Portable eye-tracking as a reliable assessment of oculomotor, cognitive and reaction time function: Normative data for 18-45 year old.

Eye movements measured by high precision eye-tracking technology represent a sensitive, objective, and non-invasive method to probe functional neural pathways. Oculomotor tests (e.g., saccades and smooth pursuit), tests that involve cognitive processing (e.g., antisaccade and predictive saccade), and reaction time tests have increasingly been showing utility in the diagnosis and monitoring of mild traumatic brain injury (mTBI) in research settings. Currently, the adoption of these tests into clinical practice is hampered by a lack of a normative data set. The goal of this study was to construct a normative database to be used as a reference for comparing patients' results. Oculomotor, cognitive, and reaction time tests were administered to male and female volunteers, aged 18-45, who were free of any neurological, vestibular disorders, or other head injuries. Tests were delivered using either a rotatory chair equipped with video-oculography goggles (VOG) or a portable virtual reality-like VOG goggle device with incorporated infrared eye-tracking technology. Statistical analysis revealed no effects of age on test metrics when participant data were divided into pediatric (i.e.,18-21 years, following FDA criteria) and adult (i.e., 21-45 years) groups. Gender (self-reported) had an effect on auditory reaction time, with males being faster than females. Pooled data were used to construct a normative database using 95% reference intervals (RI) with 90% confidence intervals on the upper and lower limits of the RI. The availability of these RIs readily allows clinicians to identify specific metrics that are deficient, therefore aiding in rapid triage, informing and monitoring treatment and/or rehabilitation protocols, and aiding in the return to duty/activity decision. This database is FDA cleared for use in clinical practice (K192186).

Normative data for ages 18-45 for ocular motor and vestibular testing using eye tracking.

OBJECTIVE: Eye tracking technology has been employed in assessing ocular motor and vestibular function following vestibular and neurologic conditions, including traumatic brain injury (TBI). Assessments include tests that provide visual and motion (rotation) stimuli while recording horizontal, vertical, and torsional eye movements. While some of these tests have shown diagnostic promise in previous studies, their use in clinical practice is limited by the lack of normative data. The goal of this study was to construct normative reference ranges to be used when comparing patients' results. METHODS: Optokinetic response, subjective visual horizontal and vertical, and rotation tests were administered to male and female volunteers, ages 18-45, who were free from neurological, vestibular disorders, or other head injuries. Tests were administered using either a rotatory chair or a portable virtual reality-like goggle equipped with video-oculography. RESULTS: Reference values for eye movements in response to different patterns of stimuli were analyzed from 290 to 449 participants. Analysis of gender (self-reported) or age when grouped as pediatric (late adolescent; 18-21 years of age) and adult (21-45 years of age) revealed no effects on the test metrics. Data were pooled and presented for each test metric as the 95% reference interval (RI) with 90% confidence intervals (CI) on upper and lower limits of the RI. CONCLUSIONS: This normative database can serve as a tool to aid in diagnosis, treatment, and/or rehabilitation protocols for vestibular and neurological conditions, including mild TBI (mTBI). This database has been cleared by the FDA for use in clinical practice (K192186). LEVEL OF EVIDENCE: 2b.

Oculomotor, Vestibular, and Reaction Time Effects of Sports-Related Concussion: Video-Oculography in Assessing Sports-Related Concussion.

OBJECTIVE: The purpose of the study was to test the ability of oculomotor, vestibular, and reaction time (OVRT) metrics to serve as a concussion assessment or diagnostic tool for general clinical use. SETTING AND PARTICIPANTS: Patients with concussion were high school-aged athletes clinically diagnosed in a hospital setting with a sports-related concussion (n = 50). Control subjects were previously recruited male and female high school student athletes from 3 local high schools (n = 170). DESIGN: Video-oculography was used to acquire eye movement metrics during OVRT tasks, combined with other measures. Measures were compared between groups, and a subset was incorporated into linear regression models that could serve as indicators of concussion. MEASURES: The OVRT test battery included multiple metrics of saccades, smooth pursuit tracking, nystagmoid movements, vestibular function, and reaction time latencies. RESULTS: Some OVRT metrics were significantly different between groups. Linear regression models distinguished control subjects from concussion subjects with high accuracy. Metrics included changes in smooth pursuit tracking, increased reaction time and reduced saccade velocity in a complex motor task, and decreased optokinetic nystagmus (OKN) gain. In addition, optokinetic gain was reduced and more variable in subjects assessed 22 or more days after injury. CONCLUSION: These results indicate that OVRT tests can be used as a reliable adjunctive tool in the assessment of concussion and that OKN results appear to be associated with a prolonged expression of concussion symptoms.

Patterns of Pupillary Activity During Binocular Disparity Resolution.

This study examined the dynamic coordination between disconjugate, vergence eye movements, and pupil size in 52 normal subjects during binocular disparity stimulation in a virtual reality display. Eye movements and pupil area were sampled with a video-oculographic system at 100 Hz during performance of two tasks, (1) fusion of a binocular disparity step (±1.5° of visual angle in the horizontal plane) and (2) pursuit of a sinusoidally varying binocular disparity stimulus (0.1 Hz, ±2.6° of visual angle in the horizontal plane). Pupil size data were normalized on the basis of responses to homogeneous illumination increments ranging from 0.42 to 65.4 cd/m2. The subjects produced robust vergence eye movements in response to disparity step shifts and high fidelity sinusoidal vergence responses (R 2 relative to stimulus profile: 0.933 ± 0.088), accompanied by changes in pupil area. Trajectory plots of pupil area as a function of vergence angle showed that the pupil area at zero vergence is altered between epochs of linear vergence angle-pupil area relations. Analysis with a modified Gath-Geva clustering algorithm revealed that the dynamic relationship between the ocular vergence angle and pupil size includes two different transient, synkinetic response patterns. The near response pattern, pupil constriction during convergence and pupil dilation during divergence, occurred ~80% of the time across subjects. An opposite, previously undescribed synkinetic pattern was pupil constriction during divergence and pupil dilatation during convergence; it occurred ~15% of the time across subjects. The remainder of the data were epochs of uncorrelated activity. The pupil size intercepts of the synkinetic segments, representing pupil size at initial tropia, had different relationships to vergence angle for the two main coordinated movement types. Hippus-like movements of the pupil could also be accompanied by vergence movements. No pupil coordination was observed during a conjugate pursuit task. In terms of the current dual interaction control model (1), findings suggest that the synkinetic eye and pupillary movements are produced by a dynamic switch of the influence of vergence related information to pupil control, accompanied by a resetting of the pupil aperture size at zero-vergence.

Histological evaluation of a chronically-implanted electrocorticographic electrode grid in a non-human primate.

OBJECTIVE: Electrocorticography (ECoG), used as a neural recording modality for brain-machine interfaces (BMIs), potentially allows for field potentials to be recorded from the surface of the cerebral cortex for long durations without suffering the host-tissue reaction to the extent that it is common with intracortical microelectrodes. Though the stability of signals obtained from chronically implanted ECoG electrodes has begun receiving attention, to date little work has characterized the effects of long-term implantation of ECoG electrodes on underlying cortical tissue. APPROACH: We implanted and recorded from a high-density ECoG electrode grid subdurally over cortical motor areas of a Rhesus macaque for 666 d. MAIN RESULTS: Histological analysis revealed minimal damage to the cortex underneath the implant, though the grid itself was encapsulated in collagenous tissue. We observed macrophages and foreign body giant cells at the tissue-array interface, indicative of a stereotypical foreign body response. Despite this encapsulation, cortical modulation during reaching movements was observed more than 18 months post-implantation. SIGNIFICANCE: These results suggest that ECoG may provide a means by which stable chronic cortical recordings can be obtained with comparatively little tissue damage, facilitating the development of clinically viable BMI systems.

Intrinsic laryngeal muscle activity in response to autonomic nervous system activation.

OBJECTIVES/HYPOTHESIS: To determine whether the intrinsic laryngeal muscles exhibit a response to induced autonomic nervous system (ANS) activation, and to characterize responses that may occur. STUDY DESIGN: Prospective within-subjects study. METHODS: A cold pressor (CP) task was used to trigger a whole-body ANS response in eight vocally normal adult females. Surface electromyography of the trapezius muscle and bipolar hook-wire electromyography of intrinsic laryngeal muscles, as well as cardiovascular measures of heart rate (HR) and blood pressure (systolic [SBP] and diastolic [DBP]), were used to characterize participants' response to CP exposure compared to at-rest baseline. RESULTS: Cardiovascular response to the CP task was confirmed for subjects via HR or blood pressure measures. Post hoc Bonferroni analysis confirmed statistically significant increases in HR (P = .027), SBP (P < .001), and DBP (P < .001) during the CP task as compared to baseline. Concurrent increases in muscle activity were generally observed in trapezius, posterior cricoarytenoid, bilateral thyroarytenoid/lateral cricoarytenoid muscle complex, and bilateral cricothyroid muscles for each subject. Three individuals elected to repeat the CP task and displayed the same pattern of laryngeal response as observed in their first exposure. Results for repeated baseline measures obtained after the cessation of the CP task were compared to pre-CP baseline. Overall laryngeal activation remained even after the cardiovascular response was attenuated. CONCLUSIONS: Results are consistent with the suggestion that human laryngeal muscles exhibit an elevated level of activation concurrent with ANS activation, and endorse the putative link between laryngeal muscle tension and acute stress. Findings are replicable within a subset of three individuals.

An electrocorticographic brain interface in an individual with tetraplegia.

Brain-computer interface (BCI) technology aims to help individuals with disability to control assistive devices and reanimate paralyzed limbs. Our study investigated the feasibility of an electrocorticography (ECoG)-based BCI system in an individual with tetraplegia caused by C4 level spinal cord injury. ECoG signals were recorded with a high-density 32-electrode grid over the hand and arm area of the left sensorimotor cortex. The participant was able to voluntarily activate his sensorimotor cortex using attempted movements, with distinct cortical activity patterns for different segments of the upper limb. Using only brain activity, the participant achieved robust control of 3D cursor movement. The ECoG grid was explanted 28 days post-implantation with no adverse effect. This study demonstrates that ECoG signals recorded from the sensorimotor cortex can be used for real-time device control in paralyzed individuals.

Delay activity of saccade-related neurons in the caudal dentate nucleus of the macaque cerebellum.

The caudal dentate nucleus (DN) in lateral cerebellum is connected with two visual/oculomotor areas of the cerebrum: the frontal eye field and lateral intraparietal cortex. Many neurons in frontal eye field and lateral intraparietal cortex produce "delay activity" between stimulus and response that correlates with processes such as motor planning. Our hypothesis was that caudal DN neurons would have prominent delay activity as well. From lesion studies, we predicted that this activity would be related to self-timing, i.e., the triggering of saccades based on the internal monitoring of time. We recorded from neurons in the caudal DN of monkeys (Macaca mulatta) that made delayed saccades with or without a self-timing requirement. Most (84%) of the caudal DN neurons had delay activity. These neurons conveyed at least three types of information. First, their activity was often correlated, trial by trial, with saccade initiation. Correlations were found more frequently in a task that required self-timing of saccades (53% of neurons) than in a task that did not (27% of neurons). Second, the delay activity was often tuned for saccade direction (in 65% of neurons). This tuning emerged continuously during a trial. Third, the time course of delay activity associated with self-timed saccades differed significantly from that associated with visually guided saccades (in 71% of neurons). A minority of neurons had sensory-related activity. None had presaccadic bursts, in contrast to DN neurons recorded more rostrally. We conclude that caudal DN neurons convey saccade-related delay activity that may contribute to the motor preparation of when and where to move.

Stable online control of an electrocorticographic brain-computer interface using a static decoder.

A brain computer interface (BCI) system was implemented by recording electrocorticographic signals (ECoG) from the motor cortex of a Rhesus macaque. These signals were used to control two-dimensional cursor movements in a standard center-out task, utilizing an optimal linear estimation (OLE) method. We examined the time course over which a monkey could acquire accurate control when operating in a co-adaptive training scheme. Accurate and maintained control was achieved after 4-5 days. We then held the decode parameters constant and observed stable control over the next 28 days. We also investigated the underlying neural strategy employed for control, asking whether neural features that were correlated with a given kinematic output (e.g. velocity in a certain direction) were clustered anatomically, and whether the features were coordinated or conflicting in their contributions to the control signal.

Craniux: a LabVIEW-based modular software framework for brain-machine interface research.

This paper presents "Craniux," an open-access, open-source software framework for brain-machine interface (BMI) research. Developed in LabVIEW, a high-level graphical programming environment, Craniux offers both out-of-the-box functionality and a modular BMI software framework that is easily extendable. Specifically, it allows researchers to take advantage of multiple features inherent to the LabVIEW environment for on-the-fly data visualization, parallel processing, multithreading, and data saving. This paper introduces the basic features and system architecture of Craniux and describes the validation of the system under real-time BMI operation using simulated and real electrocorticographic (ECoG) signals. Our results indicate that Craniux is able to operate consistently in real time, enabling a seamless work flow to achieve brain control of cursor movement. The Craniux software framework is made available to the scientific research community to provide a LabVIEW-based BMI software platform for future BMI research and development.

Bottom-up activation of the vocal motor forebrain by the respiratory brainstem.

Brainstem motor structures send output commands to the periphery and are dynamically modulated by telencephalic inputs. Little is known, however, about ascending brainstem control of forebrain motor structures. Here, we provide the first evidence for bottom-up activation of forebrain motor centers by the respiratory brainstem. We show that, in the avian vocal control system, activation of the brainstem inspiratory nucleus paraambigualus (PAm), a likely homolog of the mammalian rostral ventral respiratory group, can drive neural activity bilaterally in the forebrain vocal control nuclei HVC (used as a proper name) and the robust nucleus of the arcopallium (RA). Furthermore, this activation is abolished by lesions of nucleus uvaeformis (Uva), a thalamic nucleus necessary for song production. We identify a type of bursting neuron within PAm whose activity is correlated, in an Uva dependent manner, to bursting activity in RA, rather than to the respiratory rhythm, and is robustly active during the production of stimulus evoked vocalizations. Because this ascending input results in cross-hemisphere activation, our results suggest a crucial role for the respiratory brainstem in coordinating forebrain motor centers during vocal production.

Hemispheric coordination is necessary for song production in adult birds: implications for a dual role for forebrain nuclei in vocal motor control.

Precise coordination across hemispheres is a critical feature of many complex motor circuits. In the avian song system the robust nucleus of the arcopallium (RA) plays a key role in such coordination. It is simultaneously the major output structure for the descending vocal motor pathway, and it also sends inputs to structures in the brain stem and thalamus that project bilaterally back to the forebrain. Because all birds lack a corpus callosum and the anterior commissure does not interconnect any of the song control nuclei directly, these bottom-up connections form the only pathway that can coordinate activity across hemispheres. In this study, we show that unilateral lesions of RA in adult male zebra finches (Taeniopigia guttata) completely and permanently disrupt the bird's stereotyped song. In contrast, lesions of RA in juvenile birds do not prevent the acquisition of normal song as adults. These results highlight the importance of hemispheric interdependence once the circuit is established but show that one hemisphere is sufficient for complex vocal behavior if this interdependence is prevented during a critical period of development. The ability of birds to sing with a single RA provides the opportunity to test the effect of targeted microlesions in RA without confound of functional compensation from the contralateral RA. We show that microlesions cause significant changes in song temporal structure and implicate RA as playing a major part in the generation of song temporal patterns. These findings implicate a dual role for RA, first as part of the program generator for song and second as part of the circuit that mediates interhemispheric coordination.

Brainstem and forebrain contributions to the generation of learned motor behaviors for song.

Brainstem nuclei have well established roles in generating nonlearned rhythmic behaviors or as output pathways for more complex, forebrain-generated behaviors. However, the role of the brainstem in providing information to the forebrain that is used to initiate or assist in the control of complex behaviors is poorly understood. In this study, we used electrical microstimulation in select nuclei of the avian song system combined with recordings of acoustic and respiratory output to examine how forebrain and brainstem nuclei interact in the generation of learned vocal motor sequences. We found that brief stimulation in the forebrain nuclei HVC (used as a proper name) and RA (robust nucleus of the arcopallium) caused a short-latency truncation of ongoing song syllables, which ultimately led to a cessation of the ongoing motor sequence. Stimulation within the brainstem inspiratory-related nucleus paraambigualis, which receives input from RA and projects back to HVC via the thalamus, caused syllable truncations and interruptions similar to those observed in HVC and RA. In contrast, stimulation in the tracheosyringal portion of the hypoglossal nucleus, which innervates the syrinx (the avian vocal organ) but possesses no known projections back into the song system, did not cause any significant changes in the song motor pattern. These findings suggest that perturbation of premotor activity in any nucleus within the recurrent song system motor network will disrupt the ongoing song motor sequence. Given the anatomical organization of this network, our results are consistent with a model in which the brainstem respiratory nuclei form an integral part of the song motor programming network by providing timing signals to song control nuclei in the forebrain.

Bilateral control and interhemispheric coordination in the avian song motor system.

Birdsong is a complex learned motor behavior controlled by an interconnected network of vocal control nuclei that are present in both cerebral hemispheres. Unilateral lesions of song nuclei in the left or the right hemisphere result in different effects on song structure, suggesting that normal song output results from the activation of two parallel but functionally different motor pathways. Because each syringeal half is innervated primarily by ipsilateral motor structures and activity in both halves is tightly coordinated during singing, motor commands originating from both hemispheres must be tightly coordinated to produce the appropriate vocal output. This coordination occurs despite the absence of direct interhemispheric connections between song control nuclei. In this article, we discuss how motor commands in nucleus HVC, a key forebrain song control region, are coordinated by precisely timed inputs that act to synchronize premotor activity in both hemispheres. Synchronizing inputs are tightly linked to syllable and note onset, which suggests that bilaterally organized circuits in the midbrain or brainstem act in specifying higher-order song features, such as duration, order, and possibly even structure of individual song syllables. The challenge ahead lies in identifying the networks that generate the synchronizing timing inputs and to determine how these inputs specify the motor commands in HVC. Resolving these issues will help us gain a better understanding of how pattern-generating networks in the midbrain/brainstem interface with forebrain circuits to produce complex learned behaviors.