A machine-learning method isolating changes in wrist kinematics that identify age-related changes in arm movement.

Normal aging often results in an increase in physiological tremors and slowing of the movement of the hands, which can impair daily activities and quality of life. This study, using lightweight wearable non-invasive sensors, aimed to detect and identify age-related changes in wrist kinematics and response latency. Eighteen young (ages 18-20) and nine older (ages 49-57) adults performed two standard tasks with wearable inertial measurement units on their wrists. Frequency analysis revealed 5 kinematic variables distinguishing older from younger adults in a postural task, with best discrimination occurring in the 9-13 Hz range, agreeing with previously identified frequency range of age-related tremors, and achieving excellent classifier performance (0.86 AUROC score and 89% accuracy). In a second pronation-supination task, analysis of angular velocity in the roll axis identified a 71 ms delay in initiating arm movement in the older adults. This study demonstrates that an analysis of simple kinematic variables sampled at 100 Hz frequency with commercially available sensors is reliable, sensitive, and accurate at detecting age-related increases in physiological tremor and motor slowing. It remains to be seen if such sensitive methods may be accurate in distinguishing physiological tremors from tremors that occur in neurological diseases, such as Parkinson's Disease.

Understanding Cortical Streams from a Computational Perspective.

The two visual cortical stream hypothesis, which suggests object properties (what) are processed separately from spatial properties (where), has a longstanding history, and much evidence has accumulated to support its conjectures. Nevertheless, in the last few decades, conflicting evidence has mounted that demands some explanation and modification. For example, existence of (1) shape activities (fMRI) or shape selectivities (physiology) in dorsal stream, similar to ventral stream; likewise, spatial activations (fMRI) or spatial selectivities (physiology) in ventral stream, similar to dorsal stream; (2) multiple segregated subpathways within a stream. In addition, the idea of segregation of various aspects of multiple objects in a scene raises questions about how these properties of multiple objects are then properly re-associated or bound back together to accurately perceive, remember, or make decisions. We will briefly review the history of the two-stream hypothesis, discuss competing accounts that challenge current thinking, and propose ideas on why the brain has segregated pathways. We will present ideas based on our own data using artificial neural networks (1) to reveal encoding differences for what and where that arise in a two-pathway neural network, (2) to show how these encoding differences can clarify previous conflicting findings, and (3) to elucidate the computational advantages of segregated pathways. Furthermore, we will discuss whether neural networks need to have multiple subpathways for different visual attributes. We will also discuss the binding problem (how to correctly associate the different attributes of each object together when there are multiple objects each with multiple attributes in a scene) and possible solutions to the binding problem. Finally, we will briefly discuss problems and limitations with existing models and potential fruitful future directions.

Quantifying the Magnitude and Longevity of the Effect of Repetitive Head Impacts in Adolescent Soccer Players: Deleterious Effect of Long Headers Extend Beyond a Month.

There is growing interest in the effects of sports-related repetitive head impacts (RHIs) on athletes' cognitive capabilities. This study examines the effect of RHIs in data collected from adolescent athletes to estimate the magnitude and longevity of RHIs on sensorimotor and cognitive performance. A non-linear regression model estimated the longevity of RHI effects by adding a half-life parameter embedded in an exponential decay function. A model estimate of this parameter allows the possibility of RHI effects to attenuate over time and introduces a mechanism to study the cumulative effect of RHIs. The posterior distribution of the half-life parameter associated with short-distance headers (<30 m) is centered around 6 days, whereas the posterior distribution of the half-life parameter associated with long-distance headers extends beyond a month. Additionally, the magnitude of the effect of each short header is around 3 times smaller than that of a long header. The results indicate that, on both tasks, response time (RT) changes after long headers are bigger in magnitude and last longer compared to the effects of short headers. Most important, we demonstrate that deleterious effects of long headers extend beyond 1 month. Although estimates are based on data from a relatively short-duration study with a relatively small sample size, the proposed model provides a mechanism to estimate long-term behavioral slowing from RHIs, which may be helpful to reduce the risk of additional injury. Finally, differences in the longevity of the effects of short and long RHIs may help to explain the large variance found between biomechanical input and clinical outcome in studies of concussion tolerance.

Pseudosparse neural coding in the visual system of primates.

When measuring sparseness in neural populations as an indicator of efficient coding, an implicit assumption is that each stimulus activates a different random set of neurons. In other words, population responses to different stimuli are, on average, uncorrelated. Here we examine neurophysiological data from four lobes of macaque monkey cortex, including V1, V2, MT, anterior inferotemporal cortex, lateral intraparietal cortex, the frontal eye fields, and perirhinal cortex, to determine how correlated population responses are. We call the mean correlation the pseudosparseness index, because high pseudosparseness can mimic statistical properties of sparseness without being authentically sparse. In every data set we find high levels of pseudosparseness ranging from 0.59-0.98, substantially greater than the value of 0.00 for authentic sparseness. This was true for synthetic and natural stimuli, as well as for single-electrode and multielectrode data. A model indicates that a key variable producing high pseudosparseness is the standard deviation of spontaneous activity across the population. Consistently high values of pseudosparseness in the data demand reconsideration of the sparse coding literature as well as consideration of the degree to which authentic sparseness provides a useful framework for understanding neural coding in the cortex.

Heading-Related Slowing by Twenty-Four Hours in Youth Athletes.

Research suggests cumulative effects of repetitive head impacts (RHIs) on brain structure, especially with younger age of first exposure. Further, recent evidence suggests no immediate cognitive changes with increased RHIs but impairments across a sports season. The aim was to examine more closely the short-term time course of behavioral effects of exposure to RHI. Across 2 years, 18 female adolescent soccer players were tested on ProPoint (sensorimotor) and AntiPoint (cognitive) tasks with reaction time (RT) being the main outcome measure. The athletes were tested before and after workout with ball heading (immediate effect), as well as 24 h after workout (24 h effect) throughout two consecutive seasons. The number of headers performed 24 h before workout, during workout, and season average per workout were recorded. The athletes showed a decrease in ProPoint and AntiPoint RTs immediately after a workout, with no change or decrease in RTs with increasing RHIs. However, increasing RHIs during workout increased RTs in both tasks when tested 24 h later. The athletes also showed an increase in AntiPoint RTs with increasing season average RHIs. Our findings show a complex time course of effects of RHIs on sensorimotor and cognitive performance in adolescent athletes, with exposure to RHIs associated with no change or immediate benefits and then deficits by 24 h. Pathophysiological changes associated with exercise and traumatic brain injury can account for the sensorimotor and cognitive performance changes occurring within 24 h after RHIs.

Representation of shape, space, and attention in monkey cortex.

Attentional deficits are core to numerous developmental, neurological, and psychiatric disorders. At the single-cell level, much knowledge has been garnered from studies of shape and spatial properties, as well as from numerous demonstrations of attentional modulation of those properties. Despite this wealth of knowledge of single-cell responses across many brain regions, little is known about how these cellular characteristics relate to population level representations and how such representations relate to behavior; in particular, how these cellular responses relate to the representation of shape, space, and attention, and how these representations differ across cortical areas and streams. Here we will emphasize the role of population coding as a missing link for connecting single-cell properties with behavior. Using a data-driven intrinsic approach to population decoding, we show that both 'what' and 'where' cortical visual streams encode shape, space, and attention, yet demonstrate striking differences in these representations. We suggest that both pathways fully process shape and space, but that differences in representation may arise due to their differing functions and input and output constraints. Moreover, differences in the effects of attention on shape and spatial population representations in the two visual streams suggest two distinct strategies: in a ventral area, attention or task demands modulate the population representations themselves (perhaps to expand or enhance one part at the expense of other parts) while in a dorsal area, at a population representation level, attention effects are weak and nearly non-existent, perhaps in order to maintain veridical representations needed for visuomotor control. We show that an intrinsic approach, as opposed to theory-driven and labeled approaches, is useful for understanding how representations develop and differ across brain regions. Most importantly, these approaches help link cellular properties more tightly with behavior, a much-needed step to better understand and interpret cellular findings and key to providing insights to improve interventions in human disorders.

Differential benefits of olanzapine on executive function in schizophrenia patients: Preliminary findings.

OBJECTIVE: Schizophrenia patients show executive function (EF) impairments in voluntary orienting as measured by eye-movements. We tested 14 inpatients to investigate the effects of the antipsychotic olanzapine on EF, as measured by antisaccade eye-movement performance. METHODS: Patients were tested at baseline (before olanzapine), 3-5 days post-medication, and 12-14 days post-medication. Patients were also assessed on the Positive and Negative Syndrome Scale (PANSS) to measure the severity of schizophrenia-related symptoms, and administered the Stroop task, a test of EF. Nine matched controls were also tested on the antisaccade and Stroop. RESULTS: Both groups showed improvement on Stroop and antisaccade; however, the schizophrenia group improved significantly more on antisaccade, indicating an additional benefit of olanzapine on EF performance. Patients with poorer baseline antisaccade performance (High-Deficit) showed significantly greater improvement on the antisaccade task than patients with better baseline performance (Low-Deficit), suggesting that baseline EF impairment predicts the magnitude of cognitive improvement with olanzapine. These subgroups showed significant and equivalent improvement on PANSS scores, indicating that improvement on the antisaccade task with olanzapine was not a result of differences in magnitude of clinical improvement. CONCLUSIONS: This preliminary study provides evidence that olanzapine may be most advantageous for patients with greater baseline EF deficits.

Extrinsic and intrinsic representations.

We extend the discussion in the target article about distinctions between extrinsic coding (external references to known things, as required by information theory) and the alternative we and the target article both favor, intrinsic coding (internal relationships within sensory and motor signals). Central to our thinking about intrinsic coding is population coding and the concept of high-dimensional neural response spaces.

Correction: Evidence of Cognitive Dysfunction after Soccer Playing with Ball Heading Using a Novel Tablet-Based Approach.

[This corrects the article DOI: 10.1371/journal.pone.0057364.].

Attention Effects on Neural Population Representations for Shape and Location Are Stronger in the Ventral than Dorsal Stream.

We examined how attention causes neural population representations of shape and location to change in ventral stream (AIT) and dorsal stream (LIP). Monkeys performed two identical delayed-match-to-sample (DMTS) tasks, attending either to shape or location. In AIT, shapes were more discriminable when directing attention to shape rather than location, measured by an increase in mean distance between population response vectors. In LIP, attending to location rather than shape did not increase the discriminability of different stimulus locations. Even when factoring out the change in mean vector response distance, multidimensional scaling (MDS) still showed a significant task difference in AIT, but not LIP, indicating that beyond increasing discriminability, attention also causes a nonlinear warping of representation space in AIT. Despite single-cell attentional modulations in both areas, our data show that attentional modulations of population representations are weaker in LIP, likely due to a need to maintain veridical representations for visuomotor control.

Age-Dependent Performance on Pro-point and Anti-point Tasks.

Changes in prefrontal cortex are thought to be responsible for many of the characteristic behavioral changes that are seen during adolescence and late adulthood. Disruption of prefrontal cortex is an early sign for many developmental, neurological, and psychiatric disorders. Goal directed eye movements, such as Anti-saccades, have been shown to have high sensitivity as a gross assessment of prefrontal lobe function. Previous studies on the developmental changes of saccades across age have shown that stimulus-driven and goal-directed eye movements follow a U-shaped trend with peaks in performance occuring during adolescence. Using novel tablet-based pointing tasks, modeled on eye movement tests, this study aims to provide a preliminary understanding of how age affects manual pointing performance, in order to more easily track behavioral changes of the prefrontal cortex. In this study, 82 participants between the ages of 10 and 63 were recruited to participate. Results show that similarly to saccades, manual pointing responses are age dependent with fastest response times found during late adolescence to early adulthood (U-shaped curves). Importantly, we also demonstrated significant differences in the effect of age in stimulus-driven (Pro-point) and goal-directed (Anti-point) pointing tasks. The effect of age on response time (RT) is greater on Anti-point compared to Pro-point task (with a 79 ms greater mean decrease during early development and a 148 ms greater mean increase during later aging). Further, for Pro-point task, the U-shaped curve flattens at about 45 years whereas for Anti-point task the U-shaped curve continues up to the maximum age tested (about 60 years). This dissociation between age-related changes in sensorimotor and cognitive performance suggests independent development of associated brain circuity. Thus, changes of performance in disease that are specific for age and task may be able to help identify brain circuitry involved. Finally, given that these tablet-based pointing tasks show similar age-related patterns reported previously with eye-tracking technology, our findings suggest that such tablet-based tasks may provide an inexpensive, quick, and more practical way of detecting neurological deficits or tracking cognitive changes.

Slowed Prosaccades and Increased Antisaccade Errors As a Potential Behavioral Biomarker of Multiple System Atrophy.

Current clinical diagnostic tools are limited in their ability to accurately differentiate idiopathic Parkinson's disease (PD) from multiple system atrophy (MSA) and other parkinsonian disorders early in the disease course, but eye movements may stand as objective and sensitive markers of disease differentiation and progression. To assess the use of eye movement performance for uniquely characterizing PD and MSA, subjects diagnosed with PD (N = 21), MSA (N = 11), and age-matched controls (C, N = 20) were tested on the prosaccade and antisaccade tasks using an infrared eye tracker. Twenty of these subjects were retested ~7 months later. Saccade latencies, error rates, and longitudinal changes in saccade latencies were measured. Both PD and MSA patients had greater antisaccade error rates than C subjects, but MSA patients exhibited longer prosaccade latencies than both PD and C patients. With repeated testing, antisaccade latencies improved over time, with benefits in C and PD but not MSA patients. In the prosaccade task, the normal latencies of the PD group show that basic sensorimotor oculomotor function remain intact in mid-stage PD, whereas the impaired latencies of the MSA group suggest additional degeneration earlier in the disease course. Changes in antisaccade latency appeared most sensitive to differences between MSA and PD across short time intervals. Therefore, in these mid-stage patients, increased antisaccade errors combined with slowed prosaccade latencies might serve as a useful marker for early differentiation between PD and MSA, and, antisaccade performance, a measure of MSA progression. Together, our findings suggest that eye movements are promising biomarkers for early differentiation and progression of parkinsonian disorders.

Sensorimotor and executive function slowing in anesthesiology residents after overnight shifts.

STUDY OBJECTIVE: Medical residents working overnight call shifts experience sleep deprivation and circadian clock disruption. This leads to deficits in sensorimotor function and increases in workplace accidents. Using quick tablet-based tasks, we investigate whether measureable executive function differences exist following a single overnight call versus routine shift, and whether factors like stress, rest and caffeine affect these measures. DESIGN: A prospective, observational, longitudinal, comparison study was conducted. SETTING: An academic tertiary hospital's main operating room suite staffed by attending anesthesiologists, anesthesiology residents, anesthesiologist assistants and nurse anesthetists. PATIENTS: Subjects were 30 anesthesiology residents working daytime shifts and 30 peers working overnight call shifts from the University of Texas Health Science Center at Houston. INTERVENTIONS: Before and after their respective work shifts, residents completed the Stanford Sleepiness Scale (SSS) and the ProPoint and AntiPoint tablet-based tasks. These latter tasks are designed to measure sensorimotor and executive functions, respectively. MEASUREMENTS: The SSS is a self-reported measure of sleepiness. Response times (RTs) are measured in the pointing tasks. MAIN RESULTS: Call residents exhibited increased RTs across their shifts (post-pre) on both ProPoint (p=0.002) and AntiPoint (p<0.002) tasks, when compared to Routine residents. Increased stress was associated with decreases in AntiPoint RT for Routine (p=0.007), but with greater increases in sleepiness for Call residents (p<0.001). Further, whether or not a Call resident consumed caffeine habitually was associated with ProPoint RT changes; with Call residents who habitually drink caffeine having a greater Pre-Post difference (i.e., more slowing, p<0.001) in ProPoint RT. CONCLUSIONS: These results indicate that (1) overnight Call residents demonstrate both sensorimotor and cognitive slowing compared to routine daytime shift residents, (2) sensorimotor slowing is greater in overnight Call residents who drink caffeine habitually, and (3) increased stress during a shift reduces (improves) cognitive RTs during routine daytime but not overnight call shifts.

Impaired Cognitive Performance in Youth Athletes Exposed to Repetitive Head Impacts.

Worldwide, more than 22 million children and adolescents are exposed to repetitive head impacts (RHI) in soccer. Evidence indicates cumulative effects on brain structure, but it is not known whether exposure to RHI affects cognitive improvement in adolescents. The aim of the study was to determine whether exposure to RHI while heading the ball in soccer affects improvement in cognitive performance in adolescents over time. The study group consisted of a convenience sample of 16 male soccer players (mean age 15.7 ± 0.7 years). A comparison cohort of 14 male non-contact sports athletes (mean age 14.9 ± 1.1 years) was recruited from competitive athletic clubs and group-matched in age. Using the ProPoint and AntiPoint tasks, sensorimotor and cognitive functions were measured over both immediate (pre- vs. post-training) as well as across multiple time points within a play season. The number and type of head impacts that occurred during the training were counted. The main outcome measure was the change in response time (RT) in the ProPoint and AntiPoint tasks. The immediate (pre- vs. post-training) and longer-term (across a play season) change in RT was analyzed, and the effect of the number and type of head impacts was tested. Thirty athletes with and without exposure to RHI demonstrated a decrease in RT in both tasks immediately after training. Over the play season, both groups showed improvement in sensorimotor function. While the control group also improved in cognitive performance, the soccer players did not, however. Further, the more long headers performed, the slower the improvement in RT over the season. Youth athletes experience an immediate cognitive improvement after training most likely because of physical exercise. Results of this study also suggest an association between exposure to specific RHI (long headers) and lack of improvement in cognitive performance in youth athletes over time.

Detection of Subtle Cognitive Changes after mTBI Using a Novel Tablet-Based Task.

This study examined the potential for novel tablet-based tasks, modeled after eye tracking techniques, to detect subtle sensorimotor and cognitive deficits after mild traumatic brain injury (mTBI). Specifically, we examined whether performance on these tablet-based tasks (Pro-point and Anti-point) was able to correctly categorize concussed versus non-concussed participants, compared with performance on other standardized tests for concussion. Patients admitted to the emergency department with mTBI were tested on the Pro-point and Anti-point tasks, a current standard cognitive screening test (i.e., the Standard Assessment of Concussion [SAC]), and another eye movement-based tablet test, the King-Devick(®) (KD). Within hours after injury, mTBI patients showed significant slowing in response times, compared with both orthopedic and age-matched control groups, in the Pro-point task, demonstrating deficits in sensorimotor function. Mild TBI patients also showed significant slowing, compared with both control groups, on the Anti-point task, even when controlling for sensorimotor slowing, indicating deficits in cognitive function. Performance on the SAC test revealed similar deficits of cognitive function in the mTBI group, compared with the age-matched control group; however, the KD test showed no evidence of cognitive slowing in mTBI patients, compared with either control group. Further, measuring the sensitivity and specificity of these tasks to accurately predict mTBI with receiver operating characteristic analysis indicated that the Anti-point and Pro-point tasks reached excellent levels of accuracy and fared better than current standardized tools for assessment of concussion. Our findings suggest that these rapid tablet-based tasks are able to reliably detect and measure functional impairment in cognitive and sensorimotor control within hours after mTBI. These tasks may provide a more sensitive diagnostic measure for functional deficits that could prove key to earlier detection of concussion, evaluation of interventions, or even prediction of persistent symptoms.

Intact Reflexive but Deficient Voluntary Social Orienting in Autism Spectrum Disorder.

Impairment in social interactions is a primary characteristic of people diagnosed with autism spectrum disorder (ASD). Although these individuals tend to orient less to naturalistic social cues than do typically developing (TD) individuals, laboratory experiments testing social orienting in ASD have been inconclusive, possibly because of a failure to fully isolate reflexive (stimulus-driven) and voluntary (goal-directed) social orienting processes. The purpose of the present study was to separately examine potential reflexive and/or voluntary social orienting differences in individuals with ASD relative to TD controls. Subjects (ages 7-14) with high-functioning ASD and a matched control group completed three gaze cueing tasks on an iPad in which individuals briefly saw a face with averted gaze followed by a target after a variable delay. Two tasks were 100% predictive with either all congruent (target appears in gaze direction) or all incongruent (target appears opposite from gaze direction) trials, respectively. Another task was non-predictive with these same trials (half congruent and half incongruent) intermixed randomly. Response times (RTs) to the target were used to calculate reflexive (incongruent condition RT-congruent condition RT) and voluntary (non-predictive condition RT-predictive condition RT) gaze cueing effects. Subjects also completed two additional non-social orienting tasks (ProPoint and AntiPoint). Subjects with ASD demonstrate intact reflexive but deficient voluntary gaze following. Similar results were found in a separate test of non-social orienting. This suggests problems with using social cues, but only in a goal-directed fashion, in our sample of high-functioning individuals with ASD. Such findings may not only explain inconclusive previous findings but more importantly be critical for understanding social dysfunctions in ASD and for developing future interventions.

Single Canonical Model of Reflexive Memory and Spatial Attention.

Many neurons in the dorsal and ventral visual stream have the property that after a brief visual stimulus presentation in their receptive field, the spiking activity in these neurons persists above their baseline levels for several seconds. This maintained activity is not always correlated with the monkey's task and its origin is unknown. We have previously proposed a simple neural network model, based on shape selective neurons in monkey lateral intraparietal cortex, which predicts the valence and time course of reflexive (bottom-up) spatial attention. In the same simple model, we demonstrate here that passive maintained activity or short-term memory of specific visual events can result without need for an external or top-down modulatory signal. Mutual inhibition and neuronal adaptation play distinct roles in reflexive attention and memory. This modest 4-cell model provides the first simple and unified physiologically plausible mechanism of reflexive spatial attention and passive short-term memory processes.

Anti-saccade error rates as a measure of attentional bias in cocaine dependent subjects.

Cocaine-dependent (CD) subjects show attentional bias toward cocaine-related cues, and this form of cue-reactivity may be predictive of craving and relapse. Attentional bias has previously been assessed by models that present drug-relevant stimuli and measure physiological and behavioral reactivity (often reaction time). Studies of several CNS diseases outside of substance use disorders consistently report anti-saccade deficits, suggesting a compromise in the interplay between higher-order cortical processes in voluntary eye control (i.e., anti-saccades) and reflexive saccades driven more by involuntary midbrain perceptual input (i.e., pro-saccades). Here, we describe a novel attentional-bias task developed by using measurements of saccadic eye movements in the presence of cocaine-specific stimuli, combining previously unique research domains to capitalize on their respective experimental and conceptual strengths. CD subjects (N = 46) and healthy controls (N = 41) were tested on blocks of pro-saccade and anti-saccade trials featuring cocaine and neutral stimuli (pictures). Analyses of eye-movement data indicated (1) greater overall anti-saccade errors in the CD group; (2) greater attentional bias in CD subjects as measured by anti-saccade errors to cocaine-specific (relative to neutral) stimuli; and (3) no differences in pro-saccade error rates. Attentional bias was correlated with scores on the obsessive-compulsive cocaine scale. The results demonstrate increased saliency and differential attentional to cocaine cues by the CD group. The assay provides a sensitive index of saccadic (visual inhibitory) control, a specific index of attentional bias to drug-relevant cues, and preliminary insight into the visual circuitry that may contribute to drug-specific cue reactivity.

Characteristics of Eye-Position Gain Field Populations Determine Geometry of Visual Space.

We have previously demonstrated differences in eye-position spatial maps for anterior inferotemporal cortex (AIT) in the ventral stream and lateral intraparietal cortex (LIP) in the dorsal stream, based on population decoding of gaze angle modulations of neural visual responses (i.e., eye-position gain fields). Here we explore the basis of such spatial encoding differences through modeling of gain field characteristics. We created a population of model neurons, each having a different eye-position gain field. This population was used to reconstruct eye-position visual space using multidimensional scaling. As gain field shapes have never been well-established experimentally, we examined different functions, including planar, sigmoidal, elliptical, hyperbolic, and mixtures of those functions. All functions successfully recovered positions, indicating weak constraints on allowable gain field shapes. We then used a genetic algorithm to modify the characteristics of model gain field populations until the recovered spatial maps closely matched those derived from monkey neurophysiological data in AIT and LIP. The primary differences found between model AIT and LIP gain fields were that AIT gain fields were more foveally dominated. That is, gain fields in AIT operated on smaller spatial scales and smaller dispersions than in LIP. Thus, we show that the geometry of eye-position visual space depends on the population characteristics of gain fields, and that differences in gain field characteristics for different cortical areas may underlie differences in the representation of space.

Oculomotor executive function abnormalities with increased tic severity in Tourette syndrome.

BACKGROUND: Reports conflict as to whether Tourette syndrome (TS) confers deficits in executive function. This study's aim was to evaluate executive function in youths with TS using oculomotor tasks while controlling for confounds of tic severity, age, medication, and severity of comorbid disorders. METHOD: Four saccade tasks requiring the executive functions of response generation, response inhibition, and working memory (prosaccade, antisaccade, 0-back, and 1-back) were administered. Twenty youths with TS and low tic severity (TS-low), nineteen with TS and moderate tic severity (TS-moderate), and 29 typically developing control subjects (Controls) completed the oculomotor tasks. RESULTS: There were small differences across groups in the prosaccade task. Controlling for any small sensorimotor differences, TS-moderate subjects had significantly higher error rates than Controls and TS-low subjects in the 0-back and 1-back tasks. In the 1-back task, these patients also took longer to respond than Controls or TS-low subjects. CONCLUSIONS: In a highly controlled design, the findings demonstrate for the first time that increased tic severity in TS is associated with impaired response inhibition and impaired working memory and that these executive function deficits cannot be accounted for by differences in age, medication or comorbid symptom severity.