Intrinsic functional boundaries of lateral frontal cortex in the common marmoset monkey

© 2019 the authors. 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 (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 the marmoset lateral frontal cortex (LFC) using ultra-high field (9.4 T) resting-state functional magnetic resonance imaging (RS-fMRI). We collectedRS-fMRIdatainseven(fourfemales,threemales)lightlyanesthetizedmarmosetsandusedadata-drivenhierarchicalclustering approach to derive subdivisions of the 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 withintheLFC.Thefunctionalconnectivitypatternsoftheseclusterswiththerestofthebrainwerealsofoundtobedistinctandorganized along a rostrocaudal gradient, consonant with those found in humans and macaques. Overall, these results support the view that marmosets are a promising preclinical modeling species for studying LFC dysfunction related to neuropsychiatric or neurodegenerative human brain diseases

The Organization of Local and Distant Functional Connectivity in the Human Brain

Information processing in the human brain arises from both interactions between adjacent areas and from distant projections that form distributed brain systems. Here we map interactions across different spatial scales by estimating the degree of intrinsic functional connectivity for the local (≤14 mm) neighborhood directly surrounding brain regions as contrasted with distant (>14 mm) interactions. The balance between local and distant functional interactions measured at rest forms a map that separates sensorimotor cortices from heteromodal association areas and further identifies regions that possess both high local and distant cortical-cortical interactions. Map estimates of network measures demonstrate that high local connectivity is most often associated with a high clustering coefficient, long path length, and low physical cost. Task performance changed the balance between local and distant functional coupling in a subset of regions, particularly, increasing local functional coupling in regions engaged by the task. The observed properties suggest that the brain has evolved a balance that optimizes information-processing efficiency across different classes of specialized areas as well as mechanisms to modulate coupling in support of dynamically changing processing demands. We discuss the implications of these observations and applications of the present method for exploring normal and atypical brain function.Psycholog

Dwelling Quietly in the Rich Club: Brain Network Determinants of Slow Cortical Fluctuations

For more than a century, cerebral cartography has been driven by investigations of structural and morphological properties of the brain across spatial scales and the temporal/functional phenomena that emerge from these underlying features. The next era of brain mapping will be driven by studies that consider both of these components of brain organization simultaneously -- elucidating their interactions and dependencies. Using this guiding principle, we explored the origin of slowly fluctuating patterns of synchronization within the topological core of brain regions known as the rich club, implicated in the regulation of mood and introspection. We find that a constellation of densely interconnected regions that constitute the rich club (including the anterior insula, amygdala, and precuneus) play a central role in promoting a stable, dynamical core of spontaneous activity in the primate cortex. The slow time scales are well matched to the regulation of internal visceral states, corresponding to the somatic correlates of mood and anxiety. In contrast, the topology of the surrounding "feeder" cortical regions show unstable, rapidly fluctuating dynamics likely crucial for fast perceptual processes. We discuss these findings in relation to psychiatric disorders and the future of connectomics.Comment: 35 pages, 6 figure

Relationships between human auditory cortical structure and function

The human auditory cortex comprises multiple areas, largely distributed across the supratemporal plane, but the precise number and configuration of auditory areas and their functional significance have not yet been clearly established. In this paper, we discuss recent research concerning architectonic and functional organisation within the human auditory cortex, as well as architectonic and neurophysiological studies in non-human species, which can provide a broad conceptual framework for interpreting functional specialisation in humans. We review the pattern in human auditory cortex of the functional responses to various acoustic cues, such as frequency, pitch, sound level, temporal variation, motion and spatial location, and we discuss their correspondence to what is known about the organisation of the auditory cortex in other primates. There is some neuroimaging evidence of multiple tonotopically organised fields in humans and of functional specialisations of the fields in the processing of different sound features. It is thought that the primary area, on Heschl's gyrus, may have a larger involvement in processing basic sound features, such as frequency and level, and that posterior non-primary areas on the planum temporale may play a larger role in processing more spectrotemporally complex sounds. Ways in which current knowledge of auditory cortical organisation and different data analysis approaches may benefit future functional neuroimaging studies which seek to link auditory cortical structure and function are discussed

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

Measuring macroscopic brain connections in vivo

Decades of detailed anatomical tracer studies in non-human animals point to a rich and complex organization of long-range white matter connections in the brain. State-of-the art in vivo imaging techniques are striving to achieve a similar level of detail in humans, but multiple technical factors can limit their sensitivity and fidelity. In this review, we mostly focus on magnetic resonance imaging of the brain. We highlight some of the key challenges in analyzing and interpreting in vivo connectomics data, particularly in relation to what is known from classical neuroanatomy in laboratory animals. We further illustrate that, despite the challenges, in vivo imaging methods can be very powerful and provide information on connections that is not available by any other means

A Putative Multiple-Demand System in the Macaque Brain.

UNLABELLED: In humans, cognitively demanding tasks of many types recruit common frontoparietal brain areas. Pervasive activation of this "multiple-demand" (MD) network suggests a core function in supporting goal-oriented behavior. A similar network might therefore be predicted in nonhuman primates that readily perform similar tasks after training. However, an MD network in nonhuman primates has not been described. Single-cell recordings from macaque frontal and parietal cortex show some similar properties to human MD fMRI responses (e.g., adaptive coding of task-relevant information). Invasive recordings, however, come from limited prespecified locations, so they do not delineate a macaque homolog of the MD system and their positioning could benefit from knowledge of where MD foci lie. Challenges of scanning behaving animals mean that few macaque fMRI studies specifically contrast levels of cognitive demand, so we sought to identify a macaque counterpart to the human MD system using fMRI connectivity in 35 rhesus macaques. Putative macaque MD regions, mapped from frontoparietal MD regions defined in humans, were found to be functionally connected under anesthesia. To further refine these regions, an iterative process was used to maximize their connectivity cross-validated across animals. Finally, whole-brain connectivity analyses identified voxels that were robustly connected to MD regions, revealing seven clusters across frontoparietal and insular cortex comparable to human MD regions and one unexpected cluster in the lateral fissure. The proposed macaque MD regions can be used to guide future electrophysiological investigation of MD neural coding and in task-based fMRI to test predictions of similar functional properties to human MD cortex. SIGNIFICANCE STATEMENT: In humans, a frontoparietal "multiple-demand" (MD) brain network is recruited during a wide range of cognitively demanding tasks. Because this suggests a fundamental function, one might expect a similar network to exist in nonhuman primates, but this remains controversial. Here, we sought to identify a macaque counterpart to the human MD system using fMRI connectivity. Putative macaque MD regions were functionally connected under anesthesia and were further refined by iterative optimization. The result is a network including lateral frontal, dorsomedial frontal, and insular and inferior parietal regions closely similar to the human counterpart. The proposed macaque MD regions can be useful in guiding electrophysiological recordings or in task-based fMRI to test predictions of similar functional properties to human MD cortex

Unravelling the Intrinsic Functional Organization of the Human Lateral Frontal Cortex: A Parcellation Scheme Based on Resting State fMRI

Human and nonhuman primates exhibit flexible behavior. Functional, anatomical, and lesion studies indicate that the lateral frontal cortex (LFC) plays a pivotal role in such behavior. LFC consists of distinct subregions exhibiting distinct connectivity patterns that possibly relate to functional specializations. Inference about the border of each subregion in the human brain is performed with the aid of macroscopic landmarks and/or cytoarchitectonic parcellations extrapolated in a stereotaxic system. However, the high interindividual variability, the limited availability of cytoarchitectonic probabilistic maps, and the absence of robust functional localizers render the in vivo delineation and examination of the LFC subregions challenging. In this study, we use resting state fMRI for the in vivo parcellation of the human LFC on a subjectwise and data-driven manner. This approach succeeds in uncovering neuroanatomically realistic subregions, with potential anatomical substrates includingBA46, 44, 45, 9 and related (sub)divisions. Ventral LFC subregions exhibit different functional connectivity (FC), which can account for different contributions in the language domain, while more dorsal adjacent subregions mark a transition to visuospatial/sensorimotor networks. Dorsal LFC subregions participate in known large-scale networks obeying an external/internal information processing dichotomy. Furthermore, we traced “families” of LFC subregions organized along the dorsal–ventral and anterior–posterior axis with distinct functional networks also encompassing specialized cingulate divisions. Similarities with the connectivity of macaque candidate homologs were observed, such as the premotor affiliation of presumed BA 46. The current findings partially support dominant LFC models

Cortex, countercurrent context, and dimensional integration of lifetime memory

The correlation between relative neocortex size and longevity in mammals encourages a search for a cortical function specifically related to the life-span. A candidate in the domain of permanent and cumulative memory storage is proposed and explored in relation to basic aspects of cortical organization. The pattern of cortico-cortical connectivity between functionally specialized areas and the laminar organization of that connectivity converges on a globally coherent representational space in which contextual embedding of information emerges as an obligatory feature of cortical function. This brings a powerful mode of inductive knowledge within reach of mammalian adaptations, a mode which combines item specificity with classificatory generality. Its neural implementation is proposed to depend on an obligatory interaction between the oppositely directed feedforward and feedback currents of cortical activity, in countercurrent fashion. Direct interaction of the two streams along their cortex-wide local interface supports a scheme of "contextual capture" for information storage responsible for the lifelong cumulative growth of a uniquely cortical form of memory termed "personal history." This approach to cortical function helps elucidate key features of cortical organization as well as cognitive aspects of mammalian life history strategies