Functional connectivity in mild traumatic brain injury

Objectives: Research suggests that the majority of mild traumatic brain injury (mTBI) patients exhibit both cognitive and emotional dysfunction within the first weeks of injury, followed by symptom resolution 3–6 months postinjury. The neuronal correlates of said dysfunction are difficult to detect with standard clinical neuroimaging, complicating differential diagnosis and early identification of patients who may not recover. This study examined whether resting state functional magnetic resonance imaging (fMRI) provides objective markers of injury and predicts cognitive, emotional, and somatic complaints in mTBI patients semiacutely (<3 weeks postinjury) and in late recovery (3–5 month) phases. Methods: Twenty‐seven semiacute mTBI patients and 26 gender, age, and education‐matched controls were studied. Fifteen of 27 patients returned for a follow‐up visit 3–5 months postinjury. The main dependent variables were spontaneous fluctuations (temporal correlation) in the default‐mode (DMN) and fronto‐parietal task‐related networks as measured by fMRI. Results: Significant differences in self‐reported cognitive, emotional, and somatic complaints were observed (all P < 0.05), despite normal clinical (T1 and T2) imaging and neuropsychological testing results. Mild TBI patients demonstrated decreased functional connectivity within the DMN and hyper‐connectivity between the DMN and lateral prefrontal cortex. Measures of functional connectivity exhibited high levels of sensitivity and specificity for patient classification and predicted cognitive complaints in the semi‐acute injury stage. However, no changes in functional connectivity were observed across a 4‐month recovery period. Conclusions: Abnormal connectivity between the DMN and frontal cortex may provide objective biomarkers of mTBI and underlie cognitive impairment. Hum Brain Mapp, 2011. © 2011 Wiley‐Liss, Inc.     

Impairment of functional integration of the default mode network correlates with cognitive outcome at three months after stroke

Resting‐state studies conducted with stroke patients are scarce. The study of brain activity and connectivity at rest provides a unique opportunity for the investigation of brain rewiring after stroke and plasticity changes. This study sought to identify dynamic changes in the functional organization of the default mode network (DMN) of stroke patients at three months after stroke. Eleven patients (eight male and three female; age range: 48–72) with right cortical and subcortical ischemic infarctions and 17 controls (eleven males and six females; age range: 57–69) were assessed by neurological and neuropsychological examinations and scanned with resting‐state functional magnetic ressonance imaging. First, we explored group differences in functional activity within the DMN by means of probabilistic independent component analysis followed by a dual regression approach. Second, we estimated functional connectivity between 11 DMN nodes both locally by means of seed‐based connectivity analysis, as well as globally by means of graph‐computation analysis. We found that patients had greater DMN activity in the left precuneus and the left anterior cingulate gyrus when compared with healthy controls (P < 0.05 family‐wise error corrected). Seed‐based connectivity analysis showed that stroke patients had significant impairment (P = 0.014; threshold = 2.00) in the connectivity between the following five DMN nodes: left superior frontal gyrus (lSFG) and posterior cingulate cortex (t = 2.01); left parahippocampal gyrus and right superior frontal gyrus (t = 2.11); left parahippocampal gyrus and lSFG (t = 2.39); right parietal and lSFG (t = 2.29). Finally, mean path length obtained from graph‐computation analysis showed positive correlations with semantic fluency test (r _s = 0.454; P = 0.023), phonetic fluency test (r _s = 0.523; P = 0.007) and the mini mental state examination (r _s = 0.528; P = 0.007). In conclusion, the ability to regulate activity of the DMN appears to be a central part of normal brain function in stroke patients. Our study expands the understanding of the changes occurring in the brain after stroke providing a new avenue for investigating lesion‐induced network plasticity. Hum Brain Mapp 36:577–590, 2015. © 2014 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.     

Cardiorespiratory fitness predicts effective connectivity between the hippocampus and default mode network nodes in young adults

Rodent and human studies examining the relationship between aerobic exercise, brain structure, and brain function indicate that the hippocampus (HC), a brain region critical for episodic memory, demonstrates striking plasticity in response to exercise. Beyond the hippocampal memory system, human studies also indicate that aerobic exercise and cardiorespiratory fitness (CRF) are associated with individual differences in large‐scale brain networks responsible for broad cognitive domains. Examining network activity in large‐scale resting‐state brain networks may provide a link connecting the observed relationships between aerobic exercise, hippocampal plasticity, and cognitive enhancement within broad cognitive domains. Previously, CRF has been associated with increased functional connectivity of the default mode network (DMN), specifically in older adults. However, how CRF relates to the magnitude and directionality of connectivity, or effective connectivity, between the HC and other DMN nodes remains unknown. We used resting‐state fMRI and conditional Granger causality analysis (CGCA) to test the hypothesis that CRF positively predicts effective connectivity between the HC and other DMN nodes in healthy young adults. Twenty‐six participants (ages 18–35 years) underwent a treadmill test to determine CRF by estimating its primary determinant, maximal oxygen uptake (V^.O_2max), and a 10‐min resting‐state fMRI scan to examine DMN effective connectivity. We identified the DMN using group independent component analysis and examined effective connectivity between nodes using CGCA. Linear regression analyses demonstrated that CRF significantly predicts causal influence from the HC to the ventromedial prefrontal cortex, posterior cingulate cortex, and lateral temporal cortex and to the HC from the dorsomedial prefrontal cortex. The observed relationship between CRF and hippocampal effective connectivity provides a link between the rodent literature, which demonstrates a relationship between aerobic exercise and hippocampal plasticity, and the human literature, which demonstrates a relationship between aerobic exercise and CRF and the enhancement of broad cognitive domains including, but not limited to, memory.     

Multimodal investigation of triple network connectivity in patients with 22q11DS and association with executive functions

Large‐scale brain networks play a prominent role in cognitive abilities and their activity is impaired in psychiatric disorders, such as schizophrenia. Patients with 22q11.2 deletion syndrome (22q11DS) are at high risk of developing schizophrenia and present similar cognitive impairments, including executive functions deficits. Thus, 22q11DS represents a model for the study of neural biomarkers associated with schizophrenia. In this study, we investigated structural and functional connectivity within and between the Default Mode (DMN), the Central Executive (CEN), and the Saliency network (SN) in 22q11DS using resting‐state fMRI and DTI. Furthermore, we investigated if triple network impairments were related to executive dysfunctions or the presence of psychotic symptoms. Sixty‐three patients with 22q11DS and sixty‐eighty controls (age 6–33 years) were included in the study. Structural connectivity between main nodes of DMN, CEN, and SN was computed using probabilistic tractography. Functional connectivity was computed as the partial correlation between the time courses extracted from each node. Structural and functional connectivity measures were then correlated to executive functions and psychotic symptom scores. Our results showed mainly reduced structural connectivity within the CEN, DMN, and SN, in patients with 22q11DS compared with controls as well as reduced between‐network connectivity. Functional connectivity appeared to be more preserved, with impairments being evident only within the DMN. Structural connectivity impairments were also related to executive dysfunctions. These findings show an association between triple network structural alterations and executive deficits in patients with the microdeletion, suggesting that 22q11DS and schizophrenia share common psychopathological mechanisms. Hum Brain Mapp 38:2177–2189, 2017. © 2017 Wiley Periodicals, Inc.     

Functional segregation loss over time is moderated by APOE genotype in healthy elderly

We investigated the influence of the apolipoprotein E‐?4 allele (APOE‐?4) on longitudinal age‐related changes in brain functional connectivity (FC) and cognition, in view of mixed cross‐sectional findings. One hundred and twenty‐two healthy older adults (aged 58–79; 25 APOE‐?4 carriers) underwent task‐free fMRI scans at baseline. Seventy‐eight (16 carriers) had at least one follow‐up (every 2 years). Changes in intra‐ and internetwork FCs among the default mode (DMN), executive control (ECN), and salience (SN) networks, as well as cognition, were quantified using linear mixed models. Cross‐sectionally, APOE‐?4 carriers had lower functional connectivity between the ECN and SN than noncarriers. Carriers also showed a stronger age‐dependent decrease in visuospatial memory performance. Longitudinally, carriers had steeper increase in inter‐ECN‐DMN FC, indicating loss of functional segregation. The longitudinal change in processing speed performance was not moderated by APOE‐?4 genotype, but the brain–cognition association was. In younger elderly, faster loss of segregation was correlated with greater decline in processing speed regardless of genotype. In older elderly, such relation remained for noncarriers but reversed for carriers. APOE‐?4 may alter aging by accelerating the change in segregation between high‐level cognitive systems. Its modulation on the longitudinal brain–cognition relationship was age‐dependent.     

Acute tryptophan loading decreases functional connectivity between the default mode network and emotion‐related brain regions

It has been shown that the functional architecture of the default mode network (DMN) can be affected by serotonergic challenges and these effects may provide insights on the neurobiological bases of depressive symptomatology. To deepen our understanding of this possible interplay, we used a double‐blind, randomized, cross‐over design, with a control condition and two interventions to decrease (tryptophan depletion) and increase (tryptophan loading) brain serotonin synthesis. Resting‐state fMRI from 85 healthy subjects was acquired for all conditions 3 hr after the ingestion of an amino acid mixture containing different amounts of tryptophan, the dietary precursor of serotonin. The DMN was derived for each participant and session. Permutation testing was performed to detect connectivity changes within the DMN as well as between the DMN and other brain regions elicited by the interventions. We found that tryptophan loading increased tryptophan plasma levels and decreased DMN connectivity with visual cortices and several brain regions involved in emotion and affect regulation (i.e., putamen, subcallosal cortex, thalamus, and frontal cortex). Tryptophan depletion significantly reduced tryptophan levels but did not affect brain connectivity. Subjective ratings of mood, anxiety, sleepiness, and impulsive choice were not strongly affected by any intervention. Our data indicate that connectivity between the DMN and emotion‐related brain regions might be modulated by changes in the serotonergic system. These results suggest that functional changes in the brain associated with different brain serotonin levels may be relevant to understand the neural bases of depressive symptoms.     

The developmental trajectory of fronto‐temporoparietal connectivity as a proxy of the default mode network: a longitudinal fNIRS investigation

The default mode network (DMN) is a network of brain regions that is activated while we are not engaged in any particular task. While there is a large volume of research documenting functional connectivity within the DMN in adults, knowledge of the development of this network is still limited. There is some evidence for a gradual increase in the functional connections within the DMN during the first 2 years of life, in contrast to other functional resting‐state networks that support primary sensorimotor functions, which are online from very early in life. Previous studies that investigated the development of the DMN acquired data from sleeping infants using fMRI. However, sleep stages are known to affect functional connectivity. In the current longitudinal study, fNIRS was used to measure spontaneous fluctuations in connectivity within fronto‐temporoparietal areas—as a proxy for the DMN—in awake participants every 6 months from 11 months till 36 months. This study validates a method for recording resting‐state data from awake infants, and presents a data analysis pipeline for the investigation of functional connections with infant fNIRS data, which will be beneficial for researchers in this field. A gradual development of fronto‐temporoparietal connectivity was found, supporting the idea that the DMN develops over the first years of life. Functional connectivity reached its maximum peak at about 24 months, which is consistent with previous findings showing that, by 2 years of age, DMN connectivity is similar to that observed in adults.     

Disrupted functional connectivity of default mode and salience networks in chronic pancreatitis patients

ObjectiveThe functional connectivity of the brain in chronic pancreatitis (CP) remains unknown. This study aimed to investigate functional connectivity in CP patients using resting state functional magnetic resonance imaging (fMRI) and explore the associations to clinical parameters and altered cerebral metabolites.MethodsSeed-based and ROI-to-ROI analyses were performed to assess connectivity within and between the default mode network (DMN) and salience network (SN). Additionally, functional connectivity in these networks were investigated in relation to clinical parameters (CP etiology, pain, medication, etc.) and cerebral glutamate/creatine level in the anterior cingulate cortex.ResultsThirty CP patients and 23 healthy controls were analyzed. CP patients showed hyper-connectivity in DMN and SN as compared to healthy controls. Furthermore, CP patients had reduced anti-correlated functional connectivity between DMN and SN (all P ≤ 0.009). The altered DMN connectivity correlated to glutamate/creatine level (r = 0.503, P = 0.020) in patients with pain, but not to the clinical parameters.ConclusionsCP patients had altered functional connectivity within and between brain networks. Altered DMN functional connectivity had an association to cerebral metabolic changes.SignificanceAltered functional connectivity in CP share similarities with other chronic pain conditions, and support our understanding of altered brain circuitry associated with the CP disease.     

Increased “default mode” activity in adolescents prenatally exposed to cocaine

Prenatal cocaine exposure (PCE) is associated with attention/arousal dysregulation and possible inefficiencies in some cognitive functions. However, the neurobiological bases of these teratogenic effects have not been well characterized. Because activities in the default mode network (DMN) reflect intrinsic brain functions that are closely associated with arousal regulation and cognition, alterations in the DMN could underlie cognitive effects related to PCE. With resting‐state and task activation functional magnetic resonance imaging (fMRI), this study investigated the possible PCE related changes in functional brain connectivity and brain activation in the DMN. In the resting state, the PCE group was found to have stronger functional connectivity in the DMN, as compared to the nonexposed controls. During a working memory task with emotional distracters, the PCE group exhibited less deactivation in the DMN and their fMRI signal was more increased by emotional arousal. These data revealed additional neural effects related to PCE, and consistent with previous findings, indicate that PCE may affect behavior and functioning by increasing baseline arousal and altering the excitatory/inhibitory balancing mechanisms involved in cognitive resource allocation. Hum Brain Mapp, 2011. © 2010 Wiley‐Liss, Inc.     

Lesion network mapping demonstrates that mind‐wandering is associated with the default mode network

Functional neuroimaging research has consistently associated brain structures within the default mode network (DMN) and frontoparietal network (FPN) with mind‐wandering. Targeted lesion research has documented impairments in mind‐wandering after damage to the medial prefrontal cortex (mPFC) and hippocampal regions associated with the DMN. However, no lesion studies to date have applied lesion network mapping to identify common networks associated with deficits in mind‐wandering. In lesion network mapping, resting‐state functional connectivity data from healthy participants are used to infer which brain regions are functionally connected to each lesion location from a sample with brain injury. In the current study, we conducted a lesion network mapping analysis to test the hypothesis that lesions affecting the DMN and FPN would be associated with diminished mind‐wandering. We assessed mind‐wandering frequency on the Imaginal Processes Inventory (IPI) in participants with brain injury (n = 29) and healthy comparison participants without brain injury (n = 19). Lesion network mapping analyses showed the strongest association of reduced mind‐wandering with the left inferior parietal lobule within the DMN. In addition, traditional lesion symptom mapping results revealed that reduced mind‐wandering was associated with lesions of the dorsal, ventral, and anterior sectors of mPFC, parietal lobule, and inferior frontal gyrus in the DMN (p < 0.05 uncorrected). These findings provide novel lesion support for the role of the DMN in mind‐wandering and contribute to a burgeoning literature on the neural correlates of spontaneous cognition.     

Default mode network modifications in Fabry disease: A resting‐state fMRI study with structural correlations

Aim of the study was to evaluate the presence of Default Mode Network (DMN) modifications in Fabry Disease (FD), and their possible correlations with structural alterations and neuropsychological scores. Thirty‐two FD patients with a genetically confirmed diagnosis of classical FD (12 males, mean age 43.3 ± 12.2) were enrolled, along with 35 healthy controls (HC) of comparable age and sex (14 males, mean age 42.1 ± 14.5). Resting‐State fMRI data were analyzed using a seed‐based approach, with six different seeds sampling the main hubs of the DMN. Structural modifications were assessed by means of Voxel‐Based Morphometry (VBM) and Tract‐Based Spatial Statistics analyses. Between‐group differences and correlations with neuropsychological variables were probed voxelwise over the whole brain. Possible correlations between FC modifications and global measures of microstructural alteration were also tested in FD patients with a partial correlation analysis. In the FD group, clusters of increased functional connectivity involving both supratentorial and infratentorial regions emerged, partially correlated to the widespread white matter (WM) damage found in these patients. No gray matter volume differences were found at VBM between the two groups. The connectivity between right inferior frontal gyrus and precuneus was significantly correlated with the Corsi block‐tapping test results (p = .0001). Widespread DMN changes are present in FD patients that correlate with WM alterations and cognitive performance. Our results confirm the current view of a cerebral involvement in FD patients not simply associated to major cerebrovascular events, but also related to significant and diffuse microstructural and functional changes.     

Functional–structural relationship in large‐scale brain networks of patients with end stage renal disease after kidney transplantation: A longitudinal study

It is unclear how the brain network changed after kidney transplantation (KT). We explored the patterns of large‐scale complex network after KT in end‐stage renal disease (ESRD) patients with resting‐state functional MRI (rs‐fMRI) and diffusion tensor imaging (DTI). Twenty‐one ESRD patients (14 men; mean age, 31.5 ± 9.9 years) scheduled for KT and 17 age‐ and gender‐matched healthy controls (HC) (8 men; mean age, 28.9 ± 7.2 years) were enrolled in this study. Each participant underwent rs‐fMRI and DTI scans in three time points (pre‐KT, 1 and 6 months after KT [for ESRD]). Graph theory analysis was used to characterize the topological properties by using functional and structural network connectivities intergroup correlation analysis was performed between functional/structural MR indexes and clinical markers. Compared with HC, pre‐KT ESRD patients showed an altered topological organization in both functional and structural networks. Compared with pre‐KT, increased node degree and node efficiency were observed for both functional and structural networks at 1 month after KT (all p < .05), which were further increased at 6 months after KT (p < .05). Both functional and structural networks did not recover completely at 6 months after KT (all p < .05). The patients showed an increased functional–structural connectivity coupling at 1 month after KT compared with HC (p = .041). A trend of progressive recovery of functional and structural connectivity networks was observed in ERSD patients after KT, which did not recover to the normal levels even in 6 months after KT. The study results underlie cognitive function recovery in ESRD patients following KT in the neuropathophysiological perspective.     

Disrupted thalamocortical connectivity in PSP: a resting-state fMRI, DTI, and VBM study

Progressive supranuclear palsy (PSP) is associated with pathological changes along the dentatorubrothalamic tract and in premotor cortex. We aimed to assess whether functional neural connectivity is disrupted along this pathway in PSP, and to determine how functional changes relate to changes in structure and diffusion. Eighteen probable PSP subjects and 18 controls had resting-state (task-free) fMRI, diffusion tensor imaging and structural MRI. Functional connectivity was assessed between thalamus and the rest of the brain, and within the basal ganglia, salience and default mode networks (DMN). Patterns of atrophy were assessed using voxel-based morphometry, and patterns of white matter tract degeneration were assessed using tract-based spatial statistics. Reduced in-phase functional connectivity was observed between the thalamus and premotor cortex including supplemental motor area (SMA), striatum, thalamus and cerebellum in PSP. Reduced connectivity in premotor cortex, striatum and thalamus were observed in the basal ganglia network and DMN, with subcortical salience network reductions. Tract degeneration was observed between cerebellum and thalamus and in superior longitudinal fasciculus, with grey matter loss in frontal lobe, premotor cortex, SMA and caudate nucleus. SMA functional connectivity correlated with SMA volume and measures of cognitive and motor dysfunction, while thalamic connectivity correlated with degeneration of superior cerebellar peduncles. PSP is therefore associated with disrupted thalamocortical connectivity that is associated with degeneration of the dentatorubrothalamic tract and the presence of cortical atrophy.     

Breakdown of the affective‐cognitive network in functional dystonia

Previous studies suggested that brain regions subtending affective‐cognitive processes can be implicated in the pathophysiology of functional dystonia (FD). In this study, the role of the affective‐cognitive network was explored in two phenotypes of FD: fixed (FixFD) and mobile dystonia (MobFD). We hypothesized that each of these phenotypes would show peculiar functional connectivity (FC) alterations in line with their divergent disease clinical expressions. Resting state fMRI (RS‐fMRI) was obtained in 40 FD patients (12 FixFD; 28 MobFD) and 43 controls (14 young FixFD‐age‐matched [yHC]; 29 old MobFD‐age‐matched [oHC]). FC of brain regions of interest, known to be involved in affective‐cognitive processes, and independent component analysis of RS‐fMRI data to explore brain networks were employed. Compared to HC, all FD patients showed reduced FC between the majority of affective‐cognitive seeds of interest and the fronto‐subcortical and limbic circuits; enhanced FC between the right affective‐cognitive part of the cerebellum and the bilateral associative parietal cortex; enhanced FC of the bilateral amygdala with the subcortical and posterior cortical brain regions; and altered FC between the left medial dorsal nucleus and the sensorimotor and associative brain regions (enhanced in MobFD and reduced in FixFD). Compared with yHC and MobFD patients, FixFD patients had an extensive pattern of reduced FC within the cerebellar network, and between the majority of affective‐cognitive seeds of interest and the sensorimotor and high‐order function (“cognitive”) areas with a unique involvement of dorsal anterior cingulate cortex connectivity. Brain FC within the affective‐cognitive network is altered in FD and presented specific features associated with each FD phenotype, suggesting an interaction between brain connectivity and clinical expression of the disease.     

Altered resting‐state connectivity during interictal generalized spike‐wave discharges in drug‐naïve childhood absence epilepsy

Purpose: To investigate the intrinsic brain connections at the time of interictal generalized spike‐wave discharges (GSWDs) to understand their mechanism of effect on brain function in untreated childhood absence epilepsy (CAE). Methods: The EEG‐functional MRI (fMRI) was used to measure the resting state functional connectivity during interictal GSWDs in drug‐naïve CAE, and three different brain networks—the default mode network (DMN), cognitive control network (CCN), and affective network (AN)—were investigated. Results: Cross‐correlation functional connectivity analysis with priori seed revealed decreased functional connectivity within each of these three networks in the CAE patients during interictal GSWDS. It included precuneus‐dorsolateral prefrontal cortex (DLPFC), dorsomedial prefrontal cortex (DMPFC), and inferior parietal lobule in the DMN; DLPFC‐inferior frontal junction (IFJ), and pre‐supplementary motor area (pre‐SMA) subregions connectivity disruption in CCN; ACC‐ventrolateral prefrontal cortex (VLPFC) and DMPFC in AN; There were also some regions, primarily the parahippcampus, paracentral in AN, and the left frontal mid orb in the CCN, which showed increased connectivity. Conclusions: The current findings demonstrate significant alterations of resting‐state networks in drug naïve CAE subjects during interictal GSWDs and interictal GSWDs can cause dysfunction in specific networks important for psychosocial function. Impairment of these networks may cause deficits both during and between seizures. Our study may contribute to the understanding of neuro‐pathophysiological mechanism of psychosocial function impairments in patients with CAE. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.     

Altered segregation between task-positive and task-negative regions in mild traumatic brain injury

Changes in large-scale brain networks that accompany mild traumatic brain injury (mTBI) were investigated using functional magnetic resonance imaging (fMRI) during the N-back working memory task at two cognitive loads (1-back and 2-back). Thirty mTBI patients were examined during the chronic stage of injury and compared to 28 control participants. Demographics and behavioral performance were matched across groups. Due to the diffuse nature of injury, we hypothesized that there would be an imbalance in the communication between task-positive and Default Mode Network (DMN) regions in the context of effortful task execution. Specifically, a graph-theoretic measure of modularity was used to quantify the extent to which groups of brain regions tended to segregate into task-positive and DMN sub-networks. Relative to controls, mTBI patients showed reduced segregation between the DMN and task-positive networks, but increased functional connectivity within the DMN regions during the more cognitively demanding 2-back task. Together, our findings reveal that patients exhibit alterations in the communication between and within neural networks during a cognitively demanding task. These findings reveal altered processes that persist through the chronic stage of injury, highlighting the need for longitudinal research to map the neural recovery of mTBI patients.     

Sex‐related differences in resting‐state brain activity and connectivity in the orbital frontal cortex and insula in patients with functional constipation

Functional magnetic resonance imaging (fMRI) has been used to investigate sex‐related differences in brain abnormalities in patients with irritable bowel syndrome (IBS). Like IBS, women with functional constipation (FC) are 2.1 times as many as men. No study has been performed yet to examine sex‐related differences in brain activity and connectivity in patients with FC. Here, we employed resting‐state fMRI with amplitude of low‐frequency fluctuation (ALFF) to investigate brain functional differences in 51 patients with FC (34 females) and 52 healthy controls (34 females). Results showed abdominal pain and abdominal distension correlated with trait (TAI) and state (SAI) anxiety ratings in the female FC group, and abdominal distension correlated with sensation of incomplete evacuation in the male FC group. Two‐way ANOVA revealed sex effects on ALFF in precentral gyrus, thalamus, insula (INS), and orbital frontal cortex (OFC, P_FWE < 0.05). Post hoc test showed that the female FC group had lower ALFF than males in these brain regions (P < 0.01), and ALFF in INS and OFC was correlated with abdominal pain and difficulty of defecation, respectively. Seed voxel correlation analysis showed that the female FC group had weaker connectivity than males between INS and lateral OFC (lOFC). INS‐lOFC connectivity was negatively correlated with the anxiety score in the female FC group and was negatively correlated with abdominal distension in the male FC group. These findings provide the first insight into sex‐related differences in patients with FC and highlight that INS and OFC play an important role in modulating the intrinsic functional connectivity of the resting brain network showing that this role is influenced by sex.     

Default mode network abnormalities in mesial temporal lobe epilepsy: A study combining fMRI and DTI

Studies of in mesial temporal lobe epilepsy (mTLE) patients with hippocampal sclerosis (HS) have reported reductions in both functional and structural connectivity between hippocampal structures and adjacent brain regions. However, little is known about the connectivity among the default mode network (DMN) in mTLE. Here, we hypothesized that both functional and structural connectivity within the DMN were disturbed in mTLE. To test this hypothesis, functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) were applied to examine the DMN connectivity of 20 mTLE patients, and 20 gender‐ and age‐matched healthy controls. Combining these two techniques, we explored the changes in functional (temporal correlation coefficient derived from fMRI) and structural (path length and connection density derived from DTI tractography) connectivity of the DMN. Compared to the controls, we found that both functional and structural connectivity were significantly decreased between the posterior cingulate cortex (PCC)/precuneus (PCUN) and bilateral mesial temporal lobes (mTLs) in patients. No significant between‐group difference was found between the PCC/PCUN and medial prefrontal cortex (mPFC). In addition, functional connectivity was found to be correlated with structural connectivity in two pairwise regions, namely between the PCC/PCUN and bilateral mTLs, respectively. Our results suggest that the decreased functional connectivity within the DMN in mTLE may be a consequence of the decreased connection density underpinning the degeneration of structural connectivity. Hum Brain Mapp, 2011. © 2010 Wiley‐Liss, Inc.     

Objective sleep disturbances are associated with greater waking resting-state connectivity between the retrosplenial cortex/hippocampus and various nodes of the default mode network

BackgroundPsychological models highlight the bidirectional role of self-referential processing, introspection, worry and rumination in the development and maintenance of insomnia; however, little is known about the underlying neural substrates. Default mode network (DMN) functional connectivity has been previously linked to these cognitive processes.MethodsWe used fMRI to investigate waking DMN functional connectivity in a well-characterized sample of patients with primary insomnia (PI) and good sleeper controls.ResultsWe included 20 patients with PI (8 men and 12 women, mean age 42.7 ± 13.4 yr) and 20 controls (8 men and 12 women, mean age 44.1 ± 10.6 yr) in our study. While no between-group differences in waking DMN connectivity were observed, exploratory analyses across all participants suggested that greater waking connectivity between the retrosplenial cortex/hippocampus and various nodes of the DMN was associated with lower sleep efficiency, lower amounts of rapid eye movement sleep and greater sleep-onset latency.LimitationsOwing to the cross-sectional nature of the study, conclusions about causality cannot be drawn.ConclusionAs sleep disturbances represent a transdiagnostic symptom that is characteristic of nearly all psychiatric disorders, our results may hold particular relevance to previous findings of increased DMN connectivity levels in patients with psychiatric disorders.     

Measuring vascular reactivity with breath‐holds after stroke: A method to aid interpretation of group‐level BOLD signal changes in longitudinal fMRI studies

Blood oxygenation level‐dependent (BOLD) contrast functional magnetic resonance imaging (fMRI) is a widely used technique to map brain function, and to monitor its recovery after stroke. Since stroke has a vascular etiology, the neurovascular coupling between cerebral blood flow and neural activity may be altered, resulting in uncertainties when interpreting longitudinal BOLD signal changes. The purpose of this study was to demonstrate the feasibility of using a recently validated breath‐hold task in patients with stroke, both to assess group level changes in cerebrovascular reactivity (CVR) and to determine if alterations in regional CVR over time will adversely affect interpretation of task‐related BOLD signal changes. Three methods of analyzing the breath‐hold data were evaluated. The CVR measures were compared over healthy tissue, infarcted tissue and the peri‐infarct tissue, both sub‐acutely (～2 weeks) and chronically (～4 months). In this cohort, a lack of CVR differences in healthy tissue between the patients and controls indicates that any group level BOLD signal change observed in these regions over time is unlikely to be related to vascular alterations. CVR was reduced in the peri‐infarct tissue but remained unchanged over time. Therefore, although a lack of activation in this region compared with the controls may be confounded by a reduced CVR, longitudinal group‐level BOLD changes may be more confidently attributed to neural activity changes in this cohort. By including this breath‐hold‐based CVR assessment protocol in future studies of stroke recovery, researchers can be more assured that longitudinal changes in BOLD signal reflect true alterations in neural activity. Hum Brain Mapp 36:1755–1771, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc .