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Understanding the similarity of cortico-subcortical networks topologies between humans and nonhuman primate species is critical to study the origin of network alternations underlying human neurologic and neuropsychiatric diseases. The New World common marmoset (Callithrix jacchus) has become popular as a nonhuman primate model for human brain function. Most marmoset connectomic research, however, has exclusively focused on cortical areas, with connectivity to subcortical networks less extensively explored. Here, we aimed to first isolate patterns of subcortical connectivity with cortical resting-state networks in awake marmosets using resting-state fMRI, then to compare these networks with those in humans using connectivity fingerprinting. In this study, we used 5 marmosets (4 males, 1 female). While we could match several marmoset and human resting-state networks based on their functional fingerprints, we also found a few striking differences, for example, strong functional connectivity of the default mode network with the superior colliculus in marmosets that was much weaker in humans. Together, these findings demonstrate that many of the core cortico-subcortical networks in humans are also present in marmosets, but that small, potentially functionally relevant differences exist. [ABSTRACT FROM AUTHOR]

With the medial frontal cortex (MFC) centrally implicated in several major neuropsychiatric disorders, it is critical to understand the extent to which MFC organization is comparable between humans and animals commonly used in preclinical research (namely rodents and nonhuman primates). Although the cytoarchitectonic structure of the rodent MFC has mostly been conserved in humans, it is a long-standing question whether the structural analogies translate to functional analogies. Here, we probed this question using ultra high field fMRI data to compare rat, marmoset, and human MFC functional connectivity. First, we applied hierarchical clustering to intrinsically define the functional boundaries of the MFC in all three species, independent of cytoarchitectonic definitions. Then, we mapped the functional connectivity "fingerprints" of these regions with a number of different brain areas. Because rats do not share cytoarchitectonically defined regions of the lateral frontal cortex (LFC) with primates, the fingerprinting method also afforded the unique ability to compare the rat MFC and marmoset LFC, which have often been suggested to be functional analogs. The results demonstrated remarkably similar intrinsic functional organization of the MFC across the species, but clear differences between rodent and primate MFCwhole-brain connectivity. Rat MFC patterns of connectivity showed greatest similarity with premotor regions in the marmoset, rather than dorsolateral prefrontal regions, which are often suggested to be functionally comparable. These results corroborate the viability of the marmoset as a preclinical model of human MFC dysfunction, and suggest divergence of functional connectivity between rats and primates in both the MFC and LFC. [ABSTRACT FROM AUTHOR]

The complex network dynamics that arise from the interaction of the brain's structural and functional architectures give rise to mental function. Theoretical models demonstrate that the structure-function relation is maximal when the global network dynamics operate at a critical point of state transition. In the present work, we used a dynamic mean-field neural model to fit empirical structural connectivity (SC) and functional connectivity (FC) data acquired in humans and macaques and developed a new iterative-fitting algorithm to optimize the SC matrix based on the FC matrix. A dramatic improvement of the fitting of the matrices was obtained with the addition of a small number of anatomical links, particularly cross-hemispheric connections, and reweighting of existing connections. We suggest that the notion of a critical working point, where the structure-function interplay is maximal, may provide a new way to link behavior and cognition, and a new perspective to understand recovery of function in clinical conditions. [ABSTRACT FROM AUTHOR]

Characterization of large-scale brain networks using blood-oxygenation-level-dependent functional magnetic resonance imaging is typically based on the assumption of network stationarity across the duration of scan. Recent studies in humans have questioned this assumption by showing that within-network functional connectivity fluctuates on the order of seconds to minutes. Time-varying profiles of resting-state networks (RSNs) may relate to spontaneously shifting, electrophysiological network states and are thus mechanistically of particular importance. However, because these studies acquired data from awake subjects, the fluctuating connectivity could reflect various forms of conscious brain processing such as passive mind wandering, active monitoring, memory formation, or changes in attention and arousal during image acquisition. Here, we characterize RSN dynamics of anesthetized macaques that control for these accounts, and compare them to awake human subjects. We find that functional connectivity among nodes comprising the 'oculomotor (OCM) network' strongly fluctuated over time during awake as well as anaesthetized states. For time dependent analysis with short windows (<60 s), periods of positive functional correlations alternated with prominent anticorrelations that were missed when assessed with longer time windows. Similarly, the analysis identified network nodes that transiently link to the OCM network and did not emerge in average RSN analysis. Furthermore, time-dependent analysis reliably revealed transient states of large-scale synchronization that spanned all seeds. The results illustrate that resting-state functional connectivity is not static and that RSNs can exhibit nonstationary, spontaneous relationships irrespective of conscious, cognitive processing. The findings imply that mechanistically important network information can be missed when using average functional connectivity as the single network measure. Hum Brain Mapp 34:2154-2177, 2013. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

In EEG data acquired in the presence of fMRI, gradient-related spike artifacts contaminate the signal following the common preprocessing step of average artifact subtraction. Spike artifacts compromise EEG data quality since they overlap with the EEG signal in frequency, thereby confounding frequency-based inferences on activity. As well, spike artifacts can inflate or deflate correlations among time series, thereby confounding inferences on functional connectivity. We present Schrödinger filtering, which uses the Schrödinger equation to decompose the spike-containing input. The basis functions of the decomposition are localized and pulse-shaped, and selectively capture the various input peaks, with the spike components clustered at the beginning of the spectrum. Schrödinger filtering automatically subtracts the spike components from the data. On real and simulated data, we show that Schrödinger filtering (1) simultaneously accomplishes high spike removal and high signal preservation without affecting evoked activity, and (2) reduces spurious pairwise correlations in spontaneous activity. In these regards, Schrödinger filtering was significantly better than three other despiking techniques: median filtering, amplitude thresholding, and wavelet denoising. These results encourage the use of Schrödinger filtering in future EEG-fMRI pipelines, as well as in other spike-related applications (e.g. , fMRI motion artifact removal or action potential extraction). Image, graphical abstract [ABSTRACT FROM AUTHOR]

Background The temporoparietal junction (TPJ) has been linked to lower-level attentional and higher-level social processing, both of which are affected in schizophrenia (SZ) and major depressive disorder (MDD). We examined resting functional connectivity of bilateral anterior and posterior TPJ in SZ and MDD to evaluate potential anomalies in each disorder and differences between disorders. Methods Resting-state functional magnetic resonance imaging data were acquired from 24 patients with SZ, 24 patients with MDD, and 24 age-matched healthy controls. We performed seed-based functional connectivity analyses with seed regions in bilateral anterior and posterior TPJ, covarying for gender and smoking. Results SZ had reduced connectivity versus controls between left anterior TPJ and dorsolateral prefrontal cortex (dlPFC) and posterior cingulate cortex (PCC); between left posterior TPJ and middle cingulate cortex, left dorsal PFC, and right lateral PFC; between right anterior TPJ and bilateral PCC; and between right posterior TPJ and middle cingulate cortex, left posterior insula, and right insula. MDD had reduced connectivity versus controls between left posterior TPJ and right dlPFC and between right posterior TPJ and PCC and dlPFC. SZ had reduced connectivity versus MDD between right posterior TPJ and left fusiform gyrus and right superior-posterior temporal cortex. Conclusion Functional connectivity to the TPJ was demonstrated to be disrupted in both SZ and MDD. However, TPJ connectivity may differ in these disorders with reduced connectivity in SZ versus MDD between TPJ and posterior brain regions. [ABSTRACT FROM AUTHOR]

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. • We created ischemic lesions of the right caudal PFC in macaque monkeys. • Target selection deficits resemble visual extinction and recover by 2–4 months. • We measure longitudinal changes in FC during recovery using rsfMRI at 7 T. • Functional network reorganization differs based on lesion size and location. • Frontoparietal networks in both hemispheres play a role in the functional recovery. [ABSTRACT FROM AUTHOR]

The pulvinar and the mediodorsal (MDN) nuclei of the thalamus are higher order nuclei which have been implicated in directed effort and corollary discharge systems. We used seed-based resting fMRI to examine functional connectivity to bilateral pulvinar and MDN in 24 schizophrenic patients (SZ), 24 major depressive disorder patients (MDD), and 24 age-matched healthy controls. SZ had less connectivity than controls between the left pulvinar and precuneus, left ventral-lateral prefrontal cortex (vlPFC), and superior and medial-frontal regions, between the right pulvinar and right frontal pole, and greater connectivity between the right MDN and left dorsolateral prefrontal cortex (dlPFC). SZ had less connectivity than MDD between the left pulvinar and ventral anterior cingulate (vACC), left vlPFC, anterior insula, posterior cingulate cortex (PCC), and right hippocampus, between the right pulvinar and right PCC, and between the right MDN and right dorsal anterior cingulate (dACC). This is the first study to measure the functional connectivity to the higher order nuclei of the thalamus in both SZ and MDD. We observed less connectivity in SZ than MDD between pulvinar and emotional encoding regions, a directed effort region, and a region involved in representation and salience, and between MDN and a directed effort region. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The common marmoset (Callithrix jacchus) is quickly gaining traction as a premier neuroscientific model. However, considerable progress is still needed in understanding the functional and structural organization of the marmoset brain to rival that documented in longstanding preclinical model species, like mice, rats, and Old World primates. To accelerate such progress, we present the Marmoset Functional Brain Connectivity Resource (marmosetbrainconnectome.org), currently consisting of over 70 h of resting-state fMRI (RS-fMRI) data acquired at 500 µm isotropic resolution from 31 fully awake marmosets in a common stereotactic space. Three-dimensional functional connectivity (FC) maps for every cortical and subcortical gray matter voxel are stored online. Users can instantaneously view, manipulate, and download any whole-brain functional connectivity (FC) topology (at the subject- or group-level) along with the raw datasets and preprocessing code. Importantly, researchers can use this resource to test hypotheses about FC directly – with no additional analyses required – yielding whole-brain correlations for any gray matter voxel on demand. We demonstrate the resource's utility for presurgical planning and comparison with tracer-based neuronal connectivity as proof of concept. Complementing existing structural connectivity resources for the marmoset brain, the Marmoset Functional Brain Connectivity Resource affords users the distinct advantage of exploring the connectivity of any voxel in the marmoset brain, not limited to injection sites nor constrained by regional atlases. With the entire raw database (RS-fMRI and structural images) and preprocessing code openly available for download and use, we expect this resource to be broadly valuable to test novel hypotheses about the functional organization of the marmoset brain. [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]

Objective: To use functional magnetic resonance imaging (fMRI) to investigate functional connectivity, and hence, underlying neural networks, in never-treated, first-episode patients with schizophrenia using a word fluency paradigm known to activate prefrontal, anterior cingulate, and thalamic regions. Abnormal connectivity between the prefrontal cortex (PFC) and other brain regions has been demonstrated in chronic, medicated patients in previous positron emission tomography (PET) studies, but has not to our knowledge, previously been demonstrated using both first-episode, drug-naïve patients and fMRI technology. Methods: A 4.0-Tesla (T) fMRI was used to examine activation and functional connectivity [psychophysiological interactions (PPIs)] during a word fluency task compared to silent reading in 10 never-treated, first-episode patients with schizophrenia and 10 healthy volunteers of comparable age, sex, handedness, and parental education. Results: Compared to healthy volunteers, the schizophrenia patient group exhibited less activation during the word fluency task, mostly in the right anterior cingulate and prefrontal regions. Psychophysiological interactions between right anterior cingulate and other parts of the brain revealed a localized interaction with the left temporal lobe in healthy volunteers during the task and a widespread unfocussed interaction in patients. Conclusion: These findings suggest anterior cingulate involvement in the neuronal circuitry underlying schizophrenia. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to assess interregional brain activity covariations during traumatic script-driven imagery in subjects with posttraumatic stress disorder (PTSD). Methods: Functional magnetic resonance imaging and functional connectivity analyses were used to assess interregional brain activity covariations during script-driven imagery in PTSD subjects with a dissociative response, PTSD subjects with a flashback response, and healthy control subjects. Results: Significant between-group differences in functional connectivity were found. Comparing dissociated PTSD patients and control subjects’ connectivity maps in the left ventrolateral thalamus (VLT) [−14, −16, 4] revealed that control subjects had higher covariations between activations in VLT and in the left superior frontal gyrus (Brodmann’s area [BA] 10), right parahippocampal gyrus (BA 30), and right superior occipital gyrus (BA 19, 39), whereas greater covariation with VLT in dissociated PTSD subjects occurred in the right insula (BA 13, 34), left parietal lobe (BA 7), right middle frontal gyrus (BA 8), superior temporal gyrus (BA 38, 34), and right cuneus (BA 19). Comparing dissociated PTSD and flashback PTSD connectivity maps in the right cingulate gyrus [3, 16, 30] revealed that dissociated PTSD subjects had higher covariations between activations in this region and the left inferior frontal gyrus (BA 47). Conclusions: Greater activation of neural networks involved in representing bodily states was seen in dissociated PTSD subjects than in non-PTSD control subjects. These findings might illuminate the mechanisms underlying distorted body perceptions often observed clinically during dissociative episodes. [Copyright &y& Elsevier]

• We characterized resting-state functional connectivity gradients that underlie structural organization of primary somatosensory cortex (S1). • We demonstrated that these gradients are strongly associated to anatomical hierarchy, underlying microstructure, and Brodmann areas. • We provided evidence suggesting the division of the primary somatosensory cortex into two distinct functional parcels – Brodmann areas 3a & 3b and areas 1 & 2. • Seed-based connectivity analyses using these parcels demonstrated thalamocortical connectivity patterns reflect S1 Brodmann areas. The primary somatosensory cortex (S1) plays a key role in the processing and integration of afferent somatosensory inputs along an anterior-to-posterior axis, contributing towards necessary human function. It is believed that anatomical connectivity can be used to probe hierarchical organization, however direct characterization of this principle in-vivo within humans remains elusive. Here, we use resting-state functional connectivity as a complement to anatomical connectivity to investigate topographical principles of human S1. We employ a novel approach to examine mesoscopic variations of functional connectivity, and demonstrate a topographic organisation spanning the region's hierarchical axis that strongly correlates with underlying microstructure while tracing along architectonic Brodmann areas. Our findings characterize anatomical hierarchy of S1 as a 'continuous spectrum' with evidence supporting a functional boundary between areas 3b and 1. The identification of this topography bridges the gap between structure and connectivity, and may be used to help further current understanding of sensorimotor deficits. [ABSTRACT FROM AUTHOR]

Changes in resting-state functional connectivity (rs-FC) under general anesthesia have been widely studied with the goal of identifying neural signatures of consciousness. This work has commonly revealed an apparent fragmentation of whole-brain network structure during unconsciousness, which has been interpreted as reflecting a break-down in connectivity and a disruption of the brain's ability to integrate information. Here we show, by studying rs-FC under varying depths of isoflurane-induced anesthesia in nonhuman primates, that this apparent fragmentation, rather than reflecting an actual change in network structure, can be simply explained as the result of a global reduction in FC. Specifically, by comparing the actual FC data to surrogate data sets that we derived to test competing hypotheses of how FC changes as a function of dose, we found that increases in whole-brain modularity and the number of network communities – considered hallmarks of fragmentation – are artifacts of constructing FC networks by thresholding based on correlation magnitude. Taken together, our findings suggest that deepening levels of unconsciousness are instead associated with the increasingly muted expression of functional networks, an observation that constrains current interpretations as to how anesthesia-induced FC changes map onto existing neurobiological theories of consciousness. [ABSTRACT FROM AUTHOR]