Intrinsic functional clustering of ventral premotor F5 in the macaque brain

© 2020 Neurophysiological and anatomical data suggest the existence of several functionally distinct regions in the lower arcuate sulcus and adjacent postarcuate convexity of the macaque monkey. Ventral premotor F5c lies on the postarcuate convexity and consists of a dorsal hand-related and ventral mouth-related field. The posterior bank of the lower arcuate contains two additional premotor F5 subfields at different anterior-posterior levels, F5a and F5p. Anterior to F5a, area 44 has been described as a dysgranular zone occupying the deepest part of the fundus of the inferior arcuate. Finally, area GrFO occupies the most rostral portion of the fundus and posterior bank of inferior arcuate and extends ventrally onto the frontal operculum. Recently, data-driven exploratory approaches using resting-state fMRI data have been suggested as a promising non-invasive method for examining the functional organization of the primate brain. Here, we examined to what extent partitioning schemes derived from data-driven clustering analysis of resting-state fMRI data correspond with the proposed organization of the fundus and posterior bank of the macaque arcuate sulcus, as suggested by invasive architectonical, connectional and functional investigations. Using a hierarchical clustering analysis, we could retrieve clusters corresponding to the dorsal and ventral portions of F5c on the postarcuate convexity, F5a and F5p at different antero-posterior locations on the posterior bank of the lower arcuate, area 44 in the fundus, as well as part of area GrFO in the most anterior portion of the fundus. Additionally, each of these clusters displayed distinct whole-brain functional connectivity, in line with previous anatomical tracer and seed-based functional connectivity investigations of F5/44 subdivisions. Overall, our data suggests that hierarchical clustering analysis of resting-state fMRI data can retrieve a fine-grained level of cortical organization that resembles detailed parcellation schemes derived from invasive functional and anatomical investigations

Intrinsic functional clustering of anterior cingulate cortex in the common marmoset

© 2018 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 4ab and putative eye movement areas (8aD and 8aV). 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

Frontoparietal networks underlying saccadic eye movements in the common marmoset

Common marmosets (Callithrix jacchus) are small-bodied New World primates that are increasingly popular as model animals for neuroscience research. Their lissencephalic cortex provides substantial advantages for the application of high-density electrophysiological techniques to enhance our understanding of local cortical circuits and their cognitive and motor functions. The oculomotor circuitry underlying saccadic eye movements has been a popular system to study cognitive control. Most of what we know about this system, comes from electrophysiological studies on macaques, but most of their cortical oculomotor areas are buried within sulci and harder to access for high-density recordings. In contrast, marmosets provide greater advantages for studies of the oculomotor system, since critical areas of this network such as the frontal eye fields (FEF) and lateral intraparietal area (LIP) are easily accessible at the cortical surface. In contrast to the well-established macaques, little is known about functional connectivity patterns of common marmosets. In this thesis, we used resting-state ultra-high-field fMRI on anesthetized marmosets and macaques along with awake human subjects, to examine and compare the functional organization of the brain, with emphasis on the saccade system. Independent component analysis revealed homologous resting-state networks in marmoset to those in macaques and humans, including a distributed frontoparietal network. Seed-region analyses of the marmoset superior colliculus (SC) revealed the strongest frontal functional connectivity with area 8aD bordering area 6DR. This frontal region exhibited a similar functional connectivity pattern to the FEF in macaques and humans. The results supported an evolutionarily preserved frontoparietal system and provided a starting point for invasive neurophysiological studies in the marmoset saccade system. We started by investigating the function of the marmoset posterior parietal cortex with electrical microstimulation. We implanted 32-channel Utah arrays at the location of area LIP as identified from our resting-state fMRI study and applied microstimulation while animals watched videos. Similar to macaque studies, stimulation evoked fixed-vector and goal-directed saccades, staircase saccades, and eyeblinks in marmosets. These findings demonstrated that the marmoset area LIP plays a role in the regulation of eye movements and is potentially homologous to that of the macaque. Next, we recorded the neuronal activity in marmoset areas LIP and 8aD using linear electrode arrays while animals performed a pro/antisaccade task. The antisaccade task is a popular paradigm to probe executive control. In this task, participants suppress a prepotent stimulus-driven response in favor of a less potent response away from the stimulus. Our behavioral findings indicated that area 8aD neurons were significantly more active for correct than errorenous antisaccades in contralateral directions, with respect to the recording site. We found neurons with significant stimulus-related activity in area LIP and significant saccade-related neurons in both areas 8aD and LIP. These findings provided further evidence on the role of marmoset frontal and parietal oculomotor areas in oculomotor control, supporting marmosets as alternative primate models of the oculomotor system