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Long term monocular deprivation is considered to be necessary for the induction of significant ocular dominance plasticity in the adult visual cortex. In this study, we subjected adult mice to monocular deprivation for various durations and screened for changes in ocular dominance using dual-wavelength intrinsic signal optical imaging. We found that short-term deprivation was sufficient to cause a shift in ocular dominance and that these early-stage changes were detected only by near-infrared illumination. In addition, single-unit recordings showed that these early-stage changes primarily occurred in deep cortical layers. This early-stage ocular dominance shift was abolished by the blockade of NMDA receptors. In summary, our findings reveal an early phase of adult ocular dominance plasticity and provide the dynamics of adult plasticity.

MR images of the effective relaxation rate R2* and magnetic susceptibility χ derived from multi-echo T2*-weighted (T2*w) MRI can provide insight into iron and myelin distributions in the brain, with the potential of providing biomarkers for neurological disorders. Quantification of R2* and χ at submillimeter resolution in the cortex in vivo has been difficult because of challenges such as head motion, limited signal to noise ratio, long scan time, and motion related magnetic field fluctuations. This work aimed to improve the robustness for quantifying intracortical R2* and χ and analyze the effects from motion, spatial resolution, and cortical orientation. T2*w data was acquired with a spatial resolution of 0.3 × 0.3 × 0.4 mm3 at 7 T and downsampled to various lower resolutions. A combined correction for motion and B0 changes was deployed using volumetric navigators. Such correction improved the T2*w image quality rated by experienced image readers and test-retest reliability of R2* and χ quantification with reduced median inter-scan differences up to 10 s−1 and 5 ppb, respectively. R2* and χ near the line of Gennari, a cortical layer high in iron and myelin, were as much as 10 s−1 and 10 ppb higher than the region at adjacent cortical depth. In addition, a significant effect due to the cortical orientation relative to the static field (B0) was observed in χ with a peak-to-peak amplitude of about 17 ppb. In retrospectively downsampled data, the capability to distinguish different cortical depth regions based on R2* or χ contrast remained up to isotropic 0.5 mm resolution. This study highlights the unique characteristics of R2* and χ along the cortical depth at submillimeter resolution and the need for motion and B0 corrections for their robust quantification in vivo.

High-resolution diffusion tensor imaging (DTI) can noninvasively probe the microstructure of cortical gray matter in vivo. In this study, 0.9-mm isotropic whole-brain DTI data were acquired in healthy subjects with an efficient multi-band multi-shot echo-planar imaging sequence. A column-based analysis that samples the fractional anisotropy (FA) and radiality index (RI) along radially oriented cortical columns was then performed to quantitatively analyze the FA and RI dependence on the cortical depth, cortical region, cortical curvature, and cortical thickness across the whole brain, which has not been simultaneously and systematically investigated in previous studies. The results showed characteristic FA and RI vs. cortical depth profiles, with an FA local maximum and minimum (or two inflection points) and a single RI maximum at intermediate cortical depths in most cortical regions, except for the postcentral gyrus where no FA peaks and a lower RI were observed. These results were consistent between repeated scans from the same subjects and across different subjects. They were also dependent on the cortical curvature and cortical thickness in that the characteristic FA and RI peaks were more pronounced i) at the banks than at the crown of gyri or at the fundus of sulci and ii) as the cortical thickness increases. This methodology can help characterize variations in microstructure along the cortical depth and across the whole brain in vivo, potentially providing quantitative biomarkers for neurological disorders.

Human ventral temporal cortex (VTC) is critical for visual recognition. It is thought that this ability is supported by large-scale patterns of activity across VTC that contain information about visual categories. However, it is unknown how category representations in VTC are organized at the submillimeter scale and across cortical depths. To fill this gap in knowledge, we measured BOLD responses in medial and lateral VTC to images spanning 10 categories from five domains (written characters, bodies, faces, places, and objects) at an ultra-high spatial resolution of 0.8 mm using 7 Tesla fMRI in both male and female participants. Representations in lateral VTC were organized most strongly at the general level of domains (e.g., places), whereas medial VTC was also organized at the level of specific categories (e.g., corridors and houses within the domain of places). In both lateral and medial VTC, domain-level and category-level structure decreased with cortical depth, and downsampling our data to standard resolution (2.4 mm) did not reverse differences in representations between lateral and medial VTC. The functional diversity of representations across VTC partitions may allow downstream regions to read out information in a flexible manner according to task demands. These results bridge an important gap between electrophysiological recordings in single neurons at the micron scale in nonhuman primates and standard-resolution fMRI in humans by elucidating distributed responses at the submillimeter scale with ultra-high-resolution fMRI in humans. [ABSTRACT FROM AUTHOR]

Abstract Advances in hardware, pulse sequences, and reconstruction techniques have made it possible to perform functional magnetic resonance imaging (fMRI) at sub-millimeter resolution while maintaining high spatial coverage and acceptable signal-to-noise ratio. Here, we examine whether sub-millimeter fMRI can be used as a routine method for obtaining accurate measurements of fine-scale local neural activity. We conducted fMRI in human visual cortex during a simple event-related visual experiment (7 T, gradient-echo EPI, 0.8-mm isotropic voxels, 2.2-s sampling rate, 84 slices), and developed analysis and visualization tools to assess the quality of the data. Our results fall along three lines of inquiry. First, we find that the acquired fMRI images, combined with appropriate surface-based processing, provide reliable and accurate measurements of fine-scale blood oxygenation level dependent (BOLD) activity patterns. Second, we show that the highly folded structure of cortex causes substantial biases on spatial resolution and data visualization. Third, we examine the well-recognized issue of venous contributions to fMRI signals. In a systematic assessment of large sections of cortex measured at a fine scale, we show that time-averaged T 2 *-weighted EPI intensity is a simple, robust marker of venous effects. These venous effects are unevenly distributed across cortex, are more pronounced in gyri and outer cortical depths, and are, to a certain degree, in consistent locations across subjects relative to cortical folding. Furthermore, we show that these venous effects are strongly correlated with BOLD responses evoked by the experiment. We conclude that sub-millimeter fMRI can provide robust information about fine-scale BOLD activity patterns, but special care must be exercised in visualizing and interpreting these patterns, especially with regards to the confounding influence of the brain's vasculature. To help translate these methodological findings to neuroscience research, we provide practical suggestions for both high-resolution and standard-resolution fMRI studies. [ABSTRACT FROM AUTHOR]

• Red and near-infrared intrinsic signal optical imaging show similar contralateral ocular dominance. • Near-infrared rather than red light reveals the early-stage ocular dominance shift in adult mice, but both similarly detect the saturated ocular dominance shift. • Neurons in deep layers of the visual cortex shift ocular dominance earlier than neurons in superficial layers during deprivation. • The early phase of adult ocular dominance plasticity depends on the activation of N-methyl-D-aspartic acid (NMDA) receptors. Long term monocular deprivation is considered to be necessary for the induction of significant ocular dominance plasticity in the adult visual cortex. In this study, we subjected adult mice to monocular deprivation for various durations and screened for changes in ocular dominance using dual-wavelength intrinsic signal optical imaging. We found that short-term deprivation was sufficient to cause a shift in ocular dominance and that these early-stage changes were detected only by near-infrared illumination. In addition, single-unit recordings showed that these early-stage changes primarily occurred in deep cortical layers. This early-stage ocular dominance shift was abolished by the blockade of NMDA receptors. In summary, our findings reveal an early phase of adult ocular dominance plasticity and provide the dynamics of adult plasticity. [ABSTRACT FROM AUTHOR]

• Fractional anisotropy (FA) and radiality index (RI) sampled along cortical columns. • FA local max/min and RI max at intermediate cortical depths in most regions. • Results consistent between repeated scans and across different healthy subjects. • FA and RI peaks more notable at the banks than the crown of gyri or fundus of sulci. • FA and RI peaks more notable as the cortical thickness increases. High-resolution diffusion tensor imaging (DTI) can noninvasively probe the microstructure of cortical gray matter in vivo. In this study, 0.9-mm isotropic whole-brain DTI data were acquired in healthy subjects with an efficient multi-band multi-shot echo-planar imaging sequence. A column-based analysis that samples the fractional anisotropy (FA) and radiality index (RI) along radially oriented cortical columns was then performed to quantitatively analyze the FA and RI dependence on the cortical depth, cortical region, cortical curvature, and cortical thickness across the whole brain, which has not been simultaneously and systematically investigated in previous studies. The results showed characteristic FA and RI vs. cortical depth profiles, with an FA local maximum and minimum (or two inflection points) and a single RI maximum at intermediate cortical depths in most cortical regions, except for the postcentral gyrus where no FA peaks and a lower RI were observed. These results were consistent between repeated scans from the same subjects and across different subjects. They were also dependent on the cortical curvature and cortical thickness in that the characteristic FA and RI peaks were more pronounced i) at the banks than at the crown of gyri or at the fundus of sulci and ii) as the cortical thickness increases. This methodology can help characterize variations in microstructure along the cortical depth and across the whole brain in vivo , potentially providing quantitative biomarkers for neurological disorders. [Display omitted] [ABSTRACT FROM AUTHOR]

MR images of the effective relaxation rate R 2 * and magnetic susceptibility χ derived from multi-echo T 2 *-weighted (T 2 *w) MRI can provide insight into iron and myelin distributions in the brain, with the potential of providing biomarkers for neurological disorders. Quantification of R 2 * and χ at submillimeter resolution in the cortex in vivo has been difficult because of challenges such as head motion, limited signal to noise ratio, long scan time, and motion related magnetic field fluctuations. This work aimed to improve the robustness for quantifying intracortical R 2 * and χ and analyze the effects from motion, spatial resolution, and cortical orientation. T 2 *w data was acquired with a spatial resolution of 0.3 × 0.3 × 0.4 mm3 at 7 T and downsampled to various lower resolutions. A combined correction for motion and B 0 changes was deployed using volumetric navigators. Such correction improved the T 2 *w image quality rated by experienced image readers and test-retest reliability of R 2 * and χ quantification with reduced median inter-scan differences up to 10 s−1 and 5 ppb, respectively. R 2 * and χ near the line of Gennari, a cortical layer high in iron and myelin, were as much as 10 s−1 and 10 ppb higher than the region at adjacent cortical depth. In addition, a significant effect due to the cortical orientation relative to the static field (B 0) was observed in χ with a peak-to-peak amplitude of about 17 ppb. In retrospectively downsampled data, the capability to distinguish different cortical depth regions based on R 2 * or χ contrast remained up to isotropic 0.5 mm resolution. This study highlights the unique characteristics of R 2 * and χ along the cortical depth at submillimeter resolution and the need for motion and B 0 corrections for their robust quantification in vivo. [ABSTRACT FROM AUTHOR]

Although electroencephalography (EEG) is a valuable tool to investigate neural activity in patients and controls, exactly how local anatomy impacts the measured signal remains unclear. Better characterizing this relationship is important to improve the understanding of how inter-subject differences in the EEG signal are related to neural activity. We hypothesized that cortical structure might affect event-related desynchronization (ERD) in EEG. Since aging is a well-documented cause of cortical thinning, we investigated the effects of cortical thickness (CT) and cortical depth (CD – the skull-to-cortex distance) on ERD using anatomical MRI and motor-evoked EEG in 17 healthy young adults and 20 healthy older persons. Results showed a significant negative correlation between ERD and CT, but no consistent relationship between ERD and CD. A thinner cortex was associated with a larger ERD in the alpha/beta band and correcting for CT removed most of the inter-group difference in ERD. This indicates that differences in neural activity might not be the primary cause for the observed aging-related differences in ERD, at least in the motor cortex. Further, it emphasizes the importance of considering conditions affecting the EEG signal, such as cortical anatomical changes due to aging, when interpreting differences between healthy controls and/or patients.

Although electroencephalography (EEG) is a valuable tool to investigate neural activity in patients and controls, exactly how local anatomy impacts the measured signal remains unclear. Better characterizing this relationship is important to improve the understanding of how inter-subject differences in the EEG signal are related to neural activity. We hypothesized that cortical structure might affect event-related desynchronization (ERD) in EEG. Since aging is a well-documented cause of cortical thinning, we investigated the effects of cortical thickness (CT) and cortical depth (CD-the skull-to-cortex distance) on ERD using anatomical MRI and motor-evoked EEG in 17 healthy young adults and 20 healthy older persons. Results showed a significant negative correlation between ERD and CT, but no consistent relationship between ERD and CD. A thinner cortex was associated with a larger ERD in the a/b band and correcting for CT removed most of the inter-group difference in ERD. This indicates that differences in neural activity might not be the primary cause for the observed aging-related differences in ERD, at least in the motor cortex. Further, it emphasizes the importance of considering conditions affecting the EEG signal, such as cortical anatomical changes due to aging, when interpreting differences between healthy controls and/or patients. [ABSTRACT FROM AUTHOR]

Purpose Owing to variability in vascular dynamics across cerebral cortex, blood-oxygenation-level-dependent (BOLD) spatial and temporal characteristics should vary as a function of cortical-depth. Here, the positive response, initial dip (ID), and post-stimulus undershoot (PSU) of the BOLD response in human visual cortex are investigated as a function of cortical depth and stimulus duration at 7 Tesla (T). Methods Gradient-echo echo-planar-imaging BOLD fMRI with high spatial and temporal resolution was performed in 7 healthy volunteers and measurements of the ID, PSU, and positive BOLD response were made as a function of cortical depth and stimulus duration (0.5-8 s). Exploratory analyses were applied to understand whether functional mapping could be achieved using the ID, rather than positive, BOLD signal characteristics Results The ID was largest in outer cortical layers, consistent with previously reported upstream propagation of vasodilation along the diving arterioles in animals. The positive BOLD signal and PSU showed different relationships across the cortical depth with respect to stimulus duration. Conclusion The ID and PSU were measured in humans at 7T and exhibited similar trends to those recently reported in animals. Furthermore, while evidence is provided for the ID being a potentially useful feature for better understanding BOLD signal dynamics, such as laminar neurovascular coupling, functional mapping based on the ID is extremely difficult. Magn Reson Med 73:2283-2295, 2015. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

• We develop a physiologically based 3D hemodynamic model to capture 3D blood flows. • The model accurately predicts empirical visual BOLD-fMRI responses versus cortical depth. • The model provides better predictions and is more parsimonious than existing models. • The model allows better physiological understanding of the depth-dependence of visual BOLD responses. A physiologically based three-dimensional (3D) hemodynamic model is developed to predict the experimentally observed blood oxygen level dependent (BOLD) responses versus the cortical depth induced by visual stimuli. Prior 2D approximations are relaxed in order to analyze 3D blood flow dynamics as a function of cortical depth. Comparison of the predictions with experimental data for evoked stimuli demonstrates that the full 3D model performs at least as well as previous approaches while remaining parsimonious. In particular, the 3D model requires significantly fewer assumptions and model parameters than previous models such that there is no longer need to define depth-specific parameter values for spatial spreading, peak amplitude, and hemodynamic velocity. [ABSTRACT FROM AUTHOR]

Abstract: Although the blood oxygenation level-dependent (BOLD) contrast is widely used in functional MRI (fMRI), its spatial specificity is compromised by the diversity of the participating vasculature, including large draining veins. Previous studies have shown that an alternative contrast mechanism based on functional changes of the apparent diffusion coefficient (ADC) can be sensitized to small vessels more closely tied to the sites of neural activity. Such an improved functional localization, however, has not yet been demonstrated at the cortical level in humans. Here, we investigate the cortical depth dependence and neuronal specificity of the functional ADC contrast in the human primary visual cortex by performing high-resolution BOLD and ADC imaging during visual stimulation at 4 T. Our results show that, by using optimal parameters, the functional ADC changes are significantly higher in the middle cortical layers, whereas the BOLD signal changes are higher at the cortical surface and vary much less significantly across the cortex. These results are in good agreement with previous studies performed in anesthetized cats at 9.4 T and demonstrate the improved spatial specificity of the functional ADC contrast as compared to the BOLD contrast. [Copyright &y& Elsevier]

• Layer fMRI has been applied almost exclusively in primary brain regions. • We argue layer fMRI now can and should expand to association cortex. • We review methodological and theoretical challenges and opportunities. • Studying higher-order regions may help transform our understanding of cognition. Recent advances in fMRI have enabled non-invasive measurements of brain function in awake, behaving humans at unprecedented spatial resolutions, allowing us to separate activity in distinct cortical layers. While most layer fMRI studies to date have focused on primary cortices, we argue that the next big steps forward in our understanding of cognition will come from expanding this technology into higher-order association cortex, to characterize depth-dependent activity during increasingly sophisticated mental processes. We outline phenomena and theories ripe for investigation with layer fMRI, including perception and imagery, selective attention, and predictive coding. We discuss practical and theoretical challenges to cognitive applications of layer fMRI, including localizing regions of interest in the face of substantial anatomical heterogeneity across individuals, designing appropriate task paradigms within the confines of acquisition parameters, and generating hypotheses for higher-order brain regions where the laminar circuitry is less well understood. We consider how applying layer fMRI in association cortex may help inform computational models of brain function as well as shed light on consciousness and mental illness, and issue a call to arms to our fellow methodologists and neuroscientists to bring layer fMRI to this next frontier. [ABSTRACT FROM AUTHOR]

Morphometric alterations in the anterior cingulate cortex (ACC) have been reported in schizophrenia and mood disorders. Parameters affected include glial and neuronal density, neuronal size and cortical thickness. Some data, especially in mood disorders, suggest that the left subgenual ACC is preferentially involved. Qualitative studies show that the ACC cytoarchitecture is heterogeneous, but there are few quantitative data. We performed a quantitative morphometric study of five anatomical levels within the ACC (caudal and rostral subgenual [area 24b sg], rostral and intermediate supragenual [area 24b] and caudal supragenual [area 24b′]) in both hemispheres of five normal brains. We measured cortical depth, layer depths, neuronal density, neuronal size, and glial density, using the optical disector and nucleator. Relative to the subgenual ACC, the supragenual ACC was thicker, with a deeper layer V. Supragenual neurons were substantially larger in all layers, and were less densely packed in layers V and VI, than subgenual neurons. Glial density, and the glia to neuron ratio, was higher in supragenual than subgenual ACC. Only minor differences were seen between left and right ACC, between caudal and rostral subgenual ACC, and between the three supragenual levels. These data complement the qualitative descriptions of the heterogeneity of human ACC cytoarchitecture, connections, and functions, especially between supragenual and subgenual regions. Our findings also indicate that care must be taken when selecting ACC tissue to be used for morphometric studies of psychiatric disorders, since the normal anatomical variation is of a similar magnitude as the reported disease-related alterations. [Copyright &y& Elsevier]

Columns and layers are fundamental organizational units of the brain. Well known examples of cortical columns are the ocular dominance columns (ODCs) in primary visual cortex and the column-like stripe-based arrangement in the second visual area V2. The spatial scale of columns and layers is beyond the reach of conventional neuroimaging, but the advent of high field magnetic resonance imaging (MRI) scanners (UHF, 7 Tesla and above) has opened the possibility to acquire data at this spatial scale, in-vivo and non-invasively in humans. The most prominent non-invasive technique to measure brain function is blood oxygen level dependent (BOLD) fMRI, measuring brain activity indirectly, via changes in hemodynamics. A key determinant of the ability of high-resolution BOLD fMRI to accurately resolve columns and layers is the point-spread function (PSF) of the BOLD response in relation to the spatial extent of neuronal activity. In this study we take advantage of the stripe-based arrangement present in visual area V2, coupled with sub-millimetre anatomical and gradient-echo BOLD (GE BOLD) acquisition at 7 T to obtain PSF estimates and along cortical depth in human participants. Results show that the BOLD PSF is maximal in the superficial part of the cortex (1.78 mm), and it decreases with increasing cortical depth (0.83 mm close to white matter)., (Copyright © 2021. Published by Elsevier Ltd.)

The primary visual cortex of humans contains patches of neurons responding preferentially to stimulation of one eye (the ocular dominance columns). Multiple previous studies attempted to detect their activity using fMRI. The majority of these fMRI studies used magnetic field strengths of 4 ​T and higher. However, there have been reports of reliable eye-selective activations at 3 ​T as well. In this study we investigated the possibility of detecting eye-selective V1 activity using high-resolution GE-EPI fMRI at 3 ​T and sub-millimeter resolution fMRI at ultrahigh 9.4 ​T magnetic field strengths with acquisition parameters optimized for each field strength. High-resolution fMRI at 9.4 ​T also allowed us to examine the eye-selectivity responses across the cortical depth, which are expected to be strongest in the middle layers. We observed a substantial increase in the percentage of eye-selective voxels, as well as a doubling in run-to-run consistency of eye preference at ultrahigh field compared to 3 ​T. We also found that across cortical depth, eye selectivity increased towards the superficial layers, and that signal contrast increased while noise remained nearly constant towards the surface. The depth-resolved results are consistent with a distortion of spatial specificity of the GE-EPI signal by ascending venules and large draining veins on the cortical surface. The effects of larger vessels cause increasing signal amplitude, but also displacement of the maximum BOLD signal relative to neural activity. In summary, our results show that increase in spatial resolution, reduced partial volume effects, and improved sensitivity at 9.4 ​T allow for better detection of eye-selective signals related to ocular dominance columns. However, although ultrahigh field yields higher sensitivity to the ocular dominance signal, GE-EPI still suffers from specificity issues, with a prominent signal contribution at shallow depths from larger cortical vessels. • We examined the detectability of eye-dominance signal in V1 using high-resolution fMRI. • High-resolution GE-EPI at 3 ​T was compared to sub-millimeter resolution at 9.4 ​T. • 9.4 ​T yielded more reliable eye-selectivity in a larger fraction of voxels. • Cortical depth analysis showed strongest eye-selectivity at the cortical surface. • Eye-selectivity in GE-EPI at 9.4 ​T is dominated by vascular rather than neural effects. [ABSTRACT FROM AUTHOR]

Objective . Intracortical microstimulation of the primary somatosensory cortex (S1) has shown great progress in restoring touch sensations to patients with paralysis. Stimulation parameters such as amplitude, phase duration, and frequency can influence the quality of the evoked percept as well as the amount of charge necessary to elicit a response. Previous studies in V1 and auditory cortices have shown that the behavioral responses to stimulation amplitude and phase duration change across cortical depth. However, this depth-dependent response has yet to be investigated in S1. Similarly, to our knowledge, the response to microstimulation frequency across cortical depth remains unexplored. Approach . To assess these questions, we implanted rats in S1 with a microelectrode with electrode-sites spanning all layers of the cortex. A conditioned avoidance behavioral paradigm was used to measure detection thresholds and responses to phase duration and frequency across cortical depth. Main results . Analogous to other cortical areas, the sensitivity to charge and strength-duration chronaxies in S1 varied across cortical layers. Likewise, the sensitivity to microstimulation frequency was layer dependent. Significance . These findings suggest that cortical depth can play an important role in the fine-tuning of stimulation parameters and in the design of intracortical neuroprostheses for clinical applications., (© 2021 IOP Publishing Ltd.)