Differential cortical and subcortical visual processing with eyes shut.

Closing our eyes largely shuts down our ability to see. That said, our eyelids still pass some light, allowing our visual system to coarsely process information about visual scenes, such as changes in luminance. However, the specific impact of eye closure on processing within the early visual system remains largely unknown. To understand how visual processing is modulated when eyes are shut, we used functional magnetic resonance imaging (fMRI) to measure responses to a flickering visual stimulus at high (100%) and low (10%) temporal contrasts, while participants viewed the stimuli with their eyes open or closed. Interestingly, we discovered that eye closure produced a qualitatively distinct pattern of effects across the visual thalamus and visual cortex. We found that with eyes open, low temporal contrast stimuli produced smaller responses across the lateral geniculate nucleus (LGN), primary (V1) and extrastriate visual cortex (V2). However, with eyes closed, we discovered that the LGN and V1 maintained similar blood oxygenation level-dependent (BOLD) responses as the eyes open condition, despite the suppressed visual input through the eyelid. In contrast, V2 and V3 had strongly attenuated BOLD response when eyes were closed, regardless of temporal contrast. Our findings reveal a qualitatively distinct pattern of visual processing when the eyes are closed-one that is not simply an overall attenuation but rather reflects distinct responses across visual thalamocortical networks, wherein the earliest stages of processing preserve information about stimuli but are then gated off downstream in visual cortex.NEW & NOTEWORTHY When we close our eyes coarse luminance information is still accessible by the visual system. Using functional magnetic resonance imaging, we examined whether eyelid closure plays a unique role in visual processing. We discovered that while the LGN and V1 show equivalent responses when the eyes are open or closed, extrastriate cortex exhibited attenuated responses with eye closure. This suggests that when the eyes are closed, downstream visual processing is blind to this information.

Sub-bundle based analysis reveals the role of human optic radiation in visual working memory.

White matter (WM) functional activity has been reliably detected through functional magnetic resonance imaging (fMRI). Previous studies have primarily examined WM bundles as unified entities, thereby obscuring the functional heterogeneity inherent within these bundles. Here, for the first time, we investigate the function of sub-bundles of a prototypical visual WM tract-the optic radiation (OR). We use the 7T retinotopy dataset from the Human Connectome Project (HCP) to reconstruct OR and further subdivide the OR into sub-bundles based on the fiber's termination in the primary visual cortex (V1). The population receptive field (pRF) model is then applied to evaluate the retinotopic properties of these sub-bundles, and the consistency of the pRF properties of sub-bundles with those of V1 subfields is evaluated. Furthermore, we utilize the HCP working memory dataset to evaluate the activations of the foveal and peripheral OR sub-bundles, along with LGN and V1 subfields, during 0-back and 2-back tasks. We then evaluate differences in 2bk-0bk contrast between foveal and peripheral sub-bundles (or subfields), and further examine potential relationships between 2bk-0bk contrast and 2-back task d-prime. The results show that the pRF properties of OR sub-bundles exhibit standard retinotopic properties and are typically similar to the properties of V1 subfields. Notably, activations during the 2-back task consistently surpass those under the 0-back task across foveal and peripheral OR sub-bundles, as well as LGN and V1 subfields. The foveal V1 displays significantly higher 2bk-0bk contrast than peripheral V1. The 2-back task d-prime shows strong correlations with 2bk-0bk contrast for foveal and peripheral OR fibers. These findings demonstrate that the blood oxygen level-dependent (BOLD) signals of OR sub-bundles encode high-fidelity visual information, underscoring the feasibility of assessing WM functional activity at the sub-bundle level. Additionally, the study highlights the role of OR in the top-down processes of visual working memory beyond the bottom-up processes for visual information transmission. Conclusively, this study innovatively proposes a novel paradigm for analyzing WM fiber tracts at the individual sub-bundle level and expands understanding of OR function.

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.

Intra-Areal Visual Topography in Primate Brains Mapped with Probabilistic Tractography of Diffusion-Weighted Imaging.

Noninvasive diffusion-weighted magnetic resonance imaging (dMRI) can be used to map the neural connectivity between distinct areas in the intact brain, but the standard resolution achieved fundamentally limits the sensitivity of such maps. We investigated the sensitivity and specificity of high-resolution postmortem dMRI and probabilistic tractography in rhesus macaque brains to produce retinotopic maps of the lateral geniculate nucleus (LGN) and extrastriate cortical visual area V5/MT based on their topographic connections with the previously established functional retinotopic map of primary visual cortex (V1). We also replicated the differential connectivity of magnocellular and parvocellular LGN compartments with V1 across visual field positions. Predicted topographic maps based on dMRI data largely matched the established retinotopy of both LGN and V5/MT. Furthermore, tractography based on in vivo dMRI data from the same macaque brains acquired at standard field strength (3T) yielded comparable topographic maps in many cases. We conclude that tractography based on dMRI is sensitive enough to reveal the intrinsic organization of ordered connections between topographically organized neural structures and their resultant functional organization.

Mapping the human lateral geniculate nucleus and its cytoarchitectonic subdivisions using quantitative MRI.

The human lateral geniculate nucleus (LGN) of the visual thalamus is a key subcortical processing site for visual information analysis. Due to its small size and deep location within the brain, a non-invasive characterization of the LGN and its microstructurally distinct magnocellular (M) and parvocellular (P) subdivisions in humans is challenging. Here, we investigated whether structural quantitative MRI (qMRI) methods that are sensitive to underlying microstructural tissue features enable MR-based mapping of human LGN M and P subdivisions. We employed high-resolution 7 Tesla in-vivo qMRI in N = 27 participants and ultra-high resolution 7 Tesla qMRI of a post-mortem human LGN specimen. We found that a quantitative assessment of the LGN and its subdivisions is possible based on microstructure-informed qMRI contrast alone. In both the in-vivo and post-mortem qMRI data, we identified two components of shorter and longer longitudinal relaxation time (T1) within the LGN that coincided with the known anatomical locations of a dorsal P and a ventral M subdivision, respectively. Through ground-truth histological validation, we further showed that the microstructural MRI contrast within the LGN pertains to cyto- and myeloarchitectonic tissue differences between its subdivisions. These differences were based on cell and myelin density, but not on iron content. Our qMRI-based mapping strategy paves the way for an in-depth understanding of LGN function and microstructure in humans. It further enables investigations into the selective contributions of LGN subdivisions to human behavior in health and disease.

Functional quantitative susceptibility mapping (fQSM) of rat brain during flashing light stimulation.

Functional magnetic resonance imaging (fMRI) based on the blood oxygenation level-dependent (BOLD) contrast has become an indispensable tool in neuroscience. However, the BOLD signal is nonlocal, lacking quantitative measurement of oxygenation fluctuation. This preclinical study aimed to introduced functional quantitative susceptibility mapping (fQSM) to complement BOLD-fMRI to quantitatively assess the local susceptibility and venous oxygen saturation (SvO2). Rats were subjected to a 5 Hz flashing light and the different inhaled oxygenation levels (30% and 100%) were used to observe the venous susceptibility to quantify SvO2. Phase information was extracted to produce QSM, and the activation responses of magnitude (conventional BOLD) and the QSM time-series were analyzed. During light stimulation, the susceptibility change of fQSM was four times larger than the BOLD signal change in both inhalation oxygenation conditions. Moreover, the responses in the fQSM map were more restricted to the visual pathway, such as the lateral geniculate nucleus and superior colliculus, compared with the relatively diffuse distributions in the BOLD map. Also, the calibrated SvO2 was approximately 84% (88%) when the task was on, 83% (87%) when the task was off during 30% (and during 100%) oxygen inhalation. This is the first fQSM study in a small animal model and increases our understanding of fQSM in the brains of small animals. This study demonstrated the feasibility, sensitivity, and specificity of fQSM using light stimulus, as fQSM provides quantitative clues as well as localized information, complementing the defects of BOLD-fMRI. In addition to neural activity, fQSM also assesses SvO2 as supplementary information while BOLD-fMRI dose not. Accordingly, the fQSM technique could be a useful quantitative tool for functional studies, such as longitudinal follow up of neurodegenerative diseases, functional recovery after brain surgery, and negative BOLD studies.

Comparison of multiple tractography methods for reconstruction of the retinogeniculate visual pathway using diffusion MRI.

The retinogeniculate visual pathway (RGVP) conveys visual information from the retina to the lateral geniculate nucleus. The RGVP has four subdivisions, including two decussating and two nondecussating pathways that cannot be identified on conventional structural magnetic resonance imaging (MRI). Diffusion MRI tractography has the potential to trace these subdivisions and is increasingly used to study the RGVP. However, it is not yet known which fiber tracking strategy is most suitable for RGVP reconstruction. In this study, four tractography methods are compared, including constrained spherical deconvolution (CSD) based probabilistic (iFOD1) and deterministic (SD-Stream) methods, and multi-fiber (UKF-2T) and single-fiber (UKF-1T) unscented Kalman filter (UKF) methods. Experiments use diffusion MRI data from 57 subjects in the Human Connectome Project. The RGVP is identified using regions of interest created by two clinical experts. Quantitative anatomical measurements and expert anatomical judgment are used to assess the advantages and limitations of the four tractography methods. Overall, we conclude that UKF-2T and iFOD1 produce the best RGVP reconstruction results. The iFOD1 method can better quantitatively estimate the percentage of decussating fibers, while the UKF-2T method produces reconstructed RGVPs that are judged to better correspond to the known anatomy and have the highest spatial overlap across subjects. Overall, we find that it is challenging for current tractography methods to both accurately track RGVP fibers that correspond to known anatomy and produce an approximately correct percentage of decussating fibers. We suggest that future algorithm development for RGVP tractography should take consideration of both of these two points.

Brain mapping of auditory steady-state responses: A broad view of cortical and subcortical sources.

Auditory steady-state responses (ASSRs) are evoked brain responses to modulated or repetitive acoustic stimuli. Investigating the underlying neural generators of ASSRs is important to gain in-depth insight into the mechanisms of auditory temporal processing. The aim of this study is to reconstruct an extensive range of neural generators, that is, cortical and subcortical, as well as primary and non-primary ones. This extensive overview of neural generators provides an appropriate basis for studying functional connectivity. To this end, a minimum-norm imaging (MNI) technique is employed. We also present a novel extension to MNI which facilitates source analysis by quantifying the ASSR for each dipole. Results demonstrate that the proposed MNI approach is successful in reconstructing sources located both within (primary) and outside (non-primary) of the auditory cortex (AC). Primary sources are detected in different stimulation conditions (four modulation frequencies and two sides of stimulation), thereby demonstrating the robustness of the approach. This study is one of the first investigations to identify non-primary sources. Moreover, we show that the MNI approach is also capable of reconstructing the subcortical activities of ASSRs. Finally, the results obtained using the MNI approach outperform the group-independent component analysis method on the same data, in terms of detection of sources in the AC, reconstructing the subcortical activities and reducing computational load.

Visual Dysfunction of the Superior Colliculus in De Novo Parkinsonian Patients.

OBJECTIVE: The dual hit hypothesis about the pathogenesis of Parkinson disease (PD) suggests that the brainstem is a convergent area for the propagation of pathological α-synuclein from the periphery to the brain. Although brainstem structures are likely to be affected early in the course of the disease, detailed information regarding specific brainstem regions is lacking. The aim of our study was to investigate the function of the superior colliculus, a sensorimotor brainstem structure, in de novo PD patients compared to controls using brain functional magnetic imaging and visual stimulation paradigms. METHODS: De novo PD patients and controls were recruited. PD subjects were imaged before and after starting PD medications. A recently developed functional magnetic resonance imaging protocol was used to stimulate and visualize the superior colliculus and 2 other visual structures: the lateral geniculate nucleus and the primary visual cortex. RESULTS: In the 22 PD patients, there was no modulation of the superior colliculus responses to the luminance contrasts compared to controls. This implies a hypersensitivity to low luminance contrast and abnormal rapid blood oxygenation level-dependent signal saturation to high luminance contrasts. The lateral geniculate nucleus was only modulated by 3 to 9% luminance contrasts compared to controls. No major differences were found in the primary visual cortex between both groups. INTERPRETATION: Our findings suggest that pathological superior colliculus visual responses in de novo PD patients are present early in the course of the disease. Changes in imaging the superior colliculus could play an important role as a preclinical biomarker of the disease. ANN NEUROL 2020;87:533-546.

Hemorrhagic Intracranial Cavernoma Presenting as a Homonymous Horizontal Sectoranopia.

ABSTRACT: Hemorrhagic lateral geniculate nucleus (LGN) insults are rare but have been reported in association with tumors, vascular malformations, and trauma. The localization of LGN lesions is facilitated by recognition of pathognomonic visual field defects. A 21-year old woman developed a sudden onset painless left homonymous horizontal sectoranopia. Magnetic resonance imaging revealed a hemorrhagic cavernous malformation of the right temporal lobe. Optical coherence tomography (OCT) and Humphrey perimetry findings localized the lesion to the right LGN. Specifically, OCT testing revealed a right homonymous sectoranopia pattern of hemi-retinal macular ganglion layer-inner plexiform layer (mGCIPL) thinning contralateral to the left sided visual field defect. The OCT pattern reflected retrograde neuroaxonal degeneration from the right LGN lesion. This case highlights a unique pattern of mGCIPL thinning characteristic for a posterior lateral choroidal artery injury, affecting the LGN. These findings illustrate how functional eloquence correlates with topographical elegance in the afferent visual pathway.

Reduced Structural Connectivity Between Left Auditory Thalamus and the Motion-Sensitive Planum Temporale in Developmental Dyslexia.

Developmental dyslexia is characterized by the inability to acquire typical reading and writing skills. Dyslexia has been frequently linked to cerebral cortex alterations; however, recent evidence also points toward sensory thalamus dysfunctions: dyslexics showed reduced responses in the left auditory thalamus (medial geniculate body, MGB) during speech processing in contrast to neurotypical readers. In addition, in the visual modality, dyslexics have reduced structural connectivity between the left visual thalamus (lateral geniculate nucleus, LGN) and V5/MT, a cerebral cortex region involved in visual movement processing. Higher LGN-V5/MT connectivity in dyslexics was associated with the faster rapid naming of letters and numbers (RANln), a measure that is highly correlated with reading proficiency. Here, we tested two hypotheses that were directly derived from these previous findings. First, we tested the hypothesis that dyslexics have reduced structural connectivity between the left MGB and the auditory-motion-sensitive part of the left planum temporale (mPT). Second, we hypothesized that the amount of left mPT-MGB connectivity correlates with dyslexics RANln scores. Using diffusion tensor imaging-based probabilistic tracking, we show that male adults with developmental dyslexia have reduced structural connectivity between the left MGB and the left mPT, confirming the first hypothesis. Stronger left mPT-MGB connectivity was not associated with faster RANln scores in dyslexics, but was in neurotypical readers. Our findings provide the first evidence that reduced cortico-thalamic connectivity in the auditory modality is a feature of developmental dyslexia and it may also affect reading-related cognitive abilities in neurotypical readers.SIGNIFICANCE STATEMENT Developmental dyslexia is one of the most widespread learning disabilities. Although previous neuroimaging research mainly focused on pathomechanisms of dyslexia at the cerebral cortex level, several lines of evidence suggest an atypical functioning of subcortical sensory structures. By means of diffusion tensor imaging, we here show that dyslexic male adults have reduced white matter connectivity in a cortico-thalamic auditory pathway between the left auditory motion-sensitive planum temporale and the left medial geniculate body. Connectivity strength of this pathway was associated with measures of reading fluency in neurotypical readers. This is novel evidence on the neurocognitive correlates of reading proficiency, highlighting the importance of cortico-subcortical interactions between regions involved in the processing of spectrotemporally complex sound.

The association between subcortical and cortical fMRI and lifetime noise exposure in listeners with normal hearing thresholds.

In animal models, exposure to high noise levels can cause permanent damage to hair-cell synapses (cochlear synaptopathy) for high-threshold auditory nerve fibers without affecting sensitivity to quiet sounds. This has been confirmed in several mammalian species, but the hypothesis that lifetime noise exposure affects auditory function in humans with normal audiometric thresholds remains unconfirmed and current evidence from human electrophysiology is contradictory. Here we report the auditory brainstem response (ABR), and both transient (stimulus onset and offset) and sustained functional magnetic resonance imaging (fMRI) responses throughout the human central auditory pathway across lifetime noise exposure. Healthy young individuals aged 25-40 years were recruited into high (n = 32) and low (n = 30) lifetime noise exposure groups, stratified for age, and balanced for audiometric threshold up to 16 kHz fMRI demonstrated robust broadband noise-related activity throughout the auditory pathway (cochlear nucleus, superior olivary complex, nucleus of the lateral lemniscus, inferior colliculus, medial geniculate body and auditory cortex). fMRI responses in the auditory pathway to broadband noise onset were significantly enhanced in the high noise exposure group relative to the low exposure group, differences in sustained fMRI responses did not reach significance, and no significant group differences were found in the click-evoked ABR. Exploratory analyses found no significant relationships between the neural responses and self-reported tinnitus or reduced sound-level tolerance (symptoms associated with synaptopathy). In summary, although a small effect, these fMRI results suggest that lifetime noise exposure may be associated with central hyperactivity in young adults with normal hearing thresholds.

Functional connectivity during smooth pursuit eye movements.

Smooth pursuit eye movements (SPEM) hold the image of a slowly moving stimulus on the fovea. The neural system underlying SPEM primarily includes visual, parietal, and frontal areas. In the present study, we investigated how these areas are functionally coupled and how these couplings are influenced by target motion frequency. To this end, healthy participants (n = 57) were instructed to follow a sinusoidal target stimulus moving horizontally at two different frequencies (0.2 Hz, 0.4 Hz). Eye movements and blood oxygen level-dependent (BOLD) activity were recorded simultaneously. Functional connectivity of the key areas of the SPEM network was investigated with a psychophysiological interaction (PPI) approach. How activity in five eye movement-related seed regions (lateral geniculate nucleus, V1, V5, posterior parietal cortex, frontal eye fields) relates to activity in other parts of the brain during SPEM was analyzed. The behavioral results showed clear deterioration of SPEM performance at higher target frequency. BOLD activity during SPEM versus fixation occurred in a geniculo-occipito-parieto-frontal network, replicating previous findings. PPI analysis yielded widespread, partially overlapping networks. In particular, frontal eye fields and posterior parietal cortex showed task-dependent connectivity to large parts of the entire cortex, whereas other seed regions demonstrated more regionally focused connectivity. Higher target frequency was associated with stronger activations in visual areas but had no effect on functional connectivity. In summary, the results confirm and extend previous knowledge regarding the neural mechanisms underlying SPEM and provide a valuable basis for further investigations such as in patients with SPEM impairments and known alterations in brain connectivity.NEW & NOTEWORTHY This study provides a comprehensive investigation of blood oxygen level-dependent (BOLD) functional connectivity during smooth pursuit eye movements. Results from a large sample of healthy participants suggest that key oculomotor regions interact closely with each other but also with regions not primarily associated with eye movements. Understanding functional connectivity during smooth pursuit is important, given its potential role as an endophenotype of psychoses.

Diffusion Tensor Imaging Studies on Recovery of Injured Optic Radiation: A Minireview.

The optic radiation (OR) is a visual neural fiber pathway for the transfer of visual information from the lateral geniculate body of the thalamus to the primary visual cortex. To demonstrate the recovery of an OR injury, quantification and visualization of changes to the injured OR are necessary. Diffusion tensor imaging (DTI) allows determination of the state of an OR by assessing the obtained DTI parameters. In particular, diffusion tensor tractography (DTT), which is derived from DTI data, allows three-dimensional visualization of the OR. Thus, recovery of an injured OR can be demonstrated by examining changes in DTI parameters and/or configuration on follow-up DTI scans or via DTT of the injured OR. Herein, we review nine DTI-based studies that demonstrated recovery of OR injuries. The results reported in these studies suggest that an OR injury has a potential for recovery. Moreover, the results of these studies can form a basis for elucidating the recovery mechanisms of injured OR. These studies have suggested two recovery mechanisms for OR injury: recovery via the original OR pathway or via the transcallosal fibers of the corpus callosum. However, only nine studies on this topic have been conducted to date and six of those nine studies were case reports. Therefore, further studies involving larger numbers of subjects and reporting precise evaluations of changes in OR injury during recovery are warranted.

Lateral geniculate nucleus volumetry at 3T and 7T: Four different optimized magnetic-resonance-imaging sequences evaluated against a 7T reference acquisition.

PURPOSE: The lateral geniculate nucleus (LGN) is an essential nucleus of the visual pathway, occupying a small volume (60-160 mm3) among the other thalamic nuclei. The reported LGN volumes vary greatly across studies due to technical limitations and due to methodological differences of volume assessment. Yet, structural and anatomical alterations in ophthalmologic and neurodegenerative pathologies can only be revealed by a precise and reliable LGN representation. To improve LGN volume assessment, we first implemented a reference acquisition for LGN volume determination with optimized Contrast to Noise Ratio (CNR) and high spatial resolution. Next, we compared CNR efficiency and rating reliability of 3D Magnetization Prepared Rapid Gradient Echo (MPRAGE) images using white matter nulled (WMn) and grey matter nulled (GMn) sequences and its subtraction (WMn-GMn) relative to the clinical standard Proton Density Turbo Spin Echo (PD 2D TSE) and the reference acquisition. We hypothesized that 3D MPRAGE should provide a higher CNR and volume determination accuracy than the currently used 2D sequences. MATERIALS AND METHODS: In 31 healthy subjects, we obtained at 3 and 7 T the following MR sequences: PD-TSE, MPRAGE with white/grey matter signal nulled (WMn/GMn), and a motion-corrected segmented MPRAGE sequence with a resolution of 0.4 × 0.4 × 0.4 mm3 (reference acquisition). To increase CNR, GMn were subtracted from WMn (WMn-GMn). Four investigators manually segmented the LGN independently. RESULTS: The reference acquisition provided a very sharp depiction of the LGN and an estimated mean LGN volume of 124 ±â€¯3.3 mm3. WMn-GMn had the highest CNR and gave the most reproducible LGN volume estimations between field strengths. Even with the highest CNR efficiency, PD-TSE gave inconsistent LGN volumes with the weakest reference acquisition correlation. The LGN WM rim induced a significant difference between LGN volumes estimated from WMn and GMn. WMn and GMn LGN volume estimations explained most of the reference acquisition volumes' variance. For all sequences, the volume rating reliability were good. On the other hand, the best CNR rating reliability, LGN volume and CNR correlations with the reference acquisition were obtained with GMn at 7 T. CONCLUSION: WMn and GMn MPRAGE allow reliable LGN volume determination at both field strengths. The precise location and identification of the LGN (volume) can help to optimize neuroanatomical and neurophysiological studies, which involve the LGN structure. Our optimized imaging protocol may be used for clinical applications aiming at small nuclei volumetric and CNR quantification.

Differential coupling between subcortical calcium and BOLD signals during evoked and resting state through simultaneous calcium fiber photometry and fMRI.

Task based and resting state fMRI has been widely utilized to study brain functions. As the foundation of fMRI, the underlying neural basis of the BOLD signal has been extensively studied, but the detailed mechanism remains elusive, particularly during the resting state. To examine the neurovascular coupling, it is important to simultaneously record neural and vascular signals. Here we developed a novel setup of camera based, scalable simultaneous calcium fiber photometry and fMRI in rats. Using this setup, we recorded calcium signals of superior colliculus (SC) and lateral geniculate nucleus (LGN) and fMRI simultaneously during visual stimulation and the resting state. Our results revealed robust, region-specific coupling between calcium and BOLD signals in the task state and weaker, whole brain correlation in the resting state. Interestingly, the spatial specificity of such correlation in the resting state was improved upon regression of white matter, ventricle signals and global signals in fMRI data. Overall, our results suggest differential coupling of calcium and BOLD signals for subcortical regions between evoked and resting states, and the coupling relationship in the resting state was related with resting state BOLD preprocessing strategies.

Waxholm Space atlas of the rat brain auditory system: Three-dimensional delineations based on structural and diffusion tensor magnetic resonance imaging.

The mammalian auditory system comprises a complex network of brain regions. Interpretations and comparisons of experimental results from this system depend on appropriate anatomical identification of auditory structures. The Waxholm Space (WHS) atlas of the Sprague Dawley rat brain (Papp et al., Neuroimage 97:374-86, 2014) is an open access, three-dimensional reference atlas defined in an ex-vivo magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) volume. Version 2.0 of the atlas (Kjonigsen et al., Neuroimage 108:441-9, 2015) includes detailed delineations of the hippocampus and several major subcortical regions, but only few auditory structures. To amend this, we have delineated the complete ascending auditory system from the cochlea to the cerebral cortex. 40 new brain structure delineations have been added, and the delineations of 10 regions have been revised based on the interpretation of image features in the WHS rat brain MRI/DTI volumes. We here describe and validate the new delineations in relation to corresponding cell- and myelin-stained histological sections and previous literature. We found it possible to delineate all main regions and the majority of subregions and fibre tracts of the ascending auditory pathway, apart from the auditory cortex, for which delineations were extrapolated from a conventional two-dimensional atlas. By contrast, only parts of the descending pathways were discernible in the template. Version 3.0 of the atlas, with altogether 118 anatomical delineations, is shared via the NeuroImaging Tools and Resources Collaboratory (www.nitrc.org).

Attack-related damage of thalamic nuclei in neuromyelitis optica spectrum disorders.

OBJECTIVES: In neuromyelitis optica spectrum disorders (NMOSD) thalamic damage is controversial, but thalamic nuclei were never studied separately. We aimed at assessing volume loss of thalamic nuclei in NMOSD. We hypothesised that only specific nuclei are damaged, by attacks affecting structures from which they receive afferences: the lateral geniculate nucleus (LGN), due to optic neuritis (ON) and the ventral posterior nucleus (VPN), due to myelitis. METHODS: Thirty-nine patients with aquaporin 4-IgG seropositive NMOSD (age: 50.1±14.1 years, 36 women, 25 with prior ON, 36 with prior myelitis) and 37 healthy controls (age: 47.8 ± 12.5 years, 32 women) were included in this cross-sectional study. Thalamic nuclei were assessed in magnetic resonance images, using a multi-atlas-based approach of automated segmentation. Retinal optical coherence tomography was also performed. RESULTS: Patients with ON showed smaller LGN volumes (181.6±44.2 mm3) compared with controls (198.3±49.4 mm3; B=-16.97, p=0.004) and to patients without ON (206.1±50 mm3 ; B=-23.74, p=0.001). LGN volume was associated with number of ON episodes (Rho=-0.536, p<0.001), peripapillary retinal nerve fibre layer thickness (B=0.70, p<0.001) and visual function (B=-0.01, p=0.002). Although VPN was not smaller in patients with myelitis (674.3±67.5 mm3) than controls (679.7±68.33; B=-7.36, p=0.594), we found reduced volumes in five patients with combined myelitis and brainstem attacks (B=-76.18, p=0.017). Volumes of entire thalamus and other nuclei were not smaller in patients than controls. CONCLUSION: These findings suggest attack-related anterograde degeneration rather than diffuse thalamic damage in NMOSD. They also support a potential role of LGN volume as an imaging marker of structural brain damage in these patients.

Stimulus-dependent hemodynamic response timing across the human subcortical-cortical visual pathway identified through high spatiotemporal resolution 7T fMRI.

Recent developments in fMRI acquisition techniques now enable fast sampling with whole-brain coverage, suggesting fMRI can be used to track changes in neural activity at increasingly rapid timescales. When images are acquired at fast rates, the limiting factor for fMRI temporal resolution is the speed of the hemodynamic response. Given that HRFs may vary substantially in subcortical structures, characterizing the speed of subcortical hemodynamic responses, and how the hemodynamic response shape changes with stimulus duration (i.e. the hemodynamic nonlinearity), is needed for designing and interpreting fast fMRI studies of these regions. We studied the temporal properties and nonlinearities of the hemodynamic response function (HRF) across the human subcortical visual system, imaging superior colliculus (SC), lateral geniculate nucleus of the thalamus (LGN) and primary visual cortex (V1) with high spatiotemporal resolution 7 Tesla fMRI. By presenting stimuli of varying durations, we mapped the timing and nonlinearity of hemodynamic responses in these structures at high spatiotemporal resolution. We found that the hemodynamic response is consistently faster and narrower in subcortical structures than in cortex. However, the nonlinearity in LGN is similar to that in cortex, with shorter duration stimuli eliciting larger and faster responses than would have been predicted by a linear model. Using oscillatory visual stimuli, we tested the frequency response in LGN and found that its BOLD response tracked high-frequency (0.5 Hz) oscillations. The LGN response magnitudes were comparable to V1, allowing oscillatory BOLD signals to be detected in LGN despite the small size of this structure. These results suggest that the increase in the speed and amplitude of the hemodynamic response when neural activity is brief may be the key physiological driver of fast fMRI signals, enabling detection of high-frequency oscillations with fMRI. We conclude that subcortical visual structures exhibit fast and nonlinear hemodynamic responses, and that these dynamics enable detection of fast BOLD signals even within small deep brain structures when imaging is performed at ultra-high field.

Hemispheric asymmetries in the orientation and location of the lateral geniculate nucleus in dyslexia.

Human brain asymmetry reflects normal specialization of functional roles and may derive from evolutionary, hereditary, developmental, experiential, and pathological factors (Toga & Thompson, 2003). Geschwind and Galaburda (1985) suggested that processing difficulties in dyslexia are due to structural differences between hemispheres. Because of its potential significance to the controversial magnocellular theory of dyslexia, we investigated hemispheric differences in the human lateral geniculate nucleus (LGN), the primary visual relay and control nucleus in the thalamus, in subjects with dyslexia compared to normal readers. We acquired and averaged multiple high-resolution proton density (PD) weighted structural magnetic resonance imaging (MRI) volumes to measure in detail the anatomical boundaries of the LGN in each hemisphere. We observed hemispheric asymmetries in the orientation of the nucleus in subjects with dyslexia that were absent in controls. We also found differences in the location of the LGN between hemispheres in controls but not in subjects with dyslexia. Neither the precise anatomical differences in the LGN nor their functional consequences are known, nor is it clear whether the differences might be causes or effects of dyslexia.