Exploring the physiological correlates of chronic mild traumatic brain injury symptoms.
ABSTRACT: We report on the results of a multimodal imaging study involving behavioral assessments, evoked and resting-state BOLD fMRI, and DTI in chronic mTBI subjects. We found that larger task-evoked BOLD activity in the MT+/LO region in extra-striate visual cortex correlated with mTBI and PTSD symptoms, especially light sensitivity. Moreover, higher FA values near the left optic radiation (OR) were associated with both light sensitivity and higher BOLD activity in the MT+/LO region. The MT+/LO region was localized as a region of abnormal functional connectivity with central white matter regions previously found to have abnormal physiological signals during visual eye movement tracking (Astafiev et al., 2015). We conclude that mTBI symptoms and light sensitivity may be related to excessive responsiveness of visual cortex to sensory stimuli. This abnormal sensitivity may be related to chronic remodeling of white matter visual pathways acutely injured.
Project description:The neural substrate of the phenomenological experience of a stable visual world remains obscure. One possible mechanism would be to construct spatiotopic neural maps where the response is selective to the position of the stimulus in external space, rather than to retinal eccentricities, but evidence for these maps has been inconsistent. Here we show, with fMRI, that when human subjects perform concomitantly a demanding attentive task on stimuli displayed at the fovea, BOLD responses evoked by moving stimuli irrelevant to the task were mostly tuned in retinotopic coordinates. However, under more unconstrained conditions, where subjects could attend easily to the motion stimuli, BOLD responses were tuned not in retinal but in external coordinates (spatiotopic selectivity) in many visual areas, including MT, MST, LO and V6, agreeing with our previous fMRI study. These results indicate that spatial attention may play an important role in mediating spatiotopic selectivity.
Project description:Concussion, or mild traumatic brain injury (mTBI), can cause persistent behavioral symptoms and cognitive impairment, but it is unclear if this condition is associated with detectable structural or functional brain changes. At two sites, chronic mTBI human subjects with persistent post-concussive symptoms (three months to five years after injury) and age- and education-matched healthy human control subjects underwent extensive neuropsychological and visual tracking eye movement tests. At one site, patients and controls also performed the visual tracking tasks while blood-oxygen-level-dependent (BOLD) signals were measured with functional magnetic resonance imaging. Although neither neuropsychological nor visual tracking measures distinguished patients from controls at the level of individual subjects, abnormal BOLD signals were reliably detected in patients. The most consistent changes were localized in white matter regions: anterior internal capsule and superior longitudinal fasciculus. In contrast, BOLD signals were normal in cortical regions, such as the frontal eye field and intraparietal sulcus, that mediate oculomotor and attention functions necessary for visual tracking. The abnormal BOLD signals accurately differentiated chronic mTBI patients from healthy controls at the single-subject level, although they did not correlate with symptoms or neuropsychological performance. We conclude that subjects with persistent post-concussive symptoms can be identified years after their TBI using fMRI and an eye movement task despite showing normal structural MRI and DTI.
Project description:What is the relationship between retinotopy and object selectivity in human lateral occipital (LO) cortex? We used functional magnetic resonance imaging (fMRI) to examine sensitivity to retinal position and category in LO, an object-selective region positioned posterior to MT along the lateral cortical surface. Six subjects participated in phase-encoded retinotopic mapping experiments as well as block-design experiments in which objects from six different categories were presented at six distinct positions in the visual field. We found substantial position modulation in LO using standard nonobject retinotopic mapping stimuli; this modulation extended beyond the boundaries of visual field maps LO-1 and LO-2. Further, LO showed a pronounced lower visual field bias: more LO voxels represented the lower contralateral visual field, and the mean LO response was higher to objects presented below fixation than above fixation. However, eccentricity effects produced by retinotopic mapping stimuli and objects differed. Whereas LO voxels preferred a range of eccentricities lying mostly outside the fovea in the retinotopic mapping experiment, LO responses were strongest to foveally presented objects. Finally, we found a stronger effect of position than category on both the mean LO response, as well as the distributed response across voxels. Overall these results demonstrate that retinal position exhibits strong effects on neural response in LO and indicates that these position effects may be explained by retinotopic organization.
Project description:<h4>Introduction</h4>Following mild traumatic brain injury (mTBI), a substantial number of patients experience disabling fatigue for months after the initial injury. To date, the underlying mechanisms of fatigue remain unclear. Recently, it was shown that mTBI patients with persistent fatigue do not demonstrate increased performance fatigability (i.e., objective performance decline) during a sustained motor task. However, it is not known whether the neural activation required to sustain this performance is altered after mTBI.<h4>Methods</h4>Blood oxygen level-dependent (BOLD) fMRI data were acquired from 19 mTBI patients (>3 months post-injury) and 19 control participants during two motor tasks. Force was recorded from the index finger abductors of both hands during submaximal contractions and a 2-minute maximal voluntary contraction (MVC) with the right hand. Voluntary muscle activation (i.e., CNS drive) was indexed during the sustained MVC using peripheral nerve stimulation. Fatigue was quantified using the Fatigue Severity Scale (FSS) and Modified Fatigue Impact Scale (MFIS). Questionnaire, task, and BOLD data were compared across groups, and linear regression was used to evaluate the relationship between BOLD-activity and fatigue in the mTBI group.<h4>Results</h4>The mTBI patients reported significantly higher levels of fatigue (FSS: 5.3 vs. 2.6, p < 0.001). Both mTBI- and control groups demonstrated significant performance fatigability during the sustained MVC, but no significant differences in task performance or BOLD-activity were observed between groups. However, mTBI patients reporting higher FSS scores showed increased BOLD-activity in the bilateral visual cortices (mainly extrastriate) and the left midcingulate gyrus. Furthermore, across all participants mean voluntary muscle activation during the sustained MVC correlated with long lasting post-contraction BOLD-activation in the right insula and midcingulate cortex.<h4>Conclusion</h4>The fMRI findings suggest that self-reported fatigue in mTBI may relate to visual processing and effort perception. Long lasting activation associated with high levels of CNS drive might be related to changes in cortical homeostasis in the context of high effort.
Project description:Approximately, 275,000 American service members deployed to Iraq or Afghanistan have sustained a mild traumatic brain injury (mTBI), with 75% of these incidents involving an explosive blast. Visual processing problems and cognitive dysfunction are common complaints following blast-related mTBI.In 127 veterans, we examined resting fMRI functional connectivity (FC) of four key nodes within the visual system: lateral geniculate nucleus (LGN), primary visual cortex (V1), lateral occipital gyrus (LO), and fusiform gyrus (FG). Regression analyses were performed (i) to obtain correlations between time-series from each seed and all voxels in the brain, and (ii) to identify brain regions in which FC variability was related to blast mTBI severity. Blast-related mTBI severity was quantified as the sum of the severity scores assigned to each of the three most significant blast-related injuries self-reported by subjects. Correlations between FC and performance on executive functioning tasks were performed across participants with available behavioral data (n = 94).Greater blast mTBI severity scores were associated with lower FC between: (A) LGN seed and (i) medial frontal gyrus, (ii) lingual gyrus, and (iii) right ventral anterior nucleus of thalamus; (B) V1 seed and precuneus; (C) LO seed and middle and superior frontal gyri; (D) FG seed and (i) superior and medial frontal gyrus, and (ii) left middle frontal gyrus. Finally, lower FC between visual network regions and frontal cortical regions predicted worse performance on the WAIS digit-symbol coding task.These are the first published results that directly illustrate the relationship between blast-related mTBI severity, visual pathway neural networks, and executive dysfunction - results that highlight the detrimental relationship between blast-related brain injury and the integration of visual sensory input and executive processes.
Project description:Although optically based imaging techniques provide valuable functional and physiological information of the retina, they are mostly limited to the probing of the retinal surface and require an unobstructed light path. MRI, in contrast, could offer physiological and functional data without depth limitation. Blood oxygenation level-dependent functional MRI (BOLD fMRI) of the thin rat retina is, however, challenging because of the need for high spatial resolution, and the potential presence of eye movement and susceptibility artifacts. This study reports a novel application of high-resolution (111 × 111 × 1000 µm(3)) BOLD fMRI of visual stimulation in the anesthetized rat retina at 11.7 T. A high-field MRI scanner was utilized to improve the signal-to-noise ratio, spatial resolution and BOLD sensitivity. Visual stimuli (8 Hz diffuse achromatic light) robustly increased BOLD responses in the retina [5.0 ± 0.8% from activated pixels and 3.1 ± 1.1% from the whole-retina region of interest (mean ± SD), n = 12 trials on six rats, p < 0.05 compared with baseline]. Some activated pixels were detected surrounding the pupil and ciliary muscle because of accommodation reflex to visual stimuli, and were reduced with atropine and phenylephrine eye drops. BOLD fMRI scans without visual stimulations showed no significantly activated pixels (whole-retina BOLD changes were 0.08 ± 0.34%, n = 6 trials on five rats, not statistically different from baseline, p > 0.05). BOLD fMRI of visual stimulation has the potential to provide clinically relevant data to probe hemodynamic neurovascular coupling and dysfunction of the retina with depth resolution.
Project description:Functional magnetic resonance imaging (fMRI) is increasingly used in cognitive neuroscience and has become a valuable tool in the study of auditory processing in zebra finches, a well-established model of learned vocal communication. Due to its sensitivity to head motion, most fMRI studies in animals are performed in anaesthetized conditions, which might significantly impact neural activity evoked by stimuli and cognitive tasks. In this study, we (1) demonstrate the feasibility of fMRI in awake zebra finches and (2) explore how light anaesthesia regimes affect auditory-evoked BOLD responses to biologically relevant songs. After an acclimation procedure, we show that fMRI can be successfully performed during wakefulness, enabling the detection of reproducible BOLD responses to sound. Additionally, two light anaesthesia protocols were tested (isoflurane and a combination of medetomidine and isoflurane), of which isoflurane alone appeared to be the most promising given the high success rate, non-invasive induction, and quick recovery. By comparing auditory evoked BOLD responses in awake versus lightly anaesthetized conditions, we observed overall effects of anaesthetics on cerebrovascular reactivity as reflected in the extent of positive and negative BOLD responses. Further, our results indicate that light anaesthesia has limited effects on selective BOLD responses to natural versus synthetic sounds.
Project description:To investigate whether individuals' ongoing neuronal activity at resting state can affect their response to brain stimulation, fMRI BOLD signals were imaged from the human visual cortex of fifteen healthy subjects in the absence and presence of visual stimulation. It was found that the temporal correlation strength but not amplitude of baseline BOLD signal fluctuations acquired under the eyes-fixed condition is positively correlated with the amplitude of stimulus-evoked BOLD responses across subjects. Moreover, the spatiotemporal correlations of baseline BOLD signals imply a coherent network covering the visual system, which is topographically indistinguishable from the "resting-state visual network" observed under the eyes-closed condition. The overall findings suggest that the synchronization of ongoing brain activity plays an important role in determining stimulus-evoked brain activity even at an early stage of the sensory system. The tight relationship between baseline BOLD correlation and stimulus-evoked BOLD amplitude provides an essential basis for understanding and interpreting the large inter-subject BOLD variability commonly observed in numerous fMRI studies and potentially for improving group fMRI analysis. This study highlights the importance to integrate the information from both resting-state coherent networks and task-evoked neural responses for a better understanding of how the brain functions.
Project description:The shape of the blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) signal can vary considerably even across structures of the same sensory pathway. Here, we characterized the temporal behavior of the stimulus-evoked BOLD response in the primary cortical and subcortical regions of the visual and somatosensory whisker systems in awake rabbits. Despite similar BOLD responses in the thalamic nuclei, considerable differences in shape and duration emerged between the sensory cortices. Whereas the BOLD response in the whisker barrel cortex (WBC) was non-adaptive, BOLD in the visual cortex (V1) showed adaptation similar to simultaneously-recorded LFP and single unit activity. Analysis of baseline neuronal activity revealed significantly lower firing rates in V1 vs. WBC. We hypothesized that these changes point to region-dependent differences in the inhibitory systems which shape the hemodynamic response in each structure. To test the effect of neuronal baseline level inhibition on the BOLD signal shape, we locally injected the GABAA agonist muscimol in WBC. Adaptation emerged in the BOLD response after injection, along with an overall decrease in baseline firing rate. These findings point to the importance of region-specific inhibitory shaping in determining the temporal behavior of the BOLD response in different brain areas.
Project description:Damage to the primary visual cortex (V1) leads to a visual field loss (scotoma) in the retinotopically corresponding part of the visual field. Nonetheless, a small amount of residual visual sensitivity persists within the blind field. This residual capacity has been linked to activity observed in the middle temporal area complex (V5/MT+). However, it remains unknown whether the organization of hV5/MT+ changes following early visual cortical lesions. We studied the organization of area hV5/MT+ of five patients with dense homonymous defects in a quadrant of the visual field as a result of partial V1+ or optic radiation lesions. To do so, we developed a new method, which models the boundaries of population receptive fields directly from the BOLD signal of each voxel in the visual cortex. We found responses in hV5/MT+ arising inside the scotoma for all patients and identified two possible sources of activation: 1) responses might originate from partially lesioned parts of area V1 corresponding to the scotoma, and 2) responses can also originate independent of area V1 input suggesting the existence of functional V1-bypassing pathways. Apparently, visually driven activity observed in hV5/MT+ is not sufficient to mediate conscious vision. More surprisingly, visually driven activity in corresponding regions of V1 and early extrastriate areas including hV5/MT+ did not guarantee visual perception in the group of patients with post-geniculate lesions that we examined. This suggests that the fine coordination of visual activity patterns across visual areas may be an important determinant of whether visual perception persists following visual cortical lesions.