Functional Parcellation Research Articles

Resting-state white matter-cortical connectivity in non-human primate brain

Numerous studies have used functional magnetic resonance imaging (fMRI) to characterize functional connectivity between cortical regions by analyzing correlations in blood oxygenation level dependent (BOLD) signals in a resting state. However, to date, there have been only a handful of studies reporting resting state BOLD signals in white matter. Nonetheless, a growing number of reports has emerged in recent years suggesting white matter BOLD signals can be reliably detected, though their biophysical origins remain unclear. Moreover, recent studies have identified robust correlations in a resting state between signals from cortex and specific white matter tracts. In order to further validate and interpret these findings, we studied a non-human primate model to investigate resting-state connectivity patterns between parcellated cortical volumes and specific white matter bundles. Our results show that resting-state connectivity patterns between white and gray matter structures are not randomly distributed but share notable similarities with diffusion- and histology-derived anatomic connectivities. This suggests that resting-state BOLD correlations between white matter fiber tracts and the gray matter regions to which they connect are directly related to the anatomic arrangement and density of WM fibers. We also measured how different levels of baseline neural activity, induced by varying levels of anesthesia, modulate these patterns. As anesthesia levels were raised, we observed weakened correlation coefficients between specific white matter tracts and gray matter regions while key features of the connectivity pattern remained similar. Overall, results from this study provide further evidence that neural activity is detectable by BOLD fMRI in both gray and white matter throughout the resting brain. The combined use of gray and white matter functional connectivity could also offer refined full-scale functional parcellation of the entire brain to characterize its functional architecture.

The role of Prefrontal Cortex in a Battle of the Sexes Dilemma involving a Conflict between Tribal and Romantic love

The neural basis of dilemmas involving decisions with profound affective impact, such as in romantic life, remains to be understood. The “Battle of the Sexes” is a paradigm from Game Theory that can be used to experimentally address such dilemmas. A form of in-group love, tribal love in football fans, provides the opportunity to study strong affective dilemmas when tribal and romantic love compete for hedonic decision-making. Here, we used for the first time a “Battle of the Sexes” dilemma using fMRI. We investigated, in 44 male football fans, the neural correlates of cooperative behaviour under conflicting choices in the context of romantic versus tribal love. We identified a critical functional segregation of prefrontal regions in affective decision-making. The orbitofrontal cortex signalled emotional appraisal of the dilemma. The medial anterolateral and the ventromedial prefrontal cortices reflected reciprocal cooperation instead of selfish engagement in football-related activities. The lateral portion of anterolateral prefrontal cortex was recruited during ultimate deliberation. In sum, emotional appraisal and rational choice reflected a contiguous functional parcellation in anterolateral prefrontal cortex: appraisal (medial) vs. choice (lateral region).

Are you thinking what I'm thinking? Synchronization of resting fMRI time-series across subjects

We describe BrainSync, an orthogonal transform that allows direct comparison of resting fMRI (rfMRI) time-series across subjects. For this purpose, we exploit the geometry of the rfMRI signal space to propose a novel orthogonal transformation that synchronizes rfMRI time-series across sessions and subjects. When synchronized, rfMRI signals become approximately equal at homologous locations across subjects. The method is based on the observation that rfMRI data exhibit similar connectivity patterns across subjects, as reflected in the pairwise correlations between different brain regions. We show that if the data for two subjects have similar correlation patterns then their time courses can be approximately synchronized by an orthogonal transformation. This transform is unique, invertible, efficient to compute, and preserves the connectivity structure of the original data for all subjects. Analogously to image registration, where we spatially align structural brain images, this temporal synchronization of brain signals across a population, or within-subject across sessions, facilitates cross-sectional and longitudinal studies of rfMRI data. The utility of the BrainSync transform is illustrated through demonstrative simulations and applications including quantification of rfMRI variability across subjects and sessions, cortical functional parcellation across a population, timing recovery in task fMRI data, comparison of task and resting state data, and an application to complex naturalistic stimuli for annotation prediction.

MIST: A multi-resolution parcellation of functional brain networks

Functional brain connectomics investigates functional connectivity between distinct brain parcels. There is an increasing interest to investigate connectivity across several levels of spatial resolution, from networks down to localized areas. Here we present the Multiresolution Intrinsic Segmentation Template (MIST), a multi-resolution parcellation of the cortical, subcortical and cerebellar gray matter. We provide annotated functional parcellations at nine resolutions from 7 to 444 functional parcels. The MIST parcellations compare well with prior work in terms of homogeneity and generalizability. We found that parcels at higher resolutions largely fell within the boundaries of larger parcels at lower resolutions. This allowed us to provide an overlap based pseudo-hierarchical decomposition tree that relates parcels across resolutions in a meaningful way. We provide an interactive web interface to explore the MIST parcellations and also made it accessible in the neuroimaging library nilearn. We believe that the MIST parcellation will facilitate future investigations of the multiresolution basis of brain function.

Finer parcellation reveals detailed correlational structure of resting-state fMRI signals

BackgroundEven in resting state, the human brain generates functional signals (fMRI) with complex correlational structure. To simplify this structure, it is common to parcellate a standard brain into coarse chunks. Finer parcellations are considered less reproducible and informative, due to anatomical and functional variability of individual brains. New methodsGrouping signals with similar local correlation profiles, restricted to each anatomical region (Tzourio-Mazoyer et al., 2002), we divide a standard brain into 758 ‘functional clusters’ averaging 1.7cm3 gray matter volume (‘MD758’ parcellation). We compare 758 ‘spatial clusters’ of similar size (‘S758’). Results‘Functional clusters’ are spatially contiguous and cluster quality (integration and segregation of temporal variance) is far superior to ‘spatial clusters’, comparable to multi-modal parcellations of half the resolution (Craddock et al., 2012; Glasser et al., 2016). Moreover, ‘functional clusters’ capture many long-range functional correlations, with O(105) reproducibly correlated cluster pairs in different anatomical regions. The pattern of functional correlations closely mirrors long-range anatomical connectivity established by fibre tracking. Comparison to existing methodsMD758 is comparable to coarser parcellations (Craddock et al., 2012; Glasser et al., 2016) in terms of cluster quality, correlational structure (54% relative mutual entropy vs 60% and 61%), and sparseness (35% significant pairwise correlations vs 36% and 44%). ConclusionWe describe and evaluate a simple path to finer functional parcellations of the human brain. Detailed correlational structure is surprisingly consistent between individuals, opening new possibilities for comparing functional correlations between cognitive conditions, states of health, or pharmacological interventions.

A Bayesian spatial model for neuroimaging data based on biologically informed basis functions

The dominant approach to neuroimaging data analysis employs the voxel as the unit of computation. While convenient, voxels lack biological meaning and their size is arbitrarily determined by the resolution of the image. Here, we propose a multivariate spatial model in which neuroimaging data are characterised as a linearly weighted combination of multiscale basis functions which map onto underlying brain nuclei or networks or nuclei. In this model, the elementary building blocks are derived to reflect the functional anatomy of the brain during the resting state. This model is estimated using a Bayesian framework which accurately quantifies uncertainty and automatically finds the most accurate and parsimonious combination of basis functions describing the data. We demonstrate the utility of this framework by predicting quantitative SPECT images of striatal dopamine function and we compare a variety of basis sets including generic isotropic functions, anatomical representations of the striatum derived from structural MRI, and two different soft functional parcellations of the striatum derived from resting-state fMRI (rfMRI). We found that a combination of ∼50 multiscale functional basis functions accurately represented the striatal dopamine activity, and that functional basis functions derived from an advanced parcellation technique known as Instantaneous Connectivity Parcellation (ICP) provided the most parsimonious models of dopamine function. Importantly, functional basis functions derived from resting fMRI were more accurate than both structural and generic basis sets in representing dopamine function in the striatum for a fixed model order. We demonstrate the translational validity of our framework by constructing classification models for discriminating parkinsonian disorders and their subtypes. Here, we show that ICP approach is the only basis set that performs well across all comparisons and performs better overall than the classical voxel-based approach. This spatial model constitutes an elegant alternative to voxel-based approaches in neuroimaging studies; not only are their atoms biologically informed, they are also adaptive to high resolutions, represent high dimensions efficiently, and capture long-range spatial dependencies, which are important and challenging objectives for neuroimaging data.

Examination of the validity of the atlas-informed approach to functional parcellation: a resting functional MRI study.

With the advancement in MRI, functional parcellation (FP) of brain structure(s) has become an important topic. However, the large number of voxels is a major obstacle. A-priori partitioning of the brain into several regions of interest (ROIs) is the main data-reduction strategy to simplify brain informatics. This study aims to examine the validity of ROI-based approach to FP by exploring the concordance of the relative distance structures between voxel-wise (raw data) and atlas-informed analyses. Structural and resting state functional MRI (rfMRI) scans of 26 right-handed healthy individuals were selected from the Rockland dataset. Four target regions were included in the analyses, that is, left and right thalamus and amygdala. For each voxel in the target region, four classes of correlation maps (sampling strategies) were constructed from the rfMRI: whole brain, cortex, 150 ROIs, and 70 ROIs (ROIs are informed by anatomical atlases). The relative distance metric between two different voxels was defined as the mean absolute difference of their associated correlation maps. Considering all the possible pairs of voxels in a target region, the relative distance structure was derived and stored in a matrix (distance map). For every target region, the distance maps were very similar across the four classes of sampling strategies, with the grand mean correlation coefficient reaching 0.95. The results confirm the validity of previous ROI-based analyses of rfMRI data in FP. The rationale and limitation are discussed and an analytic strategy of whole-brain FP is proposed.

Detecting stable individual differences in the functional organization of the human basal ganglia

Moving from group level to individual level functional parcellation maps is a critical step for developing a rich understanding of the links between individual variation in functional network architecture and cognitive and clinical phenotypes. Still, the identification of functional units in the brain based on intrinsic functional connectivity and its dynamic variations between and within subjects remains challenging. Recently, the bootstrap analysis of stable clusters (BASC) framework was developed to quantify the stability of functional brain networks both across and within subjects. This multi-level approach utilizes bootstrap resampling for both individual and group-level clustering to delineate functional units based on their consistency across and within subjects, while providing a measure of their stability. Here, we optimized the BASC framework for functional parcellation of the basal ganglia by investigating a variety of clustering algorithms and similarity measures. Reproducibility and test-retest reliability were computed to validate this analytic framework as a tool to describe inter-individual differences in the stability of functional networks. The functional parcellation revealed by stable clusters replicated previous divisions found in the basal ganglia based on intrinsic functional connectivity. While we found moderate to high reproducibility, test-retest reliability was high at the boundaries of the functional units as well as within their cores. This is interesting because the boundaries between functional networks have been shown to explain most individual phenotypic variability. The current study provides evidence for the consistency of the parcellation of the basal ganglia, and provides the first group level parcellation built from individual-level cluster solutions. These novel results demonstrate the utility of BASC for quantifying inter-individual differences in the functional organization of brain regions, and encourage usage in future studies.

The impact of hemodynamic variability and signal mixing on the identifiability of effective connectivity structures in BOLD fMRI.

PurposeMultiple computational studies have demonstrated that essentially all current analytical approaches to determine effective connectivity perform poorly when applied to synthetic functional Magnetic Resonance Imaging (fMRI) datasets. In this study, we take a theoretical approach to investigate the potential factors facilitating and hindering effective connectivity research in fMRI.Materials and MethodsIn this work, we perform a simulation study with use of Dynamic Causal Modeling generative model in order to gain new insights on the influence of factors such as the slow hemodynamic response, mixed signals in the network and short time series, on the effective connectivity estimation in fMRI studies.ResultsFirst, we perform a Linear Discriminant Analysis study and find that not the hemodynamics itself but mixed signals in the neuronal networks are detrimental to the signatures of distinct connectivity patterns. This result suggests that for statistical methods (which do not involve lagged signals), deconvolving the BOLD responses is not necessary, but at the same time, functional parcellation into Regions of Interest (ROIs) is essential. Second, we study the impact of hemodynamic variability on the inference with use of lagged methods. We find that the local hemodynamic variability provide with an upper bound on the success rate of the lagged methods. Furthermore, we demonstrate that upsampling the data to TRs lower than the TRs in state‐of‐the‐art datasets does not influence the performance of the lagged methods.ConclusionsFactors such as background scale‐free noise and hemodynamic variability have a major impact on the performance of methods for effective connectivity research in functional Magnetic Resonance Imaging.

Individual parcellation of resting fMRI with a group functional connectivity prior

Cortical parcellation based on resting fMRI is an important tool for investigating the functional organization and connectivity of the cerebral cortex. Group parcellation based on co-registration of anatomical images to a common atlas will inevitably result in errors in the locations of the boundaries of functional parcels when they are mapped back from the atlas to the individual. This is because areas of functional specialization vary across individuals in a manner that cannot be fully determined from the sulcal and gyral anatomy that is used for mapping between atlas and individual. We describe a method that avoids this problem by refining an initial group parcellation so that for each subject the parcel boundaries are optimized with respect to that subject's resting fMRI. Initialization with a common parcellation results in automatic correspondence between parcels across subjects. Further, by using a group sparsity constraint to model connectivity, we exploit group similarities in connectivity between parcels while optimizing their boundaries for each individual. We applied this approach with initialization on both high and low density group cortical parcellations and used resting fMRI data to refine across a group of individuals. Cross validation studies show improved homogeneity of resting activity within the refined parcels. Comparisons with task-based localizers show consistent reduction of variance of statistical parametric maps within the refined parcels relative to the group-based initialization indicating improved delineation of regions of functional specialization. This method enables a more accurate estimation of individual subject functional areas, facilitating group analysis of functional connectivity, while maintaining consistency across individuals with a standardized topological atlas.

Functional Brain Parcellations of the Infant Brain and the Associated Developmental Trends.

Resting-state functional connectivity studies have dramatically improved our understanding of the early human brain functional development during the past decade. However, one emerging problem that could potentially impede future progresses in the field is the definition of regions of interest (ROI), since it is well known that functional connectivity estimation can be seriously contaminated by within-ROI signal heterogeneity. In this study, based on a large-scale rsfMRI data set in human infants (230 neonates, 143 1-year olds, and 107 2-year olds), we aimed to derive a set of anatomically constrained, infant-specific functional brain parcellations using functional connectivity-based clustering. Our results revealed significantly higher levels of signal homogeneity within the newly defined functional parcellations compared with other schemes. Importantly, the global functional connectivity patterns associated with the newly defined functional subunits demonstrated significantly increasing levels of differentiation with age, confirming increasing levels of local specialization. Subsequent whole brain connectivity analysis revealed intriguing patterns of regional-level functional connectivity developments and system-level hub redistribution during infancy. Overall, the newly derived infant-specific functional brain parcellations and the associated novel developmental patterns will likely prove valuable for future early developmental studies using the functional connectivity technique.

Groupwise structural parcellation of the whole cortex: A logistic random effects model based approach

Current theories hold that brain function is highly related to long-range physical connections through axonal bundles, namely extrinsic connectivity. However, obtaining a groupwise cortical parcellation based on extrinsic connectivity remains challenging. Current parcellation methods are computationally expensive; need tuning of several parameters or rely on ad-hoc constraints. Furthermore, none of these methods present a model for the cortical extrinsic connectivity of the cortex. To tackle these problems, we propose a parsimonious model for the extrinsic connectivity and an efficient parceling technique based on clustering of tractograms. Our technique allows the creation of single subject and groupwise parcellations of the whole cortex. The parcellations obtained with our technique are in agreement with structural and functional parcellations in the literature. In particular, the motor and sensory cortex are subdivided in agreement with the human homunculus of Penfield. We illustrate this by comparing our resulting parcels with the motor strip mapping included in the Human Connectome Project data.

Let's Not Waste Time: Using Temporal Information in Clustered Activity Estimation with Spatial Adjacency Restrictions (CAESAR) for Parcellating FMRI Data.

We have proposed a Bayesian approach for functional parcellation of whole-brain FMRI measurements which we call Clustered Activity Estimation with Spatial Adjacency Restrictions (CAESAR). We use distance-dependent Chinese restaurant processes (dd-CRPs) to define a flexible prior which partitions the voxel measurements into clusters whose number and shapes are unknown a priori. With dd-CRPs we can conveniently implement spatial constraints to ensure that our parcellations remain spatially contiguous and thereby physiologically meaningful. In the present work, we extend CAESAR by using Gaussian process (GP) priors to model the temporally smooth haemodynamic signals that give rise to the measured FMRI data. A challenge for GP inference in our setting is the cubic scaling with respect to the number of time points, which can become computationally prohibitive with FMRI measurements, potentially consisting of long time series. As a solution we describe an efficient implementation that is practically as fast as the corresponding time-independent non-GP model with typically-sized FMRI data sets. We also employ a population Monte-Carlo algorithm that can significantly speed up convergence compared to traditional single-chain methods. First we illustrate the benefits of CAESAR and the GP priors with simulated experiments. Next, we demonstrate our approach by parcellating resting state FMRI data measured from twenty participants as taken from the Human Connectome Project data repository. Results show that CAESAR affords highly robust and scalable whole-brain clustering of FMRI timecourses.

Inferring Individual-Level Variations in the Functional Parcellation of the Cerebral Cortex.

Functional parcellation of the cerebral cortex is variable across different subjects or between cognitive states. Ignoring individual-or state-dependent variations in the functional parcellation may lead to inaccurate representations of individual functional connectivity, limiting the precision of interpretations of differences in individual connectivity profiles. However, it is difficult to infer the individual-level variations due to the relatively low robustness of methods for parcellation of individual subjects. We propose a method called "joint K-means" to robustly parcellate the cerebral cortex using functional magnetic resonance imaging (fMRI) data for contrasts between two states or subjects that intended to characterize variance in individual functional parcellations. The key idea of the proposed method is to jointly infer parcellations in contrasted datasets by iterative descent, while constraining the similarity of the two pathways in searches for local minima to reduce spurious variations. Parcellations of resting-state fMRI datasets from the Human Connectome Project show that the similarity of parcellations for an individual subject studied on two sessions is greater than that between different subjects. Differences in parcellations between subjects are nonuniformly distributed across the cerebral cortex, with clusters of higher variance in the prefrontal, lateral temporal, and occipito-parietal cortices. This pattern is reproducible across sessions, between groups, and using different numbers of parcels. The individual-level variations inferred by the proposed method are plausible and consistent with the previously reported functional connectivity variability. The proposed method is a promising tool for investigating relationships between the cerebral functional organization and behavioral differences.

SGraSP: A graph-based method for the derivation of subject-specific functional parcellations of the brain

BackgroundResting-state fMRI (rs-fMRI) has emerged as a prominent tool for the study of functional connectivity. The identification of the regions associated with the different brain functions has received significant interest. However, most of the studies conducted so far have focused on the definition of a common set of regions, valid for an entire population. The variation of the functional regions within a population has rarely been accounted for. New methodIn this paper, we propose sGraSP, a graph-based approach for the derivation of subject-specific functional parcellations. Our method generates first a common parcellation for an entire population, which is then adapted to each subject individually. ResultsSeveral cortical parcellations were generated for 859 children being part of the Philadelphia Neurodevelopmental Cohort. The stability of the parcellations generated by sGraSP was tested by mixing population and subject rs-fMRI signals, to generate subject-specific parcels increasingly closer to the population parcellation. We also checked if the parcels generated by our method were better capturing a development trend underlying our data than the original parcels, defined for the entire population. Comparison with existing methodsWe compared sGraSP with a simpler and faster approach based on a Voronoi tessellation, by measuring their ability to produce functionally coherent parcels adapted to the subject data. ConclusionsOur parcellations outperformed the Voronoi tessellations. The parcels generated by sGraSP vary consistently with respect to signal mixing, the results are highly reproducible and the neurodevelopmental trend is better captured with the subject-specific parcellation, under all the signal mixing conditions.

Functional Parcellation of Frontal Higher Order Motor Cortex

Motor areas in the frontal cortex are classified into medial and lateral functional groups. The dorsal premotor areas in the lateral groups are involved in motor guidance based on behavioral rules. The ventral premotor cortex contributes to motor guidance relying on spatial aspects of sensory information. The supplementary motor complex in the medial groups is related to the bimanual and temporal organization of multiple motor acts. The cingulate motor area is involved in motor control based on reward-prediction errors. The supplementary eye field is involved in monitoring performance and the adjustment of sequential visual search. The motor areas are coordinated in a context-dependent manner, influenced by top-down signals from the prefrontal cortex and by bottom-up signals from the parietal cortex, which are also organized into the lateral and medial functional groups. Evidence suggests that the medial and lateral functional groups are balanced by the insula cortex and anterior cingulate cortex which serve as salience detectors for changes in bodily states.

Distinct neural mechanisms underlie the success, precision, and vividness of episodic memory.

A network of brain regions have been linked with episodic memory retrieval, but limited progress has been made in identifying the contributions of distinct parts of the network. Here, we utilized continuous measures of retrieval to dissociate three components of episodic memory: retrieval success, precision, and vividness. In the fMRI scanner, participants encoded objects that varied continuously on three features: color, orientation, and location. Participants' memory was tested by having them recreate the appearance of the object features using a continuous dial, and continuous vividness judgments were recorded. Retrieval success, precision, and vividness were dissociable both behaviorally and neurally: successful versus unsuccessful retrieval was associated with hippocampal activity, retrieval precision scaled with activity in the angular gyrus, and vividness judgments tracked activity in the precuneus. The ability to dissociate these components of episodic memory reveals the benefit afforded by measuring memory on a continuous scale, allowing functional parcellation of the retrieval network.

Altered functional organization within the insular cortex in adult males with high-functioning autism spectrum disorder: evidence from connectivity-based parcellation.

BackgroundThe insular cortex comprises multiple functionally differentiated sub-regions, each of which has different patterns of connectivity with other brain regions. Such diverse connectivity patterns are thought to underlie a wide range of insular functions, including cognitive, affective, and sensorimotor processing, many of which are abnormal in autism spectrum disorder (ASD). Although past neuroimaging studies of ASD have shown structural and functional abnormalities in the insula, possible alterations in the sub-regional organization of the insula and the functional characteristics of each sub-region have not been examined in the ASD brain.MethodsResting-state functional magnetic resonance imaging (rs-fMRI) data were acquired from 36 adult males with ASD and 38 matched typically developed (TD) controls. A data-driven clustering analysis was applied to rs-fMRI data of voxels in the left and right insula to automatically group voxels with similar intrinsic connectivity pattern into a cluster. After determining the optimal number of clusters based on information theoretic measures of variation of information and mutual information, functional parcellation patterns in both the left and the right insula were compared between the TD and ASD groups. Furthermore, functional profiles of each sub-region were meta-analytically decoded using Neurosynth and were compared between the groups.ResultsWe observed notable alterations in the anterior sector of the left insula and the middle ventral sub-region of the right insula in the ASD brain. Meta-analytic decoding revealed that whereas the anterior sector of the left insula contained two functionally differentiated sub-regions for cognitive, sensorimotor, and emotional/affective functions in TD brain, only a single functional cluster for cognitive and sensorimotor functions was identified in the anterior sector in the ASD brain. In the right insula, the middle ventral sub-region, which is primarily specialized for sensory- and auditory-related functions, showed a significant volumetric increase in the ASD brain compared with the TD brain.ConclusionsThe results indicate an altered organization of sub-regions in specific parts of the left and right insula of the ASD brain. The alterations in the left and right insula may constitute neural substrates underlying abnormalities in emotional/affective and sensory functions in ASD.Electronic supplementary materialThe online version of this article (doi:10.1186/s13229-016-0106-8) contains supplementary material, which is available to authorized users.

208 Connectivity-Based Functional Parcellation and Localization of the Human Supplementary Motor Area Based on Resting-State Functional Magnetic Resting Imaging and Its Utility in Brain Tumor Surgery

208 Connectivity-Based Functional Parcellation and Localization of the Human Supplementary Motor Area Based on Resting-State Functional Magnetic Resting Imaging and Its Utility in Brain Tumor Surgery

Functional atlas of the awake rat brain: A neuroimaging study of rat brain specialization and integration

Connectivity-based parcellation approaches present an innovative method to segregate the brain into functionally specialized regions. These approaches have significantly advanced our understanding of the human brain organization. However, parallel progress in animal research is sparse. Using resting-state fMRI data and a novel, data-driven parcellation method, we have obtained robust functional parcellations of the rat brain. These functional parcellations reveal the regional specialization of the rat brain, which exhibited high within-parcel homogeneity and high reproducibility across animals. Graph analysis of the whole-brain network constructed based on these functional parcels indicates that the rat brain has a topological organization similar to humans, characterized by both segregation and integration. Our study also provides compelling evidence that the cingulate cortex is a functional hub region conserved from rodents to humans. Together, this study has characterized the rat brain specialization and integration, and has significantly advanced our understanding of the rat brain organization. In addition, it is valuable for studies of comparative functional neuroanatomy in mammalian brains.