The effect of doorway characteristics on freezing of gait in Parkinson's disease.

Background: Freezing of gait is a debilitating symptom in Parkinson's disease, during which a sudden motor block prevents someone from moving forward. Remarkably, doorways can provoke freezing. Most research has focused on the influence of doorway width, and little is known about other doorway characteristics influencing doorway freezing. Objective: Firstly, to provide guidelines on how to design doorways for people with freezing. Secondly, to compare people with doorway freezing to people without doorway freezing, and to explore the underlying mechanisms of doorway freezing. Methods: We designed a web-based, structured survey consisting of two parts. Part I (n = 171 responders), open to people with Parkinson's disease with freezing in general, aimed to compare people with doorway freezing to people without doorway freezing. We explored underlying processes related to doorway freezing with the Gait-Specific Attention Profile (G-SAP), inquiring about conscious movement processes occurring during doorway passing. Part II (n = 60), open for people experiencing weekly doorway freezing episodes, inquired about the influence of specific doorway characteristics on freezing. Results: People with doorway freezing (69% of Part I) had higher freezing severity, longer disease duration, and scored higher on all sub scores of the G-SAP (indicating heightened motor, attentional, and emotional thoughts when passing through doorways) than people without doorway freezing. The main categories provoking doorway freezing were: dimensions of the door and surroundings, clutter around the door, lighting conditions, and automatic doors. Conclusion: We provide recommendations on how to maximally avoid freezing in a practical setting. Furthermore, we suggest that doorways trigger freezing based on visuomotor, attentional, and emotional processes.

Effectiveness of an outpatient rehabilitation programme in patients with neuralgic amyotrophy and scapular dyskinesia: a randomised controlled trial.

BACKGROUND: Neuralgic amyotrophy (NA) is an acute inflammation of nerves within the brachial plexus territory leading to severe pain and multifocal paresis resulting in >60% of patients having residual complaints and functional limitations correlated with scapular dyskinesia. Our primary aim was to compare the effects of multidisciplinary rehabilitation (MR), focused on motor relearning to improve scapular dyskinesia and self-management strategies for reducing pain and fatigue, with usual care (UC) on shoulder, arm and hand functional capability in patients with NA. METHODS: In a non-blinded randomised controlled trial (RCT), patients with NA (aged≥18 years, scapular dyskinesia, >8 weeks after onset) were randomised to either an MR or an UC group. MR consisted of a diagnostic multidisciplinary consultation and eight sessions of physical and occupational therapy. Primary outcome was functional capability of the shoulder, arm and hand assessed with the Shoulder Rating Questionnaire-Dutch Language Version (SRQ-DLV). RESULTS: We included 47 patients with NA; due to drop-out, there were 22 participants in MR and 15 in UC for primary analysis. The mean group difference adjusted for sex, age and SRQ-DLV baseline score was 8.60 (95%CI: 0.26 to 16.94, p=0.044). The proportion attaining a minimal clinically relevant SRQ-DLV improvement (≥12) was larger for the MR group (59%) than the UC group (33%) with a number needed to treat of 4. CONCLUSION: This RCT shows that an MR programme focused on motor relearning to improve scapular dyskinesia, combined with self-management strategies for reducing pain and fatigue, shows more beneficial effects on shoulder, arm and hand functional capability than UC in patients with NA. TRIAL REGISTRATION NUMBER: NCT03441347.

Cerebral Adaptation Associated with Peripheral Nerve Recovery in Neuralgic Amyotrophy: A Randomized Controlled Trial.

BACKGROUND: Neuralgic amyotrophy (NA) is a common peripheral nerve disorder caused by auto-immune inflammation of nerves in the brachial plexus territory, characterized by acute pain and weakness of the shoulder muscles, followed by motor impairment. Recent work has confirmed that NA patients with residual motor dysfunction have abnormal cerebral sensorimotor representations of their affected upper extremity. OBJECTIVE: To determine whether abnormal cerebral sensorimotor representations associated with NA can be altered by specialized, multidisciplinary outpatient rehabilitation focused on relearning motor control. METHODS: 27 NA patients with residual lateralized symptoms in the right upper extremity participated in a randomized controlled trial, comparing 17 weeks of multidisciplinary rehabilitation (n = 16) to usual care (n = 11). We used task-based functional MRI and a hand laterality judgment task, which involves motor imagery and is sensitive to altered cerebral sensorimotor representations of the upper extremity. RESULTS: Change in task performance and related brain activity did not differ significantly between the multidisciplinary rehabilitation and usual care groups, whereas the multidisciplinary rehabilitation group showed significantly greater clinical improvement on the Shoulder Rating Questionnaire. Both groups, however, showed a significant improvement in task performance from baseline to follow-up, and significantly increased activity in visuomotor occipito-parietal brain areas, both specific to their affected upper extremity. CONCLUSIONS: Abnormal cerebral sensorimotor representations of the upper extremity after peripheral nerve damage in NA can recover toward normality. As adaptations occurred in visuomotor brain areas, multidisciplinary rehabilitation after peripheral nerve damage may be further optimized by applying visuomotor strategies. This study is registered at ClinicalTrials.gov (NCT03441347).

Muscle ultrasound is a sensitive biomarker in oculopharyngeal muscular dystrophy.

INTRODUCTION/AIMS: Oculopharyngeal muscular dystrophy (OPMD) is a late-onset, progressive muscle disease. Quantitative muscle ultrasound (QMUS) assesses structural changes in muscles and is a sensitive biomarker in neuromuscular disorders. Our aim of this study was to determine whether QMUS can detect muscle pathology and can be used as longitudinal imaging biomarker in OPMD. METHODS: Genetically confirmed OPMD patients, recruited by their treating physicians or from the national neuromuscular database, were examined twice, 20 months apart, using QMUS of orofacial and limb muscles, and measurements of functional capacity and muscle strength. Absolute echo intensity (AEI) and muscle thickness of all muscles were analyzed and correlated with clinical data. RESULTS: The tongue, deltoid, iliopsoas, rectus femoris, and soleus muscles showed increased AEI at baseline compared with normal values in 43 OPMD patients, with the rectus femoris being most often affected (51%).The AEI and muscle thickness of 9 of 11 muscles correlated significantly with the motor function measure, 10-step stair test, swallowing capacity, dynamometry, Medical Research Council grade, tongue strength, and bite force (r = 0.302 to -0.711). Between baseline and follow-up, deterioration in AEI was found for the temporalis, tongue, and deltoid muscles, and decreased muscle thickness was detected for the temporalis, masseter, digastric, tongue, deltoid, iliopsoas, and soleus muscles (P < .05). No relation was found between the change in AEI and repeat length or disease duration. DISCUSSION: QMUS detected muscle pathology and disease progression in OPMD over 20 months. We conclude that QMUS should be considered as a biomarker in treatment trials.

Visuomotor processing is altered after peripheral nerve damage in neuralgic amyotrophy.

Neuralgic amyotrophy is a common peripheral nerve disorder caused by autoimmune inflammation of the brachial plexus, clinically characterized by acute pain and weakness of the shoulder muscles, followed by motor impairment. Despite recovery of the peripheral nerves, patients often have residual motor dysfunction of the upper extremity, leading to persistent pain related to altered biomechanics of the shoulder region. Building on clinical signs that suggest a role for cerebral mechanisms in these residual complaints, here we show and characterize cerebral alterations following neuralgic amyotrophy. Neuralgic amyotrophy patients often develop alternative motor strategies, which suggests that (mal)adaptations may occur in somatomotor and/or visuomotor brain areas. Here, we tested where changes in cerebral sensorimotor representations occur in neuralgic amyotrophy, while controlling for altered motor execution due to peripheral neuropathy. We additionally explore the relation between potential cerebral alterations in neuralgic amyotrophy and clinical symptoms. During functional MRI scanning, 39 neuralgic amyotrophy patients with persistent, lateralized symptoms in the right upper extremity and 23 matched healthy participants solved a hand laterality judgement task that can activate sensorimotor representations of the upper extremity, across somatomotor and visuomotor brain areas. Behavioural and cerebral responses confirmed the involvement of embodied, sensorimotor processes across groups. Compared with healthy participants, neuralgic amyotrophy patients were slower in hand laterality judgement and had decreased cerebral activity specific to their affected limb in two higher-order visual brain regions: the right extrastriate cortex and the parieto-occipital sulcus. Exploratory analyses revealed that across patients, extrastriate activity specific to the affected limb decreased as persistent pain increased, and affected limb-related parieto-occipital activity decreased as imagery performance of the affected limb became slower. These findings suggest that maladaptive cerebral plasticity in visuomotor areas involved in sensorimotor integration plays a role in residual motor dysfunction and subsequent persistent pain in neuralgic amyotrophy. Rehabilitation interventions that apply visuomotor strategies to improve sensorimotor integration may help to treat neuralgic amyotrophy patients.

Aerobic Exercise Alters Brain Function and Structure in Parkinson's Disease: A Randomized Controlled Trial.

OBJECTIVE: Randomized clinical trials have shown that aerobic exercise attenuates motor symptom progression in Parkinson's disease, but the underlying neural mechanisms are unclear. Here, we investigated how aerobic exercise influences disease-related functional and structural changes in the corticostriatal sensorimotor network, which is involved in the emergence of motor deficits in Parkinson's disease. Additionally, we explored effects of aerobic exercise on tissue integrity of the substantia nigra, and on behavioral and cerebral indices of cognitive control. METHODS: The Park-in-Shape trial is a single-center, double-blind randomized controlled trial in 130 Parkinson's disease patients who were randomly assigned (1:1 ratio) to aerobic exercise (stationary home trainer) or stretching (active control) interventions (duration = 6 months). An unselected subset from this trial (exercise, n = 25; stretching, n = 31) underwent resting-state functional and structural magnetic resonance imaging (MRI), and an oculomotor cognitive control task (pro- and antisaccades), at baseline and at 6-month follow-up. RESULTS: Aerobic exercise, but not stretching, led to increased functional connectivity of the anterior putamen with the sensorimotor cortex relative to the posterior putamen. Behaviorally, aerobic exercise also improved cognitive control. Furthermore, aerobic exercise increased functional connectivity in the right frontoparietal network, proportionally to fitness improvements, and it reduced global brain atrophy. INTERPRETATION: MRI, clinical, and behavioral results converge toward the conclusion that aerobic exercise stabilizes disease progression in the corticostriatal sensorimotor network and enhances cognitive performance. ANN NEUROL 2022;91:203-216.

Altered sensorimotor representations after recovery from peripheral nerve damage in neuralgic amyotrophy.

Neuralgic amyotrophy is a common peripheral nerve disorder caused by acute autoimmune inflammation of the brachial plexus. Subsequent weakness of the stabilizing shoulder muscles leads to compensatory strategies and abnormal motor control of the shoulder. Despite recovery of peripheral nerves and muscle strength over time, motor dysfunction often persists. Suboptimal motor recovery has been linked to maladaptive changes in the central motor system in several nervous system disorders. We therefore hypothesized that neuralgic amyotrophy patients with persistent motor dysfunction may have altered cerebral sensorimotor representations of the affected upper limb. To test this hypothesis, 21 neuralgic amyotrophy patients (mean age 45 ± 12 years, 5 female) with persistent lateralized symptoms in the right upper limb and 20 age- and sex-matched healthy controls, all right-handed, performed a hand laterality judgement task in a cross-sectional comparison. Previous evidence has shown that to solve this task, subjects rely on sensorimotor representations of their own upper limb, using a first-person imagery perspective without actual motor execution. This enabled us to investigate altered central sensorimotor representations while controlling for altered motor output and altered somatosensory afference. We found that neuralgic amyotrophy patients were specifically less accurate for laterality judgments of their affected right limb, as compared to healthy controls. There were no significant group differences in reaction times. Both groups used a first-person imagery perspective, as evidenced by changes in reaction times as a function of participants' own arm posture. We conclude that cerebral sensorimotor representations of the affected upper limb are altered in neuralgic amyotrophy patients. This suggests that maladaptive central neuroplasticity may occur in response to peripheral nerve damage, thereby contributing to motor dysfunction. Therapies focused on altering cerebral sensorimotor representations may help to treat peripheral nerve disorders such as neuralgic amyotrophy.

The Effects of a TMS Double Perturbation to a Cortical Network.

Transcranial magnetic stimulation (TMS) is often used to understand the function of individual brain regions, but this ignores the fact that TMS may affect network-level rather than nodal-level processes. We examine the effects of a double perturbation to two frontoparietal network nodes, compared with the effects of single lesions to either node. We hypothesized that Bayesian evidence for the absence of effects that build upon one another indicates that a single perturbation is consequential to network-level processes. Twenty-three humans performed pro-saccades (look toward) and anti-saccades (look away) after receiving continuous theta-burst stimulation (cTBS) to right frontal eye fields (FEFs), dorsolateral prefrontal cortex (DLPFC), or somatosensory cortex (S1; the control region). On a subset of trials, a TMS pulse was applied to right posterior parietal cortex (PPC). FEF, DLPFC, and PPC are important frontoparietal network nodes for generating anti-saccades. Bayesian t tests were used to test hypotheses for enhanced double perturbation effects (cTBS plus TMS pulse) on saccade behaviors, against the alternative hypothesis that double perturbation effects to a network are not greater than single perturbation effects. In one case, we observed strong evidence [Bayes factor (BF10) = 325] that PPC TMS following DLPFC cTBS enhanced impairments in ipsilateral anti-saccade amplitudes over DLPFC cTBS alone, and not over the effect of the PPC pulse alone (BF10 = 0.75), suggesting that double perturbation effects do not augment one another. Rather, this suggests that computations are distributed across the network, and in some cases there can be compensation for cTBS perturbations.

NA-CONTROL: a study protocol for a randomised controlled trial to compare specific outpatient rehabilitation that targets cerebral mechanisms through relearning motor control and uses self-management strategies to improve functional capability of the upper extremity, to usual care in patients with neuralgic amyotrophy.

BACKGROUND: Neuralgic amyotrophy (NA) is a distinct peripheral neurological disorder of the brachial plexus with a yearly incidence of 1/1000, which is characterised by acute severe upper extremity pain. Weakness of the stabilising shoulder muscles in the acute phase leads to compensatory strategies and abnormal motor control of the shoulder - scapular dyskinesia. Despite peripheral nerve recovery, scapular dyskinesia often persists, leading to debilitating residual complaints including pain and fatigue. Evidence suggests that persistent scapular dyskinesia in NA may result from maladaptive cerebral neuroplasticity, altering motor planning. Currently there is no proven effective causative treatment for the residual symptoms in NA. Moreover, the role of cerebral mechanisms in persistent scapular dyskinesia remains unclear. METHODS: NA-CONTROL is a single-centre, randomised controlled trial comparing specific rehabilitation to usual care in NA. The rehabilitation programme combines relearning of motor control, targeting cerebral mechanisms, with self-management strategies. Fifty patients will be included. Patients are recruited through the Radboud university medical center Nijmegen, the Netherlands. Patients with a (suspected) diagnosis of NA, with lateralized symptoms and scapular dyskinesia in the right upper extremity, who are 18 years or older and not in the acute phase can be included. The primary outcome is the Shoulder Rating Questionnaire score, which measures functional capability of the upper extremity. Secondary clinical outcomes include measures of pain, fatigue, participation, reachable workspace, muscle strength and quality of life. In addition, motor planning is assessed with first-person motor imagery and functional magnetic resonance imaging. In a sub-study the patients are compared to 25 healthy participants, to determine the involvement of cerebral mechanisms. This will enable interpretation of cerebral changes associated with the rehabilitation programme and functional impairments in NA. DISCUSSION: NA-CONTROL is the first randomised trial to investigate the effect of specific rehabilitation on residual complaints in NA. It also is the first study into the cerebral mechanisms that might underlie persistent scapular dyskinesia in NA. It thus may aid the further development of mechanism-based interventions for disturbed motor control in NA and in other peripheral neurological disorders. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03441347 . Registered on 20 February 2018.

Effects of tolcapone and bromocriptine on cognitive stability and flexibility.

RATIONALE: The prefrontal cortex (PFC) and basal ganglia (BG) have been associated with cognitive stability and cognitive flexibility, respectively. We hypothesized that increasing PFC dopamine tone by administering tolcapone (a catechol-O-methyltransferase (COMT) inhibitor) to human subjects should promote stability; conversely, increasing BG dopamine tone by administering bromocriptine (a D2 receptor agonist) should promote flexibility. OBJECTIVE: We assessed these hypotheses by administering tolcapone, bromocriptine, and a placebo to healthy subjects who performed a saccadic eye movement task requiring stability and flexibility. METHODS: We used a randomized, double-blind, within-subject design that was counterbalanced across drug administration sessions. In each session, subjects were cued to prepare for a pro-saccade (look towards a visual stimulus) or anti-saccade (look away) on every trial. On 60% of the trials, subjects were instructed to switch the response already in preparation. We hypothesized that flexibility would be required on switch trials, whereas stability would be required on non-switch trials. The primary measure of performance was efficiency (the percentage correct divided by reaction time for each trial type). RESULTS: Subjects were significantly less efficient across all trial types under tolcapone, and there were no significant effects of bromocriptine. After grouping subjects based on Val158Met COMT polymorphism, we found that Met/Met and Val/Met subjects (greater PFC dopamine) were less efficient compared to Val/Val subjects. CONCLUSIONS: Optimal behavior was based on obeying the environmental stimuli, and we found reduced efficiency with greater PFC dopamine tone. We suggest that greater PFC dopamine interfered with the ability to flexibly follow the environment.

Dissociable Roles of Dorsolateral Prefrontal Cortex and Frontal Eye Fields During Saccadic Eye Movements.

The dorsolateral prefrontal cortex (DLPFC) and the frontal eye fields (FEF) have both been implicated in the executive control of saccades, yet possible dissociable roles of each region have not been established. Specifically, both establishing a "task set" as well as suppressing an inappropriate response have been linked to DLPFC and FEF activity, with behavioral outcome measures of these mechanisms mainly being the percentage of pro-saccade errors made on anti-saccade trials. We used continuous theta-burst stimulation (cTBS) to disrupt FEF or DLPFC function in humans during an anti-saccade task to assess the causal role of these regions in these executive control processes, and in programming saccades towards (pro-saccade) or away (anti-saccade) from visual targets. After right FEF cTBS, as compared to control cTBS to the right primary somatosensory cortex (rS1), anti-saccade amplitude of the first saccade decreased and the number of anti-saccades to acquire final position increased; however direction errors to the visual target were not different. In contrast, after left DLPFC cTBS, as compared to left S1 cTBS, subjects displayed greater direction errors for contralateral anti-saccades; however, there were no impairments on the number of saccades or the saccade amplitude. These results are consistent with the notion that DLPFC is necessary for executive control of saccades, whereas FEF is necessary for visuo-motor aspects of anti-saccade programming.

Changes to saccade behaviors in Parkinson's disease following dancing and observation of dancing.

BACKGROUND: The traditional view of Parkinson's disease (PD) as a motor disorder only treated by dopaminergic medications is now shifting to include non-pharmacologic interventions. We have noticed that patients with PD obtain an immediate, short-lasting benefit to mobility by the end of a dance class, suggesting some mechanism by which dancing reduces bradykinetic symptoms. We have also found that patients with PD are unimpaired at initiating highly automatic eye movements to visual stimuli (pro-saccades) but are impaired at generating willful eye movements away from visual stimuli (anti-saccades). We hypothesized that the mechanisms by which a dance class improves movement initiation may generalize to the brain networks impacted in PD (frontal lobe and basal ganglia, BG), and thus could be assessed objectively by measuring eye movements, which rely on the same neural circuitry. METHODS: Participants with PD performed pro- and anti-saccades before, and after, a dance class. "Before" and "after" saccade performance measurements were compared. These measurements were then contrasted with a control condition (observing a dance class in a video), and with older and younger adult populations, who rested for an hour between measurements. RESULTS: We found an improvement in anti-saccade performance following the observation of dance (but not following dancing), but we found a detriment in pro-saccade performance following dancing. CONCLUSION: We suggest that observation of dance induced plasticity changes in frontal-BG networks that are important for executive control. Dancing, in contrast, increased voluntary movement signals that benefited mobility, but interfered with the automaticity of efficient pro-saccade execution.

High-throughput classification of clinical populations from natural viewing eye movements.

Many high-prevalence neurological disorders involve dysfunctions of oculomotor control and attention, including attention deficit hyperactivity disorder (ADHD), fetal alcohol spectrum disorder (FASD), and Parkinson's disease (PD). Previous studies have examined these deficits with clinical neurological evaluation, structured behavioral tasks, and neuroimaging. Yet, time and monetary costs prevent deploying these evaluations to large at-risk populations, which is critically important for earlier detection and better treatment. We devised a high-throughput, low-cost method where participants simply watched television while we recorded their eye movements. We combined eye-tracking data from patients and controls with a computational model of visual attention to extract 224 quantitative features. Using machine learning in a workflow inspired by microarray analysis, we identified critical features that differentiate patients from control subjects. With eye movement traces recorded from only 15 min of videos, we classified PD versus age-matched controls with 89.6 % accuracy (chance 63.2 %), and ADHD versus FASD versus control children with 77.3 % accuracy (chance 40.4 %). Our technique provides new quantitative insights into which aspects of attention and gaze control are affected by specific disorders. There is considerable promise in using this approach as a potential screening tool that is easily deployed, low-cost, and high-throughput for clinical disorders, especially in young children and elderly populations who may be less compliant to traditional evaluation tests.

Impaired executive function signals in motor brain regions in Parkinson's disease.

Recent evidence has shown that patients with Parkinson's disease (PD) often display deficits in executive functions, such as planning for future behavior, and these deficits may stem from pathologies in prefrontal cortex and basal ganglia circuits that are critical to executive control. Using the antisaccade task (look away from a visual stimulus), we show that when the preparatory 'readiness' to perform a given action is dissociated from the actual execution of that action, PD patients off and on dopamine medication display behavioral impairments and reduced cortical brain activation that cannot be explained by a pathology related to dysfunction in movement execution. Rather, they show that the appropriate task set signals were not in place in motor regions prior to execution, resulting in impairments in the control of subsequent voluntary movement. This is the first fMRI study of antisaccade deficits in Parkinson's disease, and importantly, the findings point to a critical role of the basal ganglia in translating signals related to rule representation (executive) into those governing voluntary motor behavior.

Differential contributions of thalamic nuclei in the generation of antisaccades.

Our knowledge of thalamus function comes largely from anatomical studies showing, for example, that the ventroanterior (VA) and ventrolateral (VL) nuclei are connected to "motor" regions, whereas the mediodorsal (MD) nucleus is connected to prefrontal "executive" regions. Interestingly, Kunimatsu and Tanaka recently showed that preparatory signals for antisaccades (a motor response requiring executive control) were enhanced compared with prosaccades in the VA/VL but not in the MD, which is surprising given MD's connection to executive regions.

Executive impairment in Parkinson's disease: response automaticity and task switching.

Patients with Parkinson's disease (PD) show slowed movement initiation and can have deficits in executive function, leading to impairments in controlling involuntary behavior. This results in difficulties performing an antisaccade, which requires one to suppress an automatic eye movement (a prosaccade) to a visual stimulus, and execute a voluntary eye movement in the opposite direction. Antisaccade deficits are similar to those seen in task switching, whereby one is required to change a response after performing a different behavior. Both antisaccade (Hood et al., 2007) and task switching (Cools, Barker, Sahakian, & Robbins, 2001) deficits in PD have been attributed to fronto-basal ganglia (BG) dysfunction. Previously, we demonstrated with functional magnetic resonance imaging that BG circuitry is important to both task switching and voluntary saccade generation, as greater caudate activation was seen when healthy young adults first prepared a prosaccade, but then switched to an antisaccade (Cameron, Coe, et al., 2009). Therefore, we hypothesized that PD patients would have difficulty switching from one saccade response to the other, with particular impairment in switching from a pro to an antisaccade. Here, we not only confirmed this prediction, but also showed that PD patients performed better than controls in switching from an anti to a prosaccade. This suggests that task switching deficits in PD are particularly pronounced when more automatic behavior needs to be overridden with alternative behavior. We suggest that this occurs primarily at the level of establishing the appropriate task set, which is an internalized rule that governs how to respond.

Quantifying center bias of observers in free viewing of dynamic natural scenes.

Human eye-tracking studies have shown that gaze fixations are biased toward the center of natural scene stimuli ("center bias"). This bias contaminates the evaluation of computational models of attention and oculomotor behavior. Here we recorded eye movements from 17 participants watching 40 MTV-style video clips (with abrupt scene changes every 2-4 s), to quantify the relative contributions of five causes of center bias: photographer bias, motor bias, viewing strategy, orbital reserve, and screen center. Photographer bias was evaluated by five naive human raters and correlated with eye movements. The frequently changing scenes in MTV-style videos allowed us to assess how motor bias and viewing strategy affected center bias across time. In an additional experiment with 5 participants, videos were displayed at different locations within a large screen to investigate the influences of orbital reserve and screen center. Our results demonstrate quantitatively for the first time that center bias is correlated strongly with photographer bias and is influenced by viewing strategy at scene onset, while orbital reserve, screen center, and motor bias contribute minimally. We discuss methods to account for these influences to better assess computational models of visual attention and gaze using natural scene stimuli.

Role of the basal ganglia in switching a planned response.

The ability to perform an appropriate response in the presence of competing alternatives is a critical facet of human behavioral control. This is especially important if a response is prepared for execution but then has to be changed suddenly. A popular hypothesis of basal ganglia (BG) function suggests that its direct and indirect pathways could provide a neural mechanism to rapidly switch from one planned response to an alternative. However, if one response is more dominant or 'automatic' than the other, the BG might have a different role depending on switch direction. We built upon the pro- and antisaccade tasks, two models of automatic and voluntary behavior, respectively, and investigated whether the BG are important for switching any planned response in general, or if they are more important for switching from a more automatic response to a response that is more difficult to perform. Subjects prepared either a pro- or antisaccade but then had to switch it unexpectedly on a subset of trials. The results revealed increased striatal activation for switching from a pro- to an antisaccade but this did not occur for switching from an anti- to a prosaccade. This activation pattern depended on the relative difficulty in switching, and it was distinct from frontal eye fields, an area shown to be more active for antisaccade trials than for prosaccade trials. This suggests that the BG are important for compensating for differences in response difficulty, facilitating the rapid switching of one response for another.

Contrasting instruction change with response change in task switching.

Switching between two tasks results in switch costs, which are increased error rates and response times in comparison to repeating a task. Switch costs are attributed to a change in task set, which is the internalized rule of how to respond to a stimulus. However, it is not clear if this is because the instruction about which task to perform has changed, or because a programmed response has changed. We examined this question by changing the instruction about whether to perform a pro or an antisaccade to a stimulus, before or after the stimulus was presented. As a saccade response is specified by instruction plus stimulus position, changing the instruction after the stimulus was present resulted in a change in the specified response, whereas changing the instruction beforehand did not. Three experiments investigated; (i) if changing instruction alone or changing the specified response produced switch costs; (ii) if predictability of switching instruction influenced switch costs; and (iii) if predictability of stimulus position influenced switch costs. Regardless of instruction or stimulus predictability, switch costs for both pro and antisaccades consistently resulted if the specified response switched. This suggests that a pro or antisaccade motor program was automatically programmed based on a presented instruction and stimulus position. Therefore, the given physical information drove switch costs, even if subjects could predict a change in task. This study demonstrates that switch costs result if changing an instruction changes a programmed response.