The common marmoset (Callithrix jacchus) is a small New World primate species that has been recently targeted as a potentially powerful preclinical model of human prefrontal cortex dysfunction. Although the structural boundaries of frontal cortex were described in marmosets at the start of the 20th century (Brodmann, 1909) and refined more recently (e.g., Paxinos et al., 2012), the broad functional boundaries of marmoset frontal cortex have yet to be established. In this study, we sought to functionally derive boundaries of marmoset lateral frontal cortex (LFC) using ultra-high field (9.4 T) resting state functional magnetic resonance imaging (RS-fMRI). We collected RS-fMRI in seven (4 females, 3 males) lightly anesthetized marmosets and employed a data-driven hierarchical clustering approach to derive subdivisions of LFC based on intrinsic functional connectivity. We then conducted seed-based analyses to assess the functional connectivity between these clusters and the rest of the brain. The results demonstrated seven distinct functional clusters within LFC. The functional connectivity patterns of these clusters with the rest of the brain were also found to be distinct and organized along a rostro-caudal gradient, consonant to that found in humans and macaques. Overall, these results support the view that marmosets are a promising preclinical modelling species for studying LFC dysfunction related to neuropsychiatric or neurodegenerative human brain diseases.
The common marmoset (Callithrix jacchus) has garnered recent attention as a potentially powerful preclinical model and complement to other canonical mammalian models of human brain diseases (e.g., rodents and Old World non-human primates). With a granular frontal cortex and the advent of transgenic modifications, marmosets are well positioned to serve as neuropsychiatric models of prefrontal cortex dysfunction. A critical step in the development of marmosets for such models is to characterize functional network topologies of frontal cortex in healthy, normally functioning marmosets. Here, we sought to characterize the intrinsic functional connectivity of anterior cingulate cortex (ACC) in marmosets using resting state functional magnetic resonance imaging (RS-fMRI). Seven lightly anesthetized marmosets were imaged at ultra-high field (9.4 T) and hierarchical clustering was employed to extract functional clusters of ACC from the RS-fMRI data. The data demonstrated three functionally discrete clusters within ACC. The functional connectivity between these clusters with the rest of the brain was also found to be distinct, supporting the hypothesis that ACC subregions serve different circuits and their concomitant functions. In a separate seed-based analysis, we also sought to delineate finer-grained patterns of ACC connectivity between marmoset primary motor area 4 ab and putative eye movement areas (8aD and 8 aV). This analysis demonstrated distinct patterns of ACC functional connectivity between motor and eye movement regions that overlapped well with what has been shown in humans and macaques. Overall, these results demonstrate that marmosets have a network topology of ACC that resembles that of Old World primates, giving further credence to the use of marmosets for preclinical studies of intractable human brain diseases.
Intrinsic functional boundaries of lateral frontal cortex in the common marmoset monkey.
Schaeffer DJ, Gilbert KM, Gati JS, Menon RS, Everling S (2018) J Neurosci. 2018 Dec 10. pii: 2595-18.
Alpha-oscillations modulate preparatory activity in marmoset area 8Ad. Johnston K, Ma L, Schaeffer L, Everling S (2019) J Neurosci. 2019 Jan 16. pii: 2703-18.
Cognitive control often requires suppression of prepotent stimulus-driven responses in favour of less potent alternatives. Suppression of prepotent saccades has been shown to require proactive inhibition in the frontoparietal saccade network. Electrophysiological evidence in macaque monkeys has revealed neural correlates of such inhibition in this network, however the interlaminar instantiation of inhibitory processes remains poorly understood as these areas lie deep within sulci in macaques, rendering them inaccessible to laminar recordings. Here we addressed this gap by exploiting the mostly lissencephalic cortex of the common marmoset (Callithrix jacchus). We inserted linear electrode arrays into areas 8Ad - the putative marmoset frontal eye field - and lateral intraparietal area (LIP) of two male marmosets, and recorded neural activity during performance of a task comprised of alternating blocks of trials requiring a saccade either toward a large, high-luminance stimulus or the inhibition of this prepotent response in favour of a saccade toward a small, low-luminance stimulus. We observed prominent task-dependent activity in both alpha/gamma bands of the local field potential and discharge rates of single neurons in area 8Ad during a prestimulus task epoch in which the animals had been instructed which of these two tasks to perform but prior to peripheral stimulus onset. These data are consistent with a model in which rhythmic alpha-band activity in deeper layers inhibits spiking in upper layers to support proactive inhibitory saccade control.