Suril Gohel

Graph Theoretical Analysis of Functional Brain Networks: Test-Retest Evaluation on Short- and Long-Term Resting-State Functional MRI Data

Graph-based computational network analysis has proven a powerful tool to quantitatively characterize functional architectures of the brain. However, the test-retest (TRT) reliability of graph metrics of functional networks has not been systematically examined. Here, we investigated TRT reliability of topological metrics of functional brain networks derived from resting-state functional magnetic resonance imaging data. Specifically, we evaluated both short-term (<1 hour apart) and long-term (>5 months apart) TRT reliability for 12 global and 6 local nodal network metrics. We found that reliability of global network metrics was overall low, threshold-sensitive and dependent on several factors of scanning time interval (TI, long-term>short-term), network membership (NM, networks excluding negative correlations>networks including negative correlations) and network type (NT, binarized networks>weighted networks). The dependence was modulated by another factor of node definition (ND) strategy. The local nodal reliability exhibited large variability across nodal metrics and a spatially heterogeneous distribution. Nodal degree was the most reliable metric and varied the least across the factors above. Hub regions in association and limbic/paralimbic cortices showed moderate TRT reliability. Importantly, nodal reliability was robust to above-mentioned four factors. Simulation analysis revealed that global network metrics were extremely sensitive (but varying degrees) to noise in functional connectivity and weighted networks generated numerically more reliable results in compared with binarized networks. For nodal network metrics, they showed high resistance to noise in functional connectivity and no NT related differences were found in the resistance. These findings provide important implications on how to choose reliable analytical schemes and network metrics of interest.

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 Integration Between Brain Regions at Rest Occurs in Multiple-Frequency Bands

Studies of resting-state fMRI have shown that blood oxygen level dependent (BOLD) signals giving rise to temporal correlation across voxels (or regions) are dominated by low-frequency fluctuations in the range of ∼ 0.01-0.1 Hz. These low-frequency fluctuations have been further divided into multiple distinct frequency bands (slow-5 and -4) based on earlier neurophysiological studies, though low sampling frequency of fMRI (∼ 0.5 Hz) has substantially limited the exploration of other known frequency bands of neurophysiological origins (slow-3, -2, and -1). In this study, we used resting-state fMRI data acquired from 21 healthy subjects at a higher sampling frequency of 1.5 Hz to assess the presence of resting-state functional connectivity (RSFC) across multiple frequency bands: slow-5 to slow-1. The effect of different frequency bands on spatial extent and connectivity strength for known resting-state networks (RSNs) was also evaluated. RSNs were derived using independent component analysis and seed-based correlation. Commonly known RSNs, such as the default mode, the fronto-parietal, the dorsal attention, and the visual networks, were consistently observed at multiple frequency bands. Significant inter-hemispheric connectivity was observed between each seed and its contra lateral brain region across all frequency bands, though overall spatial extent of seed-based correlation maps decreased in slow-2 and slow-1 frequency bands. These results suggest that functional integration between brain regions at rest occurs over multiple frequency bands and RSFC is a multiband phenomenon. These results also suggest that further investigation of BOLD signal in multiple frequency bands for related cognitive processes should be undertaken.

Task vs. rest-different network configurations between the coactivation and the resting-state brain networks.

There is a growing interest in studies of human brain networks using resting-state functional magnetic resonance imaging (fMRI). However, it is unclear whether and how brain networks measured during the resting-state exhibit comparable properties to brain networks during task performance. In the present study, we investigated meta-analytic coactivation patterns among brain regions based upon published neuroimaging studies, and compared the coactivation network configurations with those in the resting-state network. The strength of resting-state functional connectivity between two regions were strongly correlated with the coactivation strength. However, the coactivation network showed greater global efficiency, smaller mean clustering coefficient, and lower modularity compared with the resting-state network, which suggest a more efficient global information transmission and between system integrations during task performing. Hub shifts were also observed within the thalamus and the left inferior temporal cortex. The thalamus and the left inferior temporal cortex exhibited higher and lower degrees, respectively in the coactivation network compared with the resting-state network. These results shed light regarding the reconfiguration of the brain networks between task and resting-state conditions, and highlight the role of the thalamus in change of network configurations in task vs. rest.

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.

Functional topography of the thalamocortical system in human

Various studies have indicated that the thalamus is involved in controlling both cortico-cortical information flow and cortical communication with the rest of the brain. Detailed anatomy and functional connectivity patterns of the thalamocortical system are essential to understanding the cortical organization and pathophysiology of a wide range of thalamus-related neurological and neuropsychiatric diseases. The current study used resting-state fMRI to investigate the topography of the human thalamocortical system from a functional perspective. The thalamus-related cortical networks were identified by performing independent component analysis on voxel-based thalamic functional connectivity maps across a large group of subjects. The resulting functional brain networks were very similar to well-established resting-state network maps. Using these brain network components in a spatial regression model with each thalamic voxel’s functional connectivity map, we localized the thalamic subdivisions related to each brain network. For instance, the medial dorsal nucleus was shown to be associated with the default mode, the bilateral executive, the medial visual networks; and the pulvinar nucleus was involved in both the dorsal attention and the visual networks. These results revealed that a single nucleus may have functional connections with multiple cortical regions or even multiple functional networks, and may be potentially related to the function of mediation or modulation of multiple cortical networks. This observed organization of thalamocortical system provided a reference for studying the functions of thalamic sub-regions. The importance of intrinsic connectivity-based mapping of the thalamocortical relationship is discussed, as well as the applicability of the approach for future studies.

Recovery of resting brain connectivity ensuing mild traumatic brain injury

Brains reveal amplified plasticity as they recover from an injury. We aimed to define time dependent plasticity changes in patients recovering from mild traumatic brain injury (mTBI). Twenty-five subjects with mild head injury were longitudinally evaluated within 36 h, 3 and 6 months using resting state functional connectivity (RSFC). Region of interest (ROI) based connectivity differences over time within the patient group and in comparison with a healthy control group were analyzed at p < 0.005. We found 33 distinct ROI pairs that revealed significant changes in their connectivity strength with time. Within 3 months, the majority of the ROI pairs had decreased connectivity in mTBI population, which increased and became comparable to healthy controls at 6 months. Within this diffuse decreased connectivity in the first 3 months, there were also few regions with increased connections. This hyper connectivity involved the salience network and default mode network within 36 h, and lingual, inferior frontal and fronto-parietal networks at 3 months. Our findings in a fairly homogenous group of patients with mTBI evaluated during the 6 month window of recovery defines time varying brain connectivity changes as the brain recovers from an injury. A majority of these changes were seen in the frontal and parietal lobes between 3 and 6 months after injury. Hyper connectivity of several networks supported normal recovery in the first 6 months and it remains to be seen in future studies whether this can predict an early and efficient recovery of brain function.

Repetitive transcranial magnetic stimulation induced modulations of resting state motor connectivity in writer's cramp.

Writers cramp (WC) is a focal task‐specific dystonia of the hand which is increasingly being accepted as a network disorder. Non‐invasive cortical stimulation using repetitive transcranial magnetic stimulation (rTMS) has produced therapeutic benefits in some of these patients. This study aimed to visualize the motor network abnormalities in WC and also its rTMS induced modulations using resting state functional magnetic resonance imaging (rsfMRI).

Altered Functional Connectivity Strength in Abstinent Chronic Cocaine Smokers Compared to Healthy Controls

Past research involving cocaine and resting-state functional connectivity (RSFC) has shown altered functional connectivity within the frontal and between the frontal and other cortical and subcortical brain regions in chronic users of cocaine. However, there have been discrepancies in literature regarding the relationship between RSFC between brain regions and cocaine use behavior. This study explored the RSFC between brain regions in cocaine smokers abstinent from cocaine use for 72 h and healthy controls. Also, the relationship between RSFC between brain regions and various cocaine use measures (cocaine use duration; frequency, and money spent on cocaine/week) was examined. Twenty chronic cocaine users and 17 controls completed a resting-state scan and an anatomical MPRAGE scan. Group independent component analysis performed on functional magnetic resonance imaging data identified 13 ICs pertaining to distinct resting-state networks, and group-level differences were examined. To examine inter-network functional connectivity between brain regions, these 13 ICs were divided into 61 distinct regions of interest (ROIs). Correlations were calculated between 61 ROI time series. For the ROI pairs that significantly differed from controls in connectivity strength, correlations were computed between connectivity strength and cocaine use measures. Results showed an enhanced RSFC within the sensory motor cortex and the left frontal-parietal network in cocaine users than controls. An increased inter-network RSFC between frontal-temporal and frontal-parietal brain regions, and a decreased RSFC between parietal-parietal, occipital-limbic, occipital-occipital, and occipital-parietal brain regions was found in cocaine users. This study demonstrated that intra-network connectivity strength of sensory motor cortex was negatively correlated with years of cocaine use. Inter-network connectivity strength between occipital-limbic brain regions was positively correlated with years of cocaine use, while connectivity strength within occipital brain regions was negatively related to cocaine use frequency and money spent on cocaine per week in abstinent cocaine users.

Task-modulated coactivation of vergence neural substrates.

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).