Holly Bridge

Background: Visual training can improve residual vision in hemianopia, but there is significant variability in patient outcomes which may reflect differences in neural structures preserved after injury. Diffusion MRI tractography offers a means of assessing white-matter microstructure in vivo, however substantial overlap between neighbouring visual pathways complicates attribution of differences to specific tracts. We quantified tract overlap to identify relatively unique pathway segments to assess training-related microstructural change. Methods: Diffusion MRI data was acquired in six participants with homonymous hemianopia before and after 3-6 months of visual training. Tractography was used to reconstruct three pathways implicated in residual vision: lateral geniculate nucleus (LGN)-V1, LGN-V5 and pulvinar-V5, together with secondary superior colliculus-LGN and superior colliculus-pulvinar pathways. Streamline overlap was quantified along neighbouring tracts, and comparison of pre- to post-training fractional anisotropy was restricted to unique or pair-specific non-overlapping segments. Exploratory relationships with visual outcomes were also examined. Results: Fractional anisotropy increased after training in both early and late pair-specific segments of the LGN-V5 pathway in the lesioned hemisphere. In the late segment, this increase was significantly greater than in the corresponding unique LGN-V1 segment, whereas change in the early LGN-V5 segment did not differ significantly from the unique pulvinar-V5 segment. No significant training-related changes were observed in collicular pathways. Brain-behaviour analyses also preferentially implicated LGN-V5: baseline fractional anisotropy was strongly associated with post-training Gabor detection, and training-related fractional anisotropy change showed a positive association with improvement in Gabor detection, although the latter did not survive multiple comparison correction. Conclusion: These findings support a role for the LGN-V5 pathway in visual plasticity after hemianopia and demonstrate the importance of explicitly quantifying tract overlap when attributing microstructural change to small, neighbouring white-matter pathways.

BACKGROUND: Damage to the early visual cortex after an occipital stroke typically results in the loss of conscious vision in the contralateral hemifield. Nonetheless, extensive perceptual training can restore visual motion discrimination in the blind-field. Here, we assessed, in a cohort study, whether improvements transferred to an untrained Gabor detection task and whether awareness within the blind field increased. We then explored the neural underpinnings of these changes. METHODS: Eighteen participants (6 female; aged 24-74 years; >6 months post-stroke) completed at least six months of visual rehabilitation in their blind field. Rehabilitation consisted of participants practicing a two-alternative, forced-choice, motion discrimination task using random dot stimuli, five days/week, at home, at one or two non-overlapping, locations in their blind-field. Each participant also completed two in-lab visits: one pre- and one post-training. A subset returned to the lab for a follow-up visit three months later to assess persistence of recovery. In addition to the trained task, an untrained, drifting-Gabor detection task was used to measure transfer of learning and changes in visual awareness at the trained locations. To investigate neural mechanisms underlying generalisation of improvements, participants completed MRI scanning at each lab visit. Magnetic resonance spectroscopy (MRS) was used to quantify GABA and glutamate concentrations in the ipsilesional motion sensitive area, hMT+, and a control voxel in the sensorimotor cortex. Functional MRI was conducted to assess BOLD signal changes in hMT+ and across the rest of the brain during passive viewing of high contrast Gabor stimuli in the blind field. RESULTS: Participants showed significant improvements in motion direction discrimination (trained task) between pre- and post-training in-lab visits, which generalised to improvements in Gabor detection and awareness (untrained task). Reduced GABA and glutamate in ipsilesional hMT+ was linked to improved Gabor detection, but not awareness. Increased BOLD signals in hMT+ and dorsolateral prefrontal cortex also correlated with improved Gabor detection, while awareness changes were linked to higher-level areas associated with visual attention in the contralesional prefrontal cortex (area 46) and inferior parietal lobule. CONCLUSIONS: Long-term visual rehabilitation using a global motion discrimination task generalised to enhance both detection and awareness of moving Gabors within the blind field of occipital stroke survivors. Improvements were supported by selective changes in brain regions known to be involved in motion perception and attention respectively, suggesting that a broad network supports recovery, which could be targeted to enhance outcomes.

A unilateral lesion in a post-geniculate section of the retino-geniculo-striate pathway (hereafter: optic pathway) leads to binocular vision loss in the contralateral visual hemifield. The extent of additional damage following such a lesion is not fully understood. Although degeneration of the ipsilesional optic tract and both retinas has been reported, potential degeneration in the contralesional post-chiasmal optic pathway has largely been overlooked. We aimed to investigate the presence and extent of contralesional degeneration in individuals with post-geniculate optic pathway lesions. In this case-control study, we examined the optic pathways of study cohorts with 10 (dataset 1) and 22 (dataset 2) individuals with unilateral post-geniculate lesions and 12 (dataset 1) and 17 (dataset 2) neurologically healthy controls. For both datasets, we applied a higher-order analysis framework, i.e. fixel-based analysis, to diffusion-weighted imaging data to evaluate the white matter of optic pathway tracts. Fixel-based analysis showed reduced fibre density and fibre-bundle cross-section in the ipsi- and contralesional optic pathways. Post-hoc analysis and observations further demonstrated reduced fibre density and fibre-bundle cross-section in the forceps major. In individuals with unilateral post-geniculate optic pathway lesions, degeneration extends beyond their primary site to the optic pathway tracts, including contralesional ones. This pattern of widespread transhemispheric degeneration suggests that it spreads more extensively than previously recognized and highlights the need for understanding its implications for visual function.

Successful navigation and interactions with objects in a complex, three-dimensional (3D) world are essential to survival, yet studies of the neural basis of visual perception and action often treat the world as a flat, two-dimensional (2D) canvas. Here, we review recent discoveries about how the visual systems of different mammals have adapted under the constraint of a 3D world. Many neurons in primate visual cortex are sensitive to 3D depth cues constructed from input differences to the two eyes (binocular disparities). Similar neuronal selectivity has recently been characterized in tree shrews and mice, though constrained anatomically and functionally. Disparity-sensitive receptive field structures can now be assessed noninvasively across human visual cortex and functionally linked to depth perception. At later stages in the nonhuman primate (NHP) ventral (“what”) pathway, supporting object recognition, complex 3D objects are represented as spatial configurations of geometric parts. In studies of the dorsal (“where”/“how”) pathway of NHPs, underlying visuospatial processing, the inclusion of 3D structure in visual tasks has established tighter links between neuronal mechanisms and perception. This has also revealed neuronal representations of 3D object position and orientation that are tolerant to 3D gaze location, providing a basis for robust perception and action. The cross-species analysis presented here provides new perspectives on neural coding mechanisms underpinning the richness of 3D visual experience. Elucidation of these mechanisms will be essential for understanding the neural basis of cognition and behavior, which in turn will enable the development of therapies and neuroprosthetics for those suffering from visual impairments.

The population receptive field (pRF) approach to functional measurement of the sensory properties of magnetic resonance (MR)-identified locations in the human brain was extended to include the third dimension of binocular depth. In total, pRFs were extracted from nine different visual areas (V1, V2, V3, V3AB, V4, V5, V7, Ventral Occipital Cortex: VOC, Lateral Occipital Cortex: LOC) of the human cortex and, where possible, comparisons were made with electrophysiological recordings from homologous areas in the macaque cortex. Human and macaque V1 showed strikingly similar information profiles for the encoding of binocular depth. Further, both human and macaque V5 showed consistent changes in preferred binocular depth of the stimulus, dependent on whether the stimuli were binocularly correlated or anticorrelated. Across the nine areas of the visual cortex explored, the population profiles of pRFs for binocular depth showed evidence of a greater responsiveness to relative depth in higher visual cortical areas, again consistent with the findings from macaque electrophysiology. Overall, the pRF measures of cortical response were more sensitive to fine-scale differences of binocular depth, compared with many existing electrophysiological measures of tuning for binocular depth. Our results show that the pRF method can be extended beyond the characterization of RFs in retinotopic coordinates to reveal higher-order, derived visual properties. The parallels between noninvasive, MR-based measures of pRFs in humans and the electrophysiological recordings of single neurons in experimental animals make a further step toward validation of the pRF methodology.

The Superior Colliculus (SC) is a multimodal integration midbrain structure receiving input from various sensory systems (visual, auditory, and somatosensory) and using this information to guide rapid, reflexive responses. Research using invasive animal model techniques has extensively characterized the SC connectional fingerprint and subcomponent differentiation. However, the extent to which these findings can be generalized to humans remains largely unknown. Here, we developed a fully data-driven approach to examine the wiring diagram of each voxel in the human SC in a cohort of 200 participants. Using diffusion MRI to infer probabilistic tractography, we identified three subregions within the human SC with distinct topography and unique brain-wide connectivity patterns. A superficial division is primarily linked with visual cortical areas, the amygdala, and the posterior thalamus. An intermediate-lateral division is connected predominantly with the auditory and somatosensory cortices and with sectors of the posterior parietal cortex. A deep subregion exhibits preferential connectivity with the brainstem and cerebellum. These in vivo features highlight the heterogeneity in the extrinsic connectivity of the human SC. Probabilistic coupling partly reflects conserved SC interaction motifs reported in other mammals with direct tracing methods, while also showing potential adaptations of cortical–midbrain interactions compatible with human neocortical expansion.

Sleep is often disrupted after stroke. However, little is known about how stroke lesion extent or location influences sleep, particularly at the chronic stage of recovery. In this pragmatic study, we aimed to explore whether lesion characteristics could explain sleep variability in chronic stroke survivors. We analysed previously collected structural brain images (Magnetic Resonance Imaging) from 38 stroke participants (11 female, mean (SD) age 64 (12), mean (SD) time since stroke 95 (66) months) and sleep data (questionnaires (N=38, actigraphy (N=37), and electrophysiology (N=18)) which were collected in their home environment. Neither lesion volume nor lesion overlap with regions of interest (brainstem, basal ganglia, amygdala, hippocampus, thalamus) significantly predicted interindividual variability in subjective or objective sleep measures. However, a data-driven approach revealed clusters of voxels disconnected by the stroke lesions were linked to lower spindle density and amplitude (threshold free cluster enhancement p < 0.050). Overall, these results provide preliminary insights that lesion induced brain disconnection, rather than the extent and overlap of the lesion with grey matter regions, may be more informative when explaining sleep variability. However, larger prospective studies are needed to fully understand the effect of stroke lesions on sleep.

Binocular disparity is used for perception and action in three dimensions. Neurons in the primary visual cortex respond to binocular disparity in random dot patterns, even when the contrast is inverted between eyes (false depth cue). In contrast, neurons in the ventral stream largely cease to respond to false depth cues. This study evaluated whether GABAergic inhibition is involved in suppressing false depth cues in the human ventral visual cortex. We compared GABAergic inhibition (GABA+) and glutamatergic excitation (Glx) during the viewing of correlated and anticorrelated binocular disparity in 18 participants using single-voxel proton magnetic resonance spectroscopy. Measurements were taken from the early visual cortex (EVC) and the lateral occipital cortex (LO). Three visual conditions were presented per voxel location: correlated binocular disparity, anticorrelated binocular disparity, or a blank gray screen with a fixation cross. To identify differences in neurochemistry, GABA+ or Glx levels were compared across viewing conditions. In EVC, correlated disparity increased Glx over anticorrelated and rest conditions, also mirrored in the Glx/GABA+ ratio. In LO, anticorrelated disparity decreased GABA+ and increased Glx. The Glx/GABA+ ratio showed increased excitatory over inhibitory drive to anticorrelated disparity in LO. Glx during viewing of anticorrelation in LO was predictive of object-selective BOLD activity in the same region. We provide evidence that early and ventral visual cortices change GABA+ and Glx concentrations during presentation of correlated and anticorrelated disparity, suggesting a contribution of cortical excitation and inhibition to disparity selectivity.

Our visual percept of small differences in depth is largely informed by binocular stereopsis, the ability to decode depth from the horizontal offset between the retinal images in each eye. While multiple cortical areas are associated with stereoscopic processing, it is unclear how tuning to specific binocular disparities is organized across the human visual cortex. We used 3 T functional magnetic resonance imaging to generate population receptive fields (pRFs) in response to modulation of binocular disparity to characterize the neural tuning to disparity. We also used psychophysics to measure stereoacuity thresholds compared with backgrounds at different depths (pedestal disparity). Ten human participants (seven females) observed correlated or anticorrelated random-dot stereograms with disparity ranging from −0.3 to 0.3°, and responses were modeled as one-dimensional tuning curves along the depth dimension. First, we demonstrate that lateral and dorsal visual areas show the greatest proportion of vertices selective for binocular disparity. Second, with binocularly correlated stimuli, we show a polynomial relationship between preferred disparity and tuning curve width, with sharply tuned disparity responses at near-zero disparities, and broader disparity tuning profiles at near or far disparities. This relationship held across visual areas and was not present for anticorrelated stimuli. Finally, the individual thresholds for psychophysical stereoacuity at the three different pedestal disparities were broadly related to pRF tuning width in area V1, suggesting a possible limit for fine stereopsis at the earliest level of cortical processing. Together, these findings point to heterogeneity of disparity processing across human visual areas, comparable with nonhuman primates.

Damage to the primary visual cortex (V1) results in visual field deficits on the contralateral side of the world corresponding to the damaged region. Patients with such loss nonetheless show varying residual vision within this apparently blind region, with the neural mechanisms underlying this ability obscured by small study populations. We identified lesions on structural scans from 39 patients (12 female) with hemianopia and occipital lobe damage. We estimated the proportion of damage throughout the visual cortex and correlated this with performance in up to three different tests of residual vision in the blind field. We then performed voxel-based lesion–symptom mapping (VLSM) to determine the precise neural regions associated with residual vision. V1 damage did not show a relationship with residual vision measured with any task, although the extent of damage to V4 and hMT+/V5 both correlated with the ability to detect contrast-modulated stimuli. Indeed, damage to hMT+/V5 severely impacted performance across all three tasks, particularly motion detection. Although hMT+/V5 appeared necessary for residual vision, some patients with intact hMT+/V5 had no residual vision, indicating this area alone was not sufficient. VLSM revealed that damage to the optic radiation laterally was most highly associated with poor residual vision. Thus, VLSM indicates that hMT+/V5 and the optic radiation specifically are critical for residual vision in hemianopia.