Cortical Functional Organization Research Articles

Sex differences in functional cortical organization reflect differences in network topology rather than cortical morphometry

Differences in brain size between the sexes are consistently reported. However, the consequences of this anatomical difference on sex differences in intrinsic brain function remain unclear. In the current study, we investigate whether sex differences in intrinsic cortical functional organization may be associated with differences in cortical morphometry, namely different measures of brain size, microstructure, and the geodesic distance of connectivity profiles. For this, we compute a low dimensional representation of functional cortical organization, the sensory-association axis, and identify widespread sex differences. Contrary to our expectations, sex differences in functional organization do not appear to be systematically associated with differences in total surface area, microstructural organization, or geodesic distance, despite these morphometric properties being per se associated with functional organization and differing between sexes. Instead, functional sex differences in the sensory-association axis are associated with differences in functional connectivity profiles and network topology. Collectively, our findings suggest that sex differences in functional cortical organization extend beyond sex differences in cortical morphometry.

A shifting role of thalamocortical connectivity in the emergence of cortical functional organization.

The cortical patterning principle has been a long-standing question in neuroscience, yet how this translates to macroscale functional specialization in the human brain remains largely unknown. Here we examine age-dependent differences in resting-state thalamocortical connectivity to investigate its role in the emergence of large-scale functional networks during early life, using a primarily cross-sectional but also longitudinal approach. We show that thalamocortical connectivity during infancy reflects an early differentiation of sensorimotor networks and genetically influenced axonal projection. This pattern changes in childhood, when connectivity is established with the salience network, while decoupling externally and internally oriented functional systems. A developmental simulation using generative network models corroborated these findings, demonstrating that thalamic connectivity contributes to developing key features of the mature brain, such as functional segregation and the sensory-association axis, especially across 12-18 years of age. Our study suggests that the thalamus plays an important role in functional specialization during development, with potential implications for studying conditions with compromised internal and external processing.

Individual variability in functional connectivity of human auditory cortex.

Individual variability in functional connectivity underlies individual differences in cognition and behaviors, yet its association with functional specialization in the auditory cortex remains elusive. Using resting-state functional magnetic resonance imaging data from the Human Connectome Project, this study was designed to investigate the spatial distribution of auditory cortex individual variability in its whole-brain functional network architecture. An inherent hierarchical axis of the variability was discerned, which radiates from the medial to lateral orientation, with the left auditory cortex demonstrating more pronounced variations than the right. This variability exhibited a significant correlation with the variations in structural and functional metrics in the auditory cortex. Four auditory cortex subregions, which were identified from a clustering analysis based on this variability, exhibited unique connectional fingerprints and cognitive maps, with certain subregions showing specificity to speech perception functional activation. Moreover, the lateralization of the connectional fingerprint exhibited a U-shaped trajectory across the subregions. These findings emphasize the role of individual variability in functional connectivity in understanding cortical functional organization, as well as in revealing its association with functional specialization from the activation, connectome, and cognition perspectives.

Multimodal measures of spontaneous brain activity reveal both common and divergent patterns of cortical functional organization

Large-scale functional networks have been characterized in both rodent and human brains, typically by analyzing fMRI-BOLD signals. However, the relationship between fMRI-BOLD and underlying neural activity is complex and incompletely understood, which poses challenges to interpreting network organization obtained using this technique. Additionally, most work has assumed a disjoint functional network organization (i.e., brain regions belong to one and only one network). Here, we employ wide-field Ca2+ imaging simultaneously with fMRI-BOLD in mice expressing GCaMP6f in excitatory neurons. We determine cortical networks discovered by each modality using a mixed-membership algorithm to test the hypothesis that functional networks exhibit overlapping organization. We find that there is considerable network overlap (both modalities) in addition to disjoint organization. Our results show that multiple BOLD networks are detected via Ca2+ signals, and networks determined by low-frequency Ca2+ signals are only modestly more similar to BOLD networks. In addition, the principal gradient of functional connectivity is nearly identical for BOLD and Ca2+ signals. Despite similarities, important differences are also detected across modalities, such as in measures of functional connectivity strength and diversity. In conclusion, Ca2+ imaging uncovers overlapping functional cortical organization in the mouse that reflects several, but not all, properties observed with fMRI-BOLD signals.

Prefrontal cortical hemodynamics and functional network organization during Tai Chi standing meditation: an fNIRS study.

Tai Chi standing meditation (Zhan Zhuang, also called pile standing) is characterized by meditation, deep breathing, and mental focus based on theories of traditional Chinese medicine. The purpose of the present study was to explore prefrontal cortical hemodynamics and the functional network organization associated with Tai Chi standing meditation by using functional near-infrared spectroscopy (fNIRS). Twenty-four channel fNIRS signals were recorded from 24 male Tai Chi Quan practitioners (54.71 ± 8.04 years) while standing at rest and standing during Tai Chi meditation. The general linear model and the SPM method were used to analyze the fNIRS signals. Pearson correlation was calculated to determine the functional connectivity between the prefrontal cortical sub-regions. The small world properties of the FC networks were then further analyzed based on graph theory. During Tai Chi standing meditation, significantly higher concentrations of oxygenated hemoglobin were observed in bilateral dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC), frontal eye field (FEF), and pre-motor cortex (PMC) compared with the values measured during standing rest (p < 0.05). Simultaneously, significant decreases in deoxygenated hemoglobin concentration were observed in left VLPFC, right PMC and DLPFC during Tai Chi standing meditation than during standing rest (p < 0.05). Functional connectivity between the left and right PFC was also significantly stronger during the Tai Chi standing meditation (p < 0.05). The functional brain networks exhibited small-world architecture, and more network hubs located in DLPFC and VLPFC were identified during Tai Chi standing meditation than during standing rest. These findings suggest that Tai Chi standing meditation introduces significant changes in the cortical blood flow and the brain functional network organization.

Examining resting-state network connectivity in children exposed to perinatal maternal adversity using anatomically weighted functional connectivity (awFC) analyses; A preliminary report.

Environmental perturbations during critical periods can have pervasive, organizational effects on neurodevelopment. To date, the literature examining the long-term impact of early life adversity has largely investigated structural and functional imaging data outcomes independently. However, emerging research points to a relationship between functional connectivity and the brain's underlying structural architecture. For instance, functional connectivity can be mediated by the presence of direct or indirect anatomical pathways. Such evidence warrants the use of structural and functional imaging in tandem to study network maturation. Accordingly, this study examines the impact of poor maternal mental health and socioeconomic context during the perinatal period on network connectivity in middle childhood using an anatomically weighted functional connectivity (awFC) approach. awFC is a statistical model that identifies neural networks by incorporating information from both structural and functional imaging data. Resting-state fMRI and DTI scans were acquired from children aged 7-9 years old. Our results indicate that maternal adversity during the perinatal period can affect offspring's resting-state network connectivity during middle childhood. Specifically, in comparison to controls, children of mothers who had poor perinatal maternal mental health and/or low socioeconomic status exhibited greater awFC in the ventral attention network. These group differences were discussed in terms of the role this network plays in attention processing and maturational changes that may accompany the consolidation of a more adult-like functional cortical organization. Furthermore, our results suggest that there is value in using an awFC approach as it may be more sensitive in highlighting connectivity differences in developmental networks associated with higher-order cognitive and emotional processing, as compared to stand-alone FC or SC analyses.

Frontoparietal connectivity as a product of convergent evolution in rodents and primates: functional connectivity topologies in grey squirrels, rats, and marmosets

Robust frontoparietal connectivity is a defining feature of primate cortical organization. Whether mammals outside the primate order, such as rodents, possess similar frontoparietal functional connectivity organization is a controversial topic. Previous work has primarily focused on comparing mice and rats to primates. However, as these rodents are nocturnal and terrestrial, they rely much less on visual input than primates. Here, we investigated the functional cortical organization of grey squirrels which are diurnal and arboreal, thereby better resembling primate ecology. We used ultra-high field resting-state fMRI data to compute and compare the functional connectivity patterns of frontal regions in grey squirrels (Sciurus carolinensis), rats (Rattus norvegicus), and marmosets (Callithrix jacchus). We utilized a fingerprinting analysis to compare interareal patterns of functional connectivity from seeds across frontal cortex in all three species. The results show that grey squirrels, but not rats, possess a frontoparietal connectivity organization that resembles the connectivity pattern of marmoset lateral prefrontal cortical areas. Since grey squirrels and marmosets have acquired an arboreal way of life but show no common arboreal ancestor, the expansion of the visual system and the formation of a frontoparietal connectivity architecture might reflect convergent evolution driven by similar ecological niches in primates and tree squirrels.

Heritability and cross-species comparisons of human cortical functional organization asymmetry.

The human cerebral cortex is symmetrically organized along large-scale axes but also presents inter-hemispheric differences in structure and function. The quantified contralateral homologous difference, that is asymmetry, is a key feature of the human brain left-right axis supporting functional processes, such as language. Here, we assessed whether the asymmetry of cortical functional organization is heritable and phylogenetically conserved between humans and macaques. Our findings indicate asymmetric organization along an axis describing a functional trajectory from perceptual/action to abstract cognition. Whereas language network showed leftward asymmetric organization, frontoparietal network showed rightward asymmetric organization in humans. These asymmetries were heritable in humans and showed a similar spatial distribution with macaques, in the case of intra-hemispheric asymmetry of functional hierarchy. This suggests (phylo)genetic conservation. However, both language and frontoparietal networks showed a qualitatively larger asymmetry in humans relative to macaques. Overall, our findings suggest a genetic basis for asymmetry in intrinsic functional organization, linked to higher order cognitive functions uniquely developed in humans.

Serotonergic psychedelic drugs LSD and psilocybin reduce the hierarchical differentiation of unimodal and transmodal cortex

Lysergic acid diethylamide (LSD) and psilocybin are serotonergic psychedelic compounds with potential in the treatment of mental health disorders. Past neuroimaging investigations have revealed that both compounds can elicit significant changes to whole-brain functional organization and dynamics. A recent proposal linked past findings into a unified model and hypothesized reduced whole-brain hierarchical organization as a key mechanism underlying the psychedelic state, but this has yet to be directly tested. We applied a non-linear dimensionality reduction technique previously used to map hierarchical connectivity gradients to assess cortical organization in the LSD and psilocybin state from two previously published pharmacological resting-state fMRI datasets (N = 15 and 9, respectively). Results supported our primary hypothesis: The principal gradient of cortical connectivity, describing a hierarchy from unimodal to transmodal cortex, was significantly flattened under both drugs relative to their respective placebo conditions. Between-condition contrasts revealed that this was driven by a reduction of functional differentiation at both hierarchical extremes – default and frontoparietal networks at the upper end, and somatomotor at the lower. Gradient-based connectivity mapping indicated that this was underpinned by a disruption of modular unimodal connectivity and increased unimodal-transmodal crosstalk. Results involving the second and third gradient, which, respectively represent axes of sensory and executive differentiation, also showed significant alterations across both drugs. These findings provide support for a recent mechanistic model of the psychedelic state relevant to therapeutic applications of psychedelics. More fundamentally, we provide the first evidence that macroscale connectivity gradients are sensitive to an acute pharmacological manipulation, supporting a role for psychedelics as scientific tools to perturb cortical functional organization.

The gray mouse lemur (Microcebus murinus) as a model for early primate brain evolution.

The gray mouse lemur (Microcebus murinus), one of the world's smallest primates, is thought to share a similar ecological niche and many anatomical traits with early euprimates. As a result, it has been considered a suitable model system for early primate physiology and behavior. Moreover, recent studies have demonstrated that mouse lemurs have comparable cognitive abilities and cortical functional organization as haplorhines. Finally, the small brain size of mouse lemurs provides us with actual lower limits for miniaturization of functional brain circuits within the primate clade. Considering its phylogenetic positionand early primate-like traits, the mouse lemurs are a perfect model species to study the early evolution of primate brains.

Developmental plasticity of texture discrimination following early vision loss in the marsupial Monodelphis domestica

ABSTRACTBehavioral strategies that depend on sensory information are not immutable; rather they can be shaped by the specific sensory context in which animals develop. This behavioral plasticity depends on the remarkable capacity of the brain to reorganize in response to alterations in the sensory environment, particularly when changes in sensory input occur at an early age. To study this phenomenon, we utilize the short-tailed opossum, a marsupial that has been a valuable animal model to study developmental plasticity due to the extremely immature state of its nervous system at birth. Previous studies in opossums have demonstrated that removal of retinal inputs early in development results in profound alterations to cortical connectivity and functional organization of visual and somatosensory cortex; however, behavioral consequences of this plasticity are not well understood. We trained early blind and sighted control opossums to perform a two-alternative forced choice texture discrimination task. Whisker trimming caused an acute deficit in discrimination accuracy for both groups, indicating the use of a primarily whisker-based strategy to guide choices based on tactile cues. Mystacial whiskers were important for performance in both groups; however, genal whiskers only contributed to behavioral performance in early blind animals. Early blind opossums significantly outperformed their sighted counterparts in discrimination accuracy, with discrimination thresholds that were lower by ∼75 μm. Our results support behavioral compensation following early blindness using tactile inputs, especially the whisker system.

Cortical gradients of functional connectivity are robust to state-dependent changes following sleep deprivation

Sleep deprivation leads to significant impairments in cognitive performance and changes to the interactions between large scale cortical networks, yet the hierarchical organization of cortical activity across states is still being explored. We used functional magnetic resonance imaging to assess activations and connectivity during cognitive tasks in 20 healthy young adults, during three states: (i) following a normal night of sleep, (ii) following 24hr of total sleep deprivation, and (iii) after a morning recovery nap. Situating cortical activity during cognitive tasks along hierarchical organizing gradients based upon similarity of functional connectivity patterns, we found that regional variations in task-activations were captured by an axis differentiating areas involved in executive control from default mode regions and paralimbic cortex. After global signal regression, the range of functional differentiation along this axis at baseline was significantly related to decline in working memory performance (2-back task) following sleep deprivation, as well as the extent of recovery in performance following a nap. The relative positions of cortical regions within gradients did not significantly change across states, except for a lesser differentiation of the visual system and increased coupling of the posterior cingulate cortex with executive control areas after sleep deprivation. This was despite a widespread increase in the magnitude of functional connectivity across the cortex following sleep deprivation. Cortical gradients of functional differentiation thus appear relatively insensitive to state-dependent changes following sleep deprivation and recovery, suggesting that there are no large-scale changes in cortical functional organization across vigilance states. Certain features of particular gradient axes may be informative for the extent of decline in performance on more complex tasks following sleep deprivation, and could be beneficial over traditional voxel- or parcel-based approaches in identifying realtionships between state-dependent brain activity and behavior.

Core and matrix thalamic sub-populations relate to spatio-temporal cortical connectivity gradients

Recent neuroimaging experiments have defined low-dimensional gradients of functional connectivity in the cerebral cortex that subserve a spectrum of capacities that span from sensation to cognition. Despite well-known anatomical connections to the cortex, the subcortical areas that support cortical functional organization have been relatively overlooked. One such structure is the thalamus, which maintains extensive anatomical and functional connections with the cerebral cortex across the cortical mantle. The thalamus has a heterogeneous cytoarchitecture, with at least two distinct cell classes that send differential projections to the cortex: granular-projecting ‘Core’ cells and supragranular-projecting ‘Matrix’ cells. Here we use high-resolution 7T resting-state fMRI data and the relative amount of two calcium-binding proteins, parvalbumin and calbindin, to infer the relative distribution of these two cell-types (Core and Matrix, respectively) in the thalamus. First, we demonstrate that thalamocortical connectivity recapitulates large-scale, low-dimensional connectivity gradients within the cerebral cortex. Next, we show that diffusely-projecting Matrix regions preferentially correlate with cortical regions with longer intrinsic fMRI timescales. We then show that the Core–Matrix architecture of the thalamus is important for understanding network topology in a manner that supports dynamic integration of signals distributed across the brain. Finally, we replicate our main results in a distinct 3T resting-state fMRI dataset. Linking molecular and functional neuroimaging data, our findings highlight the importance of the thalamic organization for understanding low-dimensional gradients of cortical connectivity.

LittleBrain: A gradient-based tool for the topographical interpretation of cerebellar neuroimaging findings.

Gradient-based approaches to brain function have recently unmasked fundamental properties of brain organization. Diffusion map embedding analysis of resting-state fMRI data revealed a primary-to-transmodal axis of cerebral cortical macroscale functional organization. The same method was recently used to analyze resting-state data within the cerebellum, revealing for the first time a sensorimotor-fugal macroscale organization principle of cerebellar function. Cerebellar gradient 1 extended from motor to non-motor task-unfocused (default-mode network) areas, and cerebellar gradient 2 isolated task-focused processing regions. Here we present a freely available and easily accessible tool that applies this new knowledge to the topographical interpretation of cerebellar neuroimaging findings. LittleBrain illustrates the relationship between cerebellar data (e.g., volumetric patient study clusters, task activation maps, etc.) and cerebellar gradients 1 and 2. Specifically, LittleBrain plots all voxels of the cerebellum in a two-dimensional scatterplot, with each axis corresponding to one of the two principal functional gradients of the cerebellum, and indicates the position of cerebellar neuroimaging data within these two dimensions. This novel method of data mapping provides alternative, gradual visualizations that complement discrete parcellation maps of cerebellar functional neuroanatomy. We present application examples to show that LittleBrain can also capture subtle, progressive aspects of cerebellar functional neuroanatomy that would be difficult to visualize using conventional mapping techniques. Download and use instructions can be found at https://xaviergp.github.io/littlebrain.

Alpha-band functional connectivity during cued versus implicit modality-specific anticipatory attention: EEG-source coherence analysis.

The anticipation of future events based on a background experience is one of the main components of any goal-directed behavior. Anticipatory attention can be either voluntary (explicit) or involuntary (implicit). We presumed that these two types of anticipatory attention differed in terms of cortical functional organization. We examined this assumption with an experimental model consisting of three experimental sessions (cued attention, implicit learning, and baseline) that were equal in terms of stimuli, motor responses, and cognitive task. Participants were asked to discriminate the temporal order of stimuli within a pair presented in either the visual or auditory sensory modality. Prestimulus functional connectivity was assessed via alpha-band coherence computed in the source space for preselected regions of interests. Functional links between the cortices of the frontoparietal control system increased during the cued attention condition and did not increase during the implicit anticipation condition. The buildup of implicit anticipation was accompanied by the strengthening of functional links between the intraparietal, ventral premotor, and presupplementary motor areas. It was discovered that both cued and implicit types of anticipation were underlain by functional modality-specific cortical links.

Congenital Deafness Reduces, But Does Not Eliminate Auditory Responsiveness in Cat Extrastriate Visual Cortex

Congenital deafness not only affects the development of the auditory cortex, but also the interrelation between the visual and auditory system. For example, congenital deafness leads to visual modulation of the deaf auditory cortex in the form of cross-modal plasticity. Here we asked, whether congenital deafness additionally affects auditory modulation in the visual cortex. We demonstrate that auditory activity, which is normally present in the lateral suprasylvian visual areas in normal hearing cats, can also be elicited by electrical activation of the auditory system with cochlear implants. We then show that in adult congenitally deaf cats auditory activity in this region was reduced when tested with cochlear implant stimulation. However, the change in this area was small and auditory activity was not completely abolished despite years of congenital deafness. The results document that congenital deafness leads not only to changes in the auditory cortex but also affects auditory modulation of visual areas. However, the results further show a persistence of fundamental cortical sensory functional organization despite congenital deafness.

Psychiatric polygenic risk associates with cortical morphology and functional organization in aging

Common brain abnormalities in cortical morphology and functional organization are observed in psychiatric disorders and aging, reflecting shared genetic influences. This preliminary study aimed to examine the contribution of a polygenetic risk for psychiatric disorders (PRScross) to aging brain and to identify molecular mechanisms through the use of multimodal brain images, genotypes, and transcriptome data. We showed age-related cortical thinning in bilateral inferior frontal cortex (IFC) and superior temporal gyrus and alterations in the functional connectivity between bilateral IFC and between right IFC and right inferior parietal lobe as a function of PRScross. Interestingly, the genes in PRScross, that contributed most to aging neurodegeneration, were expressed in the functioanlly connected cortical regions. Especially, genes identified through the genotype-functional connectivity association analysis were commonly expressed in both cortical regions and formed strong gene networks with biological processes related to neural plasticity and synaptogenesis, regulated by glutamatergic and GABAergic transmission, neurotrophin signaling, and metabolism. This study suggested integrating genotype and transcriptome with neuroimage data sheds new light on the mechanisms of aging brain.

Rapid Long-Range Disynaptic Inhibition Explains the Formation of Cortical Orientation Maps.

Competitive interactions are believed to underlie many types of cortical processing, ranging from memory formation, attention and development of cortical functional organization (e.g., development of orientation maps in primary visual cortex). In the latter case, the competitive interactions happen along the cortical surface, with local populations of neurons reinforcing each other, while competing with those displaced more distally. This specific configuration of lateral interactions is however in stark contrast with the known properties of the anatomical substrate, i.e., excitatory connections (mediating reinforcement) having longer reach than inhibitory ones (mediating competition). No satisfactory biologically plausible resolution of this conflict between anatomical measures, and assumed cortical function has been proposed. Recently a specific pattern of delays between different types of neurons in cat cortex has been discovered, where direct mono-synaptic excitation has approximately the same delay, as the combined delays of the disynaptic inhibitory interactions between excitatory neurons (i.e., the sum of delays from excitatory to inhibitory and from inhibitory to excitatory neurons). Here we show that this specific pattern of delays represents a biologically plausible explanation for how short-range inhibition can support competitive interactions that underlie the development of orientation maps in primary visual cortex. We demonstrate this statement analytically under simplifying conditions, and subsequently show using network simulations that development of orientation maps is preserved when long-range excitation, direct inhibitory to inhibitory interactions, and moderate inequality in the delays between excitatory and inhibitory pathways is added.

Direct electrical bipolar electrostimulation for functional cortical and subcortical cerebral mapping in awake craniotomy. Practical considerations

IntroductionThe aim of brain glioma surgery is to maximize the quality of resection, while minimizing the risk of sequelae. Due to the frequent location of gliomas near or within eloquent areas, owing to their infiltrative feature, and because of major interindividual variability, the anatomofunctional organization and connectivity must be studied individually. Therefore, to optimize the benefit-to-risk ratio of surgery, intraoperative functional mapping is extensively used. Material and methodsThis article aims at describing the rationale, indications and practical aspects of intraoperative direct electrical bipolar electrostimulation for cortical and subcortical mapping under awake conditions using the asleep-awake asleep anaesthetic protocol in the setting of cerebral gliomas. We will address the operative approach, including patient positioning, functional mapping resection strategy, anaesthetic conditions, as well as tips and pitfalls. ResultsThe intraoperative direct electrical bipolar electrostimulation enables: (i) to study the real-time individual cortical functional organization; (ii) to study the anatomofunctional subcortical connectivity along the resection; (iii) to tailor the resection according to individual corticosubcortical functional boundaries. This is an easy, accurate, reliable, well-tolerated and safe detection technique of both cortical and subcortical functionally essential structures during resection. It should be performed in the context of a standardized protocol involving members of both anaesthesiology and neurosurgery teams at neurosurgical centers specialized in surgical neuro-oncology. ConclusionIntraoperative direct electrical bipolar electrostimulation for cortical and subcortical mapping under awake conditions is currently considered the “gold standard” clinical tool for brain mapping during cerebral resection in neuro-oncology.

Hyperbrain features of team mental models within a juggling paradigm: a proof of concept

BackgroundResearch on cooperative behavior and the social brain exists, but little research has focused on real-time motor cooperative behavior and its neural correlates. In this proof of concept study, we explored the conceptual notion of shared and complementary mental models through EEG mapping of two brains performing a real-world interactive motor task of increasing difficulty. We used the recently introduced participative “juggling paradigm,” and collected neuro-physiological and psycho-social data. We were interested in analyzing the between-brains coupling during a dyadic juggling task, and in exploring the relationship between the motor task execution, the jugglers’skill level and the task difficulty. We also investigated how this relationship could be mirrored in the coupled functional organization of the interacting brains.MethodsTo capture the neural schemas underlying the notion of shared and complementary mental models, we examined the functional connectivity patterns and hyperbrain features of a juggling dyad involved in cooperative motor tasks of increasing difficulty. Jugglers’ cortical activity was measured using two synchronized 32-channel EEG systems during dyadic juggling performed with 3, 4, 5 and 6 balls. Individual and hyperbrain functional connections were quantified through coherence maps calculated across all electrode pairs in the theta and alpha bands (4–8 and 8–12 Hz). Graph metrics were used to typify the global topology and efficiency of the functional networks for the four difficulty levels in the theta and alpha bands.ResultsResults indicated that, as task difficulty increased, the cortical functional organization of the more skilled juggler became progressively more segregated in both frequency bands, with a small-world organization in the theta band during easier tasks, indicative of a flow-like state in line with the neural efficiency hypothesis. Conversely, more integrated functional patterns were observed for the less skilled juggler in both frequency bands, possibly related to cognitive overload due to the difficulty of the task at hand (reinvestment hypothesis). At the hyperbrain level, a segregated functional organization involving areas of the visuo-attentional networks of both jugglers was observed in both frequency bands and for the easier task only.DiscussionThese results suggest that cooperative juggling is supported by integrated activity of specialized cortical areas from both brains only during easier tasks, whereas it relies on individual skills, mirrored in uncorrelated individual brain activations, during more difficult tasks. These findings suggest that task difficulty and jugglers’ personal skills may influence the features of the hyperbrain network in its shared/integrative and complementary/segregative tendencies.