Joseph C. Griffis

Voxel-based Gaussian naïve Bayes classification of ischemic stroke lesions in individual T1-weighted MRI scans.

BACKGROUND Manual lesion delineation by an expert is the standard for lesion identification in MRI scans, but it is time-consuming and can introduce subjective bias. Alternative methods often require multi-modal MRI data, user interaction, scans from a control population, and/or arbitrary statistical thresholding. NEW METHOD We present an approach for automatically identifying stroke lesions in individual T1-weighted MRI scans using naïve Bayes classification. Probabilistic tissue segmentation and image algebra were used to create feature maps encoding information about missing and abnormal tissue. Leave-one-case-out training and cross-validation was used to obtain out-of-sample predictions for each of 30 cases with left hemisphere stroke lesions. RESULTS Our method correctly predicted lesion locations for 30/30 un-trained cases. Post-processing with smoothing (8mm FWHM) and cluster-extent thresholding (100 voxels) was found to improve performance. COMPARISON WITH EXISTING METHOD Quantitative evaluations of post-processed out-of-sample predictions on 30 cases revealed high spatial overlap (mean Dice similarity coefficient=0.66) and volume agreement (mean percent volume difference=28.91; Pearsons r=0.97) with manual lesion delineations. CONCLUSIONS Our automated approach agrees with manual tracing. It provides an alternative to automated methods that require multi-modal MRI data, additional control scans, or user interaction to achieve optimal performance. Our fully trained classifier has applications in neuroimaging and clinical contexts.

White matter diffusion abnormalities in patients with psychogenic non-epileptic seizures.

The purpose of this study was to conduct a preliminary investigation of the white matter characteristics in patients with psychogenic non-epileptic seizures (PNES). Diffusion Tensor Imaging (DTI) data were collected at 3T in 16 patients with PNES and 16 age- and sex-matched healthy controls (HC). All patients with PNES had their diagnosis confirmed via video/EEG monitoring; HCs had no comorbid neurological or psychiatric conditions. DTI indices including fractional anisotropy (FA), and mean diffusivity (MD) were calculated and compared between patients with PNES and HCs using Tract-Based Spatial Statistics (TBSS). Significantly higher FA values were observed in patients with PNES in the left corona radiata, left internal and external capsules, left superior temporal gyrus, as well as left uncinate fasciculus (UF) (P<0.05; corrected for multiple comparisons). There was no significant change in other indices between patients with PNES and HCs. These findings suggest that patients with PNES have significantly altered white matter structural connectivity when compared to age- and sex-matched HCs. These abnormalities are present in left hemispheric regions associated with emotion regulation and motor pathways. While the relationship between the pathophysiology of PNES and these abnormalities is not entirely clear, this work provides an initial basis to guide future prospective studies.

Cortical thickness in human V1 associated with central vision loss.

Better understanding of the extent and scope of visual cortex plasticity following central vision loss is essential both for clarifying the mechanisms of brain plasticity and for future development of interventions to retain or restore visual function. This study investigated structural differences in primary visual cortex between normally-sighted controls and participants with central vision loss due to macular degeneration (MD). Ten participants with MD and ten age-, gender-, and education-matched controls with normal vision were included. The thickness of primary visual cortex was assessed using T1-weighted anatomical scans, and central and peripheral cortical regions were carefully compared between well-characterized participants with MD and controls. Results suggest that, compared to controls, participants with MD had significantly thinner cortex in typically centrally-responsive primary visual cortex – the region of cortex that normally receives visual input from the damaged area of the retina. Conversely, peripherally-responsive primary visual cortex demonstrated significantly increased cortical thickness relative to controls. These results suggest that central vision loss may give rise to cortical thinning, while in the same group of people, compensatory recruitment of spared peripheral vision may give rise to cortical thickening. This work furthers our understanding of neural plasticity in the context of adult vision loss.

Retinotopic patterns of background connectivity between V1 and fronto-parietal cortex are modulated by task demands

Attention facilitates the processing of task-relevant visual information and suppresses interference from task-irrelevant information. Modulations of neural activity in visual cortex depend on attention, and likely result from signals originating in fronto-parietal and cingulo-opercular regions of cortex. Here, we tested the hypothesis that attentional facilitation of visual processing is accomplished in part by changes in how brain networks involved in attentional control interact with sectors of V1 that represent different retinal eccentricities. We measured the strength of background connectivity between fronto-parietal and cingulo-opercular regions with different eccentricity sectors in V1 using functional MRI data that were collected while participants performed tasks involving attention to either a centrally presented visual stimulus or a simultaneously presented auditory stimulus. We found that when the visual stimulus was attended, background connectivity between V1 and the left frontal eye fields (FEF), left intraparietal sulcus (IPS), and right IPS varied strongly across different eccentricity sectors in V1 so that foveal sectors were more strongly connected than peripheral sectors. This retinotopic gradient was weaker when the visual stimulus was ignored, indicating that it was driven by attentional effects. Greater task-driven differences between foveal and peripheral sectors in background connectivity to these regions were associated with better performance on the visual task and faster response times on correct trials. These findings are consistent with the notion that attention drives the configuration of task-specific functional pathways that enable the prioritized processing of task-relevant visual information, and show that the prioritization of visual information by attentional processes may be encoded in the retinotopic gradient of connectivty between V1 and fronto-parietal regions.

Damage to white matter bottlenecks contributes to language impairments after left hemispheric stroke

Damage to the white matter underlying the left posterior temporal lobe leads to deficits in multiple language functions. The posterior temporal white matter may correspond to a bottleneck where both dorsal and ventral language pathways are vulnerable to simultaneous damage. Damage to a second putative white matter bottleneck in the left deep prefrontal white matter involving projections associated with ventral language pathways and thalamo-cortical projections has recently been proposed as a source of semantic deficits after stroke. Here, we first used white matter atlases to identify the previously described white matter bottlenecks in the posterior temporal and deep prefrontal white matter. We then assessed the effects of damage to each region on measures of verbal fluency, picture naming, and auditory semantic decision-making in 43 chronic left hemispheric stroke patients. Damage to the posterior temporal bottleneck predicted deficits on all tasks, while damage to the anterior bottleneck only significantly predicted deficits in verbal fluency. Importantly, the effects of damage to the bottleneck regions were not attributable to lesion volume, lesion loads on the tracts traversing the bottlenecks, or damage to nearby cortical language areas. Multivariate lesion-symptom mapping revealed additional lesion predictors of deficits. Post-hoc fiber tracking of the peak white matter lesion predictors using a publicly available tractography atlas revealed evidence consistent with the results of the bottleneck analyses. Together, our results provide support for the proposal that spatially specific white matter damage affecting bottleneck regions, particularly in the posterior temporal lobe, contributes to chronic language deficits after left hemispheric stroke. This may reflect the simultaneous disruption of signaling in dorsal and ventral language processing streams.

The canonical semantic network supports residual language function in chronic post-stroke aphasia: Canonical Networks Support Aphasia Recovery

Current theories of language recovery after stroke are limited by a reliance on small studies. Here, we aimed to test predictions of current theory and resolve inconsistencies regarding right hemispheric contributions to long‐term recovery. We first defined the canonical semantic network in 43 healthy controls. Then, in a group of 43 patients with chronic post‐stroke aphasia, we tested whether activity in this network predicted performance on measures of semantic comprehension, naming, and fluency while controlling for lesion volume effects. Canonical network activation accounted for 22%–33% of the variance in language test scores. Whole‐brain analyses corroborated these findings, and revealed a core set of regions showing positive relationships to all language measures. We next evaluated the relationship between activation magnitudes in left and right hemispheric portions of the network, and characterized how right hemispheric activation related to the extent of left hemispheric damage. Activation magnitudes in each hemispheric network were strongly correlated, but four right frontal regions showed heightened activity in patients with large lesions. Activity in two of these regions (inferior frontal gyrus pars opercularis and supplementary motor area) was associated with better language abilities in patients with larger lesions, but poorer language abilities in patients with smaller lesions. Our results indicate that bilateral language networks support language processing after stroke, and that right hemispheric activations related to extensive left hemispheric damage occur outside of the canonical semantic network and differentially relate to behavior depending on the extent of left hemispheric damage. Hum Brain Mapp 38:1636–1658, 2017.

Interhemispheric Plasticity following Intermittent Theta Burst Stimulation in Chronic Poststroke Aphasia.

The effects of noninvasive neurostimulation on brain structure and function in chronic poststroke aphasia are poorly understood. We investigated the effects of intermittent theta burst stimulation (iTBS) applied to residual language-responsive cortex in chronic patients using functional and anatomical MRI data acquired before and after iTBS. Lateralization index (LI) analyses, along with comparisons of inferior frontal gyrus (IFG) activation and connectivity during covert verb generation, were used to assess changes in cortical language function. Voxel-based morphometry (VBM) was used to assess effects on regional grey matter (GM). LI analyses revealed a leftward shift in IFG activity after treatment. While left IFG activation increased, right IFG activation decreased. Changes in right to left IFG connectivity during covert verb generation also decreased after iTBS. Behavioral correlations revealed a negative relationship between changes in right IFG activation and improvements in fluency. While anatomical analyses did not reveal statistically significant changes in grey matter volume, the fMRI results provide evidence for changes in right and left IFG function after iTBS. The negative relationship between post-iTBS changes in right IFG activity during covert verb generation and improvements in fluency suggests that iTBS applied to residual left-hemispheric language areas may reduce contralateral responses related to language production and facilitate recruitment of residual language areas after stroke.

Distinct effects of trial-driven and task Set-related control in primary visual cortex

Task sets are task-specific configurations of cognitive processes that facilitate task-appropriate reactions to stimuli. While it is established that the trial-by-trial deployment of visual attention to expected stimuli influences neural responses in primary visual cortex (V1) in a retinotopically specific manner, it is not clear whether the mechanisms that help maintain a task set over many trials also operate with similar retinotopic specificity. Here, we address this question by using BOLD fMRI to characterize how portions of V1 that are specialized for different eccentricities respond during distinct components of an attention-demanding discrimination task: cue-driven preparation for a trial, trial-driven processing, task-initiation at the beginning of a block of trials, and task-maintenance throughout a block of trials. Tasks required either unimodal attention to an auditory or a visual stimulus or selective intermodal attention to the visual or auditory component of simultaneously presented visual and auditory stimuli. We found that while the retinotopic patterns of trial-driven and cue-driven activity depended on the attended stimulus, the retinotopic patterns of task-initiation and task-maintenance activity did not. Further, only the retinotopic patterns of trial-driven activity were found to depend on the presence of inter-modal distraction. Participants who performed well on the intermodal selective attention tasks showed strong task-specific modulations of both trial-driven and task-maintenance activity. Importantly, task-related modulations of trial-driven and task-maintenance activity were in opposite directions. Together, these results confirm that there are (at least) two different processes for top-down control of V1: One, working trial-by-trial, differently modulates activity across different eccentricity sectors - portions of V1 corresponding to different visual eccentricities. The second process works across longer epochs of task performance, and does not differ among eccentricity sectors. These results are discussed in the context of previous literature examining top-down control of visual cortical areas.

Retinotopic patterns of functional connectivity between V1 and large-scale brain networks during resting fixation.

Abstract Psychophysical and neurobiological evidence suggests that central and peripheral vision are specialized for different functions. This specialization of function might be expected to lead to differences in the large‐scale functional interactions of early cortical areas that represent central and peripheral visual space. Here, we characterize differences in whole‐brain functional connectivity among sectors in primary visual cortex (V1) corresponding to central, near‐peripheral, and far‐peripheral vision during resting fixation. Importantly, our analyses reveal that eccentricity sectors in V1 have different functional connectivity with non‐visual areas associated with large‐scale brain networks. Regions associated with the fronto‐parietal control network are most strongly connected with central sectors of V1, regions associated with the cingulo‐opercular control network are most strongly connected with near‐peripheral sectors of V1, and regions associated with the default mode and auditory networks are most strongly connected with far‐peripheral sectors of V1. Additional analyses suggest that similar patterns are present during eyes‐closed rest. These results suggest that different types of visual information may be prioritized by large‐scale brain networks with distinct functional profiles, and provide insights into how the small‐scale functional specialization within early visual regions such as V1 relates to the large‐scale organization of functionally distinct whole‐brain networks. HighlightsFunctional connectivity of human V1 varies among eccentricity sectors.Central sectors are more strongly connected to fronto‐parietal networks.Early peripheral sectors are more strongly connected to cingulo‐opercular networks.Far peripheral sectors are more strongly connected to task negative networks.Results provide evidence for distinct connectivity profiles within V1.

Linking left hemispheric tissue preservation to fMRI language task activation in chronic stroke patients

The preservation of near-typical function in distributed brain networks is associated with less severe deficits in chronic stroke patients. However, it remains unclear how task-evoked responses in networks that support complex cognitive functions such as semantic processing relate to the post-stroke brain anatomy. Here, we used recently developed methods for the analysis of multimodal MRI data to investigate the relationship between regional tissue concentration and functional MRI activation evoked during auditory semantic decisions in a sample of 43 chronic left hemispheric stroke patients and 43 age, handedness, and sex-matched controls. Our analyses revealed that closer-to-normal levels of tissue concentration in left temporo-parietal cortex and the underlying white matter correlated with the level of task-evoked activation in distributed regions associated with the semantic network. This association was not attributable to the effects of left hemispheric lesion or brain volumes, and similar results were obtained when using explicit lesion data. Left temporo-parietal tissue concentration and the associated task-evoked activations predicted patient performance on the in-scanner task, and also predicted patient performance on out-of-scanner naming and verbal fluency tasks. Exploratory analyses using the average HCP-842 tractography dataset revealed the presence of fronto-temporal, fronto-parietal, and temporo-parietal semantic network connections in the locations where tissue concentration was found to correlate with task-evoked activation in the semantic network. In summary, our results link the preservation of left posterior temporo-parietal structures with the preservation of task-evoked semantic network function in chronic left hemispheric stroke patients. Speculatively, this relationship may reflect the status of posterior temporo-parietal areas as cortical and white matter convergence zones that support coordinated processing in the distributed semantic network. Damage to these regions may contribute to atypical task-evoked responses during semantic processing in chronic stroke patients.