Intrinsic Functional Organization Research Articles

Unravelling the intrinsic functional organization of the human striatum: a parcellation and connectivity study based on resting-state FMRI.

As the main input hub of the basal ganglia, the striatum receives projections from the cerebral cortex. Many studies have provided evidence for multiple parallel corticostriatal loops based on the structural and functional connectivity profiles of the human striatum. A recent resting-state fMRI study revealed the topography of striatum by assigning each voxel in the striatum to its most strongly correlated cortical network among the cognitive, affective, and motor networks. However, it remains unclear what patterns of striatal parcellation would result from performing the clustering without subsequent assignment to cortical networks. Thus, we applied unsupervised clustering algorithms to parcellate the human striatum based on its functional connectivity patterns to other brain regions without any anatomically or functionally defined cortical targets. Functional connectivity maps of striatal subdivisions, identified through clustering analyses, were also computed. Our findings were consistent with recent accounts of the functional distinctions of the striatum as well as with recent studies about its functional and anatomical connectivity. For example, we found functional connections between dorsal and ventral striatal clusters and the areas involved in cognitive and affective processes, respectively, and between rostral and caudal putamen clusters and the areas involved in cognitive and motor processes, respectively. This study confirms prior findings, showing similar striatal parcellation patterns between the present and prior studies. Given such striking similarity, it is suggested that striatal subregions are functionally linked to cortical networks involving specific functions rather than discrete portions of cortical regions. Our findings also demonstrate that the clustering of functional connectivity patterns is a reliable feature in parcellating the striatum into anatomically and functionally meaningful subdivisions. The striatal subdivisions identified here may have important implications for understanding the relationship between corticostriatal dysfunction and various neurodegenerative and psychiatric disorders.

Brain differences between persistent and remitted attention deficit hyperactivity disorder

Previous resting state studies examining the brain basis of attention deficit hyperactivity disorder have not distinguished between patients who persist versus those who remit from the diagnosis as adults. To characterize the neurobiological differences and similarities of persistence and remittance, we performed resting state functional magnetic resonance imaging in individuals who had been longitudinally and uniformly characterized as having or not having attention deficit hyperactivity disorder in childhood and again in adulthood (16 years after baseline assessment). Intrinsic functional brain organization was measured in patients who had a persistent diagnosis in childhood and adulthood (n = 13), in patients who met diagnosis in childhood but not in adulthood (n = 22), and in control participants who never had attention deficit hyperactivity disorder (n = 17). A positive functional correlation between posterior cingulate and medial prefrontal cortices, major components of the default-mode network, was reduced only in patients whose diagnosis persisted into adulthood. A negative functional correlation between medial and dorsolateral prefrontal cortices was reduced in both persistent and remitted patients. The neurobiological dissociation between the persistence and remittance of attention deficit hyperactivity disorder may provide a framework for the relation between the clinical diagnosis, which indicates the need for treatment, and additional deficits that are common, such as executive dysfunctions.

Fine-grained mapping of mouse brain functional connectivity with resting-state fMRI

Understanding the intrinsic circuit-level functional organization of the brain has benefited tremendously from the advent of resting-state fMRI (rsfMRI). In humans, resting-state functional network has been consistently mapped and its alterations have been shown to correlate with symptomatology of various neurological or psychiatric disorders. To date, deciphering the mouse brain functional connectivity (MBFC) with rsfMRI remains a largely underexplored research area, despite the plethora of human brain disorders that can be modeled in this specie. To pave the way from pre-clinical to clinical investigations we characterized here the intrinsic architecture of mouse brain functional circuitry, based on rsfMRI data acquired at 7T using the Cryoprobe technology. High-dimensional spatial group independent component analysis demonstrated fine-grained segregation of cortical and subcortical networks into functional clusters, overlapping with high specificity onto anatomical structures, down to single gray matter nuclei. These clusters, showing a high level of stability and reliability in their patterning, formed the input elements for computing the MBFC network using partial correlation and graph theory. Its topological architecture conserved the fundamental characteristics described for the human and rat brain, such as small-worldness and partitioning into functional modules. Our results additionally showed inter-modular interactions via “network hubs”. Each major functional system (motor, somatosensory, limbic, visual, autonomic) was found to have representative hubs that might play an important input/output role and form a functional core for information integration. Moreover, the rostro-dorsal hippocampus formed the highest number of relevant connections with other brain areas, highlighting its importance as core structure for MBFC.

Selective Development of Anticorrelated Networks in the Intrinsic Functional Organization of the Human Brain

We examined the normal development of intrinsic functional connectivity of the default network (brain regions typically deactivated for attention-demanding tasks) as measured by resting-state fMRI in children, adolescents, and young adults ages 8-24 years. We investigated both positive and negative correlations and employed analysis methods that allowed for valid interpretation of negative correlations and that also minimized the influence of motion artifacts that are often confounds in developmental neuroimaging. As age increased, there were robust developmental increases in negative correlations, including those between medial pFC (MPFC) and dorsolateral pFC (DLPFC) and between lateral parietal cortices and brain regions associated with the dorsal attention network. Between multiple regions, these correlations reversed from being positive in children to negative in adults. Age-related changes in positive correlations within the default network were below statistical threshold after controlling for motion. Given evidence in adults that greater negative correlation between MPFC and DLPFC is associated with superior cognitive performance, the development of an intrinsic anticorrelation between MPFC and DLPFC may be a marker of the large growth of working memory and executive functions that occurs from childhood to young adulthood.

Determining functional units of tongue motion via graph-regularized sparse non-negative matrix factorization.

Tongue motion during speech and swallowing involves synergies of locally deforming regions, or functional units. Motion clustering during tongue motion can be used to reveal the tongue's intrinsic functional organization. A novel matrix factorization and clustering method for tissues tracked using tagged magnetic resonance imaging (tMRI) is presented. Functional units are estimated using a graph-regularized sparse non-negative matrix factorization framework, learning latent building blocks and the corresponding weighting map from motion features derived from tissue displacements. Spectral clustering using the weighting map is then performed to determine the coherent regions--i.e., functional units--efined by the tongue motion. Two-dimensional image data is used to ver-fy that the proposed algorithm clusters the different types of images ac-urately. Three-dimensional tMRI data from five subjects carrying out simple non-speech/speech tasks are analyzed to show how the proposed approach defines a subject/task-specific functional parcellation of the tongue in localized regions.

Escitalopram Decreases Cross-Regional Functional Connectivity within the Default-Mode Network

The default-mode network (DMN), which comprises medial frontal, temporal and parietal regions, is part of the brain’s intrinsic organization. The serotonergic (5-HT) neurotransmitter system projects to DMN regions from midbrain efferents, and manipulation of this system could thus reveal insights into the neurobiological mechanisms of DMN functioning. Here, we investigate intrinsic functional connectivity of the DMN as a function of activity of the serotonergic system, through the administration of the selective serotonin reuptake inhibitor (SSRI) escitalopram. We quantified DMN functional connectivity using an approach based on dual-regression. Specifically, we decomposed group data of a subset of the functional time series using spatial independent component analysis, and projected the group spatial modes to the same and an independent resting state time series of individual participants. We found no effects of escitalopram on global functional connectivity of the DMN at the map-level; that is, escitalopram did not alter the global functional architecture of the DMN. However, we found that escitalopram decreased DMN regional pairwise connectivity, which included anterior and posterior cingulate cortex, hippocampal complex and lateral parietal regions. Further, regional DMN connectivity covaried with alertness ratings across participants. Our findings show that escitalopram altered intrinsic regional DMN connectivity, which suggests that the serotonergic system plays an important role in DMN connectivity and its contribution to cognition. Pharmacological challenge designs may be a useful addition to resting-state functional MRI to investigate intrinsic brain functional organization.

Reduced functional connectivity and asymmetry of the planum temporale in patients with schizophrenia and first-degree relatives

The planum temporale (PT) is a highly lateralized brain area associated with auditory and language processing. In schizophrenia, reduced structural and functional laterality of the PT has been suggested, which is of clinical interest because of its potential role in the generation of auditory verbal hallucinations. We investigated whether resting-state functional imaging (fMRI) of the PT reveals aberrant functional connectivity and laterality in patients with schizophrenia (SZ) and unaffected relatives, and examined possible associations between altered intrinsic functional organization of auditory networks and hallucinations.We estimated functional connectivity between bilateral PT and whole-brain in 24 SZ patients, 22 unaffected first-degree relatives and 24 matched healthy controls. The results indicated reduced functional connectivity between PT and temporal, parietal, limbic and subcortical regions in SZ patients and relatives in comparison with controls. Altered functional connectivity correlated with predisposition towards hallucinations (measured with the Revised Hallucination Scale [RHS]) in both patients and relatives. We also observed reduced functional asymmetry of the superior temporal gyrus in patients and relatives, which correlated significantly with acute severity of hallucinations in the patient group.To conclude, SZ patients and relatives showed abnormal asymmetry and aberrant connectivity in the planum temporale during resting-state, which was related to psychopathology. These results are in line with results from auditory processing and symptom-mapping studies that suggest that the PT is a central node in the generation of hallucinations. Our findings support reduced intrinsic functional hemispheric asymmetry of the auditory network as a possible trait marker in schizophrenia.

Differences in Intrinsic Functional Organization Between Dorsolateral Prefrontal and Posterior Parietal Cortex

The dorsolateral prefrontal and posterior parietal cortex are 2 components of the cortical network controlling attention, working memory, and executive function. Little is known about how the anatomical organization of the 2 areas accounts for their functional specialization. In order to address this question, we examined the strength of intrinsic functional connectivity between neurons sampled in each area by means of cross-correlation analyses of simultaneous recordings from monkeys trained to perform working memory tasks. In both areas, effective connectivity declined as a function of distance between neurons. However, the strength of effective connectivity was higher overall and more localized over short distances in the posterior parietal than the prefrontal cortex. The difference in connectivity strength between the 2 areas could not be explained by differences in firing rate or selectivity for the stimuli and task events, it was present when the fixation period alone was analyzed, and according to simulation results, was consistent with a systematic difference either in the strength or in the relative numbers of shared inputs between neurons. Our results indicate that the 2 areas are characterized by unique intrinsic functional organization, consistent with known differences in their response patterns during working memory.

Correction: Goulas et al., Unravelling the Intrinsic Functional Organization of the Human Lateral Frontal Cortex: A Parcellation Scheme Based on Resting State fMRI

Correction: Goulas et al., Unravelling the Intrinsic Functional Organization of the Human Lateral Frontal Cortex: A Parcellation Scheme Based on Resting State fMRI

Intrinsic functional network organization in high-functioning adolescents with autism spectrum disorder

Converging theories and data suggest that atypical patterns of functional and structural connectivity are a hallmark neurobiological feature of autism. However, empirical studies of functional connectivity, or, the correlation of MRI signal between brain regions, have largely been conducted during task performance and/or focused on group differences within one network [e.g., the default mode network (DMN)]. This narrow focus on task-based connectivity and single network analyses precludes investigation of whole-brain intrinsic network organization in autism. To assess whole-brain network properties in adolescents with autism, we collected resting-state functional connectivity MRI (rs-fcMRI) data from neurotypical (NT) adolescents and adolescents with autism spectrum disorder (ASD). We used graph theory metrics on rs-fcMRI data with 34 regions of interest (i.e., nodes) that encompass four different functionally defined networks: cingulo-opercular, cerebellar, fronto-parietal, and DMN (Fair etal., 2009). Contrary to our hypotheses, network analyses revealed minimal differences between groups with one exception. Betweenness centrality, which indicates the degree to which a seed (or node) functions as a hub within and between networks, was greater for participants with autism for the right lateral parietal (RLatP) region of the DMN. Follow-up seed-based analyses demonstrated greater functional connectivity in ASD than NT groups between the RLatP seed and another region of the DMN, the anterior medial prefrontal cortex. Greater connectivity between these regions was related to lower ADOS (Autism Diagnostic Observation Schedule) scores (i.e., lower impairment) in autism. These findings do not support current theories of underconnectivity in autism, but, rather, underscore the need for future studies to systematically examine factors that can influence patterns of intrinsic connectivity such as autism severity, age, and head motion.

Unravelling the Intrinsic Functional Organization of the Human Lateral Frontal Cortex: A Parcellation Scheme Based on Resting State fMRI

Human and nonhuman primates exhibit flexible behavior. Functional, anatomical, and lesion studies indicate that the lateral frontal cortex (LFC) plays a pivotal role in such behavior. LFC consists of distinct subregions exhibiting distinct connectivity patterns that possibly relate to functional specializations. Inference about the border of each subregion in the human brain is performed with the aid of macroscopic landmarks and/or cytoarchitectonic parcellations extrapolated in a stereotaxic system. However, the high interindividual variability, the limited availability of cytoarchitectonic probabilistic maps, and the absence of robust functional localizers render the in vivo delineation and examination of the LFC subregions challenging. In this study, we use resting state fMRI for the in vivo parcellation of the human LFC on a subjectwise and data-driven manner. This approach succeeds in uncovering neuroanatomically realistic subregions, with potential anatomical substrates including BA 46, 44, 45, 9 and related (sub)divisions. Ventral LFC subregions exhibit different functional connectivity (FC), which can account for different contributions in the language domain, while more dorsal adjacent subregions mark a transition to visuospatial/sensorimotor networks. Dorsal LFC subregions participate in known large-scale networks obeying an external/internal information processing dichotomy. Furthermore, we traced "families" of LFC subregions organized along the dorsal-ventral and anterior-posterior axis with distinct functional networks also encompassing specialized cingulate divisions. Similarities with the connectivity of macaque candidate homologs were observed, such as the premotor affiliation of presumed BA 46. The current findings partially support dominant LFC models.

Functional Brain Network Modularity Captures Inter- and Intra-Individual Variation in Working Memory Capacity

BackgroundCognitive abilities, such as working memory, differ among people; however, individuals also vary in their own day-to-day cognitive performance. One potential source of cognitive variability may be fluctuations in the functional organization of neural systems. The degree to which the organization of these functional networks is optimized may relate to the effective cognitive functioning of the individual. Here we specifically examine how changes in the organization of large-scale networks measured via resting state functional connectivity MRI and graph theory track changes in working memory capacity.Methodology/Principal FindingsTwenty-two participants performed a test of working memory capacity and then underwent resting-state fMRI. Seventeen subjects repeated the protocol three weeks later. We applied graph theoretic techniques to measure network organization on 34 brain regions of interest (ROI). Network modularity, which measures the level of integration and segregation across sub-networks, and small-worldness, which measures global network connection efficiency, both predicted individual differences in memory capacity; however, only modularity predicted intra-individual variation across the two sessions. Partial correlations controlling for the component of working memory that was stable across sessions revealed that modularity was almost entirely associated with the variability of working memory at each session. Analyses of specific sub-networks and individual circuits were unable to consistently account for working memory capacity variability.Conclusions/SignificanceThe results suggest that the intrinsic functional organization of an a priori defined cognitive control network measured at rest provides substantial information about actual cognitive performance. The association of network modularity to the variability in an individual's working memory capacity suggests that the organization of this network into high connectivity within modules and sparse connections between modules may reflect effective signaling across brain regions, perhaps through the modulation of signal or the suppression of the propagation of noise.

Neuroscience and phenomenology

This text contributes to a necessary dialogue, and possibly a translation of the different notions employed by neuroscience and phenomenology. This effort is particularly significant for cognitive neuroscientists whose main topic is social cognition and the related notion of intersubjectivity. What I qualify as “embodied simulation” (which exploits, not only but mainly, the intrinsic functional organization of the motor system) is a crucial functional mechanism in social cognition, not confined to the domain of action, but encompassing other aspects of intersubjectivity such as emotion and sensation. It is “embodied” because it uses a pre-existing body model in the brain: all the brain areas showing mirror mechanisms model our interaction with the world. This model of interaction, this praktognosia, turns out to be highly relevant not only when the task is to guide our own behavior, but also to understand the behavior of others. The very last part of the text is devoted to reply to some arguments against embodied simulation coming from phenomenologists themselves.

A Shift to Randomness of Brain Oscillations in People with Autism

Resting-state functional magnetic resonance imaging (fMRI) enables investigation of the intrinsic functional organization of the brain. Fractal parameters such as the Hurst exponent, H, describe the complexity of endogenous low-frequency fMRI time series on a continuum from random (H = .5) to ordered (H = 1). Shifts in fractal scaling of physiological time series have been associated with neurological and cardiac conditions. Resting-state fMRI time series were recorded in 30 male adults with an autism spectrum condition (ASC) and 33 age- and IQ-matched male volunteers. The Hurst exponent was estimated in the wavelet domain and between-group differences were investigated at global and voxel level and in regions known to be involved in autism. Complex fractal scaling of fMRI time series was found in both groups but globally there was a significant shift to randomness in the ASC (mean H = .758, SD = .045) compared with neurotypical volunteers (mean H = .788, SD = .047). Between-group differences in H, which was always reduced in the ASC group, were seen in most regions previously reported to be involved in autism, including cortical midline structures, medial temporal structures, lateral temporal and parietal structures, insula, amygdala, basal ganglia, thalamus, and inferior frontal gyrus. Severity of autistic symptoms was negatively correlated with H in retrosplenial and right anterior insular cortex. Autism is associated with a small but significant shift to randomness of endogenous brain oscillations. Complexity measures may provide physiological indicators for autism as they have done for other medical conditions.

What can spontaneous fluctuations of the blood oxygenation-level-dependent signal tell us about psychiatric disorders?

Resting-state functional MRI (rs-fMRI) is an increasingly popular technique for studying brain dysfunction in psychiatric patients, and is widely assumed to measure intrinsic properties of functional brain organization. Here, we review rs-fMRI studies of psychiatric populations and consider how recent evidence concerning the neuronal basis, behavioural relevance, and the stability of rs-fMRI measures can inform and constrain interpretation of findings obtained using case-control designs. A range of rs-fMRI measures have been applied to different patient groups, although the findings have not always been consistent. The large-scale organization of rs-fMRI networks is robust and reproducible, and rs-fMRI measures show correlations with behavioural phenotypes relevant to psychiatry. However, evidence that such measures are also influenced by preceding psychological states and contexts, as well as individual variations in physiological arousal, may help to explain inconsistent findings in case-control comparisons. rs-fMRI measures show both stable and dynamic properties, the nature of which are only beginning to be uncovered. As such, interpreting significant differences between patients and controls on rs-fMRI measures as evidence for alterations in intrinsic functional brain organization should be done cautiously. Better understanding of the relationship between stable and transient aspects of spontaneous brain dynamics will be necessary to constrain interpretation of case-control studies and inform pathophysiological models.

Resting-state functional network correlates of psychotic symptoms in schizophrenia

Schizophrenia has been associated with aberrant intrinsic functional organization of the brain but the relationship of such deficits to psychopathology is unclear. In this study, we investigated associations between resting-state networks and individual psychopathology in sixteen patients with paranoid schizophrenia and sixteen matched healthy control participants. We estimated whole-brain functional connectivity of multiple networks using a combination of spatial independent component analysis and multiple regression analysis. Five networks (default-mode, left and right fronto-parietal, left fronto-temporal and auditory networks) were selected for analysis based on their involvement in neuropsychological models of psychosis. Between-group comparisons and correlations to psychopathology ratings were performed on both spatial (connectivity distributions) and temporal features (power-spectral densities of temporal frequencies below 0.06 Hz). Schizophrenia patients showed aberrant functional connectivity in the default-mode network, which correlated with severity of hallucinations and delusions, and decreased hemispheric separation of fronto-parietal activity, which correlated with disorganization symptoms. Furthermore, the severity of positive symptoms correlated with functional connectivity of fronto-temporal and auditory networks. Finally, default-mode and auditory networks showed increased spectral power of low frequency oscillations, which correlated with positive symptom severity. These results are in line with findings from studies that investigated the neural correlates of positive symptoms and suggest that psychopathology is associated with aberrant intrinsic organization of functional brain networks in schizophrenia.

Task-free presurgical mapping using functional magnetic resonance imaging intrinsic activity

Low-frequency components of the spontaneous functional MR imaging signal provide information about the intrinsic functional and anatomical organization of the brain. The ability to use such methods in individual patients may provide a powerful tool for presurgical planning. The authors explore the feasibility of presurgical motor function mapping in which a task-free paradigm is used. Six surgical candidates with tumors or epileptic foci near the motor cortex participated in this study. The investigators directly compared task-elicited activation of the motor system to activation obtained from intrinsic activity correlations. The motor network within the unhealthy hemisphere was identified based on intrinsic activity correlations, allowing distortions of functional anatomy caused by the tumor and epilepsy to be directly visualized. The precision of the motor function mapping was further explored in 1 participant by using direct cortical stimulation. The motor regions localized based on the spontaneous activity correlations were quite similar to the regions defined by actual movement tasks and cortical stimulation. Using intrinsic activity correlations, it was possible to map the motor cortex in presurgical patients. This task-free paradigm may provide a powerful approach to map functional anatomy in patients without task compliance and allow multiple brain systems to be determined in a single scanning session.

Increased neural resources recruitment in the intrinsic organization in major depression

Objective To investigate the functional connectivity (FC) pattern within an intrinsic functional organization, including both task-positive (TPN) and task-negative (TNN) networks, in major depressive disorder (MDD), and to examine relationships between the involved FCs and clinical variables. Methods Resting-state FC analyses were used to identify the component brain regions of the intrinsic organization and to investigate the FCs of the individual component regions in 18 first-episode, medication-naïve MDD and 20 healthy control subjects. Results We found that the intrinsic organization of the depressed group recruited more extensive regions than the control group. All of the altered FCs associated with the component regions increased in MDD. Specifically, in the TPN the increased FCs were primarily located in the bilateral lateral prefrontal cortices and the inferior parietal lobes, which have been implicated in attention and adaptive control. In the TNN, the increased FCs were primarily located in the posterior cingulate cortex and the medial orbitofrontal cortex, which are involved in episodic memory, self-reflection and emotional regulation. We also found increased anti-correlations between the two networks. Additionally, the strengths of the FCs associated with the lateral prefrontal cortices were found to be correlated with the duration of the depressive episode and the HDRS scores in the depressed patients. Limitations Clinical correlates of these abnormal FCs should be cautiously interpreted due to the small sample size in this study. Conclusions Abnormalities in the intrinsic organization may be an underlying basis for the pronounced and prolonged negative bias in processing emotional information observed in MDD.

The intrinsic functional organization of the brain is altered in autism

In higher functioning individuals with autism, a striking disparity exists between impaired social and emotional abilities and relatively preserved sustained attention and goal-directed cognitive abilities. As these two functional domains appear to map onto two distinct large-scale brain networks, the Task-Negative Network and the Task-Positive Network, respectively, we examined their intrinsically defined functional organization in individuals with autism. Using resting functional connectivity MRI (fcMRI), we found that, in autism, there was altered functional organization of the network involved in social and emotional processing, but no group difference in the functional organization of the network involved in sustained attention and goal-directed cognition. We suggest that these findings might serve to relate the seemingly disparate strengths and weaknesses of the autistic behavioral, perceptual, and cognitive phenotype into a tractable neurofunctional framework. These results also highlight the usefulness of resting fcMRI for studying the brain in neuropsychiatric and neurodevelopmental disorders.

Functional disintegration in paranoid schizophrenia using resting-state fMRI

Functional disintegration has been observed in schizophrenia during task performance. We sought to investigate functional disintegration during rest because an intrinsic functional brain organization, including both “task-negative” (i.e., “default mode”) and “task-positive” networks, has been suggested to play an important role in integrating ongoing information processing. Additionally, the brain regions that are involved in the intrinsic organization are believed to be abnormal in schizophrenia. Patients with paranoid schizophrenia ( N = 18) and healthy volunteers ( N = 18) underwent a resting-state fMRI scan. Functional connectivity analysis was used to identify the connectivity between each pair of brain regions within this intrinsic organization, and differences were examined in patients versus healthy volunteers. Compared to healthy volunteers, patients showed significant differences in connectivity within networks and between networks, most notably in the connectivities associated with the bilateral dorsal medial prefrontal cortex, the lateral parietal region, the inferior temporal gyrus of the “task-negative” network and with the right dorsolateral prefrontal cortex and the right dorsal premotor cortex of the “task-positive” network. These results suggested that the interregional functional connectivities in the intrinsic organization are altered in patients with paranoid schizophrenia. These abnormalities could be the source of abnormalities in the coordination of and competition between information processing activities in the resting brain of paranoid patients.