are established to prevent an automatic response, showed decreased activations in the anterior cingulate and the supplementary eye fields in the older group. Moreover, older adults also showed additional recruitment of the frontal pole not seen in the younger group, and larger activations in the dorsolateral prefrontal cortex during antisaccade preparation. Additional analyses to address the performance variability in the older group showed distinct behavioral-BOLD signal correlations. Larger activations in the saccade network, including the frontal pole, positively correlated with faster antisaccade reaction times, suggesting a functional recruitment of this area. However, only the activation in the dorsolateral prefrontal cortex during the antisaccade events showed a negative correlation with the number of errors across older adults. These findings support the presence of two dissociable age-related plastic mechanisms that result in different behavioral outcomes. One related to the additional recruitment of neural resources within anterior pole to facilitate modulation of cognitive responses like faster antisaccade reaction times, and another related to increased activation of the dorsolateral prefrontal cortex resulting in a better inhibitory control in aging.

Long-Term Maintenance of Executive-Related Oculomotor Improvements in Older Adults with Self-Reported Cognitive Complaints Following a 24-Week Multiple Modality Exercise Program.

Adults (≥55 years) with self-reported cognitive complaints (sCC) were randomized to: multiple-modality exercise (M2), or multiple-modality plus mind-motor exercise (M4), for 24-weeks. Participants (n = 58) were assessed on antisaccade reaction time (RT) to examine executive-related oculomotor control and self-reported physical activity (PA) at pre-intervention (V0), post-intervention (V1), and 52-weeks follow-up (V2). We previously reported significant improvements in antisaccade RT of 23 ms at V1, in both groups. We now report maintenance of antisaccade RT improvement from V1 to V2, t(57) = 0.8, p = 0.45, and improved PA from V1 to V2, t(56) = -2.4, p = 0.02. Improvements in executive-related oculomotor control attained at V1 were maintained at V2.

Contextual effects on cognitive control and BOLD activation in single versus mixed saccade tasks

The context or trial history of a task influences response efficiency in mixed paradigms based on cognitive control demands for task set selection. In the current study, the impact of context on prosaccade and antisaccade trials in single and mixed tasks was investigated with BOLD fMRI. Prosaccades require a look towards a newly appearing target, while antisaccades require cognitive control for prepotent response inhibition and generation of a saccade to the opposite location. Results indicated slower prosaccade reaction times and more antisaccade errors for switched than repeated or single trials, and slower antisaccade reaction times for single than mixed trials. BOLD activation was greater for the mixed than the single context in frontal eye fields and precuneus, while switch trials had greater activation than repeat trials in posterior parietal and middle occipital cortex. Greater antisaccade activation was observed overall in saccade circuitry, although effects were evident primarily for the mixed task when considered separately. Finally, an interaction was observed in superior frontal cortex, precuneus, anterior cingulate, and thalamus with strong responses for antisaccade switch trials in the latter two regions. Altogether this response pattern demonstrated the sensitivity of cognitive control to changing task conditions, especially due to task switching costs. Such context-specific differences highlight the importance of trial history when assessing cognitive control.

A 24-Week Multi-Modality Exercise Program Improves Executive Control inOlder Adults with a Self-Reported Cognitive Complaint: Evidence fromtheAntisaccade Task.

Exercise programs involving aerobic and resistance training (i.e., multiple-modality) have shown promise in improving cognition and executive control in older adults at risk, or experiencing, cognitive decline. It is, however, unclear whether cognitive training within a multiple-modality program elicits an additive benefit to executive/cognitive processes. This is an important question to resolve in order to identify optimal training programs that delay, or ameliorate, executive deficits in persons at risk for further cognitive decline. In the present study, individuals with a self-reported cognitive complaint (SCC) participated in a 24-week multiple-modality (i.e., the M2 group) exercise intervention program. In addition, a separate group of individuals with a SCC completed the same aerobic and resistance training as the M2 group but also completed a cognitive-based stepping task (i.e., multiple-modality, mind-motor intervention: M4 group). Notably, pre- and post-intervention executive control was examined via the antisaccade task (i.e., eye movement mirror-symmetrical to a target). Antisaccades are an ideal tool for the study of individuals with subtle executive deficits because of its hands- and language-free nature and because the task's neural mechanisms are linked to neuropathology in cognitive decline (i.e., prefrontal cortex). Results showed that M2 and M4 group antisaccade reaction times reliably decreased from pre- to post-intervention and the magnitude of the decrease was consistent across groups. Thus, multi-modality exercise training improved executive performance in persons with a SCC independent of mind-motor training. Accordingly, we propose that multiple-modality training provides a sufficient intervention to improve executive control in persons with a SCC.

A Six-Month Cognitive-Motor and Aerobic Exercise Program Improves Executive Function in Persons with an Objective Cognitive Impairment: A Pilot Investigation Using the Antisaccade Task.

Persons with an objective cognitive impairment (OCI) are at increased risk for progression to Alzheimer's disease and related dementias. The present pilot project sought to examine whether participation in a long-term exercise program involving cognitive-motor (CM) dual-task gait training and aerobic exercise training improves executive function in persons with an OCI. To accomplish our objective, individuals with an OCI (n = 12) as determined by a Montreal Cognitive Assessment (MoCA) score of less than 26 and older adults (n = 11) deemed to be cognitively healthy (i.e., control group: MoCA score ≥26) completed a six-month moderate-to-high intensity (65-85% maximum heart rate) treadmill-based CM and aerobic exercise training program wherein pre- and post-intervention executive control was examined via the antisaccade task. Notably, antisaccades require a goal-directed eye-movement mirror-symmetrical to a target and represent an ideal tool for the study of executive deficits because of its hands- and language-free nature. As well, the cortical networks mediating antisaccades represent regions associated with neuropathology in cognitive decline and dementia (e.g., dorsolateral prefrontal cortex). Results showed that antisaccade reaction times for the OCI group reliably decreased by 30 ms from pre- to post-intervention, whereas the control group did not produce a reliable pre- to post-intervention change in reaction time (i.e., 6 ms). Thus, we propose that in persons with OCI long-term CM and aerobic training improves the efficiency and effectiveness of the executive mechanisms mediating high-level oculomotor control.

Disruption of pupil size modulation correlates with voluntary motor preparation deficits in Parkinson's disease

Pupil size is an easy-to-measure, non-invasive method to index various cognitive processes. Although a growing number of studies have incorporated measures of pupil size into clinical investigation, there have only been limited studies in Parkinson's disease (PD). Convergent evidence has suggested PD patients exhibit cognitive impairment at or soon after diagnosis. Here, we used an interleaved pro- and anti-saccade paradigm while monitoring pupil size with saccadic eye movements to examine the relationship between executive function deficits and pupil size in PD patients. Subjects initially fixated a central cue, the color of which instructed them to either look at a peripheral stimulus automatically (pro-saccade) or suppress the automatic response and voluntarily look in the opposite direction of the stimulus (anti-saccade). We hypothesized that deficits of voluntary control should be revealed not only on saccadic but also on pupil responses because of the recently suggested link between the saccade and pupil control circuits. In elderly controls, pupil size was modulated by task preparation, showing larger dilation prior to stimulus appearance in preparation for correct anti-saccades, compared to correct pro-saccades, or erroneous pro-saccades made in the anti-saccade condition. Moreover, the size of pupil dilation correlated negatively with anti-saccade reaction times. However, this profile of pupil size modulation was significantly blunted in PD patients, reflecting dysfunctional circuits for anti-saccade preparation. Our results demonstrate disruptions of modulated pupil responses by voluntary movement preparation in PD patients, highlighting the potential of using low-cost pupil size measurement to examine executive function deficits in early PD.

Pupil size reveals preparatory processes in the generation of pro-saccades and anti-saccades.

The ability to generate flexible behaviors to accommodate changing goals in response to identical sensory stimuli is a signature that is inherited in humans and higher-level animals. In the oculomotor system, this function has often been examined with the anti-saccade task, in which subjects are instructed, prior to stimulus appearance, to either automatically look at the peripheral stimulus (pro-saccade) or to suppress the automatic response and voluntarily look in the opposite direction from the stimulus (anti-saccade). Distinct neural preparatory activity between the pro-saccade and anti-saccade conditions has been well documented, particularly in the superior colliculus (SC) and the frontal eye field (FEF), and this has shown higher inhibition-related fixation activity in preparation for anti-saccades than in preparation for pro-saccades. Moreover, the level of preparatory activity related to motor preparation is negatively correlated with reaction times. We hypothesised that preparatory signals may be reflected in pupil size through a link between the SC and the pupil control circuitry. Here, we examined human pupil dynamics during saccade preparation prior to the execution of pro-saccades and anti-saccades. Pupil size was larger in preparation for correct anti-saccades than in preparation for correct pro-saccades and erroneous pro-saccades made in the anti-saccade condition. Furthermore, larger pupil dilation prior to stimulus appearance accompanied saccades with faster reaction times, with a trial-by-trial correlation between dilation size and anti-saccade reaction times. Overall, our results demonstrate that pupil size is modulated by saccade preparation, and neural activity in the SC, together with the FEF, supports these findings, providing unique insights into the neural substrate coordinating cognitive processing and pupil diameter.