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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.

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.

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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12264-019-00455-9) contains supplementary material, which is available to authorized users.

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 . RESULTS: No significant baseline differences are observed between the BNC (p>0.4) or CI (p>0.3) 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

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

Introduction: Previous studies have shown that the slow, or fusion sustaining, component of disparity vergence contains oscillatory behavior. Given the delays in disparity vergence control, a feedback control system would be expected to exhibit oscillations following the initial transient period. 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 15 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 primary frequencies ranging between 0.45 and 0.6 Hz; much lower than those identified in the earlier study. All responses showed significant higher frequency components. These higher frequency components were related in both frequency and amplitude with the primary frequency indicating that they are harmonics probably generated by nonlinearities in the neural control processes. A correlation was found across subjects between the amplitude of the primary frequency and the maximum velocity of the fusion initialing component probably due 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. Data have clinical implications in that dysfunction in feedback control may manifest as additional vergence error which may be reflected in the frequency spectrum.

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).

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.

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.

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.This study aimed to determine whether NFV is normal in untreated children with symptomatic convergence insufficiency and whether NFV improves after vergence/accommodative therapy.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.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).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.

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.

Traumatic brain injury (TBI)-induced attention deficits are among the most common long-term cognitive consequences in children. Most of the existing studies attenpting 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 associations with TBI-induced attention problems in a more homogeneous subgroup of children who had severe post-TBI attention deficits (TBI-A).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 associations were all corrected for multiple comparisons using Bonferroni method.Compare to 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, while significantly lower nodal clustering coefficient in left supramarginal gyrus as well as 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.The results suggest that TBI-related structural re-modularity in the WM 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 TBI-A, and have the potential to serve as a biomarker guiding the development of more timely and tailored strategies for diagnoses and treatments to the affected individuals.

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.

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.

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.

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 p

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.

This study investigates the underlying physiological mechanisms that may lead to improved outcomes for symptomatic convergence insufficiency (CI) 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 CI 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 CI patients.

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.

Highlights • Features of nodal efficiency in right IFG, right MFG-IPL functional connectivity, and right amygdala volume for discrimination between ADHD probands and controls. • Higher nodal efficiency of right MFG greatly contributed to symptom remission. • Higher right MFG-IPL functional connectivity strongly linked to symptom persistence. • ELT-based classifiers were superior to the basic machine learning classifiers. • ELT may have the potential to identify more reliable neurobiological markers for neurodevelopmental disorder., 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.

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&rsquo, 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&rsquo, gender and nature of injury were extracted from 1408 medical records of patients who were diagnosed with a concussion at Saint Peter&rsquo, 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 &lt, 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.

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.

Aims This study aimed at understanding the neurobiological mechanisms associated with inattention induced by traumatic brain injury (TBI). To eliminate the potential confounding caused by the heterogeneity of TBI, we focused on young adults postsports-related concussion (SRC). Methods Functional near-infrared spectroscopy (fNIRS) data were collected from 27 young adults post-SRC and 27 group-matched normal controls (NCs), while performing a visual sustained attention task. Task responsive cortical activation maps and pairwise functional connectivity among six regions of interest were constructed for each subject. Correlations among the brain imaging measures and clinical measures of attention were calculated in each group. Results Compared to the NCs, the SRC group showed significantly increased brain activation in left middle frontal gyrus (MFG) and increased functional connectivity between right inferior occipital cortex (IOC) bilateral calcarine gyri (CG). The left MFG activation magnitude was significantly negatively correlated with the hyperactive/impulsive symptom severity measure in the NCs, but not in the patients. The right hemisphere CG-IOC functional connectivity showed a significant positive correlation with the hyperactive/impulsive symptom severity measure in patients, but not in NCs. Conclusion The current data suggest that abnormal left MFG activation and hyper-communications between right IOC and bilateral CG during visual attention processing may significantly contribute to behavioral manifestations of attention deficits in patients with TBI.

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).

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 20–70 years) 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 5 min of sustained fixation on a binocular target (40 cm/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.

This study assessed the prevalence of convergence insufficiency (CI) with and without simultaneous vision dysfunctions within the traumatic brain injury (TBI) sample population because although CI is commonly reported with TBI, the prevalence of concurrent visual dysfunctions with CI in TBI is unknown.A retrospective analysis of 557 medical records from TBI civilian patients was conducted. Patients were all evaluated by a single optometrist. Visual acuity, oculomotor function, binocular vision function, accommodation, visual fields, ocular health, and vestibular function were assessed. Statistical comparisons between the CI and non-CI, as well as inpatient and outpatient subgroups, were conducted using χ and Z tests.Approximately 9% of the TBI sample had CI without the following simultaneous diagnoses: saccade or pursuit dysfunction; third, fourth, or sixth cranial nerve palsy; visual field deficit; visual spatial inattention/neglect; vestibular dysfunction; or nystagmus. Photophobia with CI was observed in 16.3% (21 of 130), and vestibular dysfunction with CI was observed in 18.5% (24 of 130) of the CI subgroup. Convergence insufficiency and cranial nerve palsies were common and yielded prevalence rates of 23.3% (130 of 557) and 26.9% (150 of 557), respectively, within the TBI sample. Accommodative dysfunction was common within the nonpresbyopic TBI sample, with a prevalence of 24.4% (76 of 314). Visual field deficits or unilateral visual spatial inattention/neglect was observed within 29.6% (80 of 270) of the TBI inpatient subgroup and was significantly more prevalent compared with that of the outpatient subgroup (p0.001). Most TBI patients had visual acuities of 20/60 or better in the TBI sample (85%; 473 of 557).Convergence insufficiency without simultaneous visual or vestibular dysfunctions was observed in about 9% of the visually symptomatic TBI civilian population studied. A thorough visual and vestibular examination is recommended for all TBI patients.

Purpose The purpose of this study is to investigate the functional neural anatomy that generates vergence eye movement responses from predictive versus random symmetrical vergence step stimuli in humans and compare it to a similar saccadic task via the blood oxygenation level dependent signal from functional MRI. Methods Eight healthy subjects participated in fMRI scans obtained from a 3 T Siemens Allegra scanner. Subjects tracked random and predictable vergent steps and then tracked random and predictable saccadic steps each within a block design. A general linear model (GLM) was used to determine significantly (p 2.7, p

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.

The purpose of this study was to investigate how sustained convergence induces phoria adaptation and changes divergence dynamics.Near dissociated phoria and divergence step responses were recorded using an infrared eye movement monitor on four binocularly normal subjects. We tested three different adapting vergence positions (16 degrees , 6 degrees , and 0.5 degrees ) and measured 4 degrees divergence step responses for two different initial vergence positions (16 degrees and 4.5 degrees ). Dynamics were quantified by measuring peak velocities of the divergence responses.Phoria was significantly adapted after subjects fixated on a sustained convergent target at near (16 degrees ) and at far (0.5 degrees ). As a result of sustained convergence, divergence peak velocity from a 4 degrees step stimulus significantly changed. A regression analysis showed that when the phoria became more esophoric (near adapted) the peak velocity for the divergence steps with an initial position of 16 degrees decreased (R=0.54, p=0.04). A trend was observed between the change vergence velocity and the change in phoria. Change was defined as the post-adapted data minus the pre-adapted data for vergence steps with an initial position of 16 degrees (R=0.65) and 4.5 degrees (R=0.66). Furthermore, the modification of divergence dynamics was dependent on the initial position of those divergence steps (initial position of 16 degrees versus 4.5 degrees ).As a result of sustained convergence, phoria and divergence dynamics changed in a correlated manner. Such correlated changes in phoria and divergence dynamics are not explained by current models of disparity vergence eye movements.

Previous studies on the speed and latency of convergence and divergence eye movements have produced varied, sometimes contradictory, results. Four subjects were studied and tracked 4° disparity step changes for convergence and divergence at different initial target positions. Here we report that the dynamics of divergence movements not only differ from convergence movement, but depend on the initial vergence position. Velocities of divergence eye movements in response to targets that were initially near to the subject were approximately twice that of responses to initially distant targets and also exhibited shorter temporal properties. Hence, while convergence responses are fairly similar irrespective of the initial position, divergence dynamic and temporal properties are dependent on the initial stimulus position. It is speculated that the differences observed in divergence may be the result of nonlinear properties of the extraocular muscles or a difference in the underlying neural controller potentially a difference in the magnitude of the fusion initiating component of divergence.

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.

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

Disparity vergence eye movements occasionally exhibit two high-velocity components to a single step stimulus (Alvarez, T. L., Semmlow, J. L. & Yuan, W. (1998). Journal of Neurophysiology, 79, 37–44). This research investigates the neural strategy used to trigger the second component of double high-velocity vergence eye movements. Vergence doubles evoked by an experimental protocol that induces post-movement visual error were compared to doubles that occur normally. The second component of a visually evoked response double occurred later, and with slower dynamics, than that of a naturally occurring double. These differences in timing and dynamics indicate that natural double responses are mediated, at least in part, by a mechanism other than visual feedback. The faster dynamics and timing of natural doubles suggest that an internal monitoring process triggers these movements.