Individual Differences in Multisensory Processing Are Related to Broad Differences in the Balance of Local versus Distributed Information.

The brain's ability to extract information from multiple sensory channels is crucial to perception and effective engagement with the environment, but the individual differences observed in multisensory processing lack mechanistic explanation. We hypothesized that, from the perspective of information theory, individuals with more effective multisensory processing will exhibit a higher degree of shared information among distributed neural populations while engaged in a multisensory task, representing more effective coordination of information among regions. To investigate this, healthy young adults completed an audiovisual simultaneity judgment task to measure their temporal binding window (TBW), which quantifies the ability to distinguish fine discrepancies in timing between auditory and visual stimuli. EEG was then recorded during a second run of the simultaneity judgment task, and partial least squares was used to relate individual differences in the TBW width to source-localized EEG measures of local entropy and mutual information, indexing local and distributed processing of information, respectively. The narrowness of the TBW, reflecting more effective multisensory processing, was related to a broad pattern of higher mutual information and lower local entropy at multiple timescales. Furthermore, a small group of temporal and frontal cortical regions, including those previously implicated in multisensory integration and response selection, respectively, played a prominent role in this pattern. Overall, these findings suggest that individual differences in multisensory processing are related to widespread individual differences in the balance of distributed versus local information processing among a large subset of brain regions, with more distributed information being associated with more effective multisensory processing. The balance of distributed versus local information processing may therefore be a useful measure for exploring individual differences in multisensory processing, its relationship to higher cognitive traits, and its disruption in neurodevelopmental disorders and clinical conditions.

EEG variability: Task-driven or subject-driven signal of interest?

Neurons in the brain are seldom perfectly quiet. They continually receive input and generate output, resulting in highly variable patterns of ongoing activity. Yet the functional significance of this variability is not well understood. If brain signal variability is functionally relevant and serves as an important indicator of cognitive function, then it should be highly sensitive to the precise manner in which a cognitive system is engaged and/or relate strongly to differences in behavioral performance. To test this, we examined EEG activity in younger adults as they performed a cognitive skill learning task and during rest. Several measures of EEG variability and signal strength were calculated in overlapping time windows that spanned the trial interval. We performed a systematic examination of the factors that most strongly influenced the variability and strength of EEG activity. First, we examined the relative sensitivity of each measure to across-subject variation (within blocks) and across-block variation (within subjects). We found that the across-subject variation in EEG variability and signal strength was much stronger than the across-block variation. Second, we examined the sensitivity of each measure to different sources of across-block variation during skill acquisition. We found that key task-driven changes in EEG activity were best reflected in changes in the strength, rather than the variability, of EEG activity. Lastly, we examined across-subject variation in each measure and its relationship with behavior. We found that individual differences in response time measures were best reflected in individual differences in the variability, rather than the strength, of EEG activity. Importantly, we found that individual differences in EEG variability related strongly to stable indicators of subject identity rather than dynamic indicators of subject performance. We therefore suggest that EEG variability may provide a more sensitive subject-driven measure of individual differences than task-driven signal of interest.

Brain simulation as a cloud service: The Virtual Brain on EBRAINS.

The Virtual Brain (TVB) is now available as open-source services on the cloud research platform EBRAINS (ebrains.eu). It offers software for constructing, simulating and analysing brain network models including the TVB simulator; magnetic resonance imaging (MRI) processing pipelines to extract structural and functional brain networks; combined simulation of large-scale brain networks with small-scale spiking networks; automatic conversion of user-specified model equations into fast simulation code; simulation-ready brain models of patients and healthy volunteers; Bayesian parameter optimization in epilepsy patient models; data and software for mouse brain simulation; and extensive educational material. TVB cloud services facilitate reproducible online collaboration and discovery of data assets, models, and software embedded in scalable and secure workflows, a precondition for research on large cohort data sets, better generalizability, and clinical translation.

Exploration of salient risk factors involved in mild cognitive impairment.

Mild cognitive impairment (MCI) is a prevalent and complex condition among older adults that often progresses into Alzheimer's disease (AD). Although MCI affects individuals differently, there are specific indicators of risk commonly associated with the development of MCI. The present study explored the prevalence of seven established MCI risk categories within a large sample of older adults with and without MCI. We explored trends across the different diagnostic groups and extracted the most salient risk factors related to MCI using partial least squares. Neuropsychological risk categories showed the largest differences across groups, with the cognitively unimpaired groups outperforming the MCI groups on all measures. Apolipoprotein E4 (ApoE4) carriers were significantly more common among the more severe MCI group, whereas ApoE4 non-carriers were more common in the healthy controls. Participants with subjective and objective cognitive impairment were trending towards AD-like cerebral spinal fluid (CSF) biomarker levels. Increased age, being male and having fewer years of education were identified as important risk factors of MCI. Higher CSF tau levels were correlated with ApoE4 carrier status, age and a decrease in the ability to carry out daily activities across all diagnostic groups. Amyloid beta1-42 CSF concentration was positively correlated with cognitive and memory performance and non-ApoE4 carrier status regardless of diagnostic status. Unlike previous research, poor cardiovascular health or being female had no relation to MCI. Altogether, the results highlighted risk factors that were specific to persons with MCI, findings that will inform future research in healthy aging, MCI and AD.

Complexity Matching: Brain Signals Mirror Environment Information Patterns during Music Listening and Reward.

Understanding how the human brain integrates information from the environment with intrinsic brain signals to produce individual perspectives is an essential element of understanding the human mind. Brain signal complexity, measured with multiscale entropy, has been employed as a measure of information processing in the brain, and we propose that it can also be used to measure the information available from a stimulus. We can directly assess the correspondence between brain signal complexity and stimulus complexity as an indication of how well the brain reflects the content of the environment in an analysis that we term "complexity matching." Music is an ideal stimulus because it is a multidimensional signal with a rich temporal evolution and because of its emotion- and reward-inducing potential. When participants focused on acoustic features of music, we found that EEG complexity was lower and more closely resembled the musical complexity compared to an emotional task that asked them to monitor how the music made them feel. Music-derived reward scores on the Barcelona Music Reward Questionnaire correlated with less complexity matching but higher EEG complexity. Compared with perceptual-level processing, emotional and reward responses are associated with additional internal information processes above and beyond those linked to the external stimulus. In other words, the brain adds something when judging the emotional valence of music.

Dynamic Functional Connectivity between order and randomness and its evolution across the human adult lifespan.

Functional Connectivity (FC) during resting-state or task conditions is not static but inherently dynamic. Yet, there is no consensus on whether fluctuations in FC may resemble isolated transitions between discrete FC states rather than continuous changes. This quarrel hampers advancing the study of dynamic FC. This is unfortunate as the structure of fluctuations in FC can certainly provide more information about developmental changes, aging, and progression of pathologies. We merge the two perspectives and consider dynamic FC as an ongoing network reconfiguration, including a stochastic exploration of the space of possible steady FC states. The statistical properties of this random walk deviate both from a purely "order-driven" dynamics, in which the mean FC is preserved, and from a purely "randomness-driven" scenario, in which fluctuations of FC remain uncorrelated over time. Instead, dynamic FC has a complex structure endowed with long-range sequential correlations that give rise to transient slowing and acceleration epochs in the continuous flow of reconfiguration. Our analysis for fMRI data in healthy elderly revealed that dynamic FC tends to slow down and becomes less complex as well as more random with increasing age. These effects appear to be strongly associated with age-related changes in behavioural and cognitive performance.

Towards a standard model of musical improvisation.

Musical improvisation is a sophisticated cognitive process that combines creativity, goal-directed action, sensory monitoring and social interaction. With a renewed interest in quantifying creative processes facilitated by recent advances in neuroimaging technology, musical improvisation has emerged as an ideal paradigm to study creativity. However, many studies isolate the top-down processes related to creativity from those related to production and auditory perception, leaving the question of how creative behaviours integrate sensory information with higher cognitive processes unanswered. The bottom-up neural correlates of music perception have been extensively quantified, comprising networks for auditory processing and parsing semantic and syntactic content. In studies of spontaneously generated music and domain-general creativity, executive control and goal-directed movement networks are added to the perceptual foundation. This review summarises previous work on music perception and improvisation and presents a conceptual model of musical improvisation with known neural correlates. We make recommendations on future directions for the study of improvisation and discuss the challenges posed by this endeavour.

Unique Mapping of Structural and Functional Connectivity on Cognition.

The unique mapping of structural brain connectivity (SC) and functional brain connectivity (FC) on cognition is currently not well understood. It is not clear whether cognition is mapped via a global connectome pattern or instead is underpinned by several sets of distributed connectivity patterns. Moreover, we also do not know whether the spatial distributions of SC and FC that underlie cognition are overlapping or distinct. Here, we study the relationship between SC and FC and an array of psychological tasks in 609 subjects (males, 269; females, 340) from the Human Connectome Project. We identified several sets of connections that each uniquely map onto cognitive function. We found a small number of distributed SCs and a larger set of corticocortical and corticosubcortical FCs that express this association. Importantly, the SC and FC each show unique and distinct patterns of variance across subjects as they relate to cognition. The results suggest that a complete understanding of connectome underpinnings of cognition calls for a combination of the two modalities.SIGNIFICANCE STATEMENT Structural connectivity (SC), the physical white-matter inter-regional pathways in the brain, and functional connectivity (FC), the temporal coactivations between the activity of the brain regions, have each been studied extensively. Little is known, however, about the distribution of variance in connections as they relate to cognition. Here, in a large sample of subjects (N = 609), we showed that two sets of brain-behavior patterns capture the correlations between SC and FC with a wide range of cognitive tasks, respectively. These brain-behavior patterns reveal distinct sets of connections within the SC and the FC network and provide new evidence that SC and FC each provide unique information for cognition.

Exploring the limits of network topology estimation using diffusion-based tractography and tracer studies in the macaque cortex.

Reconstructing the anatomical pathways of the brain to study the human connectome has become an important endeavour for understanding brain function and dynamics. Reconstruction of the cortico-cortical connectivity matrix in vivo often relies on noninvasive diffusion-weighted imaging (DWI) techniques but the extent to which they can accurately represent the topological characteristics of structural connectomes remains unknown. We addressed this question by constructing connectomes using DWI data collected from macaque monkeys in vivo and with data from published invasive tracer studies. We found the strength of fiber tracts was well estimated from DWI and topological properties like degree and modularity were captured by tractography-based connectomes. Rich-club/core-periphery type architecture could also be detected but the classification of hubs using betweenness centrality, participation coefficient and core-periphery identification techniques was inaccurate. Our findings indicate that certain aspects of cortical topology can be faithfully represented in noninvasively-obtained connectomes while other network analytic measures warrant cautionary interpretations.

Multiregional integration in the brain during resting-state fMRI activity.

Data-driven models of functional magnetic resonance imaging (fMRI) activity can elucidate dependencies that involve the combination of multiple brain regions. Activity in some regions during resting-state fMRI can be predicted with high accuracy from the activities of other regions. However, it remains unclear in which regions activity depends on unique integration of multiple predictor regions. To address this question, sparse (parsimonious) models could serve to better determine key interregional dependencies by reducing false positives. We used resting-state fMRI data from 46 subjects, and for each region of interest (ROI) per subject we performed whole-brain recursive feature elimination (RFE) to select the minimal set of ROIs that best predicted activity in the modeled ROI. We quantified the dependence of activity on multiple predictor ROIs, by measuring the gain in prediction accuracy of models that incorporated multiple predictor ROIs compared to models that used a single predictor ROI. We identified regions that showed considerable evidence of multiregional integration and determined the key regions that contributed to their observed activity. Our models reveal fronto-parietal integration networks, little integration in primary sensory regions, as well as redundancy between some regions. Our study demonstrates the utility of whole-brain RFE to generate data-driven models with minimal sets of ROIs that predict activity with high accuracy. By determining the extent to which activity in each ROI depended on integration of signals from multiple ROIs, we find cortical integration networks during resting-state activity.

Stable long-range interhemispheric coordination is supported by direct anatomical projections.

The functional interaction between the brain's two hemispheres includes a unique set of connections between corresponding regions in opposite hemispheres (i.e., homotopic regions) that are consistently reported to be exceptionally strong compared with other interhemispheric (i.e., heterotopic) connections. The strength of homotopic functional connectivity (FC) is thought to be mediated by the regions' shared functional roles and their structural connectivity. Recently, homotopic FC was reported to be stable over time despite the presence of dynamic FC across both intrahemispheric and heterotopic connections. Here we build on this work by considering whether homotopic FC is also stable across conditions. We additionally test the hypothesis that strong and stable homotopic FC is supported by the underlying structural connectivity. Consistent with previous findings, interhemispheric FC between homotopic regions were significantly stronger in both humans and macaques. Across conditions, homotopic FC was most resistant to change and therefore was more stable than heterotopic or intrahemispheric connections. Across time, homotopic FC had significantly greater temporal stability than other types of connections. Temporal stability of homotopic FC was facilitated by direct anatomical projections. Importantly, temporal stability varied with the change in conductive properties of callosal axons along the anterior-posterior axis. Taken together, these findings suggest a notable role for the corpus callosum in maintaining stable functional communication between hemispheres.

Post-Traumatic Stress Constrains the Dynamic Repertoire of Neural Activity.

Post-traumatic stress disorder (PTSD) is an anxiety disorder arising from exposure to a traumatic event. Although primarily defined in terms of behavioral symptoms, the global neurophysiological effects of traumatic stress are increasingly recognized as a critical facet of the human PTSD phenotype. Here we use magnetoencephalographic recordings to investigate two aspects of information processing: inter-regional communication (measured by functional connectivity) and the dynamic range of neural activity (measured in terms of local signal variability). We find that both measures differentiate soldiers diagnosed with PTSD from soldiers without PTSD, from healthy civilians, and from civilians with mild traumatic brain injury, which is commonly comorbid with PTSD. Specifically, soldiers with PTSD display inter-regional hypersynchrony at high frequencies (80-150 Hz), as well as a concomitant decrease in signal variability. The two patterns are spatially correlated and most pronounced in a left temporal subnetwork, including the hippocampus and amygdala. We hypothesize that the observed hypersynchrony may effectively constrain the expression of local dynamics, resulting in less variable activity and a reduced dynamic repertoire. Thus, the re-experiencing phenomena and affective sequelae in combat-related PTSD may result from functional networks becoming "stuck" in configurations reflecting memories, emotions, and thoughts originating from the traumatizing experience. SIGNIFICANCE STATEMENT: The present study investigates the effects of post-traumatic stress disorder (PTSD) in combat-exposed soldiers. We find that soldiers with PTSD exhibit hypersynchrony in a circuit of temporal lobe areas associated with learning and memory function. This rigid functional architecture is associated with a decrease in signal variability in the same areas, suggesting that the observed hypersynchrony may constrain the expression of local dynamics, resulting in a reduced dynamic range. Our findings suggest that the re-experiencing of traumatic events in PTSD may result from functional networks becoming locked in configurations that reflect memories, emotions, and thoughts associated with the traumatic experience.

Mapping complementary features of cross-species structural connectivity to construct realistic "Virtual Brains".

Modern systems neuroscience increasingly leans on large-scale multi-lab neuroinformatics initiatives to provide necessary capacity for biologically realistic modeling of primate whole-brain activity. Here, we present a framework to assemble primate brain's biologically plausible anatomical backbone for such modeling initiatives. In this framework, structural connectivity is determined by adding complementary information from invasive macaque axonal tract tracing and non-invasive human diffusion tensor imaging. Both modalities are combined by means of available interspecies registration tools and a newly developed Bayesian probabilistic modeling approach to extract common connectivity evidence. We demonstrate how this novel framework is embedded in the whole-brain simulation platform called The Virtual Brain (TVB). Hum Brain Mapp 38:2080-2093, 2017. © 2017 Wiley Periodicals, Inc.

Network-Level Structure-Function Relationships in Human Neocortex.

The dynamics of spontaneous fluctuations in neural activity are shaped by underlying patterns of anatomical connectivity. While numerous studies have demonstrated edge-wise correspondence between structural and functional connections, much less is known about how large-scale coherent functional network patterns emerge from the topology of structural networks. In the present study, we deploy a multivariate statistical technique, partial least squares, to investigate the association between spatially extended structural networks and functional networks. We find multiple statistically robust patterns, reflecting reliable combinations of structural and functional subnetworks that are optimally associated with one another. Importantly, these patterns generally do not show a one-to-one correspondence between structural and functional edges, but are instead distributed and heterogeneous, with many functional relationships arising from nonoverlapping sets of anatomical connections. We also find that structural connections between high-degree hubs are disproportionately represented, suggesting that these connections are particularly important in establishing coherent functional networks. Altogether, these results demonstrate that the network organization of the cerebral cortex supports the emergence of diverse functional network configurations that often diverge from the underlying anatomical substrate.

Network structure shapes spontaneous functional connectivity dynamics.

The structural organization of the brain constrains the range of interactions between different regions and shapes ongoing information processing. Therefore, it is expected that large-scale dynamic functional connectivity (FC) patterns, a surrogate measure of coordination between brain regions, will be closely tied to the fiber pathways that form the underlying structural network. Here, we empirically examined the influence of network structure on FC dynamics by comparing resting-state FC (rsFC) obtained using BOLD-fMRI in macaques (Macaca fascicularis) to structural connectivity derived from macaque axonal tract tracing studies. Consistent with predictions from simulation studies, the correspondence between rsFC and structural connectivity increased as the sample duration increased. Regions with reciprocal structural connections showed the most stable rsFC across time. The data suggest that the transient nature of FC is in part dependent on direct underlying structural connections, but also that dynamic coordination can occur via polysynaptic pathways. Temporal stability was found to be dependent on structural topology, with functional connections within the rich-club core exhibiting the greatest stability over time. We discuss these findings in light of highly variable functional hubs. The results further elucidate how large-scale dynamic functional coordination exists within a fixed structural architecture.

Computational modeling of resting-state activity demonstrates markers of normalcy in children with prenatal or perinatal stroke.

Children who sustain a prenatal or perinatal brain injury in the form of a stroke develop remarkably normal cognitive functions in certain areas, with a particular strength in language skills. A dominant explanation for this is that brain regions from the contralesional hemisphere "take over" their functions, whereas the damaged areas and other ipsilesional regions play much less of a role. However, it is difficult to tease apart whether changes in neural activity after early brain injury are due to damage caused by the lesion or by processes related to postinjury reorganization. We sought to differentiate between these two causes by investigating the functional connectivity (FC) of brain areas during the resting state in human children with early brain injury using a computational model. We simulated a large-scale network consisting of realistic models of local brain areas coupled through anatomical connectivity information of healthy and injured participants. We then compared the resulting simulated FC values of healthy and injured participants with the empirical ones. We found that the empirical connectivity values, especially of the damaged areas, correlated better with simulated values of a healthy brain than those of an injured brain. This result indicates that the structural damage caused by an early brain injury is unlikely to have an adverse and sustained impact on the functional connections, albeit during the resting state, of damaged areas. Therefore, these areas could continue to play a role in the development of near-normal function in certain domains such as language in these children.

Short-term Music Training Enhances Complex, Distributed Neural Communication during Music and Linguistic Tasks.

Musical training is frequently associated with benefits to linguistic abilities, and recent focus has been placed on possible benefits of bilingualism to lifelong executive functions; however, the neural mechanisms for such effects are unclear. The aim of this study was to gain better understanding of the whole-brain functional effects of music and second-language training that could support such previously observed cognitive transfer effects. We conducted a 28-day longitudinal study of monolingual English-speaking 4- to 6-year-old children randomly selected to receive daily music or French language training, excluding weekends. Children completed passive EEG music note and French vowel auditory oddball detection tasks before and after training. Brain signal complexity was measured on source waveforms at multiple temporal scales as an index of neural information processing and network communication load. Comparing pretraining with posttraining, musical training was associated with increased EEG complexity at coarse temporal scales during the music and French vowel tasks in widely distributed cortical regions. Conversely, very minimal decreases in complexity at fine scales and trends toward coarse-scale increases were displayed after French training during the tasks. Spectral analysis failed to distinguish between training types and found overall theta (3.5-7.5 Hz) power increases after all training forms, with spatially fewer decreases in power at higher frequencies (>10 Hz). These findings demonstrate that musical training increased diversity of brain network states to support domain-specific music skill acquisition and music-to-language transfer effects.

An Anatomical Interface between Memory and Oculomotor Systems.

Visual behavior is guided by memories from prior experience and knowledge of the visual scene. The hippocampal system (HC), in particular, has been implicated in the guidance of saccades: Amnesic patients, following damage to the HC, exhibit selective deficits in their gaze patterns. However, the neural circuitry by which mnemonic representations influence the oculomotor system remains unknown. We used a data-driven, network-based approach on directed anatomical connectivity from the macaque brain to reveal an extensive set of polysnaptic pathways spanning the extrastriate, posterior parietal and prefrontal cortices that potentially mediate the exchange of information between the memory and visuo-oculomotor systems. We additionally show how the potential for directed information flow from the hippocampus to oculomotor control areas is exceptionally high. In particular, the dorsolateral pFC and FEF-regions known to be responsible for the cognitive control of saccades-are topologically well positioned to receive information from the hippocampus. Together with neuropsychological evidence of altered gaze patterns following damage to the hippocampus, our findings suggest that a reconsideration of hippocampal involvement in oculomotor guidance is needed.

Age-related Multiscale Changes in Brain Signal Variability in Pre-task versus Post-task Resting-state EEG.

Recent empirical work suggests that, during healthy aging, the variability of network dynamics changes during task performance. Such variability appears to reflect the spontaneous formation and dissolution of different functional networks. We sought to extend these observations into resting-state dynamics. We recorded EEG in young, middle-aged, and older adults during a "rest-task-rest" design and investigated if aging modifies the interaction between resting-state activity and external stimulus-induced activity. Using multiscale entropy as our measure of variability, we found that, with increasing age, resting-state dynamics shifts from distributed to more local neural processing, especially at posterior sources. In the young group, resting-state dynamics also changed from pre- to post-task, where fine-scale entropy increased in task-positive regions and coarse-scale entropy increased in the posterior cingulate, a key region associated with the default mode network. Lastly, pre- and post-task resting-state dynamics were linked to performance on the intervening task for all age groups, but this relationship became weaker with increasing age. Our results suggest that age-related changes in resting-state dynamics occur across different spatial and temporal scales and have consequences for information processing capacity.

Musicianship and Tone Language Experience Are Associated with Differential Changes in Brain Signal Variability.

Musicianship has been associated with auditory processing benefits. It is unclear, however, whether pitch processing experience in nonmusical contexts, namely, speaking a tone language, has comparable associations with auditory processing. Studies comparing the auditory processing of musicians and tone language speakers have shown varying degrees of between-group similarity with regard to perceptual processing benefits and, particularly, nonlinguistic pitch processing. To test whether the auditory abilities honed by musicianship or speaking a tone language differentially impact the neural networks supporting nonlinguistic pitch processing (relative to timbral processing), we employed a novel application of brain signal variability (BSV) analysis. BSV is a metric of information processing capacity and holds great potential for understanding the neural underpinnings of experience-dependent plasticity. Here, we measured BSV in electroencephalograms of musicians, tone language-speaking nonmusicians, and English-speaking nonmusicians (controls) during passive listening of music and speech sound contrasts. Although musicians showed greater BSV across the board, each group showed a unique spatiotemporal distribution in neural network engagement: Controls had greater BSV for speech than music; tone language-speaking nonmusicians showed the opposite effect; musicians showed similar BSV for both domains. Collectively, results suggest that musical and tone language pitch experience differentially affect auditory processing capacity within the cerebral cortex. However, information processing capacity is graded: More experience with pitch is associated with greater BSV when processing this cue. Higher BSV in musicians may suggest increased information integration within the brain networks subserving speech and music, which may be related to their well-documented advantages on a wide variety of speech-related tasks.