Wernicke's area homologue in chimpanzees (Pan troglodytes) and its relation to the appearance of modern human language

Human language is distinctive compared with the communication systems of other species. Yet, several questions concerning its emergence and evolution remain unresolved. As a means of evaluating the neuroanatomical changes relevant to language that accompanied divergence from the last common ancestor of chimpanzees, bonobos and humans, we defined the cytoarchitectonic boundaries of area Tpt, a component of Wernicke''s area, in 12 common chimpanzee brains and used design-based stereologic methods to estimate regional volumes, total neuron number and neuron density. In addition, we created a probabilistic map of the location of area Tpt in a template chimpanzee brain coordinate space. Our results show that chimpanzees display significant population-level leftward asymmetry of area Tpt in terms of neuron number, with volume asymmetry approaching significance. Furthermore, asymmetry in the number of neurons in area Tpt was positively correlated with asymmetry of neuron numbers in Brodmann''s area 45, a component of Broca''s frontal language region. Our findings support the conclusion that leftward asymmetry of Wernicke''s area originated prior to the appearance of modern human language and before our divergence from the last common ancestor. Moreover, this study provides the first evidence of covariance between asymmetry of anterior and posterior cortical regions that in humans are important to language and other higher order cognitive functions.     

Development of the Intrinsic Language Network in Preschool Children from Ages 3 to 5 Years

Resting state studies of spontaneous fluctuations in the functional magnetic resonance imaging (fMRI) blood oxygen level dependent signal have shown great potential in mapping the intrinsic functional connectivity of the human brain underlying cognitive functions. The aim of the present study was to explore the developmental changes in functional networks of the developing human brain exemplified with the language network in typically developing preschool children. To this end, resting-sate fMRI data were obtained from native Chinese children at ages of 3 and 5 years, 15 in each age group. Resting-state functional connectivity (RSFC) was analyzed for four regions of interest; these are the left and right anterior superior temporal gyrus (aSTG), left posterior superior temporal gyrus (pSTG), and left inferior frontal gyrus (IFG). The comparison of these RSFC maps between 3- and 5-year-olds revealed that RSFC decreases in the right aSTG and increases in the left hemisphere between aSTG seed and IFG, between pSTG seed and IFG, as well as between IFG seed and posterior superior temporal sulcus. In a subsequent analysis, functional asymmetry of the language network seeding in aSTG, pSTG and IFG was further investigated. The results showed an increase of left lateralization in both RSFC of pSTG and of IFG from ages 3 to 5 years. The IFG showed a leftward lateralized trend in 3-year-olds, while pSTG demonstrated rightward asymmetry in 5-year-olds. These findings suggest clear developmental trajectories of the language network between 3- and 5-year-olds revealed as a function of age, characterized by increasing long-range connections and dynamic hemispheric lateralization with age. Our study provides new insights into the developmental changes of a well-established functional network in young children and also offers a basis for future cross-culture and cross-age studies of the resting-state language network.     

Resting-state EEG source localization and functional connectivity in schizophrenia-like psychosis of epilepsy

Background

It is unclear whether, like in schizophrenia, psychosis-related disruption in connectivity between certain regions, as an index of intrinsic functional disintegration, occurs in schizophrenia-like psychosis of epilepsy (SLPE). In this study, we sought to determine abnormal patterns of resting-state EEG oscillations and functional connectivity in patients with SLPE, compared with nonpsychotic epilepsy patients, and to assess correlations with psychopathological deficits.

Methodology/Principal Findings

Resting EEG was recorded in 21 patients with focal epilepsy and SLPE and in 21 clinically-matched non-psychotic epilepsy controls. Source current density and functional connectivity were determined using eLORETA software. For connectivity analysis, a novel nonlinear connectivity measure called “lagged phase synchronization” was used. We found increased theta oscillations in regions involved in the default mode network (DMN), namely the medial and lateral parietal cortex bilaterally in the psychotic patients relative to their nonpsychotic counterparts. In addition, patients with psychosis had increased beta temporo-prefrontal connectivity in the hemisphere with predominant seizure focus. This functional connectivity in temporo-prefrontal circuits correlated with positive symptoms. Additionally, there was increased interhemispheric phase synchronization between the auditory cortex of the affected temporal lobe and the Broca''s area correlating with auditory hallucination scores.

Conclusions/Significance

In addition to dysfunction of parietal regions that are part of the DMN, resting-state disrupted connectivity of the medial temporal cortex with prefrontal areas that are either involved in the DMN or implicated in psychopathological dysfunction may be critical to schizophrenia-like psychosis, especially in individuals with temporal lobe epilepsy. This suggests that DMN deficits might be a core neurobiological feature of the disorder, and that abnormalities in theta oscillations and beta phase synchronization represent the underlying neural activity.     

Integrating Functional and Diffusion Magnetic Resonance Imaging for Analysis of Structure-Function Relationship in the Human Language Network

Background

The capabilities of magnetic resonance imaging (MRI) to measure structural and functional connectivity in the human brain have motivated growing interest in characterizing the relationship between these measures in the distributed neural networks of the brain. In this study, we attempted an integration of structural and functional analyses of the human language circuits, including Wernicke''s (WA), Broca''s (BA) and supplementary motor area (SMA), using a combination of blood oxygen level dependent (BOLD) and diffusion tensor MRI.

Methodology/Principal Findings

Functional connectivity was measured by low frequency inter-regional correlations of BOLD MRI signals acquired in a resting steady-state, and structural connectivity was measured by using adaptive fiber tracking with diffusion tensor MRI data. The results showed that different language pathways exhibited different structural and functional connectivity, indicating varying levels of inter-dependence in processing across regions. Along the path between BA and SMA, the fibers tracked generally formed a single bundle and the mean radius of the bundle was positively correlated with functional connectivity. However, fractional anisotropy was found not to be correlated with functional connectivity along paths connecting either BA and SMA or BA and WA.

Conclusions/Significance

These findings suggest that structure-function relations in the human language circuits may involve a number of confounding factors that need to be addressed. Nevertheless, the insights gained from this work offers a useful guidance for continued studies that may provide a non-invasive means to evaluate brain network integrity in vivo for use in diagnosing and determining disease progression and recovery.     

Broca's Region: Novel Organizational Principles and Multiple Receptor Mapping

There is a considerable contrast between the various functions assigned to Broca''s region and its relatively simple subdivision into two cytoarchitectonic areas (44 and 45). Since the regional distribution of transmitter receptors in the cerebral cortex has been proven a powerful indicator of functional diversity, the subdivision of Broca''s region was analyzed here using a multireceptor approach. The distribution patterns of six receptor types using in vitro receptor autoradiography revealed previously unknown areas: a ventral precentral transitional cortex 6r1, dorsal and ventral areas 44d and 44v, anterior and posterior areas 45a and 45p, and areas op8 and op9 in the frontal operculum. A significant lateralization of receptors was demonstrated with respect to the cholinergic M₂ receptor, particularly in area 44v+d. We propose a new concept of the anterior language region, which elucidates the relation between premotor cortex, prefrontal cortex, and Broca''s region. It offers human brain homologues to the recently described subdivision of area 45, and the segregation of the ventral premotor cortex in macaque brains. The results provide a novel structural basis of the organization of language regions in the brain.     

A Brain Network Processing the Age of Faces

Age is one of the most salient aspects in faces and of fundamental cognitive and social relevance. Although face processing has been studied extensively, brain regions responsive to age have yet to be localized. Using evocative face morphs and fMRI, we segregate two areas extending beyond the previously established face-sensitive core network, centered on the inferior temporal sulci and angular gyri bilaterally, both of which process changes of facial age. By means of probabilistic tractography, we compare their patterns of functional activation and structural connectivity. The ventral portion of Wernicke''s understudied perpendicular association fasciculus is shown to interconnect the two areas, and activation within these clusters is related to the probability of fiber connectivity between them. In addition, post-hoc age-rating competence is found to be associated with high response magnitudes in the left angular gyrus. Our results provide the first evidence that facial age has a distinct representation pattern in the posterior human brain. We propose that particular face-sensitive nodes interact with additional object-unselective quantification modules to obtain individual estimates of facial age. This brain network processing the age of faces differs from the cortical areas that have previously been linked to less developmental but instantly changeable face aspects. Our probabilistic method of associating activations with connectivity patterns reveals an exemplary link that can be used to further study, assess and quantify structure-function relationships.     

Age-Related Differences in Test-Retest Reliability in Resting-State Brain Functional Connectivity

Resting-state functional MRI (rs-fMRI) has emerged as a powerful tool for investigating brain functional connectivity (FC). Research in recent years has focused on assessing the reliability of FC across younger subjects within and between scan-sessions. Test-retest reliability in resting-state functional connectivity (RSFC) has not yet been examined in older adults. In this study, we investigated age-related differences in reliability and stability of RSFC across scans. In addition, we examined how global signal regression (GSR) affects RSFC reliability and stability. Three separate resting-state scans from 29 younger adults (18–35 yrs) and 26 older adults (55–85 yrs) were obtained from the International Consortium for Brain Mapping (ICBM) dataset made publically available as part of the 1000 Functional Connectomes project www.nitrc.org/projects/fcon_1000. 92 regions of interest (ROIs) with 5 cubic mm radius, derived from the default, cingulo-opercular, fronto-parietal and sensorimotor networks, were previously defined based on a recent study. Mean time series were extracted from each of the 92 ROIs from each scan and three matrices of z-transformed correlation coefficients were created for each subject, which were then used for evaluation of multi-scan reliability and stability. The young group showed higher reliability of RSFC than the old group with GSR (p-value = 0.028) and without GSR (p-value <0.001). Both groups showed a high degree of multi-scan stability of RSFC and no significant differences were found between groups. By comparing the test-retest reliability of RSFC with and without GSR across scans, we found significantly higher proportion of reliable connections in both groups without GSR, but decreased stability. Our results suggest that aging is associated with reduced reliability of RSFC which itself is highly stable within-subject across scans for both groups, and that GSR reduces the overall reliability but increases the stability in both age groups and could potentially alter group differences of RSFC.     

Deficit in Complex Sequence Processing after a Virtual Lesion of Left BA45

Although the contribution of Broca''s area to motor cognition is generally accepted, its exact role remains controversial. A previous functional imaging study has suggested that Broca''s area implements hierarchically organised motor behaviours and, in particular, that its anterior (Brodmann area 45, BA45) and posterior (BA44) parts process, respectively, higher and lower-level hierarchical elements. This function of Broca''s area could generalize to other cognitive functions, including language. However, because of the correlative nature of functional imaging data, the causal relationship between Broca''s region activation and its behavioural significance cannot be ascertained. To circumvent this limitation, we used on-line repetitive transcranial magnetic stimulation to disrupt neuronal processing in left BA45, left BA44 or left dorsal premotor cortex, three areas that have been shown to exhibit a phasic activation when participants performed hierarchically organised motor behaviours. The experiment was conducted in healthy volunteers performing the same two key-press sequences as those used in a previous imaging study, and which differed in terms of hierarchical organisation. The performance of the lower-order hierarchical task (Experiment #1) was unaffected by magnetic stimulation. In contrast, in the higher-order hierarchical task (Experiment #2, “superordinate” task), we found that a virtual lesion of the anterior part of Broca''s area (left BA45) delayed the processing of the cue initiating the sequence in an effector-independent way. Interestingly, in this task, the initiation cue only informed the subjects about the rules to be applied to produce the appropriate response but did not allow them to anticipate the entire motor sequence. A second important finding was a RT decrease following left PMd virtual lesions in the superordinate task, a result compatible with the view that PMd plays a critical role in impulse control. The present study therefore demonstrates the role of left BA45 in planning the higher-order hierarchical levels of motor sequences.     

Resting-State Temporal Synchronization Networks Emerge from Connectivity Topology and Heterogeneity

Spatial patterns of coherent activity across different brain areas have been identified during the resting-state fluctuations of the brain. However, recent studies indicate that resting-state activity is not stationary, but shows complex temporal dynamics. We were interested in the spatiotemporal dynamics of the phase interactions among resting-state fMRI BOLD signals from human subjects. We found that the global phase synchrony of the BOLD signals evolves on a characteristic ultra-slow (<0.01Hz) time scale, and that its temporal variations reflect the transient formation and dissolution of multiple communities of synchronized brain regions. Synchronized communities reoccurred intermittently in time and across scanning sessions. We found that the synchronization communities relate to previously defined functional networks known to be engaged in sensory-motor or cognitive function, called resting-state networks (RSNs), including the default mode network, the somato-motor network, the visual network, the auditory network, the cognitive control networks, the self-referential network, and combinations of these and other RSNs. We studied the mechanism originating the observed spatiotemporal synchronization dynamics by using a network model of phase oscillators connected through the brain’s anatomical connectivity estimated using diffusion imaging human data. The model consistently approximates the temporal and spatial synchronization patterns of the empirical data, and reveals that multiple clusters that transiently synchronize and desynchronize emerge from the complex topology of anatomical connections, provided that oscillators are heterogeneous.     

Aberrant Resting-State Corticostriatal Functional Connectivity in Cirrhotic Patients with Hyperintense Globus Pallidus on T1-Weighted MR Imaging

Neurobiological and neuroimaging studies have emphasized the structural and functional alterations in the striatum of cirrhotic patients, but alterations in the functional connections between the striatum and other brain regions have not yet been explored. Of note, manganese accumulation in the nervous system, frequently reflected by hyperintensity at the bilateral globus pallidus (GP) on T1-weighted imaging, has been considered a factor affecting the striatal and cortical functions in hepatic decompensation. We employed resting-state functional magnetic resonance imaging to analyze the temporal correlation between the striatum and the remaining brain regions using seed-based correlation analyses. The two-sample t-test was conducted to detect the differences in corticostriatal connectivity between 44 cirrhotic patients with hyperintensity at the bilateral GP and 20 healthy controls. Decreased connectivity of the caudate was detected in the anterior/middle cingulate gyrus, and increased connectivity of the caudate was found in the left motor cortex. A reduction in functional connectivity was found between the putamen and several regions, including the anterior cingulate gyrus, right insular lobe, inferior frontal gyrus, left parahippocampal gyrus, and anterior lobe of the right cerebellum; increased connectivity was detected between the putamen and right middle temporal gyrus. There were significant correlations between the corticostriatal connectivity and neuropsychological performances in the patient group, but not between the striatal connectivity and GP signal intensity. These alterations in the corticostriatal functional connectivity suggested the abnormalities in the intrinsic brain functional organiztion among the cirrhotic patients with manganese deposition, and may be associated with development of metabolic encephalopathy. The manganese deposition in nervous system, however, can not be an independent factor predicting the resting-state brain dysfunction in real time.     

Assessment of asymmetry of the Broca's area through C.A.T. imagery

It is the purpose of this study to demonstrate the lateral asymmetry, if any, in the region of the Broca's speech area in a circumscribed group of humans. Linguists espouse an all-encompassing definition of «Language». For the purpose of this study, language is construed as articulated words in proper syntax in response to one's perception, i.e., human speech.     

Increased Intrinsic Connectivity of the Default Mode Network in Temporal Lobe Epilepsy: Evidence from Resting-State MEG Recordings

The electrophysiological signature of resting state oscillatory functional connectivity within the default mode network (DMN) during spike-free periods in temporal lobe epilepsy (TLE) remains unclear. Using magnetoencephalographic (MEG) recordings, this study investigated how the connectivity within the DMN was altered in TLE, and we examined the effect of lateralized TLE on functional connectivity. Sixteen medically intractable TLE patients and 22 controls participated in this study. Whole-scalp 306-channel MEG epochs without interictal spikes generated from both MEG and EEG data were analyzed using a minimum norm estimate (MNE) and source-based imaginary coherence analysis. With this processing, we obtained the cortical activation and functional connectivity within the DMN. The functional connectivity was increased between DMN and the right medial temporal (MT) region at the delta band and between DMN and the bilateral anterior cingulate cortex (ACC) regions at the theta band. The functional change was associated with the lateralization of TLE. The right TLE showed enhanced DMN connectivity with the right MT while the left TLE demonstrated increased DMN connectivity with the bilateral MT. There was no lateralization effect of TLE upon the DMN connectivity with ACC. These findings suggest that the resting-state functional connectivity within the DMN is reinforced in temporal lobe epilepsy during spike-free periods. Future studies are needed to examine if the altered functional connectivity can be used as a biomarker for treatment responses, cognitive dysfunction and prognosis in patients with TLE.     

Changes in Thalamic Connectivity in the Early and Late Stages of Amnestic Mild Cognitive Impairment: A Resting-State Functional Magnetic Resonance Study from ADNI

We used resting-state functional magnetic resonance imaging (fMRI) to investigate changes in the thalamus functional connectivity in early and late stages of amnestic mild cognitive impairment. Data of 25 late stages of amnestic mild cognitive impairment (LMCI) patients, 30 early stages of amnestic mild cognitive impairment (EMCI) patients and 30 well-matched healthy controls (HC) were analyzed from the Alzheimer’s disease Neuroimaging Initiative (ADNI). We focused on the correlation between low frequency fMRI signal fluctuations in the thalamus and those in all other brain regions. Compared to healthy controls, we found functional connectivity between the left/right thalamus and a set of brain areas was decreased in LMCI and/or EMCI including right fusiform gyrus (FG), left and right superior temporal gyrus, left medial frontal gyrus extending into supplementary motor area, right insula, left middle temporal gyrus (MTG) extending into middle occipital gyrus (MOG). We also observed increased functional connectivity between the left/right thalamus and several regions in LMCI and/or EMCI including left FG, right MOG, left and right precuneus, right MTG and left inferior temporal gyrus. In the direct comparison between the LMCI and EMCI groups, we obtained several brain regions showed thalamus-seeded functional connectivity differences such as the precentral gyrus, hippocampus, FG and MTG. Briefly, these brain regions mentioned above were mainly located in the thalamo-related networks including thalamo-hippocampus, thalamo-temporal, thalamo-visual, and thalamo-default mode network. The decreased functional connectivity of the thalamus might suggest reduced functional integrity of thalamo-related networks and increased functional connectivity indicated that aMCI patients could use additional brain resources to compensate for the loss of cognitive function. Our study provided a new sight to understand the two important states of aMCI and revealed resting-state fMRI is an appropriate method for exploring pathophysiological changes in aMCI.     

Task-related effects on the temporal and spatial dynamics of resting-state functional connectivity in the default network

Recent evidence points to two potentially fundamental aspects of the default network (DN), which have been relatively understudied. One is the temporal nature of the functional interactions among nodes of the network in the resting-state, usually assumed to be static. The second is possible influences of previous brain states on the spatial patterns (i.e., the brain regions involved) of functional connectivity (FC) in the DN at rest. The goal of the current study was to investigate modulations in both the spatial and temporal domains. We compared the resting-state FC of the DN in two runs that were separated by a 45 minute interval containing cognitive task execution. We used partial least squares (PLS), which allowed us to identify FC spatiotemporal patterns in the two runs and to determine differences between them. Our results revealed two primary modes of FC, assessed using a posterior cingulate seed--a robust correlation among DN regions that is stable both spatially and temporally, and a second pattern that is reduced in spatial extent and more variable temporally after cognitive tasks, showing switching between connectivity with certain DN regions and connectivity with other areas, including some task-related regions. Therefore, the DN seems to exhibit two simultaneous FC dynamics at rest. The first is spatially invariant and insensitive to previous brain states, suggesting that the DN maintains some temporally stable functional connections. The second dynamic is more variable and is seen more strongly when the resting-state follows a period of task execution, suggesting an after-effect of the cognitive activity engaged during task that carries over into resting-state periods.     

Discriminative Analysis of Parkinson’s Disease Based on Whole-Brain Functional Connectivity

Recently, there has been an increasing emphasis on applications of pattern recognition and neuroimaging techniques in the effective and accurate diagnosis of psychiatric or neurological disorders. In the present study, we investigated the whole-brain resting-state functional connectivity patterns of Parkinson''s disease (PD), which are expected to provide additional information for the clinical diagnosis and treatment of this disease. First, we computed the functional connectivity between each pair of 116 regions of interest derived from a prior atlas. The most discriminative features based on Kendall tau correlation coefficient were then selected. A support vector machine classifier was employed to classify 21 PD patients with 26 demographically matched healthy controls. This method achieved a classification accuracy of 93.62% using leave-one-out cross-validation, with a sensitivity of 90.47% and a specificity of 96.15%. The majority of the most discriminative functional connections were located within or across the default mode, cingulo-opercular and frontal-parietal networks and the cerebellum. These disease-related resting-state network alterations might play important roles in the pathophysiology of this disease. Our results suggest that analyses of whole-brain resting-state functional connectivity patterns have the potential to improve the clinical diagnosis and treatment evaluation of PD.     

The Relation between Resting State Connectivity and Creativity in Adolescents before and after Training

An important component of creativity is divergent thinking, which involves the ability to generate novel and useful problem solutions. In this study, we tested the relation between resting-state functional connectivity of brain areas activated during a divergent thinking task (i.e., supramarginal gyrus, middle temporal gyrus, medial frontal gyrus) and the effect of practice in 32 adolescents aged 15–16. Over a period of two weeks, an experimental group (n = 16) conducted an 8-session Alternative Uses Task (AUT) training and an active control group (n = 16) conducted an 8-session rule switching training. Resting-state functional connectivity was measured before (pre-test) and after (post-test) training. Across groups at pre-test, stronger connectivity between the middle temporal gyrus and bilateral postcentral gyrus was associated with better divergent thinking performance. The AUT-training, however, did not significantly change functional connectivity. Post hoc analyses showed that change in divergent thinking performance over time was predicted by connectivity between left supramarginal gyrus and right occipital cortex. These results provide evidence for a relation between divergent thinking and resting-state functional connectivity in a task-positive network, taking an important step towards understanding creative cognition and functional brain connectivity.     

First-Episode Medication-Naive Major Depressive Disorder Is Associated with Altered Resting Brain Function in the Affective Network

Background

Major depressive disorder (MDD) has been associated with abnormal structure and function of the brain''s affective network, including the amygdala and orbitofrontal cortex (OFC). However, it is unclear if alterations of resting-state function in this affective network are present at the initial onset of MDD.

Aims

To examine resting-state function of the brain''s affective network in first-episode, medication-naive patients with MDD compared to healthy controls (HCs).

Methods

Resting-state functional magnetic resonance imaging (rs-fMRI) was performed on 32 first-episode, medication-naive young adult patients with MDD and 35 matched HCs. The amplitude of low-frequency fluctuations (ALFF) of the blood oxygen level-dependent (BOLD) signal and amygdala-seeded functional connectivity (FC) were investigated.

Results

Compared to HC, MDD patients showed reduced ALFF in the bilateral OFC and increased ALFF in the bilateral temporal lobe extending to the insular and left fusiform cortices. Enhanced anti-correlation of activity between the left amygdala seed and the left OFC was found in MDD patients but not in HCs.

Conclusions

Reduced ALFF in the OFC suggests hypo-functioning of emotion regulation in the affective network. Enhanced anti-correlation of activity between the amygdala and OFC may reflect dysfunction of the amygdala-OFC network and additionally represent a pathological process of MDD.     

Early Altered Resting-State Functional Connectivity Predicts the Severity of Post-Traumatic Stress Disorder Symptoms in Acutely Traumatized Subjects

The goal of this study was to investigate the relationship between resting-state functional connectivity and the severity of post-traumatic stress disorder (PTSD) symptoms in 15 people who developed PTSD following recent trauma. Fifteen participants who experienced acute traumatic events underwent a 7.3-min resting functional magnetic resonance imaging scan within 2 days post-event. All the patients were diagnosed with PTSD within 1 to 6 months after trauma. Brain areas in which activity was correlated with that of the posterior cingulate cortex (PCC) were assessed. To assess the relationship between the severity of PTSD symptoms and PCC connectivity, contrast images representing areas positively correlated with the PCC were correlated with the subject’s Clinician-Administered PTSD Scale scores (CAPS) when they were diagnosed. Furthermore, the PCC, medial prefrontal cortex and bilateral amygdala were selected to assess the correlation of the strength of functional connectivity with the CAPS. Resting state connectivity with the PCC was negatively correlated with CAPS scores in the left superior temporal gyrus and right hippocampus/amygdala. Furthermore, the strength of connectivity between the PCC and bilateral amygdala, and even between the bilateral amygdala could predict the severity of PTSD symptoms later. These results suggest that early altered resting-state functional connectivity of the PCC with the left superior temporal gyrus, right hippocampus and amygdala could predict the severity of the disease and may be a major risk factor that predisposes patients to develop PTSD.     

Functional and Anatomical Connectivity Abnormalities in Cognitive Division of Anterior Cingulate Cortex in Schizophrenia

Introduction

Current pathophysiological theories of schizophrenia highlight the role of altered brain functional and anatomical connectivity. The cognitive division of anterior cingulate cortex (ACC-cd) is a commonly reported abnormal brain region in schizophrenia for its importance in cognitive control process. The aim of this study was to investigate the functional and anatomical connectivity of ACC-cd and its cognitive and clinical manifestation significance in schizophrenia by using the resting-state functional magnetic resonance imaging (fMRI) and the diffusion tensor imaging (DTI).

Methods

Thirty-three medicated schizophrenics and 30 well-matched health controls were recruited. Region-of-interest (ROI)-based resting-state functional connectivity analysis and Tract-Based Spatial Statistics (TBSS) were performed on 30 patients and 30 controls, and 24 patients and 29 controls, respectively. The Pearson correlation was performed between the imaging measures and the Stroop performance and scores of the Positive and Negative Syndrome Scale (PANSS), respectively.

Results

Patients with schizophrenia showed significantly abnormal in the functional connectivity and its hemispheric asymmetry of the ACC-cd with multiple brain areas, e.g., decreased positive connectivity with the bilateral putamen and caudate, increased negative connectivity with the left posterior cingulated cortex (PCC), increased asymmetry of connectivity strength with the contralateral inferior frontal gyrus (IFG). The FA of the right anterior cingulum was significantly decreased in patients group (p = 0.014). The abnormal functional and structural connectivity of ACC-cd were correlated with Stroop performance and the severity of the symptoms in patients.

Conclusions

Our results suggested that the abnormal connectivity of the ACC-cd might play a role in the cognitive impairment and clinical symptoms in schizophrenia.     

Loss of 'small-world' networks in Alzheimer's disease: graph analysis of FMRI resting-state functional connectivity

Background

Local network connectivity disruptions in Alzheimer''s disease patients have been found using graph analysis in BOLD fMRI. Other studies using MEG and cortical thickness measures, however, show more global long distance connectivity changes, both in functional and structural imaging data. The form and role of functional connectivity changes thus remains ambiguous. The current study shows more conclusive data on connectivity changes in early AD using graph analysis on resting-state condition fMRI data.

Methodology/Principal Findings

18 mild AD patients and 21 healthy age-matched control subjects without memory complaints were investigated in resting-state condition with MRI at 1.5 Tesla. Functional coupling between brain regions was calculated on the basis of pair-wise synchronizations between regional time-series. Local (cluster coefficient) and global (path length) network measures were quantitatively defined. Compared to controls, the characteristic path length of AD functional networks is closer to the theoretical values of random networks, while no significant differences were found in cluster coefficient. The whole-brain average synchronization does not differ between Alzheimer and healthy control groups. Post-hoc analysis of the regional synchronization reveals increased AD synchronization involving the frontal cortices and generalized decreases located at the parietal and occipital regions. This effectively translates in a global reduction of functional long-distance links between frontal and caudal brain regions.

Conclusions/Significance

We present evidence of AD-induced changes in global brain functional connectivity specifically affecting long-distance connectivity. This finding is highly relevant for it supports the anterior-posterior disconnection theory and its role in AD. Our results can be interpreted as reflecting the randomization of the brain functional networks in AD, further suggesting a loss of global information integration in disease.