Investigating the spatiotemporal characteristics of the deoxyhemoglobin-related and deoxyhemoglobin-unrelated functional hemodynamic response across cortical layers in awake marmosets.

Blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) has become a major tool to map neural activity. However, the spatiotemporal characteristics of the BOLD functional hemodynamic response across the cortical layers remain poorly understood. While human fMRI studies suffer from low spatiotemporal resolution, the use of anesthesia in animal models introduces confounding factors. Additionally, inflow contributions to the fMRI signal become non-negligible when short repetition times (TRs) are used. In the present work, we mapped the BOLD fMRI response to somatosensory stimulation in awake marmosets. To address the above technical concerns, we used a dual-echo gradient-recalled echo planar imaging (GR-EPI) sequence to separate the deoxyhemoglobin-related response (absolute T2* differences) from the deoxyhemoglobin-unrelated response (relative S0 changes). We employed a spatial saturation pulse to saturate incoming arterial spins and reduce inflow effects. Functional GR-EPI images were obtained from a single coronal slice with two different echo times (13.5 and 40.5ms) and TR=0.2s. BOLD, T2*, and S0 images were calculated and their functional responses were detected in both hemispheres of primary somatosensory cortex, from which five laminar regions (L1+2, L3, L4, L5, and L6) were derived. The spatiotemporal distribution of the BOLD response across the cortical layers was heterogeneous, with the middle layers having the highest BOLD amplitudes and shortest onset times. ΔT2* also showed a similar trend. However, functional S0 changes were detected only in L1+2, with a fast onset time. Because inflow effects were minimized, the source of S0 functional changes in L1+2 could be attributed to a reduction of cerebrospinal fluid volume fraction due to the functional increase in cerebral blood volume and to unmodeled T2* changes in the extra- and intra-venous compartments. Caution should be exercised when interpreting laminar BOLD fMRI changes in superficial layers as surrogates of underlying neural activity.

Functional magnetic resonance imaging of auditory cortical fields in awake marmosets.

The primate auditory cortex is organized into a network of anatomically and functionally distinct processing fields. Because of its tonotopic properties, the auditory core has been the main target of neurophysiological studies ranging from sensory encoding to perceptual decision-making. By comparison, the auditory belt has been less extensively studied, in part due to the fact that neurons in the belt areas prefer more complex stimuli and integrate over a wider frequency range than neurons in the core, which prefer pure tones of a single frequency. Complementary approaches, such as functional magnetic resonance imaging (fMRI), allow the anatomical identification of both the auditory core and belt and facilitate their functional characterization by rapidly testing a range of stimuli across multiple brain areas simultaneously that can be used to guide subsequent neural recordings. Bridging these technologies in primates will serve to further expand our understanding of primate audition. Here, we developed a novel preparation to test whether different areas of the auditory cortex could be identified using fMRI in common marmosets (Callithrix jacchus), a powerful model of the primate auditory system. We used two types of stimulation, band pass noise and pure tones, to parse apart the auditory core from surrounding secondary belt fields. In contrast to most auditory fMRI experiments in primates, we employed a continuous sampling paradigm to rapidly collect data with little deleterious effects. Here we found robust bilateral auditory cortex activation in two marmosets and unilateral activation in a third utilizing this preparation. Furthermore, we confirmed results previously reported in electrophysiology experiments, such as the tonotopic organization of the auditory core and regions activating preferentially to complex over simple stimuli. Overall, these data establish a key preparation for future research to investigate various functional properties of marmoset auditory cortex.

Design and implementation of embedded 8-channel receive-only arrays for whole-brain MRI and fMRI of conscious awake marmosets.

PURPOSE: The common marmoset (Callithrix jacchus) is a New World primate of increasing interest to neuroscience and in translational brain research. The present work describes the design and implementation of individualized 8-channel receive-only radiofrequency (RF) coil arrays that provide whole-brain coverage and allow anatomical and functional MRI experiments in conscious, awake marmosets. METHODS: The coil arrays were designed with their elements embedded inside individualized restraint helmets. The size, geometry, and arrangement of the coil elements were optimized to allow whole-brain coverage. Coil-to-coil decoupling was achieved by a combination of geometric decoupling and low input impedance preamplifiers. The performance of the embedded arrays was compared against that of one 8-channel receive-only array built to fit the external surface of the helmets. RESULTS: Three individualized helmets with embedded coil arrays were built for three marmosets. Whole-brain coverage was achieved with high sensitivity extending over the entire cortex. Visual stimulation of conscious awake marmosets elicited robust BOLD fMRI responses in both primary and higher order visual areas of the occipitotemporal cortex. CONCLUSION: The high sensitivity provided by embedded receive-only coil arrays allows both anatomical and functional MRI data to be obtained with high spatial resolution in conscious, awake marmosets. Magn Reson Med 78:387-398, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Functional mapping of face-selective regions in the extrastriate visual cortex of the marmoset.

The cerebral cortex of humans and macaques has specialized regions for processing faces and other visual stimulus categories. It is unknown whether a similar functional organization exists in New World monkeys, such as the common marmoset (Callithrix jacchus), a species of growing interest as a primate model in neuroscience. To address this question, we measured selective neural responses in the brain of four awake marmosets trained to fix their gaze upon images of faces, bodies, objects, and control patterns. In two of the subjects, we measured high gamma-range field potentials from electrocorticography arrays implanted over a large portion of the occipital and inferotemporal cortex. In the other two subjects, we measured BOLD fMRI responses across the entire brain. Both techniques revealed robust, regionally specific patterns of category-selective neural responses. We report that at least six face-selective patches mark the occipitotemporal pathway of the marmoset, with the most anterior patches showing the strongest preference for faces over other stimuli. The similar appearance of these patches to previous findings in macaques and humans, including their apparent arrangement in two parallel pathways, suggests that core elements of the face processing network were present in the common anthropoid primate ancestor living ∼35 million years ago. The findings also identify the marmoset as a viable animal model system for studying specialized neural mechanisms related to high-level social visual perception in humans.

Functional MRI of visual responses in the awake, behaving marmoset.

The visual brain is composed of interconnected subcortical and cortical structures that receive and process image information originating in the retina. The visual system of nonhuman primates, in particular macaques, has been studied in great detail in order to elucidate principles of human sensation and perception. The common marmoset (Callithrix jacchus) is a small New World monkey of growing interest as a primate model for neuroscience. Marmosets have advantages over macaques because of their small size, lissencephalic cortex, and growing potential for viral and genetic manipulations. Previous anatomical studies and electrophysiological recordings in anesthetized marmosets have shown that this species' cortical visual hierarchy closely resembles that of other primates, including humans. Until now, however, there have been no attempts to systematically study visual responses throughout the marmoset brain using fMRI. Here we show that awake marmosets readily learn to carry out a simple visual task inside the bore of an MRI scanner during functional mapping experiments. Functional scanning at 500 µm in-plane resolution in a 30 cm horizontal bore at 7 T revealed robust positive blood oxygenation level-dependent (BOLD) fMRI responses to visual stimuli throughout visual cortex and associated subcortical areas. Nonvisual sensory areas showed negative contrasts to visual stimuli compared to the fixation dot only baseline. Structured images of objects and faces led to stronger responses than scrambled control images at stages beyond early visual cortex. Our study establishes fMRI mapping of visual responses in awake, behaving marmosets as a straightforward and valuable tool for assessing the functional organization of the primate brain at high resolution.

An embedded four-channel receive-only RF coil array for fMRI experiments of the somatosensory pathway in conscious awake marmosets.

fMRI has established itself as the main research tool in neuroscience and brain cognitive research. The common marmoset (Callithrix jacchus) is a non-human primate model of increasing interest in biomedical research. However, commercial MRI coils for marmosets are not generally available. The present work describes the design and construction of a four-channel receive-only surface RF coil array with excellent signal-to-noise ratio (SNR) specifically optimized for fMRI experiments in awake marmosets in response to somatosensory stimulation. The array was designed as part of a helmet-based head restraint system used to prevent motion during the scans. High SNR was obtained by building the coil array using a thin and flexible substrate glued to the inner surface of the restraint helmet, so as to minimize the distance between the array elements and the somatosensory cortex. Decoupling between coil elements was achieved by partial geometrical overlapping and by connecting them to home-built low-input-impedance preamplifiers. In vivo images show excellent coverage of the brain cortical surface with high sensitivity near the somatosensory cortex. Embedding the coil elements within the restraint helmet allowed fMRI data in response to somatosensory stimulation to be collected with high sensitivity and reproducibility in conscious, awake marmosets.