Functional MRI of visual responses in the awake, behaving marmoset

Highlights

• Awake, behaving marmosets were trained to perform visual tasks in an MRI scanner.

• Anatomical regions of interest were registered to an MRI template.

• Robust fMRI responses in both cortical and subcortical visual areas were obtained.

• Higher visual areas responded better to structured than to scrambled visual stimuli.

Abstract

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.

Introduction

Vision is the dominant sensory modality of primates, providing spatially accurate information about the environment from a distance. From an ethological point of view, vision bestows organisms with the ability to identify foods, predators, mating candidates, and numerous other objects critical to survival. The high acuity of primate vision also allows for fine motor actions under visual guidance. Mechanisms of vision have long been studied in both human and non-human primates, and these studies have demonstrated that monkeys and humans share many neural specializations for visual perception (Orban et al., 2004, Rosa and Tweedale, 2005, Tootell et al., 2003). Old World macaques have long been the most widely used animal model of human vision, traditionally via anatomical and electrophysiological studies (Felleman and Van Essen, 1991, Hubel and Wiesel, 1968, Van Essen et al., 1992), and more recently in functional MRI experiments ( Vanduffel et al., 2014).

Following the advent of new molecular and genetic technologies developed in mice, primate research would benefit greatly from the application of viral or transgenic manipulations of neural systems. As progress in the macaque has been slow, much attention has been turned to the common marmoset (Callthrix jacchus) as a genetically tractable primate model. Marmosets are New World monkeys that diverged quite recently (< 40 million years ago) from the phylogenetic lineage leading to humans (Kishi et al., 2014, Mansfield, 2003, Okano et al., 2012, Okano and Mitra, 2014, Solomon and Rosa, 2014). Marmosets are comparable in size to rats, and the combination of small body and large brain offers unique opportunities for high spatiotemporal resolution MRI imaging in a small-bore, high field animal scanner (Hikishima et al., 2013, Newman et al., 2009, Silva et al., 2011). Unlike macaques or humans, the cerebral cortex of the marmoset is lissencephalic, lacking the complex folding of sulci and gyri. Yet in spite of its superficial resemblance to the rat’s brain, the functional organization of the marmoset brain is that of a primate, with specializations in the eye and brain that closely resemble those found in macaques and humans (Cheong et al., 2013, Lui et al., 2013, McDonald et al., 2014, Mitchell and Leopold, 2015, Rosa and Tweedale, 2005, Yu and Rosa, 2014).

In a recent study, we demonstrated the spatial organization of face-selective visual responses in the marmoset visual system (Hung et al., 2015). Here we systematically describe the methodology and results of mapping basic visual fMRI responses throughout brain of the behaving marmoset. For studying visual organization, fMRI offers an important complement to single unit recording. In the awake animal, visual fMRI involves cooperation of the subject, who must reliably direct its gaze to stimuli of interest. We demonstrate here that training and collecting high-resolution fMRI data from awake marmoset subjects in a small-bore scanner is straightforward. Using a block design, we mapped responses throughout the brain to images of natural objects, as well as scrambled control patterns. We found robust positive BOLD responses to visual stimuli in the lateral geniculate nucleus (LGN), pulvinar, superior colliculus and throughout the cerebral cortex, including occipital areas V1, V2, V3 and V4, temporal lobe areas TEO, TE3, and frontal lobe area 8aV. Several nonvisual areas, including primary areas of other sensory modalities, showed suppression of BOLD activity for visual stimuli compared to the fixation baseline. A subset of ventral stream visual areas, including areas V3, V4, TEO, and TE3, responded more strongly to natural, structured images than to the corresponding scrambled control images. These results show that fMRI is an effective tool for mapping cortical and subcortical visual responses in this species. Thus high-resolution fMRI, when combined with specific molecular and genetic interventions in the marmoset, offers new avenues to probe the functional organization of the primate brain.