Yelda Alkan

Vision therapy in adults with convergence insufficiency: clinical and functional magnetic resonance imaging measures.

Purpose. This research quantified clinical measurements and functional neural changes associated with vision therapy in subjects with convergence insufficiency (CI). Methods. Convergence and divergence 4° step responses were compared between 13 control adult subjects with normal binocular vision and four CI adult subjects. All CI subjects participated in 18 h of vision therapy. Clinical parameters quantified throughout the therapy included: nearpoint of convergence, recovery point of convergence, positive fusional vergence at near, near dissociated phoria, and eye movements that were quantified using peak velocity. Neural correlates of the CI subjects were quantified with functional magnetic resonance imaging scans comparing random vs. predictable vergence movements using a block design before and after vision therapy. Images were quantified by measuring the spatial extent of activation and the average correlation within five regions of interests (ROI). The ROIs were the dorsolateral prefrontal cortex, a portion of the frontal lobe, part of the parietal lobe, the cerebellum, and the brain stem. All measurements were repeated 4 months to 1 year post-therapy in three of the CI subjects. Results. Convergence average peak velocities to step stimuli were significantly slower (p = 0.016) in CI subjects compared with controls; however, significant differences in average peak velocities were not observed for divergence step responses (p = 0.30). The investigation of CI subjects participating in vision therapy showed that the nearpoint of convergence, recovery point of convergence, and near dissociated phoria significantly decreased. Furthermore, the positive fusional vergence, average peak velocity from 4° convergence steps, and the amount of functional activity within the frontal areas, cerebellum, and brain stem significantly increased. Several clinical and cortical parameters were significantly correlated. Conclusions. Convergence peak velocity was significantly slower in CI subjects compared with controls, which may result in asthenopic complaints reported by the CI subjects. Vision therapy was associated with and may have evoked clinical and cortical activity changes.

Functional anatomy of predictive vergence and saccade eye movements in humans: A functional MRI investigation

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 3T 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 < 0.001) active regions of interest through a combination of correlation threshold and cluster extent. A paired t-test of the GLM beta weight coefficients was computed to determine significant spatial differences between the saccade and vergence data sets. RESULTS Predictive saccadic and vergent eye movements induced many common sites of significant functional cortical activity including: the dorsolateral prefrontal cortex (DLPFC), parietal eye field (PEF), cuneus, precuneus, anterior and posterior cingulate, and the cerebellum. However, differentiation in spatial location was observed within the frontal lobe for the functional activity of the saccadic and vergent network induced while studying prediction. A paired t-test of the beta weights from the individual subjects showed that peak activity induced by predictive versus random vergent eye movements was significantly (t > 2.7, p < 0.03) more anterior within the frontal eye field (FEF) and the supplementary eye field (SEF) when compared to the functional activity from predictive saccadic eye movements. CONCLUSION This research furthers our knowledge of which cortical sites facilitate a subjects ability to predict within the vergence and saccade networks. Using a predictive versus random visual task, saccadic and vergent eye movements induced activation in many shared cortical sites and also stimulated differentiation in the FEF and SEF.

Differentiation between Vergence and Saccadic Functional Activity within the Human Frontal Eye Fields and Midbrain Revealed through fMRI

Purpose Eye movement research has traditionally studied solely saccade and/or vergence eye movements by isolating these systems within a laboratory setting. While the neural correlates of saccadic eye movements are established, few studies have quantified the functional activity of vergence eye movements using fMRI. This study mapped the neural substrates of vergence eye movements and compared them to saccades to elucidate the spatial commonality and differentiation between these systems. Methodology The stimulus was presented in a block design where the ‘off’ stimulus was a sustained fixation and the ‘on’ stimulus was random vergence or saccadic eye movements. Data were collected with a 3T scanner. A general linear model (GLM) was used in conjunction with cluster size to determine significantly active regions. A paired t-test of the GLM beta weight coefficients was computed between the saccade and vergence functional activities to test the hypothesis that vergence and saccadic stimulation would have spatial differentiation in addition to shared neural substrates. Results Segregated functional activation was observed within the frontal eye fields where a portion of the functional activity from the vergence task was located anterior to the saccadic functional activity (z>2.3; p<0.03). An area within the midbrain was significantly correlated with the experimental design for the vergence but not the saccade data set. Similar functional activation was observed within the following regions of interest: the supplementary eye field, dorsolateral prefrontal cortex, ventral lateral prefrontal cortex, lateral intraparietal area, cuneus, precuneus, anterior and posterior cingulates, and cerebellar vermis. The functional activity from these regions was not different between the vergence and saccade data sets assessed by analyzing the beta weights of the paired t-test (p>0.2). Conclusion Functional MRI can elucidate the differences between the vergence and saccade neural substrates within the frontal eye fields and midbrain.

Segregation of frontoparietal and cerebellar components within saccade and vergence networks using hierarchical independent component analysis of fMRI

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.

Functional connectivity in vergence and saccade eye movement tasks assessed using Granger Causality Analysis

Throughout the day, the human visual system acquires information using saccade and vergence eye movements. Previously, functional MRI (fMRI) experiments have shown both shared neural resources and spatial differentiation between these two systems. FMRI experiments can reveal which regions are activated within an experimental task but do not yield insight into how regions of interest (ROIs) interact with each other. This study investigated the number and direction of influences among ROIs using a Granger Causality Analysis (GCA) — a statistical technique used to identify if an ROI is significantly influencing or ‘connected’ to another ROI. Two stimulus protocols were used: first, a simple block design of fixation versus random eye movements; and second, a more cognitively demanding task using random versus predictable movements. Each protocol used saccadic movements and was then repeated using vergence movements. Eight subjects participated in each of the four experiments. Results show that when prediction was evoked, more connections between ROIs were observed compared to the simple tracking experiment. More connections were also observed during the vergence prediction task compared to the saccade prediction task. Differences within the number of connections may be due to the type of oculomotor eye movements, as well as to the amount of higher-level executive cognitive demand.

Neuroplasticity in vision dysfunction

Adaptation is critical to the survival of any species and is present in many systems within the brain. Rehabilitation can evoke neuroplasticity through adaptive mechanisms. Four subjects with the vision dysfunction of convergence insufficiency where two have mild traumatic brain injury and two were congenital participated in 18 hours of vision training. Clinical, behavioral, functional imaging and diffusion tensor imaging (DTI) are measured before and after therapy. Clinical parameters show improvement. Vergence eye-movements show an increase in peak velocity where independent component analysis revealed an increase in the magnitude of the preprogrammed transient component. Functional imaging using an oculomotor learning task shows increased area and intensity of activation suggesting neuronal recruitment and synchronization. DTI shows an increase in fractional anisotropy and an increase in the number of fibers suggesting changes in structural connectivity. Preliminary data suggest that neuroplasticity from vision training results in a change in behavioral oculomotor neural control through an increased magnitude of the preprogrammed disparity transient component potentially caused in part by neuronal recruitment, synchronization and improved structural connectivity.

Diffusion tensor imaging of neural plasticity in visual dysfunction

Diffusion tensor imaging (DTI) analysis is performed on a subject that exhibits visual dysfunction as a result of mild traumatic brain injury (TBI). A comparison is made of the subjects DTI data before and after undergoing vision training in order to quantify any differences in the subjects fractional anisotropy (FA) and white matter fiber tracts. A marked increase is seen in the FA values of the designated regions of interest (ROI) as well as in the number of fibers that are present in the ROIs.

An fMRI investigation of a memory guided vergence task: Insights to the parahippocampal area

This investigation sought to systematic study the parahippocampal area using three types of vergence eye movement tasks that utilized different demands on visual memory. The percent volume change of the functional activity in the posterior parahippocampal area (PPHA) was quantified for three different experimental paradigms that stimulated vergence eye movements: random tracking versus fixation; predictable tracking versus random tracking; and memory-guided task. A general linear model (GLM) was used to determine functional activity for each of the three vergence experiments. The average signal percent change for both the PPHA and frontal eye fields (FEF) was compared for each vergence task. Significant percent change in the average signal from the voxels in the PPHA was observed for all experiments (p <; 0.005), whereas no such significant change was observed for the FEF (p >; 0.06). Lastly, percent volume change was also quantified for the PPHA among experiments. Percent volume change in the PPHA was greater for the memory-guided vergence task and the change was significant across all the experiments, (p<;0.02). This suggests that when utilization of working memory is required, the PPHA functions as one of the regions for a vergence eye movement dependent memory task.

Comparison of whole-brain to region-based fMRI analyses

Conventional fMRI analyses primarily utilize a general linear model composed of a single reference vector for the whole-brain. A single reference vector assumes the hemodynamic response is homogenous between different individuals and regions of interest. This study sought to determine whether a regional-based analysis that accounts for individual and regional differences would yield more sensitive results in terms spatial extent. Fifteen subjects without neurological dysfunction were scanned in a 3T MRI using an experimental block design of visual fixation compared to randomized vergence eye movements. Two temporal independent component analyses were conducted on individual subject data sets. The first used the data set composed of all the voxels within the brain while the second used the data from a masked region to isolate the voxels within the frontal eye fields, a critical cortical region needed to evoke vergence eye movements. A hierarchical temporal independent component analysis was used to compute group-level results. Spatial maps were compared. The regional based analysis resulted in fewer clusters which had greater spatial extent compared to the whole-brain analysis which had more dispersion within the functional activity. This technique has the potential to study individual regions while accounting for the variability of the natural heterogeneous nature of the hemodynamic response found in fMRI data.

Visual cortical circuits revealed using fMRI and ICA

This research used the Infomax ICA algorithm to search for independent circuits within the functional activity evoked during saccadic and vergence tracking fMRI experiments. Image processing determined independent components from each subjects data and then identified which components had high correlation between subjects. Using the individual independent components that had high correlation between subjects, a group ICA was performed. The temporal properties between ROIs were then examined. The results of this study indicated that there are two separate spatial pathways; fronto-parietal and cerebellum, involved in oculomotor tracking tasks and the cerebellar pathway was delayed compared to the fronto-parietal component.