Based upon cytoarchitectonic properties, the primate prefrontal cortex has been partitioned into different subregions that show unique structural connectivity patterns, with ongoing efforts to provide more fine-grained divisions. While meaningful divisions may be found within the sub-millimeter range, the subdivisions exist within an overall hierarchical architecture and at higher levels likely share similar activity patterns and functionality. Here, we used resting-state fMRI in lightly anesthetized macaque monkeys to measure the intrinsic functional connectivity of the prefrontal cortex. At a gross anatomical level, the data driven approach revealed five broad clusters that showed distinct brain-wide functional connectivity. Although each cluster encompasses several cytoarchitectonic subregions, the clusters overlap with the intrinsic structural connectivity of the prefrontal cortex and each cluster may subserve common functions.

Spontaneous brain activity is ubiquitous across brain structures and states. Determining the role of these metabolically costly intrinsic events may be critical for understanding the brain's fundamental physiological principles that govern cognition and behavior. To date, most investigations of large-scale fluctuations and their coupling have been conducted using electro- or magneto-encephalography, modalities that are limited in their ability to spatially resolve the origin of the signals. Invasive, electrophysiological local field potential (LFP) recordings are limited in their spatial range and studies combining the approach with functional imaging have been primarily relegated to sensory/motor areas with little basis in which to extrapolate findings to evolutionarily newer prefrontal cortical regions. Here, we acquired spontaneous fMRI data in two anesthetized macaque monkeys (Macaca fascicularis) at 7 T together with simultaneous recordings of intracortical LFPs recorded bilaterally from the prefrontal cortex (area 9/46d). High (beta-low gamma) and low (delta-theta) band-limited power (BLP) ranges of the LFP frequencies were anticorrelated in the absence of any explicit stimuli. Beyond the high LFP-BLP signal being correlated with BOLD activity at the recording site, the high and low LFP-BLP envelopes were shown to be significantly correlated with spontaneous BOLD activity recorded from positively and negatively connected prefrontal network regions, respectively. The results suggest that complementary changes in low and high frequency bands may be an intrinsic property of LFPs, that local prefrontal cortical activity is related to spontaneous BOLD fluctuations, and further, that LFP-BLPs may be correlated at a network level.

Unilateral damage to the frontoparietal network typically impairs saccade target selection within the contralesional visual hemifield. Severity of deficits and the degree of recovery have been associated with widespread network dysfunction, yet it is not clear how these behavioural and functional brain changes relate with the underlying structural white matter tracts. Here, we investigated whether recovery after unilateral prefrontal cortex (PFC) lesions was associated with changes in white matter microstructure across large-scale frontoparietal cortical and thalamocortical networks. Diffusion-weighted imaging was acquired in four male rhesus macaques at pre-lesion, week 1, and week 8-16 post-lesion when target selection deficits largely recovered. Probabilistic tractography was used to reconstruct cortical frontoparietal fiber tracts, including the superior longitudinal fasciculus (SLF) and transcallosal fibers connecting the PFC or posterior parietal cortex (PPC), as well as thalamocortical fiber tracts connecting the PFC and PPC to thalamic nuclei. We found that the two animals with small PFC lesions showed increased fractional anisotropy in both cortical and thalamocortical fiber tracts when behaviour had recovered. However, we found that fractional anisotropy decreased in cortical frontoparietal tracts after larger PFC lesions yet increased in some thalamocortical tracts at the time of behavioural recovery. These findings indicate that behavioural recovery after small PFC lesions may be supported by both cortical and subcortical areas, whereas larger PFC lesions may have induced widespread structural damage and hindered compensatory remodeling in the cortical frontoparietal network.

Based on its diverse and wide-spread patterns of connectivity, primate posteromedial cortex (PMC) is well positioned to support roles in several aspects of sensory-, cognitive- and motor-related processing. Previous work in both humans and non-human primates (NHPs) using resting-state functional MRI (rs-fMRI) suggests that a subregion of PMC, the medial parieto-occipital cortex (mPOC), by virtue of its intrinsic functional connectivity (FC) with visual cortex, may only play a role in higher-order visual processing. Recent neuroanatomical tracer studies in NHPs, however, demonstrate that mPOC also has prominent cortico-cortical connections with several frontoparietal structures involved in movement planning and control, a finding consistent with increasing observations of reach- and grasp-related activity in the mPOC of both NHPs and humans. To reconcile these observations, here we used rs-fMRI data collected from both awake humans and anesthetized macaque monkeys to more closely examine and compare parcellations of mPOC across species and explore the FC patterns associated with these subdivisions. Seed-based and voxel-wise hierarchical cluster analyses revealed four broad spatially separated functional boundaries that correspond with graded differences in whole-brain FC patterns in each species. The patterns of FC observed are consistent with mPOC forming a critical hub of networks involved in action planning and control, spatial navigation, and working memory. In addition, our comparison between species indicates that while there are several similarities, there may be some species-specific differences in functional neural organization. These findings and the associated theoretical implications are discussed.

Visual extinction has been characterized by the failure to respond to a visual stimulus in the contralesional hemifield when presented simultaneously with an ipsilesional stimulus (Corbetta and Shulman, 2011). Unilateral damage to the macaque frontoparietal cortex commonly leads to deficits in contralesional target selection that resemble visual extinction. Recently, we showed that macaque monkeys with unilateral lesions in the caudal prefrontal cortex (PFC) exhibited contralesional target selection deficits that recovered over 2-4 months (Adam et al., 2019). Here, we investigated the longitudinal changes in functional connectivity (FC) of the frontoparietal network after a small or large right caudal PFC lesion in four macaque monkeys. We collected ultra-high field resting-state fMRI at 7-T before the lesion and at weeks 1-16 post-lesion and compared the functional data with behavioural performance on a free-choice saccade task. We found that the pattern of frontoparietal network FC changes depended on lesion size, such that the recovery of contralesional extinction was associated with an initial increase in network FC that returned to baseline in the two small lesion monkeys, whereas FC continued to increase throughout recovery in the two monkeys with a larger lesion. We also found that the FC between contralesional dorsolateral PFC and ipsilesional parietal cortex correlated with behavioural recovery and that the contralesional dorsolateral PFC showed increasing degree centrality with the frontoparietal network. These findings suggest that both the contralesional and ipsilesional hemispheres play an important role in the recovery of function. Importantly, optimal compensation after large PFC lesions may require greater recruitment of distant and intact areas of the frontoparietal network, whereas recovery from smaller lesions was supported by a normalization of the functional network.

Assessment of brain connectivity has revealed that the structure and dynamics of large-scale network organization are altered in multiple disease states suggesting their use as diagnostic or prognostic indicators. Further investigation into the underlying mechanisms, organization, and alteration of large-scale brain networks requires a homologous animal model that would allow neurophysiological recordings and experimental manipulations. The current study presents a comprehensive assessment of macaque resting-state networks based on evaluation of intrinsic low-frequency fluctuations of the blood oxygen-level-dependent signal using group independent component analysis. Networks were found underlying multiple levels of sensory, motor, and cognitive processing. The results demonstrate that macaques share remarkable homologous network organization with humans, thereby providing strong support for their use as an animal model in the study of normal and abnormal brain connectivity as well as aiding the interpretation of electrophysiological recordings within the context of large-scale brain networks.

Primate occipitotemporal cortex (OTC) is composed of a mosaic of highly specialized brain regions each involved in the high-level visual analysis and recognition of particular stimulus categories (e.g., objects, faces, scenes, bodies and tools). Whereas theories attempting to account for this modular organization of category-selective responses in OTC have largely focused on visually driven, bottom-up inputs to OTC (e.g., dimensions related to the visual structure of the world and how it is experienced), other proposals have instead focused on the connectivity of OTC's outputs, emphasizing how the information processed by different OTC regions might be used by the rest of the brain. The latter proposals underscore the importance of interpreting the activity (and selectivity) of individual OTC areas within the greater context of the widely distributed network of areas in which they are embedded and that use OTC information to support behavior. Here, using resting-state fMRI, we investigated the functional connectivity (FC) patterns of OTC regions associated with object-, face-, scene-, body- and tool-related processing defined from task-based localizers acquired in the same cohort of participants. We observed notable differences in the whole-brain FC patterns, not only across OTC regions, but even between areas thought to form part of the same category-selective network. Furthermore, we found that the neuroanatomical location of OTC regions (e.g., adjacency) had little, if any, bearing on the FC networks observed. FC between certain OTC areas and other regions traditionally implicated in sensory-, motor-, affective- and/or cognitive-related processing and the associated theoretical implications is discussed.