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Introduction: The vergence neural system was stimulated to dissect the afferent and efferent components of symmetrical vergence eye movement step responses. The hypothesis tested was whether the afferent regions of interest would differ from the efferent regions to serve as comparative data for future clinical patient population studies., Methods: Thirty binocularly normal participants participated in an oculomotor symmetrical vergence step block task within a functional MRI experiment compared to a similar sensory task where the participants did not elicit vergence eye movements., Results: For the oculomotor vergence task, functional activation was observed within the parietal eye field, supplemental eye field, frontal eye field, and cerebellar vermis, and activation in these regions was significantly diminished during the sensory task. Differences between the afferent sensory and efferent oculomotor experiments were also observed within the visual cortex., Discussion: Differences between the vergence oculomotor and sensory tasks provide a protocol to delineate the afferent and efferent portion of the vergence neural circuit. Implications with clinical populations and future therapeutic intervention studies are discussed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Author TA declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2025 Sangoi, Hajebrahimi, Gohel, Scheiman and Alvarez.)

Purpose: To describe CONCUSS, a randomized clinical trial (RCT) designed to compare the following: the effectiveness of immediate office-based vergence/accommodative therapy with movement (OBVAM) to delayed OBVAM as treatments for concussion-related convergence insufficiency (CONC-CI) to understand the impact of time (watchful waiting), the effect of OBVAM dosage (12 versus 16 therapy sessions), and to investigate the underlying neuro-mechanisms of OBVAM on CONC-CI participants., Methods: CONCUSS is an RCT indexed on https://clinicaltrials.gov/study/NCT05262361 enrolling 100 participants aged 11-25 years with medically diagnosed concussion, persistent post-concussive symptoms 4-24 weeks post-injury, and symptomatic convergence insufficiency. Participants will receive standard concussion care and will be randomized to either immediate OBVAM or delayed (by six weeks) OBVAM. At the Outcome 1 examination (week 7), clinical assessments of success as determined by changes in the near point of convergence (NPC), positive fusional vergence (PFV), and symptoms will be compared between the two treatment groups. After the Outcome 1 visit, those in the delayed group receive 16 visits of OBVAM, while those in the immediate OBVAM group receive four more therapy visits. Outcome 2 assessment will be used to compare both groups after participants receive 16 sessions of OBVAM. The primary measure is the between-group differences of the composite change in the NPC and PFV at the Outcome 1 visit. Secondary outcome measures include individual clinical measures, objective eye-tracking parameters, and functional brain imaging., Conclusions: Major features of the study design include formal definitions of conditions and outcomes, standardized diagnostic and treatment protocols, a delayed treatment arm, masked outcome examinations, and the incorporation of objective eye movement recording and brain imaging as outcome measures. CONCUSS will establish best practices in the clinical care of CONC-CI. The objective eye movement and brain imaging, correlated with the clinical signs and symptoms, will determine the neuro-mechanisms of OBVAM on CONC-CI., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Alvarez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Convergence Insufficiency (CI) is the most prevalent oculomotor dysfunction of binocular vision that negatively impacts quality of life when performing visual near tasks. Decreased resting-state functional connectivity (RSFC) is reported in the CI participants compared to binocularly normal control participants. Studies report that therapeutic interventions such as office-based vergence and accommodative therapy (OBVAT) can improve CI participants' clinical signs, visual symptoms, and task-related functional activity. However, longitudinal studies investigating the RSFC changes after such treatments in participants with CI have not been conducted. This study aimed to investigate the neural basis of OBVAT using RSFC in CI participants compared to the placebo treatment to understand how OBVAT improves visual function and symptoms., Methods: A total of 51 CI participants between 18 and 35 years of age were included in the study and randomly allocated to receive either 12 one-hour sessions of OBVAT or placebo treatment for 6 to 8 weeks (1 to 2 sessions per week). Resting-state functional magnetic resonance imaging and clinical assessments were evaluated at baseline and outcome for each treatment group. Region of interest (ROI) analysis was conducted in nine ROIs of the oculomotor vergence network, including the following: cerebellar vermis (CV), frontal eye fields (FEF), supplementary eye fields (SEF), parietal eye fields (PEF), and primary visual cortices (V1). Paired t-tests assessed RSFC changes in each group. A linear regression analysis was conducted for significant ROI pairs in the group-level analysis for correlations with clinical measures., Results: Paired t-test results showed increased RSFC in 10 ROI pairs after the OBVAT but not placebo treatment (p < 0.05, false discovery rate corrected). These ROI pairs included the following: Left (L)-SEF-Right (R)-V1, L-SEF-CV, R-SEF-R-PEF, R-SEF-L-V1, R-SEF-R-V1, R-SEF-CV, R-PEF-CV, L-V1-CV, R-V1-CV, and L-V1-R-V1. Significant correlations were observed between the RSFC strength of the R-SEF-R-PEF ROI pair and the following clinical visual function parameters: positive fusional vergence and near point of convergence (p < 0.05)., Conclusion: OBVAT, but not placebo treatment, increased the RSFC in the ROIs of the oculomotor vergence network, which was correlated with the improvements in the clinical measures of the CI participants., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Purpose: To investigate the underlying resting-state functional connectivity (RSFC) of symptomatic convergence insufficiency (CI) compared with binocularly normal controls (BNC) using functional magnetic resonance imaging (fMRI) under The Convergence Insufficiency Neuro‑mechanism Adult Population Study (NCT03593031)., Methods: A total of 101 participants were eligible for this study. After removing datasets with motion artifacts, 49 CI and 47 BNC resting-state functional magnetic resonance imaging datasets were analyzed. CI was diagnosed with the following signs: (1) receded near point of convergence of 6 cm or greater, (2) decreased positive fusional vergence of less than 15∆ or failing Sheard's criteria of twice the near phoria, (3) near phoria of at least 4∆ more exophoric compared with the distance phoria, and (4) symptoms using the Convergence Insufficiency Symptom Survey (score of ≥21). RSFC was assessed using a group-level independent components analysis and dual regression. A behavioral correlation analysis using linear regression method was performed between clinical measures and RSFC using the significant difference between the CI and BNC., Results: On average, a decreased RSFC was observed within the frontoparietal network, default mode network and visual network in patients with CI, compared with the participants with BNC (P < 0.05, corrected for multiple comparisons). The default mode network RSFC strength was significantly correlated with the PFV, near point of convergence, and difference between the horizontal phoria at near compared with far (P < 0.05)., Conclusions: Results support altered RSFC in patients with CI compared with participants with BNC and suggest that these differences in underlying neurophysiology may in part be in connection with the differences in optometric visual function used to diagnose CI.

Through the purposeful stimulation and recording of eye movements, the fundamental characteristics of the underlying neural mechanisms of eye movements can be observed. VisualEyes2020 (VE2020) was developed based on the lack of customizable software-based visual stimulation available for researchers that does not rely on motors or actuators within a traditional haploscope. This new instrument and methodology have been developed for a novel haploscope configuration utilizing both eye tracking and autorefractor systems. Analysis software that enables the synchronized analysis of eye movement and accommodative responses provides vision researchers and clinicians with a reproducible environment and shareable tool. The Vision and Neural Engineering Laboratory's (VNEL) Eye Movement Analysis Program (VEMAP) was established to process recordings produced by VE2020's eye trackers, while the Accommodative Movement Analysis Program (AMAP) was created to process the recording outputs from the corresponding autorefractor system. The VNEL studies three primary stimuli: accommodation (blur-driven changes in the convexity of the intraocular lens), vergence (inward, convergent rotation and outward, divergent rotation of the eyes), and saccades (conjugate eye movements). The VEMAP and AMAP utilize similar data flow processes, manual operator interactions, and interventions where necessary; however, these analysis platforms advance the establishment of an objective software suite that minimizes operator reliance. The utility of a graphical interface and its corresponding algorithms allow for a broad range of visual experiments to be conducted with minimal required prior coding experience from its operator(s).

Background: Traumatic brain injury (TBI)-induced attention deficits are among the most common long-term cognitive consequences in children. Most of the existing studies attempting to understand the neuropathological underpinnings of cognitive and behavioral impairments in TBI have utilized heterogeneous samples and resulted in inconsistent findings. The current research proposed to investigate topological properties of the structural brain network in children with TBI and their relationship with post-TBI attention problems in a more homogeneous subgroup of children who had severe post-TBI attention deficits (TBI-A). Materials and Methods: A total of 31 children with TBI-A and 35 group-matched controls were involved in the study. Diffusion tensor imaging-based probabilistic tractography and graph theoretical techniques were used to construct the structural brain network in each subject. Network topological properties were calculated in both global level and regional (nodal) level. Between-group comparisons among the topological network measures and analyses for searching brain-behavioral were all corrected for multiple comparisons using Bonferroni method. Results: Compared with controls, the TBI-A group showed significantly higher nodal local efficiency and nodal clustering coefficient in left inferior frontal gyrus and right transverse temporal gyrus, whereas significantly lower nodal clustering coefficient in left supramarginal gyrus and lower nodal local efficiency in left parahippocampal gyrus. The temporal lobe topological alterations were significantly associated with the post-TBI inattentive and hyperactive symptoms in the TBI-A group. Conclusion: The results suggest that TBI-related structural re-modularity in the white matter subnetworks associated with temporal lobe may play a critical role in the onset of severe post-TBI attention deficits in children. These findings provide valuable input for understanding the neurobiological substrates of post-TBI attention deficits, and have the potential to serve as quantitatively measurable criteria guiding the development of more timely and tailored strategies for diagnoses and treatments to the affected individuals. Impact statement This study provides a new insight into the neurobiological substrates associated with post-traumatic brain injury attention deficits (TBI-A) in children, by evaluating topological alterations of the structural brain network. The results demonstrated that relative to group-matched controls, the children with TBI-A had significantly altered nodal local efficiency and nodal clustering coefficient in temporal lobe, which strongly linked to elevated inattentive and hyperactive symptoms in the TBI-A group. These findings suggested that white matter structural re-modularity in subnetworks associated with temporal lobe may serve as quantitatively measurable biomarkers for early prediction and diagnosis of post-TBI attention deficits in children.

Purpose: The purpose of this study was to compare changes in phoria adaptation between young adult binocularly normal controls (BNCs) and participants with symptomatic convergence insufficiency (CI), who were randomized to either office-based vergence accommodative therapy (OBVAT) or office-based placebo therapy (OBPT)., Methods: In the double-masked randomized clinical trial, 50 BNC and 50 CI participants were randomized to the following therapeutic interventions: OBVAT or OBPT with home reinforcement for 12 one-hour office sessions. A 6∆ base-out and 6∆ base-in phoria adaptation experiment at near (40 cm) was conducted using the flashed Maddox rod technique at baseline and at outcome. Measurements included the rate and the magnitude of phoria adaptation., Results: At baseline, BNC and CI participants had significantly different rates and magnitudes of base-in and base-out phoria adaptation (P < 0.001). When comparing the outcome to baseline measurements, significant main effect differences in longitudinal measurements were observed for the magnitude and the rate of phoria adaptation for both base-out and base-in experiments (P < 0.05). For the magnitude and rate of phoria adaptation, post hoc analyses using paired t-tests revealed that the CI group administered the OBVAT intervention exhibited a significant increase in the magnitude and rate of phoria adaptation compared to baseline for both base-in and base-out phoria adaptation (P < 0.01) but not for those administered OBPT., Conclusions: Phoria adaptation is significantly different at baseline between those with normal binocular vision and symptomatic CI participants. OBVAT significantly improves the rate and magnitude of both base-out and base-in phoria adaptation at near compared to OBPT. Results have clinical implications for new therapeutic interventions.

This study sought to test the hypothesis that significant differences would be observed in clinical measures, symptoms, and objective assessments of vergence eye movements between children with typically developing convergence insufficiency (TYP-CI) and children with persistent post-concussion symptoms with convergence insufficiency (PPCS-CI). Data from age-matched binocularly normal controls (BNC) were used for comparison. Data from three groups of children 11 to 17 years of age are presented: BNC (N = 11), TYP-CI (N = 10), and PPCS-CI (N = 15). Clinical measures of vergence, accommodation, and symptom severity were collected. Symmetrical 4° disparity vergence eye movements were quantified with an eye tracker integrated into a head-mounted display (Oculus DK2). Peak velocity and final response amplitude of convergence and divergence eye movement responses were assessed. The mean near point of convergence (break) was more receded (worse), the amplitude of accommodation more deficient, and convergent and divergent peak velocities slower in the PPCS-CI group compared with the TYP-CI and BNC groups. These results suggest that PPCS-CI may be a different clinical entity than TYP-CI. Hence, more research is warranted to determine whether the therapeutic interventions that are effective for TYP-CI can also be used for PPCS-CI populations., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Previous studies have shown that the slow, or fusion sustaining, component of disparity vergence contains oscillatory behavior as would be expected if fusion is sustained by visual feedback. This study extends the examination of this behavior to a wider range of frequencies and a larger number of subjects., Methods: Disparity vergence responses to symmetrical 4.0 deg step changes in target position were recorded in 20 subjects. Approximately three seconds of the late component of each response were isolated using interactive graphics and the frequency spectrum calculated. Peaks in these spectra associated with oscillatory behavior were identified and examined., Results: All subjects exhibited oscillatory behavior with fundamental frequencies ranging between 0.37 and 0.55 Hz; much lower than those identified in the earlier study. All responses showed significant higher frequency components. The relationship between higher frequency components and the fundamental frequency suggest may be harmonics. A correlation was found across subjects between the amplitude of the fundamental frequency and the maximum velocity of the fusion initiating component probably due to the gain of shared neural pathways., Conclusion: Low frequency oscillatory behavior was found in all subjects adding support that the slow, or fusion sustaining, component is mediated by a feedback control.

Significance: This study establishes normative data and a testing procedure for the oculomotor assessment tool. The oculomotor assessment tool standardizes visual targets for the Vestibular/OculoMotor Screening assessment and provides additional metrics that may aid in the differentiation between those with normal and those with abnormal oculomotor function potentially caused by a concussion., Purpose: This study aimed to assess the oculomotor endurance of healthy participants with no self-reported history of concussions using the oculomotor assessment tool., Methods: Healthy participants (n = 376, average age of 20.4 years, range of 11 to 34 years, with no self-reported history of concussions) were recruited to perform the following three tasks for 60 seconds each: (1) horizontal saccades, (2) vertical saccades, and (3) vergence jumps. The participants were instructed to alternate visual fixation between two targets for each of the tasks as fast as they could without overshooting or undershooting the visual target. The differences in the number of eye movements between the initial and latter 30 seconds of the 1-minute test were analyzed., Results: A statistical difference (P < .001) was observed in the number of eye movements for all three tasks (horizontal saccades [70 ± 15 for initial 30 seconds, 63 ± 13 for latter 30 seconds], vertical saccades [68 ± 14, 63 ± 13], and vergence jumps [43 ± 11, 39 ± 10]) between the initial and latter 30 seconds. No significant differences were identified in the number of eye movements or the change in eye movements between the initial and latter 30 seconds based on sex., Conclusions: These results establish a normative database for various eye movements. These data could potentially be used to compare different patient populations who have binocular endurance dysfunctions potentially due to traumatic brain injury, such as patients with concussion(s)., Competing Interests: Conflict of Interest Disclosure: New Jersey Institute of Technology has licensed the right to manufacture and sell the OculoMotor Assessment Tool device to Gulden Ophthalmics on behalf of the authors CY and TLA., (Copyright © 2021 American Academy of Optometry.)

Convergence insufficiency (CI) is the most common binocular vision problem, associated with blurred/double vision, headaches, and sore eyes that are exacerbated when doing prolonged near work, such as reading. The Convergence Insufficiency Neuro-mechanism Adult Population Study (NCT03593031) investigates the mechanistic neural differences between 50 binocularly normal controls (BNC) and 50 symptomatic CI participants by examining the fast and slow fusional disparity vergence systems. The fast fusional system is preprogrammed and is assessed with convergence peak velocity. The slow fusional system optimizes vergence effort and is assessed by measuring the phoria adaptation magnitude and rate. For the fast fusional system, significant differences are observed between the BNC and CI groups for convergence peak velocity, final position amplitude, and functional imaging activity within the secondary visual cortex, right cuneus, and oculomotor vermis. For the slow fusional system, the phoria adaptation magnitude and rate, and the medial cuneus functional activity, are significantly different between the groups. Significant correlations are observed between vergence peak velocity and right cuneus functional activity (p = 0.002) and the rate of phoria adaptation and medial cuneus functional activity (p = 0.02). These results map the brain-behavior of vergence. Future therapeutic interventions may consider implementing procedures that increase cuneus activity for this debilitating disorder.

Cerebrovascular reactivity (CVR) is routinely measured as a predictor of stroke in people with a high risk of ischemic attack. Neuroimaging techniques such as emission tomography, magnetic resonance imaging, and transcranial doppler are frequently used to measure CVR even though each technique has its limitations. Functional near-infrared spectroscopy (fNIRS), also based on the principle of neurovascular coupling, is relatively inexpensive, portable, and allows for the quantification of oxy- and deoxy-hemoglobin concentration changes at a high temporal resolution. This study examines the relationship between age and CVR using fNIRS in 45 young healthy adult participants aged 18-41 years (6 females, 26.64 ± 5.49 years) performing a simple breath holding task. Eighteen of the 45 participants were scanned again after a week to evaluate the feasibility of fNIRS in reliably measuring CVR. Results indicate (a) a negative relationship between age and hemodynamic measures of breath holding task in the sensorimotor cortex of 45 individuals and (b) widespread positive coactivation within medial sensorimotor regions and between medial sensorimotor regions with supplementary motor area and prefrontal cortex during breath holding with increasing age. The intraclass correlation coefficient (ICC) indicated only a low to fair/good reliability of the breath hold hemodynamic measures from sensorimotor and prefrontal cortices. However, the average hemodynamic response to breath holding from the two sessions were found to be temporally and spatially in correspondence. Future improvements in the sensitivity and reliability of fNIRS metrics could facilitate fNIRS-based assessment of cerebrovascular function as a potential clinical tool.

The corpus callosum serves as a crucial organization for understanding the information integration between the two hemispheres. Our previous study explored the functional connectivity between the corpus callosum and white-matter functional networks (WM-FNs), but the corresponding physical connectivity remains unknown. The current study uses the resting-state fMRI of Human Connectome Project data to identify ten WM-FNs in 108 healthy subjects, and then independently maps the structural and functional connectivity between the corpus callosum and above WM-FNs using the diffusion tensor images (DTI) tractography and resting-state functional connectivity (RSFC). Our results demonstrated that the structural and functional connectivity between the human corpus callosum and WM-FNs have the following high overall correspondence: orbitofrontal WM-FN, DTI map = 89% and RSFC map = 92%; sensorimotor middle WM-FN, DTI map = 47% and RSFC map = 77%; deep WM-FN, DTI map = 50% and RSFC map = 79%; posterior corona radiata WM-FN, DTI map = 82% and RSFC map = 73%. These findings reinforce the notion that the corpus callosum has unique spatial distribution patterns connecting to distinct WM-FNs. However, important differences between the structural and functional connectivity mapping results were also observed, which demonstrated a synergy between DTI tractography and RSFC toward better understanding the information integration of primary and higher-order functional systems in the human brain., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020. Published by Elsevier Inc.)

Significance: Deficits of disparity divergence found with objective eye movement recordings may not be apparent with standard clinical measures of negative fusional vergence (NFV) in children with symptomatic convergence insufficiency., Purpose: This study aimed to determine whether NFV is normal in untreated children with symptomatic convergence insufficiency and whether NFV improves after vergence/accommodative therapy., Methods: This secondary analysis of NFV measures before and after office-based vergence/accommodative therapy reports changes in (1) objective eye movement recording responses to 4° disparity divergence step stimuli from 12 children with symptomatic convergence insufficiency compared with 10 children with normal binocular vision (NBV) and (2) clinical NFV measures in 580 children successfully treated in three Convergence Insufficiency Treatment Trial studies., Results: At baseline, the Convergence Insufficiency Treatment Trial cohort's mean NFV break (14.6 ± 4.8Δ) and recovery (10.6 ± 4.2Δ) values were significantly greater (P < .001) than normative values. The post-therapy mean improvements for blur, break, and recovery of 5.2, 7.2, and 1.3Δ, respectively, were statistically significant (P < .0001). Mean pre-therapy responses to 4° disparity divergence step stimuli were worse in the convergence insufficiency group compared with the NBV group for peak velocity (P < .001), time to peak velocity (P = .01), and response amplitude (P < .001). After therapy, the convergence insufficiency group showed statistically significant improvements in mean peak velocity (11.63°/s; 95% confidence interval [CI], 6.6 to 16.62°/s), time to peak velocity (-0.12 seconds; 95% CI, -0.19 to -0.05 seconds), and response amplitude (1.47°; 95% CI, 0.83 to 2.11°), with measures no longer statistically different from the NBV cohort (P > .05)., Conclusions: Despite clinical NFV measurements that seem greater than normal, children with symptomatic convergence insufficiency may have deficient NFV when measured with objective eye movement recordings. Both objective and clinical measures of NFV can be improved with vergence/accommodative therapy., Competing Interests: Conflict of Interest Disclosure: None of the authors have reported a financial conflict of interest., (Copyright © 2020 American Academy of Optometry.)

Significance: These data confirm the effectiveness of office-based vergence/accommodative therapy for improving the near point of convergence and positive fusional vergence in young adults with symptomatic convergence insufficiency within a double-masked longitudinal randomized clinical trial., Purpose: This study aimed to report changes in clinical signs and symptoms of convergence insufficiency from a randomized clinical trial evaluating the effectiveness of office-based vergence/accommodative therapy for young adults with symptomatic convergence insufficiency., Methods: In this double-masked, randomized clinical trial, convergence insufficiency patients (n = 50; average age, 21 ± 3 years; range, 18 to 32 years) were randomized to either office-based vergence/accommodative therapy or office-based placebo therapy. Improvements in (1) near point of convergence, (2) positive fusional vergence, and (3) self-reported symptoms (Convergence Insufficiency Symptom Survey [CISS] score) were evaluated after twelve 1-hour sessions of treatment within the office comparing the results from the vergence/accommodative therapy and the placebo therapy groups., Results: The mean near point of convergence improved by 6.0 and 3.1 cm in the vergence/accommodative and placebo therapy groups, respectively (mean difference of -2.9 cm; 95% confidence interval [CI], -4.6 to -1.0 cm; P < .01). The mean positive fusional vergence increased by 17.3 and 7.4Δ in the vergence/accommodative and placebo therapy groups, respectively (mean difference of 9.9Δ; 95% CI, 4.9 to 16.0Δ; P < .001). The mean CISS score improved by 12.4 and 10.1 points in the vergence/accommodative and placebo therapy groups, respectively (mean difference of 2.3 points; 95% CI, -8.3 to +4.6 points; P = .56)., Conclusions: Our results demonstrate that office-based vergence/accommodative therapy is effective for improving the near point of convergence and positive fusional vergence in young adults with symptomatic convergence insufficiency. However, given that both treatment groups had a similar reduction in self-reported symptoms, we recommend that the CISS be revised if it is to be used as an outcome measure in future studies of convergence insufficiency.

This study was designed to identify the neural substrates activated during a phoria adaptation task using functional magnetic resonance imaging (MRI) in young adults with normal binocular vision and to test the repeatability of the fMRI measurements for this protocol. The phoria adaptation task consisted of a block protocol of 90 seconds of near visual crossed fixation followed by 90 seconds of far visual uncrossed fixation, repeated three times; the data were collected during two different experimental sessions. Results showed that the oculomotor vermis, cuneus, and primary visual cortex had the greatest functional activity within the regions of interest studied when stimulated by the phoria adaptation task. The oculomotor vermis functional activity had an intraclass correlation coefficient (ICC) of 0.3, whereas the bilateral cuneus and primary visual cortex had good ICC results of greater than 0.6. These results suggest that the sustained visual fixation task described within this study reliably activates the neural substrates of phoria adaptation. This protocol establishes a methodology that can be used in future longitudinal studies investigating therapeutic interventions that may modify phoria adaptation.

Significance: This study establishes normative data for objective outcome measures of vergence and saccade eye movements for the pediatric population. These data should facilitate future clinical trial design., Purpose: This study was designed to establish normative data for objective measures of disparity vergence and saccades in children between the ages 9 and 17 years using an objective binocular eye movement tracking system., Methods: Participants (aged 9 to 17 years) had a vision examination including refraction, accommodative, and binocular vision testing. Eligibility criteria included 20/25 visual acuity with best correction, normal accommodation, and binocular vision. The ISCAN RK-826PCI binocular tracking system (ISCAN, Woburn, MA) was used to objectively record horizontal, symmetrical disparity vergence, and saccadic eye movements. Parameters assessed included peak velocity, time to peak velocity, latency, and response amplitude for both disparity vergence and saccades., Results: One hundred eighteen participants were recruited (54.94% female; mean age, 13.5 years), and 77.1% (91/118) of the participants completed the assessment with usable data. A sample of the normative data included peak velocity (°/s), which had a mean ± standard deviation of 25.4 ± 2.9, 22.0 ± 3.0, 225 ± 16.7, and 332.5 ± 20.5 for 4° convergence, 4° divergence, 5° saccades, and 10° saccades, respectively. The mean ± standard deviation for the latency (seconds) measures were 0.28 ± 0.1, 0.28 ± 0.16, 0.23 ± 0.05, and 0.23 ± 0.05 for 4° convergence, 4° divergence, 5° saccades, and 10° saccades, respectively., Conclusions: Normative data enable researchers to have benchmark results for comparison with patient populations with binocular dysfunction. These objective disparity vergence measures can serve as outcome measures in future clinical trials to assess the effectiveness of therapeutic interventions by determining whether post-treatment results are similar to normal data.

The corpus callosum is the commissural bridge of white-matter bundles important for the human brain functions. Previous studies have analyzed the structural links between cortical gray-matter networks and subregions of corpus callosum. While meaningful white-matter functional networks (WM-FNs) were recently reported, how these networks functionally link with distinct subregions of corpus callosum remained unknown. The current study used resting-state functional magnetic resonance imaging of the Human Connectome Project test-retest data to identify 10 cerebral WM-FNs in 119 healthy subjects and then parcellated the corpus callosum into distinct subregions based on the functional connectivity between each callosal voxel and above networks. Our results demonstrated the reproducible identification of WM-FNs and their links with known gray-matter functional networks across two runs. Furthermore, we identified reliably parcellated subregions of the corpus callosum, which might be involved in primary and higher order functional systems by functionally connecting with WM-FNs. The current study extended our knowledge about the white-matter functional signals to the intrinsic functional organization of human corpus callosum, which could help researchers understand the neural substrates underlying normal interhemispheric functional connectivity as well as dysfunctions in various mental disorders., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Vergence eye movements are the inward and outward rotation of the eyes responsible for binocular coordination. While studies have mapped and investigated the neural substrates of vergence, it is not well understood whether vergence eye movements evoke the blood oxygen level-dependent signal reliably in separate experimental visits. The test-retest reliability of stimulus-induced vergence eye movement tasks during a functional magnetic resonance imaging (fMRI) experiment is important for future randomized clinical trials (RCTs). In this study, we established region of interest (ROI) masks for the vergence neural circuit. Twenty-seven binocularly normal young adults participated in two functional imaging sessions measured on different days on the same 3T Siemens scanner. The fMRI experiments used a block design of sustained visual fixation and rest blocks interleaved between task blocks that stimulated eight or four vergence eye movements. The test-retest reliability of task-activation was assessed using the intraclass correlation coefficient (ICC), and that of spatial extent was assessed using the Dice coefficient. Functional activation during the vergence eye movement task of eight movements compared to rest was repeatable within the primary visual cortex (ICC = 0.8), parietal eye fields (ICC = 0.6), supplementary eye field (ICC = 0.5), frontal eye fields (ICC = 0.5), and oculomotor vermis (ICC = 0.6). The results demonstrate significant test-retest reliability in the ROIs of the vergence neural substrates for functional activation magnitude and spatial extent using the stimulus protocol of a task block stimulating eight vergence eye movements compared to sustained fixation. These ROIs can be used in future longitudinal RCTs to study patient populations with vergence dysfunctions.

Background . Neuroimaging studies of spinal cord injury (SCI) have mostly examined the functional organization of the cortex, with only limited focus on the subcortical substrates of the injury. However, thalamus is an important modulator and sensory relay that requires investigation at a subnuclei level to gain insight into the neuroplasticity following SCI. Objective . To use resting-state functional magnetic resonance imaging to examine the functional connectivity (FC) of thalamic subnuclei in complete SCI patients. Methods . A seed-based connectivity analysis was applied for 3 thalamic subnuclei: pulvinar, mediodorsal, and ventrolateral nucleus in each hemisphere. A nonparametric 2-sample t test with permutations was applied for each of the 6 thalamic seeds to compute FC differences between 22 healthy controls and 19 complete SCI patients with paraplegia. Results . Connectivity analysis showed a decrease in the FC of the bilateral mediodorsal nucleus with right superior temporal gyrus and anterior cingulate cortex in the SCI group. Similarly, the left ventrolateral nucleus exhibited decreased FC with left superior temporal gyrus in SCI group. In contrast, left pulvinar nucleus demonstrated an increase in FC with left inferior frontal gyrus and left inferior parietal lobule in SCI group. Our findings also indicate a negative relationship between postinjury durations and thalamic FC to regions of sensorimotor and visual cortices, where longer postinjury durations (~12 months) is associated with higher negative connectivity between these regions. Conclusion . This study provides evidence for reorganization in the thalamocortical connections known to be involved in multisensory integration and affective processing, with possible implications in the generation of sensory abnormalities after SCI.

Purpose : To describe the design and methodology of the Convergence Insufficiency Neuro-mechanism in Adult Population Study (CINAPS), the first randomized clinical trial (RCT) studying young adults with symptomatic convergence insufficiency (CI) using a combination of traditional clinical tests, objective eye movement recordings, and functional brain activities as outcome measures. Methods : In this double-masked RCT, binocularly normal controls (BNC) (N = 50) and CI patients (N = 50) are randomized into office-based vergence/accommodative therapy (OBVAT) or office-based placebo therapy (OBPT). Outcome measures included clinical signs and symptoms, phoria adaptation, forced fixation disparity curves, binocular rivalry, vergence and saccadic objective eye movements, and task-induced functional brain activities. This study is registered on ClinicalTrials.gov NCT03593031. Results : No significant baseline differences are observed between the BNC ( p > .4) or CI ( p > .3) participants assigned to OBVAT or OBPT for age, near point of convergence (NPC), positive fusional vergence (PFV), phoria at distance and near, amplitude of accommodation, or the Convergence Insufficiency Symptom Survey (CISS). Significant differences are observed between the CI and BNC cohorts at baseline measurements for NPC, PFV, difference in phoria from far to near, amplitude of accommodation, and CISS ( p < .001). For the CI patients, 26% had a comorbidity of accommodation insufficiency, and 16% self-reported ADHD. Conclusion : Features of the study design include the following: standardized diagnostic and office-based therapeutic intervention, placebo treatment arm, masked clinical outcome examinations, objective eye movement recordings, functional imaging, phoria adaptation, fixation disparity curves and binocular rivalry measurements.

Functional near-infrared spectroscopy (fNIRS), an imaging tool that utilizes infrared light to measure changes within the concentration of oxygenated (HbO) and deoxygenated (HbR) hemoglobin, holds promise to study functional activity from motor, visual, and memory cortical regions using stimulus-induced tasks. This study investigated the reliability for fNIRS to examine cortical activations within the frontal eye fields (FEF) while initiating vergence eye movements, the inward and outward rotation of the eyes. FNIRS data were collected from twenty participants with normal binocular vision while performing vergence eye movements compared to sustained gaze fixation within a block design during two different sessions. Reliability of the experimental protocol was assessed using the intraclass correlation coefficient (ICC). The ICC values ranged from 0.6 to 0.7 for measuring the HbO activation within the vicinity of the FEF. A frequency power spectrum analysis revealed two predominant frequencies within the functional activation signals from the FEF. One high-intensity signal was present at 0.029 Hz, centering around the block design frequency. The peak-intensity signal was observed between 0.012 and 0.018 Hz where this very low-frequency oscillation (VLFO) was hypothesized to be generated by the macrovasculature present near the FEF and should be avoided as a block design frequency in future fNIRS studies to avoid false positive results.

Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent and heterogeneous neurodevelopmental disorder, which is diagnosed using subjective symptom reports. Machine learning classifiers have been utilized to assist in the development of neuroimaging-based biomarkers for objective diagnosis of ADHD. However, existing basic model-based studies in ADHD report suboptimal classification performances and inconclusive results, mainly due to the limited flexibility for each type of basic classifier to appropriately handle multi-dimensional source features with varying properties. This study applied ensemble learning techniques (ELTs), a meta-algorithm that combine several basic machine learning models into one predictive model in order to decrease variance, bias, or improve predictions, in multimodal neuroimaging data collected from 72 young adults, including 36 probands (18 remitters and 18 persisters of childhood ADHD) and 36 group-matched controls. All currently available optimization strategies for ELTs (i.e., voting, bagging, boosting and stacking techniques) were tested in a pool of semifinal classification results generated by seven basic classifiers. The high-dimensional neuroimaging features for classification included regional cortical gray matter (GM) thickness and surface area, GM volume of subcortical structures, volume and fractional anisotropy of major white matter fiber tracts, pair-wise regional connectivity and global/nodal topological properties of the functional brain network for cue-evoked attention process. As a result, the bagging-based ELT with the base model of support vector machine achieved the best results, with significant improvement of the area under the receiver of operating characteristic curve (0.89 for ADHD vs. controls and 0.9 for ADHD persisters vs. remitters). Features of nodal efficiency in right inferior frontal gyrus, right middle frontal (MFG)-inferior parietal (IPL) functional connectivity, and right amygdala volume significantly contributed to accurate discrimination between ADHD probands and controls; higher nodal efficiency of right MFG greatly contributed to inattentive and hyperactive/impulsive symptom remission, while higher right MFG-IPL functional connectivity strongly linked to symptom persistence in adults with childhood ADHD. Considering their improved robustness than the commonly implemented basic classifiers, findings suggest that ELTs may have the potential to identify more reliable neurobiological markers for neurodevelopmental disorders., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

This study sought to investigate whether stimulation to the fovea or the parafovea with different color combinations influenced the temporal and dynamic features of 4° disparity vergence step responses. Twelve unique types of stimuli were displayed within a haploscope presented along the participant's midsagittal plane. Vergence eye movement responses from fifteen naïve participants were recorded using video-based infrared eye tracking instrumentation. Latency and peak velocity from left and right eye movement responses were quantified. Results show that the type of stimulus projection (foveal versus parafoveal) significantly ( p <0.001) influences the vergence response latency but did not impact peak velocity. Vergence responses to eccentric circles with 6° eccentricity targeting the parafovea resulted in a significantly faster response latency compared to vergence responses to a cross with 2° eccentricity stimuli targeting the fovea. Results have implications for the stimulus design of a variety of applications from virtual reality to vision therapy interventions., Competing Interests: Ethics and Conflict of Interest The author(s) declare(s) that the contents of the article are in agreement with the ethics described by the Journal and that there is no conflict of interest regarding the publication of this paper.

The stereotypical vergence response to a step stimulus consists of two dynamic components: a high velocity fusion initiating component followed by a slower component that may mediate sustained fusion. The initial component has been well-studied and is thought to be controlled by an open-loop mechanism. Less is known about the slow, or fusion sustaining component except that it must be feedback controlled to achieve the positional precision of sustained fusion. Given the delays in disparity vergence control, a feedback control system is likely to exhibit oscillatory behavior. Vergence responses to 4 deg step changes in target position were recorded in eight subjects. The slow component of each response was isolated manually using interactive graphics and the frequency spectrum determined. The frequency spectra of all isolated slow vergence movements showed a large low frequency peak between 1.0 and 2.0 Hz and one or more higher frequency components. The higher frequency components were found to be harmonics of the low frequency oscillation. A feedback model of the slow component was developed consisting of a time delay, an integral/derivative controller and an oculomotor plant based on Robinson's model. Model simulations showed that a direction dependent asymmetry in the derivative element was primarily responsible for the higher frequency harmonic components. Simulations also showed that the base frequencies are primarily dependent on the time delay in the feedback control system. The fact that oscillatory behavior was found in all subjects provides strong support that the slow, fusion sustaining component is mediated by a feedback system., Competing Interests: Ethics and Conflict of Interest The authors declare that the contents of the article are in agreement with the ethics described by the Journal and that there is no conflict of interest regarding the publication of this paper.

This study investigates the underlying physiological mechanisms that may lead to improved outcomes for symptomatic convergence insufficiency (Cl) patients after 12 weeks of office-based vergence/accommodation therapy (OBVAT) by evaluating the change in the main sequence of vergence and saccadic eye movements. In this prospective trial, 12 participants with symptomatic Cl were recruited and treated with 12 weeks of OBVAT. Outcome measures included the objective assessment of the following: peak velocity, time to peak velocity, latency, response amplitude, and clinical changes in the near point of convergence (NPC), positive fusional vergence (PFV) and symptoms via the Convergence Insufficiency Symptom Survey (CISS). Ten of the twelve participants (83%) were categorized as "successful" and two were "improved" based on pre-determined published criteria (CISS, NPC, PFV). There were statistically significant changes in peak velocity, time to peak velocity, and response amplitude for both 4° and 6° symmetrical convergence and divergence eye movements. There was a significant change in the main sequence ratio for convergence post-OBVAT compared to baseline measurements (P=0.007) but not for divergence or saccadic responses. Phasic/step vergence movements adjust the underlying neural control of convergence and are critical within a vision therapy program for Cl patients., Competing Interests: Ethics and Conflict of Interest The author(s) declare(s) that the contents of the article are in agreement with the ethics described by the Journal and that there is no conflict of interest regarding the publication of this paper.

Background: Concussions are one of the most common head injuries acquired within the pediatric population. While sport-related concussions are well documented, concussions within other aspects of a child's life are not as well researched. The purpose of this study is to examine the incidence of a large pediatric concussion population in a broad range of daily activities., Methods: Patients' gender and nature of injury were extracted from 1408 medical records of patients who were diagnosed with a concussion at Saint Peter's Sports Medicine Institute. Statistical analyses were conducted for activities and environmental settings using chi-squared tests., Results: Concussions were most prevalent in organized sports (53.3%), followed by injuries within the following settings: school (16.5%), recreational (6.7%), motor vehicle collisions (6.6%), home (5.5%), and other (11.3%). Specifically, soccer (12.9%), school physical education (PE) class (10.6%), and football (9.8%) subcategories recorded the most incidences of concussion. For the PE class cohort ( n = 149), significantly more females were diagnosed with a concussion compared to males ( p < 0.001)., Conclusions: PE-related concussions had the second highest incidence rate after organized sports. A significant gender difference was observed in PE class. Awareness about concussions and methods to reduce the risk of concussion is suggested for PE classes.

The Vergence Endurance Test (VET), a quantitative and objective eye movement assessment, was utilized to differentiate control from concussed subjects. Nine symptomatic concussed (2 male; 30.8 ± 11 years) and 9 asymptomatic control (6 male; 25.1 ± 1.4 years) subjects participated in the VET. Symmetrical disparity vergence step targets were presented with and without visual distractors. A masked data analyst measured vergence latency, peak velocity, response amplitude, settling time, and the percentage of trials which contained blinks. A Binocular Precision Index (BPI) and a Binocular Accuracy Index (BAI) were calculated to quantify the changes that occur in the vergence parameters over the duration of the VET. Convergence and divergence peak velocity, divergence response amplitude, the percentage of trials that contained blinks during the transient portion of the response, and the BAI were significantly ( p  < 0.05) different between the concussed and the control subjects. For these parameters, the BAI and divergence response amplitude yielded the greatest accuracy, 78%, in their ability to discriminate between the groups. The VET objectively measures the change in vergence performance over time and shows promise as a method to diagnose a concussion. Future studies will determine whether the VET can be used to assess the extent of natural recovery and the effectiveness of therapeutic interventions.

Office-Based Vergence/Accommodative Therapy (OBVAT) is an effective treatment for convergence insufficiency (CI) and remediates symptoms in about 75% of patients. Hence, the study of CI patients can serve as a systems-level model to understand the neural mechanisms evoked from rehabilitation. Symptomatic young adult CI patients (N=25) participated in 12 hours of OBVAT and were compared to 25 binocularly normal controls (BNC) using unpaired t-tests. CI patients have significantly lower near point of convergence and positive fusional vergence and were more symptomatic compared to BNC (p<; 0.0001). Using paired t-tests, significant differences (p<; 0.0001) were observed between CI patients' baseline and post-OBVAT measurements where the near point of convergence decreased, positive fusional vergence increased, and the results from the Convergence Insufficiency Symptom Survey (CISS) decreased. Using paired t-tests, the mean beta weights of the functional activity significantly increased for the frontal eye fields (p<; 0.01) and the oculomotor vermis (p<; 0.05) for CI patients post-OBVAT compared to baseline measurements. These data demonstrate that OBVAT increases functional activity within the brain and improves clinical function and visual symptoms in CI patients.

Significance: This first report of the use of objective measures of disparity vergence as outcome measures for symptomatic convergence insufficiency in children provides additional information that is not accessible with clinical tests. The study results also demonstrate that objective measures of vergence could be used in future randomized clinical trials of binocular vision disorders with children., Purpose: This study was designed to evaluate changes in objective measures of disparity vergence after office-based vergence/accommodative therapy (OBVAT) for convergence insufficiency in children 12 to 17 years old., Methods: In this prospective trial, we recruited 10 participants with normal binocular vision and 12 with convergence insufficiency. All participants with convergence insufficiency were treated with 12 weeks of OBVAT. The primary outcome measure was average peak velocity for 4° symmetrical convergence steps. Other objective outcome measures of disparity vergence included time to peak velocity, latency, and accuracy. Changes in clinical measures (near point of convergence, positive fusional vergence at near) and symptoms were evaluated., Results: There was a statistically significant increase in peak velocity and more accurate response amplitude to 4° symmetrical convergence step stimuli after OBVAT compared with baseline measurements. Near point of convergence, positive fusional vergence, and symptoms also statistically significantly improved after OBVAT. Ten of the 12 participants met clinical success criteria., Conclusions: In this prospective study on the treatment of symptomatic convergence insufficiency in children in which both clinical and objective eye movement measurements were used to evaluate the results of treatment, significant changes were found in symptoms and both clinical and objective measures of disparity vergence after completion of OBVAT in children with symptomatic convergence insufficiency.

Attention deficit/hyperactivity disorder (ADHD) is a highly prevalent and impairing neurodevelopmental disorder that persists into adulthood in a sizeable portion of afflicted children. The persistence of ADHD elevates the risk for adverse outcomes that result in substantial individual and societal burden. The objective of this study is to assess neurobiological substrates associated with variability of clinical outcomes in childhood ADHD, which has considerable value for the development of novel interventions that target mechanisms associated with recovery. A total of 36 young adults who were diagnosed with ADHD combined-type during childhood and 33 group-matched controls were involved in the study. Adults with childhood ADHD were further divided into 17 persisters and 19 remitters based on DSM-5 criteria. Functional magnetic resonance imaging data during a cue-evoked attention task were collected from each subject. The cue-evoked attention processing network was constructed using graph theoretic techniques. Network properties, including global-, local-, and nodal-efficiency, and network hubs were computed. Group comparisons of the network properties were conducted. Significantly lower nodal efficiency in right inferior frontal gyrus and reduced left side frontal-parietal functional interactions were observed in both remitters and persisters relative to the controls. The ADHD persisters showed a unique pattern of significantly lower nodal efficiency in right middle frontal gyrus (MFG) and hyper-interactions between bilateral MFG. This study suggests that right MFG functional impairments may relate to inactive fronto-parietal functional interactions for sensory and cognitive information processing and symptom persistence in young adults with childhood ADHD., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

This study sought to determine whether symmetrical compared to asymmetrical horizontal prisms (base-out or base-in) evoked different rates of phoria adaptation. Sixteen young adults with normal binocular vision participated in a symmetrical phoria adaptation experiment using a 3Δ base-out or 3Δ base-in binocular prism flipper and an asymmetrical phoria adaptation experiment using a 6Δ base-out or 6Δ base-in monocular wedge prism. The experiments were randomized and counterbalanced to reduce the influence of the prism stimulation order. Asymmetrical base-out prism adaptation was significantly faster than symmetrical prism adaptation for subjects with normal binocular vision. Asymmetrical phoria adaptation with base-in prism was not significantly different from symmetrical phoria adaptation implying that there are directional asymmetries (convergent versus divergent eye movements) in the slow fusional component of vergence. Data suggest that a potential interaction between the version system and the slow fusional vergence system may exist. Results have clinical relevance because patients with convergence or divergence insufficiency/excess may potentially show more pronounced differences between symmetrical and asymmetrical phoria adaptation compared to binocularly normal controls. These differences might also be relevant to clinical measurements such as vergence fusional range, which can be measured symmetrically (with Risley prisms in a phoroptor) or asymmetrically (with prism bar)., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Visual attention is an important aspect of everyday life, which can be incorporated in the assessment of many diagnoses. Another important characteristic of visual attention is that it can be improved via therapeutic interventions. Fifteen subjects with normal binocular vision were presented with visual distractor stimuli at various spatial locations while initiating disparity vergence eye movements (inward or outward rotation of eyes) within a haploscope system. First, a stationary distractor stimulus was presented in either the far, middle, or near visual spaces while the subjects were instructed to follow a target stimulus that was either stationary, converging (moving toward subject), or diverging (moving away from subject). For the second experiment, a dynamic distractor stimulus within the far, middle, or near visual space that was converging or diverging was presented while the target stimulus was also converging or diverging. The subjects were instructed to visually follow the target stimulus and ignore the distractor stimulus. The vergence responses had a final vergence angle between the target and distractor stimuli which has been termed a center of gravity (CoG) effect. Statistically significant differences were observed between the convergence peak velocities (p < 0.001) and response amplitudes (p < 0.001) comparing responses without distractors to responses with the presence of a vergence distractor. The results support that vergence eye movements are influenced by visual distractors, which is similar to how distractors influence saccadic eye movements. The influence of visual distractors within vergence eye movements may be useful to assess binocular dysfunction and visual distraction which are common post brain injury.

Meta-analysis of neuroimaging results has proven to be a popular and valuable method to study human brain functions. A number of studies have used meta-analysis to parcellate distinct brain regions. A popular way to perform meta-analysis is typically based on the reported activation coordinates from a number of published papers. However, in addition to the coordinates associated with the different brain regions, the text itself contains considerably amount of additional information. This textual information has been largely ignored in meta-analyses where it may be useful for simultaneously parcellating brain regions and studying their characteristics. By leveraging recent advances in document clustering techniques, we introduce an approach to parcellate the brain into meaningful regions primarily based on the text features present in a document from a large number of studies. This new method is called MAPBOT (Meta-Analytic Parcellation Based On Text). Here, we first describe how the method works and then the application case of understanding the sub-divisions of the thalamus. The thalamus was chosen because of the substantial body of research that has been reported studying this functional and structural structure for both healthy and clinical populations. However, MAPBOT is a general-purpose method that is applicable to parcellating any region(s) of the brain. The present study demonstrates the powerful utility of using text information from neuroimaging studies to parcellate brain regions., (Copyright © 2017 Elsevier Inc. All rights reserved.)

People develop presbyopia as part of the normal aging process. Most presbyopes adapt to progressive additive lens (PALs), while others do not. This investigation sought to determine whether the ability to modify disparity vergence or phoria was correlated to PALs adaptation. In experiment 1, a double-step paradigm quantified the ability to modify convergence responses in sixteen presbyopes. In experiment 2, thirty-one incipient presbyopes participated in a 5-minute sustained fixation task to evoke phoria adaptation where the magnitude and rate of phoria adaptation were measured. Then, the experiment was repeated after wearing PALs for one month. Linear regression analyses were conducted between the following parameters: near point of convergence, positive fusional vergence at near, vergence facility, net change in the magnitude of phoria adaptation, and the rate of phoria adaptation. The ability to change convergence average peak velocity was significantly greater (p < 0.03) in presbyopic PALs adapters compared to presbyopic PALs non-adapters. The rate of phoria adaptation and vergence facility were significantly greater (p < 0.03) in incipient presbyopic PALs adapters compared to incipient presbyopic PALs non-adapters. Vergence facility and the rate of phoria adaptation may have potential clinical utility in differentiating which patients may adapt to PALs and which ones will have more difficulty.

A paucity of research exists to investigate whether the normal aging process influences the ability to adapt disparity vergence and phoria. Vergence eye movements and dissociated phoria were recorded from 49 healthy subjects (ages 20-70years) using an objective eye movement tracking system. Four-degree vergence responses were modified using a double-step protocol. Dynamics of vergence were quantified via peak velocity. The phoria adaptation experiment measured the magnitude (net change in phoria level) and rate (magnitude divided by the time constant) of phoria adaption during 5min of sustained fixation on a binocular target (40cm/8.44° from midline). The magnitude of phoria adaptation decreased as a function of age (r=-0.33; p=0.04). The ability to adapt vergence peak velocity and the rate of phoria adaptation showed no significant age-related influence (p>0.05). The data suggest that the ability to modify the disparity vergence system and the rate of phoria adaptation are not dependent on age; whereas, the magnitude of phoria adaptation decreases as part of the normal adult aging process. These results have clinical and basic science implications because one should consider age when assessing the changes in the magnitude of phoria adaptation which can be abnormal in those with oculomotor dysfunctions., (Copyright © 2017. Published by Elsevier Ltd.)

Purpose: To evaluate changes in objective measures of disparity vergence after office-based vision therapy (OBVT) for concussion-related convergence insufficiency (CI) and determine the feasibility of using this objective assessment as an outcome measure in a clinical trial., Methods: This was a prospective, observational trial. All participants were treated with weekly OBVT with home reinforcement. Participants included two adolescents and three young adults with concussion-related, symptomatic CI. The primary outcome measure was average peak velocity for 4° symmetrical convergence steps. Other objective outcome measures of disparity vergence included time to peak velocity, latency, accuracy, settling time, and main sequence. We also evaluated saccadic eye movements using the same outcome measures. Changes in clinical measures (near point of convergence, positive fusional vergence at near, Convergence Insufficiency Symptom Survey [CISS] score) were evaluated., Results: There were statistically significant and clinically meaningful changes in all clinical measures for convergence. Four of the five subjects met clinical success criteria. For the objective measures, we found a statistically significant increase in peak velocity, response accuracy to 4° symmetrical convergence and divergence step stimuli, and the main sequence ratio for convergence step stimuli. Objective saccadic eye movements (5 and 10°) appeared normal pre-OBVT and did not show any significant change after treatment., Conclusions: This is the first report of the use of objective measures of disparity vergence as outcome measures for concussion-related convergence insufficiency. These measures provide additional information that is not accessible with clinical tests about underlying physiological mechanisms leading to changes in clinical findings and symptoms. The study results also demonstrate that patients with concussion can tolerate the visual demands (over 200 vergence and versional eye movements) during the 25-minute testing time and suggest that these measures could be used in a large-scale randomized clinical trial of concussion-related CI as outcome measures.

This study sought to determine whether significant changes would be observed between vergence eye movements before and after 12 hr of repetitive vergence therapy (1 hr per day on different days) in subjects with normal binocular vision compared to controls. Disparity vergence responses from 23 subjects were studied. An assessment protocol that minimized the influence of the near dissociated phoria on the disparity vergence system was designed. The following parameters were quantified for the responses: latency, time to peak velocity, settling time, peak velocity, and accuracy (difference between the response and stimulus amplitudes). The following outcomes were observed when comparing the results after vergence therapy to the baseline measurements: (a) near point of convergence and near dissociated phoria did not significantly change (p > 0.15); (b) latency, time to peak velocity, and settling time significantly decreased (p ≤ 0.01); and (c) accuracy significantly improved (p < 0.01). Results support that vergence peak velocity is dependent on the subject's near dissociated phoria. The accuracy and temporal properties of vergence eye movement responses from subjects with normal binocular vision can be improved after vergence therapy. These methods can be utilized within future studies to quantitatively assess vergence therapy techniques for patients with binocular dysfunction.

Purpose: This study examined the relationship between the near dissociated phoria and disparity vergence eye movements. Convergence insufficiency (CI) patients before vergence therapy were compared to: (1) the same patients after vergence therapy; and (2) binocularly normal controls (BNC)., Methods: Sixteen subjects were studied-twelve BNC and four with CI. Measurements from the CI subjects were obtained before and after 18 h of vergence eye movement therapy. The near dissociated phoria was measured using the flashed Maddox rod technique. Vergence responses were stimulated from 4° symmetrical disparity vergence step stimuli. The peak velocity of the vergence response and the magnitude of the fusion initiating component (FIC) from an independent component analysis (ICA) were calculated. A linear regression analysis was conducted studying the vergence peak velocity as a function of the near dissociated phoria where the Pearson correlation coefficient was computed., Results: Before vergence therapy, the average with one standard deviation FIC magnitude of convergence responses from CI subjects was 0.29° ± 0.82 and significantly less than the FIC magnitude of 1.85° ± 0.84 for BNC (p < 0.02). A paired t-test reported that the FIC and near dissociated phoria before vergence therapy for CI subjects significantly increased to 1.49° ± 0.57 (p < 0.04) and became less exophoric to 3.5Δ ± 1.9 exo (p < 0.02) after vergence therapy. A significant correlation (r = 0.87; p < 0.01) was observed between the near dissociated phoria and the vergence ratio of convergence peak velocity divided by divergence peak velocity., Conclusion: The results have clinical translational impact in understanding the mechanism by which vergence therapy may be changing the vergence system leading to a sustained reduction in visual symptoms.

While functional magnetic resonance imaging (fMRI) has identified which regions of interests (ROIs) are functionally active during a vergence movement (inward or outward eye rotation), task-modulated coactivation between ROIs is less understood. This study tested the following hypotheses: (1) significant task-modulated coactivation would be observed between the frontal eye fields (FEFs), the posterior parietal cortex (PPC), and the cerebellar vermis (CV); (2) significantly more functional activity and task-modulated coactivation would be observed in binocularly normal controls (BNCs) compared with convergence insufficiency (CI) subjects; and (3) after vergence training, the functional activity and task-modulated coactivation would increase in CIs compared with their baseline measurements. A block design of sustained fixation versus vergence eye movements stimulated activity in the FEFs, PPC, and CV. fMRI data from four CI subjects before and after vergence training were compared with seven BNCs. Functional activity was assessed using the blood oxygenation level dependent (BOLD) percent signal change. Task-modulated coactivation was assessed using an ROI-based task-modulated coactivation analysis that revealed significant correlation between the FEF, PPC, and CV ROIs. Prior to vergence training, the CIs had a reduced BOLD percent signal change compared with BNCs for the CV (p<0.05), FEFs, and PPC (p<0.01). The BOLD percent signal change increased within the CV, FEF, and PPC ROIs (p<0.001) as did the task-modulated coactivation between the FEFs and CV as well as the PPC and CV (p<0.05) when comparing the CI pre- and post-training datasets. Results from the Convergence Insufficiency Symptom Survey were correlated to the percent BOLD signal change from the FEFs and CV (p<0.05).

Convergence insufficiency (CI) is a prevalent binocular vision disorder with symptoms that include double/blurred vision, eyestrain, and headaches when engaged in reading or other near work. Randomized clinical trials support that Office-Based Vergence and Accommodative Therapy with home reinforcement leads to a sustained reduction in patient symptoms. However, the underlying neurophysiological basis for treatment is unknown. Functional activity and vergence eye movements were quantified from seven binocularly normal controls (BNC) and four CI patients before and after 18 h of vergence training. An fMRI conventional block design of sustained fixation vs. vergence eye movements stimulated activity in the frontal eye fields (FEF), the posterior parietal cortex (PPC), and the cerebellar vermis (CV). Comparing the CI patients' baseline measurements to the post-vergence training data sets with a paired t-test revealed the following: (1) the percent change in the BOLD signal in the FEF, PPC, and CV significantly increased (p < 0.02), (2) the peak velocity from 4° symmetrical convergence step responses increased (p < 0.01) and (3) patient symptoms assessed using the CI Symptom Survey (CISS) improved (p < 0.05). CI patient measurements after vergence training were more similar to levels observed within BNC. A regression analysis revealed the peak velocity from BNC and CI subjects before and after vergence training was significantly correlated to the percent BOLD signal change within the FEF, PPC, and CV (r = 0.6; p < 0.05). Results have clinical implications for understanding the behavioral and neurophysiological changes after vergence training in patients with CI, which may lead to the sustained reduction in visual symptoms.

Background: This study sought to investigate whether eye dominance and age are related to the stimulus-free oculomotor resting state described via the dark disconjugate position (near or far), the dark conjugate position (left to right), and the near dissociated phoria., Methods: Nineteen non-presbyopes and 25 presbyopes with normal binocular vision participated in two identical sessions. The left-eye and the right-eye positions were recorded using a video-based infrared eye tracker while the subjects were in total darkness. Dark disconjugate responses and dark conjugate responses were calculated by computing the difference and the average of the left-eye and the right-eye response, respectively. The right-eye decaying to the phoria level was recorded for 15 s., Results: A one-way ANOVA assessed statistical differences in dark conjugate and dark disconjugate positions, comparing 1) the right-eye and the left-eye sensory and/or motor dominant groups and 2) the non-presbyope and presbyope groups. The test-retests of the dark disconjugate position, the dark conjugate position and the near dissociated heterophoria were high between sessions (r > 0.85; p < 0.00001). For non-presbyopes the right-eye (left-eye) motor and sensory dominant subjects showed a rightward (leftward) dark conjugate position (p < 0.01). The dark disconjugate position was receded in presbyopes compared to non-presbyopes (p < 0.0001)., Conclusion: The data support that the left-eye, or the right-eye, motor and sensory dominance predicts the direction of the dark conjugate position. Future studies could investigate the underlying neural substrates that may, in part, contribute to the resting state of the oculomotor system in a stimulus-free environment. Knowledge of the brain-behavior governing visual-field preference has implications for understanding the natural aging process of the visual system.

Purpose: To assess the potential peak velocity asymmetry between the left-eye and right-eye movement responses stimulated by symmetrical vergence steps in those with normal binocular vision and those with convergence insufficiency (CI) before and after vergence training. This study also evaluated whether vergence training influenced convergence peak velocity and the prevalence of saccades within the first second of the response., Methods: The peak velocities of the left-eye, right-eye, and combined vergence response evoked from symmetrical 2°, 4°, and 6° convergence step stimuli were assessed in 10 controls and 7 CI subjects. Four of the CI subjects participated in vergence training. An asymmetry ratio was calculated as the peak velocity of the slower eye movement response divided by the peak velocity of the faster eye movement response., Results: Controls were significantly more symmetrical (left-eye peak velocity was approximately equal to right-eye peak velocity) compared to CI subjects (P < 0.001). After vergence training, the CI subjects' left-eye and right-eye movements became significantly more symmetrical, convergence peak velocity increased, and the prevalence of saccades within the first 1 second decreased (P < 0.01). Peak convergence velocity was significantly correlated to the prevalence of saccades observed within the first second of the response (r = 0.8; P < 0.05)., Conclusions: Data suggest that vergence training improves the symmetry between the left-eye and right-eye movements, increases convergence peak velocity, and decreases the prevalence of saccades within the first second of the response, which facilitates binocular coordination in CI patients. Saccades may be a compensatory mechanism used by CI subjects when convergence peak velocity is reduced.

Purpose: Phoria is used in the diagnosis of binocular dysfunctions, such as convergence insufficiency. A common treatment for convergence insufficiency is vision therapy, yet it is controversial whether the phoria changes as a result of rehabilitation. Phoria can vary due to the duration and/or the type of prior visual tasks. The variability potentially observed within phoria measurements leads to difficulties in confidently assessing changes within longitudinal studies. Hence, we propose to measure phoria and vergence peak velocities on separate days to evaluate whether a more robust measurement can be attained., Methods: Eleven subjects with normal binocular vision participated in two identical experimental sessions. Four-degree convergence and divergence steps stimulated from targets at far, middle, and near initial vergence positions were recorded using a limbus tracking system. Near dissociated phoria was measured after a set of step stimuli. The vergence ratio was defined as the convergence peak velocity divided by the divergence peak velocity. Linear regression analyses calculated the correlation between the phoria and the vergence ratio, and the difference between phoria measurements and vergence ratio measurements, recorded on different days., Results: Near dissociated phoria measurements and vergence ratios were highly correlated for all three initial vergence positions (r > 0.85, p < 0.005). The change in phoria was significantly correlated to the change in vergence ratio (r > 0.94, p = 0.0001). The slope of the linear regression analysis between the phoria and the vergence ratio using individual subject data was repeatable between the sessions (r = 0.99, p < 0.00001) despite large changes in phoria observed in a few individuals., Conclusions: The change in phoria is significantly correlated to the change in vergence ratio. For longitudinal studies including the efficacy of vision therapies for patients with binocular dysfunctions, we suggest assessing both phoria and vergence velocities to reduce the variability potentially observed from different days.

In a natural environment, saccade and vergence eye movements shift gaze in different directions and distances. In a laboratory setting, targets can be positioned precisely to elicit symmetrical vergence movements; however, saccades occur during the vergence movement even though the stimulus should not stimulate a saccadic response. These saccades may facilitate the response when the kinematics of the vergence component are modest as indicated by reduced velocities. Hence, the purpose of this study is to assess whether the frequency of saccades within vergence responses are correlated with vergence peak velocity. Ten subjects with normal binocular vision participated in this study. Eye movements were quantified using a limbus tracking system. Stimuli included 4° symmetrical convergence and divergence steps with an initial vergence angle at far (2° and 6°, respectively) and near (12° and 16°, respectively) which are known to evoke different vergence peak velocities. A saccade detecting algorithm was utilized to compute the percentage of saccades present within all vergence responses. A repeated measures ANOVA confirmed with a post hoc Bonferroni test demonstrated that convergence steps at near were slower than convergence steps at far, whereas divergence steps at far were slower than divergence steps at near in all subjects (p<0.02). When the vergence peak velocity was slow, a greater number of saccades was observed. The average vergence peak velocities were inversely correlated to the number of saccades observed within the transient portion defined as after the latency to 400 ms of the movement (r=-0.41; p=0.008), between 400 ms and 1s of the response (r=-0.35; p=0.03) and within the steady-state period occurring between 1s and 3s of the response (r=-0.44; p=0.005). Peak velocity of vergence is dependent on the stimulus initial vergence angle. An increased prevalence of saccades was observed in vergence responses with reduced peak velocity, compared to responses with greater peak velocity. Prior research supports that saccades increase the peak velocity of vergence during combined vergence and saccadic tasks. This may in part explain the increased presence of saccades within vergence responses with reduced peak velocities. The recruitment of saccades may be utilized because of the longer period of diplopia resulting from slower vergence movements., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The ability to adapt is critical to survival and varies between individuals. Adaptation of one motor system may be related to the ability to adapt another. This study sought to determine whether phoria adaptation was correlated with the ability to modify the dynamics of disparity vergence. Eye movements from ten subjects were recorded during dynamic disparity vergence modification and phoria adaptation experiments. Two different convergent stimuli were presented during the dynamic vergence modification experiment: a test stimulus (4° step) and a conditioning stimulus (4° double step). Dynamic disparity vergence responses were quantified by measuring the peak velocity (°/s). Phoria adaptation experiments measured the changes in phoria over a 5-min period of sustained fixation. The maximum velocity of phoria adaptation was determined from an exponential fit of the phoria data points. Phoria and dynamic disparity vergence peak velocity were both significantly modified (P < 0.001). The maximum velocity of phoria adaptation was significantly correlated with the changes in convergence peak velocity (r > 0.89; P < 0.001). There was a strong correlation between the ability to adaptively adjust two different oculomotor parameters: a tonic and dynamic component. Future studies should investigate additional interactions between these parameters, and the ability to adaptively change other oculomotor systems such as the saccadic or smooth pursuit system. Understanding the ability to modify phoria, dynamic disparity vergence, and other oculomotor parameters can yield insights into the plasticity of short-term adaptation mechanisms.

Purpose: Cortical and subcortical functional activity stimulated via saccade and vergence eye movements were investigated to examine the similarities and differences between networks and regions of interest (ROIs)., Methods: Blood oxygenation level-dependent (BOLD) signals from stimulus-induced functional Magnetic Resonance Imaging (MRI) experiments were analyzed studying 16 healthy subjects. Six types of oculomotor experiments were conducted using a block design to study both saccade and vergence circuits. The experiments included a simple eye movement task and a more cognitively demanding prediction task. A hierarchical independent component analysis (ICA) process began by analyzing individual subject data sets with spatial ICA to extract spatial independent components (sIC), which resulted in three ROIs. Using the time series from each of the three ROIs per subject, per oculomotor experiment, a temporal ICA was used to compute individual temporal independent components (tICs). For each of the three ROIs, the individual tICs from multiple subjects were entered into a second temporal ICA to compute group-level tICs for comparison., Results: Two independent spatial maps were observed for each subject (one sIC showing activity in the frontoparietal regions and another sIC in the cerebellum) during the six oculomotor tasks. Analysis of group-level tICs revealed an increased latency in the cerebellar region when compared to the frontoparietal region., Conclusion: Shared neuronal behavior has been reported in the frontal and parietal lobes, which may in part explain the segregation of frontoparietal functional activity into one sIC. The cerebellum uses multiple time scales for motor learning. This may result in an increased latency observed in the BOLD signal of the cerebellar group-level tIC when compared to the frontal and parietal group-level tICs. The increased latency offers a possible explanation to why ICA dissects the cerebellar activity into an sIC. The hierarchical ICA process used to calculate group-level tICs can yield insight into functional connectivity within complex neural networks.

Eye movement studies have provided a strong foundation forming an understanding of how the brain acquires visual information in both the normal and dysfunctional brain.(1) However, development of a platform to stimulate and store eye movements can require substantial programming, time and costs. Many systems do not offer the flexibility to program numerous stimuli for a variety of experimental needs. However, the VisualEyes System has a flexible architecture, allowing the operator to choose any background and foreground stimulus, program one or two screens for tandem or opposing eye movements and stimulate the left and right eye independently. This system can significantly reduce the programming development time needed to conduct an oculomotor study. The VisualEyes System will be discussed in three parts: 1) the oculomotor recording device to acquire eye movement responses, 2) the VisualEyes software written in LabView, to generate an array of stimuli and store responses as text files and 3) offline data analysis. Eye movements can be recorded by several types of instrumentation such as: a limbus tracking system, a sclera search coil, or a video image system. Typical eye movement stimuli such as saccadic steps, vergent ramps and vergent steps with the corresponding responses will be shown. In this video report, we demonstrate the flexibility of a system to create numerous visual stimuli and record eye movements that can be utilized by basic scientists and clinicians to study healthy as well as clinical populations.