White matter tracts adjacent to the human cingulate sulcus visual area (CSv).

Human cingulate sulcus visual area (CSv) was first identified as an area that responds selectively to visual stimulation indicative of self-motion. It was later shown that the area is also sensitive to vestibular stimulation as well as to bodily motion compatible with locomotion. Understanding the anatomical connections of CSv will shed light on how CSv interacts with other parts of the brain to perform information processing related to self-motion and navigation. A previous neuroimaging study (Smith et al. 2018, Cerebral Cortex, 28, 3685-3596) used diffusion-weighted magnetic resonance imaging (dMRI) to examine the structural connectivity of CSv, and demonstrated connections between CSv and the motor and sensorimotor areas in the anterior and posterior cingulate sulcus. The present study aimed to complement this work by investigating the relationship between CSv and adjacent major white matter tracts, and to map CSv's structural connectivity onto known white matter tracts. By re-analysing the dataset from Smith et al. (2018), we identified bundles of fibres (i.e. streamlines) from the whole-brain tractography that terminate near CSv. We then assessed to which white matter tracts those streamlines may belong based on previously established anatomical prescriptions. We found that a significant number of CSv streamlines can be categorised as part of the dorsalmost branch of the superior longitudinal fasciculus (SLF I) and the cingulum. Given current thinking about the functions of these white matter tracts, our results support the proposition that CSv provides an interface between sensory and motor systems in the context of self-motion.

Functional and Structural Properties of Interhemispheric Interaction between Bilateral Precentral Hand Motor Regions in a Top Wheelchair Racing Paralympian.

Long-term motor training can cause functional and structural changes in the human brain. Assessing how the training of specific movements affects specific parts of the neural circuitry is essential to understand better the underlying mechanisms of motor training-induced plasticity in the human brain. We report a single-case neuroimaging study that investigated functional and structural properties in a professional athlete of wheelchair racing. As wheelchair racing requires bilateral synchronization of upper limb movements, we hypothesized that functional and structural properties of interhemispheric interactions in the central motor system might differ between the professional athlete and controls. Functional and diffusion magnetic resonance imaging (fMRI and dMRI) data were obtained from a top Paralympian (P1) in wheelchair racing. With 23 years of wheelchair racing training starting at age eight, she holds an exceptional competitive record. Furthermore, fMRI and dMRI data were collected from three other paraplegic participants (P2-P4) with long-term wheelchair sports training other than wheelchair racing and 37 able-bodied control volunteers. Based on the fMRI data analyses, P1 showed activation in the bilateral precentral hand sections and greater functional connectivity between these sections during a right-hand unimanual task. In contrast, other paraplegic participants and controls showed activation in the contralateral hemisphere and deactivation in the ipsilateral hemisphere. Moreover, dMRI data analysis revealed that P1 exhibited significantly lower mean diffusivity along the transcallosal pathway connecting the bilateral precentral motor regions than control participants, which was not observed in the other paraplegic participants. These results suggest that long-term training with bilaterally synchronized upper-limb movements may promote bilateral recruitment of the precentral hand sections. Such recruitment may affect the structural circuitry involved in the interhemispheric interaction between the bilateral precentral regions. This study provides valuable evidence of the extreme adaptability of the human brain.

Evaluation of simultaneous multi-slice readout-segmented diffusion-weighted MRI acquisition in human optic nerve measurements.

Diffusion-weighted magnetic resonance imaging (dMRI) is the only available method to measure the tissue properties of white matter tracts in living human brains and has opened avenues for neuroscientific and clinical studies on human white matter. However, dMRI using conventional simultaneous multi-slice (SMS) single-shot echo planar imaging (ssEPI) still presents challenges in the analyses of some specific white matter tracts, such as the optic nerve, which are heavily affected by susceptibility-induced artifacts. In this study, we evaluated dMRI data acquired by using SMS readout-segmented EPI (rsEPI), which aims to reduce susceptibility-induced artifacts by dividing the acquisition space into multiple segments along the readout direction to reduce echo spacing. To this end, we acquired dMRI data from 11 healthy volunteers by using SMS ssEPI and SMS rsEPI, and then compared the dMRI data of the human optic nerve between the SMS ssEPI and SMS rsEPI datasets by visual inspection of the datasets and statistical comparisons of fractional anisotropy (FA) values. In comparison with the SMS ssEPI data, the SMS rsEPI data showed smaller susceptibility-induced distortion and exhibited a significantly higher FA along the optic nerve. In summary, this study demonstrates that despite its prolonged acquisition time, SMS rsEPI is a promising approach for measuring the tissue properties of the optic nerve in living humans and will be useful for future neuroscientific and clinical investigations of this pathway.

Macromolecular tissue volume mapping of lateral geniculate nucleus subdivisions in living human brains.

The lateral geniculate nucleus (LGN) is a key thalamic nucleus in the visual system, which has an important function in relaying retinal visual input to the visual cortex. The human LGN is composed mainly of magnocellular (M) and parvocellular (P) subdivisions, each of which has different stimulus selectivity in neural response properties. Previous studies have discussed the potential relationship between LGN subdivisions and visual disorders based on psychophysical data on specific types of visual stimuli. However, these relationships remain speculative because non-invasive measurements of these subdivisions are difficult due to the small size of the LGN. Here we propose a method to identify these subdivisions by combining two structural MR measures: high-resolution proton-density weighted images and macromolecular tissue volume (MTV) maps. We defined the M and P subdivisions based on MTV fraction data and tested the validity of the definition by (1) comparing the data with that from human histological studies, (2) comparing the data with functional magnetic resonance imaging measurements on stimulus selectivity, and (3) analyzing the test-retest reliability. The findings demonstrated that the spatial organization of the M and P subdivisions was consistent across subjects and in line with LGN subdivisions observed in human histological data. Moreover, the difference in stimulus selectivity between the subdivisions identified using MTV was consistent with previous physiology literature. The definition of the subdivisions based on MTV was shown to be robust over measurements taken on different days. These results suggest that MTV mapping is a promising approach for evaluating the tissue properties of LGN subdivisions in living humans. This method potentially will enable neuroscientific and clinical hypotheses about the human LGN subdivisions to be tested.

Structural covariance and heritability of the optic tract and primary visual cortex in living human brains.

Individual differences among human brains exist at many scales, spanning gene expression, white matter tissue properties, and the size and shape of cortical areas. One notable example is an approximately 3-fold range in the size of human primary visual cortex (V1), a much larger range than is found in overall brain size. A previous study (Andrews et al., 1997) reported a correlation between optic tract cross-section area and V1 size in post-mortem human brains, suggesting that there may be a common developmental mechanism for multiple components of the visual pathways. We evaluated the relationship between properties of the optic tract and V1 in a much larger sample of living human brains by analyzing the Human Connectome Project 7 Tesla Retinotopy Dataset (including 107 females and 71 males). This dataset includes retinotopic maps measured with functional MRI (fMRI) and fiber tract data measured with diffusion MRI (dMRI). We found a negative correlation between optic tract fractional anisotropy and V1 surface area (r = -0.19). This correlation, though small, was consistent across multiple dMRI datasets differing in acquisition parameters. Further, we found that both V1 size and optic tract properties were correlated among twins, with higher correlations for monozygotic than dizygotic twins, indicating a high degree of heritability for both properties. Together, these results demonstrate covariation across individuals in properties of the retina (optic tract) and cortex (V1) and show that each is influenced by genetic factors.SIGNIFICANCE STATEMENT:The size of human primary visual cortex (V1) has large inter-individual differences. These differences do not scale with overall brain size. A previous post-mortem study reported a correlation between the size of the human optic tract and V1. In this study, we evaluated the relationship between the optic tract and V1 in living humans by analyzing a neuroimaging dataset that included functional and diffusion MRI data. We found a small, but robust correlation between optic tract tissue properties and V1 size, supporting the existence of structural covariance between the optic tract and V1 in living humans. The results suggest that characteristics of retinal ganglion cells, reflected in optic tract measurements, are related to individual differences in human V1.

Hyper-Adaptation in the Human Brain: Functional and Structural Changes in the Foot Section of the Primary Motor Cortex in a Top Wheelchair Racing Paralympian.

The human brain has the capacity to drastically alter its somatotopic representations in response to congenital or acquired limb deficiencies and dysfunctions. The main purpose of the present study was to elucidate such extreme adaptability in the brain of an active top wheelchair racing Paralympian (participant P1) who has congenital paraplegia (dysfunction of bilateral lower limbs). Participant P1 has undergone long-term wheelchair racing training using bilateral upper limbs and has won a total of 19 medals in six consecutive summer Paralympic games as of 2021. We examined the functional and structural changes in the foot section of the primary motor cortex (M1) in participant P1 as compared to able-bodied control participants. We also examined the functional and structural changes in three other individuals (participants P2, P3, and P4) with acquired paraplegia, who also had long-term non-use period of the lower limbs and had undergone long-term training for wheelchair sports (but not top athletes at the level of participant P1). We measured brain activity in all the participants using functional magnetic resonance imaging (MRI) when bimanual wrist extension-flexion movement was performed, and the structural MRI images were collected. Compared to 37 control participants, participant P1 showed significantly greater activity in the M1 foot section during the bimanual task, and significant local GM expansion in this section. Significantly greater activity in the M1 foot section was also observed in participant P4, but not in P2 and P3, and the significant local GM expansion was observed in participant P2, but not in P3 and P4. Thus, functional or structural change was observed in an acquired paraplegic participant, but was not observed in all the paraplegic participants. The functional and structural changes typically observed in participant P1 may represent extreme adaptability of the human brain. We discuss the results in terms of a new idea of hyper-adaptation.

Multi-Contrast Magnetic Resonance Imaging of Visual White Matter Pathways in Patients With Glaucoma.

Purpose: Glaucoma is a disorder that involves visual field loss caused by retinal ganglion cell damage. Previous diffusion magnetic resonance imaging (dMRI) studies have demonstrated that retinal ganglion cell damage affects tissues in the optic tract (OT) and optic radiation (OR). However, because previous studies have used a simple diffusion tensor model to analyze dMRI data, the microstructural interpretation of white matter tissue changes remains uncertain. In this study, we used a multi-contrast MRI approach to further clarify the type of microstructural damage that occurs in patients with glaucoma. Methods: We collected dMRI data from 17 patients with glaucoma and 30 controls using 3-tesla (3T) MRI. Using the dMRI data, we estimated three types of tissue property metrics: intracellular volume fraction (ICVF), orientation dispersion index (ODI), and isotropic volume fraction (IsoV). Quantitative T1 (qT1) data, which may be relatively specific to myelin, were collected from all subjects. Results: In the OT, all four metrics showed significant differences between the glaucoma and control groups. In the OR, only the ICVF showed significant between-group differences. ICVF was significantly correlated with qT1 in the OR of the glaucoma group, although qT1 did not show any abnormality at the group level. Conclusions: Our results suggest that, at the group level, tissue changes in OR caused by glaucoma might be explained by axonal damage, which is reflected in the intracellular diffusion signals, rather than myelin damage. The significant correlation between ICVF and qT1 suggests that myelin damage might also occur in a smaller number of severe cases.

Age dependency and lateralization in the three branches of the human superior longitudinal fasciculus.

The superior longitudinal fascicle/fasciculus (SLF) is a major white matter tract connecting the frontal and parietal cortices in humans. Although the SLF has often been analyzed as a single entity, several studies have reported that the SLF is segregated into three distinct branches (SLF I, II, and III). They have also reported the right lateralization of the SLF III volume and discussed its relationship with lateralized cortical functions in the fronto-parietal network. However, to date, the homogeneity or heterogeneity of the age dependency and lateralization properties of SLF branches have not been fully clarified. Through this study, we aimed to clarify the age dependency and lateralization of SLF I-III by analyzing diffusion-weighted MRI (dMRI) and quantitative R1 (qR1) map datasets collected from a wide range of age groups, mostly comprising right-handed children, adolescents, adults, and seniors (6 to 81 years old). The age dependency in dMRI measurement (fractional anisotropy, FA) was heterogeneous among the three SLF branches, suggesting that these branches are regulated by distinct developmental and aging processes. Lateralization analysis on SLF branches revealed that the right SLF III was larger than the left SLF III in adults, replicating previous reports. FA measurement also suggested that, in addition to SLF III, SLF II was lateralized to the right hemisphere in adolescents and adults. We further found a left lateralization of SLF I in qR1 data, a microstructural measurement sensitive to myelin levels, in adults. These findings suggest that the SLF sub-bundles are distinct entities in terms of age dependency and lateralization.

V1 Projection Zone Signals in Human Macular Degeneration Depend on Task Despite Absence of Visual Stimulus.

Identifying the plastic and stable components of the visual cortex after retinal loss is an important topic in visual neuroscience and neuro-ophthalmology.1-5 Humans with juvenile macular degeneration (JMD) show significant blood-oxygen-level-dependent (BOLD) responses in the primary visual area (V1) lesion projection zone (LPZ),6 despite the absence of the feedforward signals from the degenerated retina. Our previous study7 reported that V1 LPZ responds to full-field visual stimuli during the one-back task (OBT), not during passive viewing, suggesting the involvement of task-related feedback signals. Aiming to clarify whether visual inputs to the intact retina are necessary for the LPZ responses, here, we measured BOLD responses to tactile and auditory stimuli for both JMD patients and control participants with and without OBT. Participants were instructed to close their eyes during the experiment for the purpose of eliminating retinal inputs. Without OBT, no V1 responses were detected in both groups of participants. With OBT, to the contrary, both stimuli caused substantial V1 responses in JMD patients, but not controls. Furthermore, we also found that the task-dependent activity in V1 LPZ became less pronounced when JMD patients opened their eyes, suggesting that task-related feedback signals can be partially suppressed by residual feedforward signals. Modality-independent V1 LPZ responses only in the task condition suggest that V1 LPZ responses reflect task-related feedback signals rather than reorganized feedforward visual inputs.

Anatomy of nerve fiber bundles at micrometer-resolution in the vervet monkey visual system.

Although the primate visual system has been extensively studied, detailed spatial organization of white matter fiber tracts carrying visual information between areas has not been fully established. This is mainly due to the large gap between tracer studies and diffusion-weighted MRI studies, which focus on specific axonal connections and macroscale organization of fiber tracts, respectively. Here we used 3D polarization light imaging (3D-PLI), which enables direct visualization of fiber tracts at micrometer resolution, to identify and visualize fiber tracts of the visual system, such as stratum sagittale, inferior longitudinal fascicle, vertical occipital fascicle, tapetum and dorsal occipital bundle in vervet monkey brains. Moreover, 3D-PLI data provide detailed information on cortical projections of these tracts, distinction between neighboring tracts, and novel short-range pathways. This work provides essential information for interpretation of functional and diffusion-weighted MRI data, as well as revision of wiring diagrams based upon observations in the vervet visual system.

Predicting Neural Response Latency of the Human Early Visual Cortex from MRI-Based Tissue Measurements of the Optic Radiation.

Although the non-invasive measurement of visually evoked responses has been extensively studied, the structural basis of variabilities in latency in healthy humans is not well understood. We investigated how tissue properties of optic radiation could predict interindividual variability in the latency of the initial visually evoked component (C1), which may originate from the primary visual cortex (V1). We collected C1 peak latency data using magnetoencephalography (MEG) and checkerboard stimuli, and multiple structural magnetic resonance imaging (MRI) data from 20 healthy subjects. While we varied the contrast and position of the stimuli, the C1 measurement was most reliable when high-contrast stimuli were presented to the lower visual field (LVF). We then attempted to predict interindividual variability in C1 peak latency in this stimulus condition with a multiple regression model using MRI parameters along the optic radiation. We found that this model could predict >20% of variance in C1 latency, when the data were averaged across the hemispheres. The model using the corticospinal tract did not predict variability in C1 latency, suggesting that there is no evidence for generalization to a non-visual tract. In conclusion, our results suggest that the variability in neural latencies in the early visual cortex in healthy subjects can be partly explained by tissue properties along the optic radiation. We discuss the challenges of predicting neural latency using current structural neuroimaging methods and other factors that may explain interindividual variance in neural latency.

Spatial organization of occipital white matter tracts in the common marmoset.

The primate brain contains a large number of interconnected visual areas, whose spatial organization and intracortical projections show a high level of conservation across species. One fiber pathway of recent interest is the vertical occipital fasciculus (VOF), which is thought to support communication between dorsal and ventral visual areas in the occipital lobe. A recent comparative diffusion MRI (dMRI) study reported that the VOF in the macaque brain bears a similar topology to that of the human, running superficial and roughly perpendicular to the optic radiation. The present study reports a comparative investigation of the VOF in the common marmoset, a small New World monkey whose lissencephalic brain is approximately tenfold smaller than the macaque and 150-fold smaller than the human. High-resolution ex vivo dMRI of two marmoset brains revealed an occipital white matter structure that closely resembles that of the larger primate species, with one notable difference. Namely, unlike in the macaque and the human, the VOF in the marmoset is spatially fused with other, more anterior vertical tracts, extending anteriorly between the parietal and temporal cortices. We compare several aspects of this continuous structure, which we term the VOF complex (VOF +), and neighboring fasciculi to those of macaques and humans. We hypothesize that the essential topology of the VOF+ is a conserved feature of the posterior cortex in anthropoid primates, with a clearer fragmentation into multiple named fasciculi in larger, more gyrified brains.

Inter-individual Differences in Occipital Alpha Oscillations Correlate with White Matter Tissue Properties of the Optic Radiation.

Neural oscillations at ∼10 Hz, called alpha oscillations, are one of the most prominent components of neural oscillations in the human brain. In recent years, characteristics (power/frequency/phase) of occipital alpha oscillations have been correlated with various perceptual phenomena. However, the relationship between inter-individual differences in alpha oscillatory characteristics and the properties of the underlying brain structures, such as white matter pathways, is unclear. A possibility is that intrinsic occipital alpha oscillations are mediated by thalamocortical interaction; we hypothesized that the most promising candidate for characterizing the intrinsic alpha oscillation is optic radiation (OR), which is the geniculo-cortical pathway carrying signals between the lateral geniculate nucleus (LGN) and primary visual cortex (V1). We used resting-state magnetoencephalography (MEG) and diffusion-weighted/quantitative magnetic resonance imaging (MRI) (dMRI/qMRI) to correlate the frequency and power of occipital alpha oscillations with the tissue properties of the OR by focusing on the different characteristics across individuals. We found that the peak alpha frequency (PAF) negatively correlated with intracellular volume fraction (ICVF), reflecting diffusion properties in intracellular (axonal) space, whereas the peak alpha power was not correlated with any tissue properties measurements. No significant correlation was found between OR and beta frequency/amplitude or between other white matter tract connecting parietal and inferotemporal cortex and alpha frequency/amplitude. These results support the hypothesis that an interaction between thalamic nuclei and early visual areas is essential for the occipital alpha oscillatory rhythm.

Associative white matter connecting the dorsal and ventral posterior human cortex.

Historically, the primary focus of studies of human white matter tracts has been on large tracts that connect anterior-to-posterior cortical regions. These include the superior longitudinal fasciculus (SLF), the inferior longitudinal fasciculus (ILF), and the inferior fronto-occipital fasciculus (IFOF). Recently, more refined and well-understood tractography methods have facilitated the characterization of several tracts in the posterior of the human brain that connect dorsal-to-ventral cortical regions. These include the vertical occipital fasciculus (VOF), the posterior arcuate fasciculus (pArc), the temporo-parietal connection (TP-SPL), and the middle longitudinal fasciculus (MdLF). The addition of these dorso-ventral connective tracts to our standard picture of white matter architecture results in a more complicated pattern of white matter connectivity than previously considered. Dorso-ventral connective tracts may play a role in transferring information from superior horizontal tracts, such as the SLF, to inferior horizontal tracts, such as the IFOF and ILF. We present a full anatomical delineation of these major dorso-ventral connective white matter tracts (the VOF, pArc, TP-SPL, and MdLF). We show their spatial layout and cortical termination mappings in relation to the more established horizontal tracts (SLF, IFOF, ILF, and Arc) and consider standard values for quantitative features associated with the aforementioned tracts. We hope to facilitate further study on these tracts and their relations. To this end, we also share links to automated code that segments these tracts, thereby providing a standard approach to obtaining these tracts for subsequent analysis. We developed open source software to allow reproducible segmentation of the tracts: https://github.com/brainlife/Vertical_Tracts . Finally, we make the segmentation method available as an open cloud service on the data and analyses sharing platform brainlife.io. Investigators will be able to access these services and upload their data to segment these tracts.

Diffusivity and quantitative T1 profile of human visual white matter tracts after retinal ganglion cell damage.

In patients with retinal ganglion cell diseases, recent diffusion tensor imaging (DTI) studies have revealed structural abnormalities in visual white matter tracts such as the optic tract, and optic radiation. However, the microstructural origin of these diffusivity changes is unknown as DTI metrics involve multiple biological factors and do not correlate directly with specific microstructural properties. In contrast, recent quantitative T1 (qT1) mapping methods provide tissue property measurements relatively specific to myelin volume fractions in white matter. This study aims to improve our understanding of microstructural changes in visual white matter tracts following retinal ganglion cell damage in Leber's hereditary optic neuropathy (LHON) patients by combining DTI and qT1 measurements. We collected these measurements from seven LHON patients and twenty age-matched control subjects. For all individuals, we identified the optic tract and the optic radiation using probabilistic tractography, and evaluated diffusivity and qT1 profiles along them. Both diffusivity and qT1 measurements in the optic tract differed significantly between LHON patients and controls. In the optic radiation, these changes were observed in diffusivity but were not evident in qT1 measurements. This suggests that myelin loss may not explain trans-synaptic diffusivity changes in the optic radiation as a consequence of retinal ganglion cell disease.

Comparative neuroanatomy: Integrating classic and modern methods to understand association fibers connecting dorsal and ventral visual cortex.

Comparative neuroanatomy studies improve understanding of brain structure and function and provide insight regarding brain development, evolution, and also what features of the brain are uniquely human. With modern methods such as diffusion MRI (dMRI) and quantitative MRI (qMRI), we are able to measure structural features of the brain with the same methods across human and non-human primates. In this review article, we discuss how recent dMRI measurements of vertical occipital connections in humans and macaques can be compared with previous findings from invasive anatomical studies that examined connectivity, including relatively forgotten classic strychnine neuronography studies. We then review recent progress in understanding the neuroanatomy of vertical connections within the occipitotemporal cortex by combining modern quantitative MRI and classical histological measurements in human and macaque. Finally, we a) discuss current limitations of dMRI and tractography and b) consider potential paths for future investigations using dMRI and tractography for comparative neuroanatomical studies of white matter tracts between species. While we focus on vertical association connections in visual cortex in the present paper, this same approach can be applied to other white matter tracts. Similar efforts are likely to continue to advance our understanding of the neuroanatomical features of the brain that are shared across species, as well as to distinguish the features that are uniquely human.