Resting-state Functional Connectivity Studies Research Articles

Awake Rat Brain Functional Magnetic Resonance Imaging Using Standard Radio Frequency Coils and a 3D Printed Restraint Kit.

Functional magnetic resonance imaging (fMRI) is a powerful noninvasive tool for studying spontaneous resting state functional connectivity (RSFC) in laboratory animals. Brain function can be significantly affected by generally used anesthetics, however, rendering the need for awake imaging. Only a few different awake animal habituation protocols have been presented, and there is a critical need for practical and improved low-stress techniques. Here we demonstrate a novel restraint approach for awake rat RSFC studies. Our custom-made 3D printed restraint kit is compatible with a standard Bruker Biospin MRI rat bed, rat brain receiver coil, and volume transmitter coil. We also implemented a progressive habituation protocol aiming to minimize the stress experienced by the rats, and compared RSFC between awake, lightly sedated, and isoflurane-anesthetized rats. Our results demonstrated that the 3D printed restraint kit was suitable for RSFC studies of awake rats. During the short 4-day habituation period, the plasma corticosterone concentration, movement, and heart rate, which were measured as stress indicators, decreased significantly, indicating adaptation to the restraint protocol. Additionally, 10 days after the awake MRI session, rats exhibited no signs of depression or anxiety based on open-field and sucrose preference behavioral tests. The RSFC data revealed significant changes in the thalamo-cortical and cortico-cortical networks between the awake, lightly sedated, and anesthetized groups, emphasizing the need for awake imaging. The present work demonstrates the feasibility of our custom-made 3D printed restraint kit. Using this kit, we found that isoflurane markedly affected brain connectivity compared with that in awake rats, and that the effect was less pronounced, but still significant, when light isoflurane sedation was used instead.

Nonlinear neuroplasticity corresponding to sports experience: A voxel-based morphometry and resting-state functional connectivity study.

We aimed to investigate the structural neuroplasticity associated with different levels of sports experience and its effect on the corresponding resting-state functional circuitry. We recruited 18 skilled baseball batters (SB), 19 intermediate baseball batters (IB), and 17 healthy controls (HC), and used magnetic resonance imaging methods to compare their regional gray-matter volume (GMV) and seed-based resting-state functional connectivity (rsFC). Our results revealed that a quadratic function could better depict intergroup differences in regional GMV than a linear function. In particular, the IB showed lower or higher regional GMV than the other two groups. The difference in GMV in the supplementary motor area and areas belonging to the ventral stream, including the middle temporal gyrus and middle temporal pole, might be possibly related to baseball-specific motor and perceptual experience, such as inhibitory action control and pitch identification. On the other hand, the stronger rsFC seeded from the right middle temporal pole to the default mode network, particularly in the precuneus, in the SB and IB relative to that in the HC might be possibly associated with the theory of mind, such as deciding whether to swing or not against the pitcher by detecting the spatial information of pitches. In conclusion, our three-group design enabled the capture of the unique and transient changes that occur during the intermediate phase of expertise development. Our findings indicated that structural and functional brain changes do not necessarily linearly increase as a function of experience as previously suggested by the literature.

Resting-state functional connectivity in prefrontal cortex investigated by functional near-infrared spectroscopy: A longitudinal and cross-sectional study

Functional near-infrared spectroscopy (fNIRS) was used to investigate the stability of resting state functional connectivity (RSFC) in the prefrontal cortex. In a longitudinal study for investigating the stability of RSFC with time, we recruited 6 healthy adult subjects to undergo a 10-min resting state fNIRS scan once per day for 7 consecutive days. In a cross-sectional study, 62 healthy subjects underwent a single 10-min RSFC measurement. Three regions-of-interest (ROIs) were studied, the superior frontal gyrus (SFG), the middle frontal gyrus (MFG), and the inferior frontal gyrus (IFG). Homologous RSFC between the left and right hemisphere was computed for each ROI. The longitudinal RSFC study showed no significant variation with time in each ROI, implying that a one-time scan was sufficient for evaluating RSFC for an individual. The cross-sectional study showed significant difference in RSFC between SFG and MFG/IFG. Based on these observations, a lower bound of RSFC with an 85% confidence level for healthy adults was given for each gender: in IFG, 0.6894 (male) and 0.5392 (female), in MFG, 0.6487 (male) and 0.5713 (female), and in SFG: 0.8042(male) and 0.7436(female). To test ability of the lower bound to differentiate between healthy adults and adults with neurological disorders (showing weaker RSFC), 15 patients with affective disorders or sleep disorder were recruited for the resting state scan. The results showed that IFG was the most predictive ROI. This study may help to establish a quantitative range of RSFC for healthy adults and serve as a reference for screening patients with neurological disorders.

The Comorbidity Between Internet Gaming Disorder and Depression: Interrelationship and Neural Mechanisms.

Internet gaming disorder (IGD) is characterized by cognitive and emotional deficits. Previous studies have reported the co-occurrence of IGD and depression. However, extant brain imaging research has largely focused on cognitive deficits in IGD. Few studies have addressed the comorbidity between IGD and depression symptoms and underlying neural mechanisms. Here, we systematically investigated this issue by combining a longitudinal survey study, a cross-sectional resting-state functional connectivity (rsFC) study and an intervention study. Autoregressive cross-lagged modeling on a longitudinal dataset of college students showed that IGD severity and depression are reciprocally predictive. At the neural level, individuals with IGD exhibited enhanced rsFC between the left amygdala and right dorsolateral prefrontal cortex (DLPFC), inferior frontal and precentral gyrus, compared with control participants, and the amygdala-frontoparietal connectivity at the baseline negatively predicted reduction in depression symptoms following a psychotherapy intervention. Further, following the intervention, individuals with IGD showed decreased connectivity between the left amygdala and left middle frontal and precentral gyrus, as compared with the non-intervention group. These findings together suggest that IGD may be closely associated with depression; aberrant rsFC between emotion and executive control networks may underlie depression and represent a therapeutic target in individuals with IGD.Registry name: The behavioral and brain mechanism of IGD;URL: https://www.clinicaltrials.gov/ct2/show/NCT02550405;Registration number: NCT02550405.

O3.4. INCREASED ENGAGEMENT OF THE FRONTO-PARIETAL NETWORK AND DECREASED ENGAGEMENT OF THE DEFAULT-MODE – CINGULO-OPERCULAR – SENSORIMOTOR BETWEEN-NETWORK CONNECTIVITY IN FIRST-EPISODE PSYCHOSIS PATIENTS

BackgroundThe brain basis of psychotic disorders is still inadequately understood; however, evidence strongly suggests a central role of the dysfunctional integration of signaling between brain systems, i.e. “dysconnectivity”. Resting-state functional connectivity (FC) studies of chronic schizophrenia have revealed several illness-related, network-level changes. Patients have shown reduced modular structure, changes in the subcortical-cortical interactions, increased FC within the default-mode network (DMN) and reduced FC between fronto-parietal (FP) network components. Network-level changes in earlier stages of psychotic illnesses are less studied but DMN hyperconnectivity, loss of anticorrelation between task-positive and task-negative networks and both hypo- and hyper- corticostriatal connectivity have been reported in early and at-risk stages of psychosis. While studies using tasks and resting-state have yielded plenty of valuable information, regular fmri tasks capture only a narrow field of brain functioning and during rest, behavior may vary greatly between subjects. In this study we assessed subnetworks of first-episode psychosis (FEP) patients during processing of a movie stimulus that includes every-day-like rich variety of stimuli.MethodsWe recorded 3T fMRI of 71 FEP patients and 57 control subjects, recruited from the Helsinki Early Psychosis Study, while they watched scenes from the movie Alice in Wonderland (Tim Burton, 2010). We then constructed a network of 160 nodes based upon a meta-analysis of regions related to a wide range of cognitive and emotional processing, we extracted signal time courses from each node and created a 160x160 correlation matrix for each subject. Using GraphVar software, we first identified all pairs of nodes where FC was statistically significantly different between groups (p < 0.05, FDR-corrected for multiple comparisons) and then extracted Graph-Components, or subnetworks, in which all pairs of nodes are connected by significant links.ResultsWe identified a statistically significant subnetwork of 49 nodes with mainly decreased but also some increased links of FC in patients. Nodes that had a high number of decreased FC links in patients were mostly situated bilaterally in the medial prefrontal (mPFC) regions of the DMN and subcortical regions of the cingulo-opercular (CO) network, concentrated in the basal ganglia. The decreased FC links of the DMN were relatively wide-spread, connecting to some nodes within the DMN and several nodes of the CO and sensorimotor (SM) networks as well as the cerebellum. The decreased FC links of the basal ganglia were mainly connected to nodes of the SM network and the cerebellum. Patients had nodes with several links of increased FC mainly in the FP network, connecting to nodes within the FP as well as nodes of the CO network and the cerebellum.DiscussionOur results indicate that during naturalistic stimulus, network-level changes in FC are already present at the early stages of psychoses implicating similar networks and links as seen in earlier studies using resting state and simple stimuli in mainly chronic patients. However, we found the within FP as well as FP-CO connectivity to be increased in patients, seemingly contradicting earlier evidence of reduced FC between FP components. It would seem that during movie viewing patients engage more regions involved in attentional control (perhaps for compensatory purposes) whereas control subjects have stronger involvement of regions related to spontaneous cognition and high-order integration.

Intrinsic optical signal imaging of the blood volume changes is sufficient for mapping the resting state functional connectivity in the rodent cortex

Objective. Resting state functional connectivity (RSFC) allows the study of functional organization in normal and diseased brain by measuring the spontaneous brain activity generated under resting conditions. Intrinsic optical signal imaging (IOSI) based on multiple illumination wavelengths has been used successfully to compute RSFC maps in animal studies. The IOSI setup complexity would be greatly reduced if only a single wavelength can be used to obtain comparable RSFC maps. Approach. We used anesthetized mice and performed various comparisons between the RSFC maps based on single wavelength as well as oxy-, deoxy- and total hemoglobin concentration changes. Main results. The RSFC maps based on IOSI at a single wavelength selected for sensitivity to the blood volume changes are quantitatively comparable to the RSFC maps based on oxy- and total hemoglobin concentration changes obtained by the more complex IOSI setups. Moreover, RSFC maps do not require CCD cameras with very high frame acquisition rates, since our results demonstrate that they can be computed from the data obtained at frame rates as low as 5 Hz. Significance. Our results will have general utility for guiding future RSFC studies based on IOSI and making decisions about the IOSI system designs.

Resting-state thalamic dysconnectivity in schizophrenia and relationships with symptoms.

Schizophrenia (SZ) is a severe neuropsychiatric disorder associated with disrupted connectivity within the thalamic-cortico-cerebellar network. Resting-state functional connectivity studies have reported thalamic hypoconnectivity with the cerebellum and prefrontal cortex as well as thalamic hyperconnectivity with sensory cortical regions in SZ patients compared with healthy comparison participants (HCs). However, fundamental questions remain regarding the clinical significance of these connectivity abnormalities. Resting state seed-based functional connectivity was used to investigate thalamus to whole brain connectivity using multi-site data including 183 SZ patients and 178 matched HCs. Statistical significance was based on a voxel-level FWE-corrected height threshold of p < 0.001. The relationships between positive and negative symptoms of SZ and regions of the brain demonstrating group differences in thalamic connectivity were examined. HC and SZ participants both demonstrated widespread positive connectivity between the thalamus and cortical regions. Compared with HCs, SZ patients had reduced thalamic connectivity with bilateral cerebellum and anterior cingulate cortex. In contrast, SZ patients had greater thalamic connectivity with multiple sensory-motor regions, including bilateral pre- and post-central gyrus, middle/inferior occipital gyrus, and middle/superior temporal gyrus. Thalamus to middle temporal gyrus connectivity was positively correlated with hallucinations and delusions, while thalamus to cerebellar connectivity was negatively correlated with delusions and bizarre behavior. Thalamic hyperconnectivity with sensory regions and hypoconnectivity with cerebellar regions in combination with their relationship to clinical features of SZ suggest that thalamic dysconnectivity may be a core neurobiological feature of SZ that underpins positive symptoms.

Aberrant hemodynamic responses in autism: Implications for resting state fMRI functional connectivity studies.

Functional MRI (fMRI) is modeled as a convolution of the hemodynamic response function (HRF) and an unmeasured latent neural signal. However, HRF itself is variable across brain regions and subjects. This variability is induced by both neural and non-neural factors. Aberrations in underlying neurochemical mechanisms, which control HRF shape, have been reported in autism spectrum disorders (ASD). Therefore, we hypothesized that this will lead to voxel-specific, yet systematic differences in HRF shape between ASD and healthy controls. As a corollary, we also hypothesized that such alterations will lead to differences in estimated functional connectivity in fMRI space compared to latent neural space. To test these hypotheses, we performed blind deconvolution of resting-state fMRI time series acquired from large number of ASD and control subjects obtained from the Autism Brain Imaging Data Exchange (ABIDE) database (N = 1102). Many brain regions previously implicated in autism showed systematic differences in HRF shape in ASD. Specifically, we found that precuneus had aberrations in all HRF parameters. Consequently, we obtained precuneus-seed-based functional connectivity differences between ASD and controls using fMRI as well as using latent neural signals. We found that non-deconvolved fMRI data failed to detect group differences in connectivity between precuneus and certain brain regions that were instead observed in deconvolved data. Our results are relevant for the understanding of hemodynamic and neurochemical aberrations in ASD, as well as have methodological implications for resting-state functional connectivity studies in Autism, and more generally in disorders that are accompanied by neurochemical alterations that may impact HRF shape.

A pilot resting-state functional connectivity study of the kynurenine pathway in adolescents with depression and healthy controls

BackgroundThe neuroimmunological kynurenine pathway (KP) has been hypothesized to play a role in depressive/anhedonic symptoms and related CNS disturbances. Indoleamine 2,3-dioxygenase (IDO) is the rate limiting enzyme which leads to neurotrophic [kynurenic acid (KA)] and neurotoxic [Quinolinic acid (QUIN)] branches. In this pilot, we sought to examine associations between blood KP neuro-toxic/trophic measures and anhedonia/depression associated networks in youth with major depression (MDD) and healthy controls (HC). MethodsSubjects were 14 psychotropic-medication free adolescents with MDD and 7 HC, ages 12–19 yo. All underwent resting-state functional magnetic resonance imagining (fMRI) scans. Voxel-wise maps were generated indicating correlation strengths among 4 bilateral seeds [(dorsal anterior cingulate cortex (dACC), perigenual ACC (pgACC), subgenual ACC (sgACC) and nucleus accumbens (NAc)] and remaining brain regions. FMRI analyses were family-wise error corrected. KP metabolites were measured using liquid chromatography–tandem mass spectrometry. ResultsConnectivity between the right dACC and the right precuneus was positively correlated with KA levels. This same cluster demonstrated an inverse correlation with IDO activity. Exploratory analysis at a more liberal clustering threshold showed the KA/QUIN ratio was positively correlated with connectivity between the pgACC and the right medial prefrontal cortex. Lastly, connectivity between the pgACC and the left inferior temporal gyrus was positively correlated with QUIN levels. LimitationsFindings are preliminary due to the small sample size. ConclusionsThis pilot study is the first report in depressed adolescents demonstrating associations between the KP and anhedonia/depression-associated brain networks. This pilot adds evidence to the putative role of the KP in MDD.

1.23 A Pilot Resting State Functional Connectivity Study of the Kynurenine Pathway in Adolescents With Depression and Healthy Controls

The neuroimmunological kynurenine pathway (KP) has been hypothesized to play a role in depressive/anhedonic symptoms and related central nervous system disturbances. Indoleamine 2,3-dioxygenase (IDO) is the rate limiting enzyme which leads to neurotrophic [kynurenic acid (KA)] and neurotoxic [quinolinic acid (QUIN)] branches. In this pilot, we sought to examine associations between blood KP neuro-toxic/trophic measures and an anhedonia/depression associated network in youth with MDD and healthy controls (HC).

Dual-echo ASL contributes to decrypting the link between functional connectivity and cerebral blow flow.

Arterial spin labeling (ASL) MRI with a dual-echo readout module (DE-ASL) enables noninvasive simultaneous acquisition of cerebral blood flow (CBF)-weighted images and blood oxygenation level dependent (BOLD) contrast. Up to date, resting-state functional connectivity (FC) studies based on CBF fluctuations have been very limited, while the BOLD is still the method most frequently used. The purposes of this technical report were (i) to assess the potentiality of the DE-ASL sequence for the quantification of resting-state FC and brain organization, with respect to the conventional BOLD (cvBOLD) and (ii) to investigate the relationship between a series of complex network measures and the CBF information. Thirteen volunteers were scanned on a 3T scanner acquiring a pseudocontinuous multislice DE-ASL sequence, from which the concomitant BOLD (ccBOLD) simultaneously to the ASL can be extracted. In the proposed comparison, the brain FC and graph-theoretical analysis were used for quantifying the connectivity strength between pairs of regions and for assessing the network model properties in all the sequences. The main finding was that the ccBOLD part of the DE-ASL sequence provided highly comparable connectivity results compared to cvBOLD. As expected, because of its different nature, ASL sequence showed different patterns of brain connectivity and graph indices compared to BOLD sequences. To conclude, the resting-state FC can be reliably detected using DE-ASL, simultaneously to CBF quantifications, whereas a single fMRI experiment precludes the quantitative measurement of BOLD signal changes. Hum Brain Mapp 38:5831-5844, 2017. © 2017 Wiley Periodicals, Inc.

Electroencephalography Source Functional Connectivity Reveals Abnormal High-Frequency Communication Among Large-Scale Functional Networks in Depression

BackgroundFunctional magnetic resonance imaging studies of resting-state functional connectivity have shown that major depressive disorder (MDD) is characterized by increased connectivity within the default mode network (DMN) and between the DMN and the frontoparietal network (FPN). However, much remains unknown about abnormalities in higher frequency (>1 Hz) synchronization. Findings of abnormal synchronization in specific frequencies would contribute to a better understanding of the potential neurophysiological origins of disrupted functional connectivity in MDD. MethodsWe used the high temporal resolution of electroencephalography to compare the spectral properties of resting-state functional connectivity in individuals with MDD (n = 65) with healthy control subjects (n = 79) and examined the extent to which connectivity disturbances were evident in a third sample of individuals in remission from depression (n = 30). Exact low resolution electromagnetic tomography was used to compute intracortical activity from regions within the DMN and FPN, and functional connectivity was computed using lagged phase synchronization. ResultsCompared to control subjects, the MDD group showed greater within-DMN beta 2 band (18.5–21 Hz) connectivity and greater beta 1 band (12.5–18 Hz) connectivity between the DMN and FPN. This hyperconnectivity was not observed in the remitted MDD group. However, greater beta 1 band DMN–FPN connectivity was associated with more frequent depressive episodes since first depression onset, even after controlling for current symptom severity. ConclusionsThese findings extend our understanding of the neurophysiological basis of abnormal resting-state functional connectivity in MDD and indicate that elevations in high-frequency DMN–FPN connectivity may be a neural marker linked to a more recurrent illness course.

Neural substrates underlying balanced time perspective: A combined voxel-based morphometry and resting-state functional connectivity study

Balanced time perspective (BTP), which is defined as a mental ability to switch flexibly among different time perspectives Zimbardo and Boyd (1999), has been suggested to be a central component of positive psychology Boniwell and Zimbardo (2004). BTP reflects individual's cognitive flexibility towards different time frames, which leads to many positive outcomes, including positive mood, subjective wellbeing, emotional intelligence, fluid intelligence, and executive control. However, the neural basis of BTP is still unclear. To address this question, we quantified individual's deviation from the BTP (DBTP), and investigated the neural substrates of DBTP using both voxel-based morphometry (VBM) and resting-state functional connectivity (RSFC) methods VBM analysis found that DBTP scores were positively correlated with gray matter volume (GMV) in the ventral precuneus. We further found that DBTP scores were negatively associated with RSFCs between the ventral precuneus seed region and medial prefrontal cortex (mPFC), bilateral temporoparietal junction (TPJ), parahippocampa gyrus (PHG), and middle frontal gyrus (MFG). These brain regions found in both VBM and RSFC analyses are commonly considered as core nodes of the default mode network (DMN) that is known to be involved in many functions, including episodic and autobiographical memory, self-related processing, theory of mind, and imagining the future. These functions of the DMN are also essential to individuals with BTP. Taken together, we provide the first evidence for the structural and functional neural basis of BTP, and highlight the crucial role of the DMN in cultivating an individual's BTP.

Sex Differences in Brain Regions Modulating Pain Among Older Adults: A Cross-Sectional Resting State Functional Connectivity Study.

A long-standing hypothesis is that when compared with males, females may be at increased risk of experiencing greater pain sensitivity and unpleasantness. The purpose of this study was to examine sex differences in pain psychophysics and resting state functional connectivity (RSFC) in core pain regions in an age- and sex-matched sample of healthy older adults. Between groups, cross-sectional. Vanderbilt University and Medical Center. The sample in the analyses reported here consisted of 19 cognitively intact males matched with 19 cognitively intact females of similar ages (median ages: females = 70 years, males = 68 years). Psychophysical assessment of experimental thermal pain and RSFC. There were no significant differences in perceptual thresholds or unpleasantness ratings in response to thermal stimuli. Older males showed greater RSFC between the affective and sensory networks and between affective and descending modulatory networks. Conversely, older females showed greater RSFC between the descending modulatory network and both sensory and affective networks. The strongest evidence for sex differences emerged in the associations of thermal pain with RSFC between the anterior cingulate cortex (ACC) and amygdala and between the ACC and periaqueductal gray matter in older females relative to older males. We found no differences in pain sensitivity or pain affect between older males and older females. Additionally, we found that older females exhibited a greater association between thermal pain sensitivity and RSFC signal between regions typically associated with pain affect and the descending modulatory system. One interpretation of these findings is that older females may better engage the descending pain modulatory system. This better engagement possibly translates into older females having similar perceptual thresholds for temperature sensitivity and unpleasantness associated with mild and moderate pain. These findings contrast with studies demonstrating that younger females find thermal pain more sensitive and more unpleasant.

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

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

Fronto-limbic disconnection in depressed patients with suicidal ideation: A resting-state functional connectivity study

BackgroundSuicidal ideation (SI) is highly prevalent and a known symptom of Major Depressive Disorder (MDD), but its underlying biological mechanisms are relatively unknown. Several studies linked suicidal ideation to dysfunctional brain circuits, specifically fronto-limbic connections. The purpose of this work was to investigate fronto-limbic disconnection in MDD patients with or without SI. MethodsMDD patients with SI (SI, n=28) or without SI (NSI, n=20), identified by the Scale for Suicide Ideation and healthy controls (HCs, n=30) underwent resting-state functional MRI scanning. The functional properties of correlations in neural activity (intrinsic functional connectivity, iFC) of the rostral anterior cingulate cortex (rACC) were analyzed among the three groups. Furthermore, correlation analyses between iFC, SI severity and depression severity were performed. ResultsWe found that the SI group exhibited decreased iFC between the rACC, the orbitomedial prefrontal cortex and the right middle temporal pole compared to HCs and NSI groups. The NSI group showed decreased iFC between the rACC and the orbitomedial prefrontal cortex compared to HCs. In the SI group, iFC strength between the right rACC and the middle temporal pole positively correlated with SI severity. ConclusionTransdiagnostic and diagnosis-specific alterations of fronto-limbic iFC were found in MDD patients with or without SI. Disrupted fronto-limbic circuits may impact decision-making and emotional processing in SI. These results provide useful information about the pathophysiological mechanisms of MDD patients with SI.

Risperidone Effects on Brain Dynamic Connectivity-A Prospective Resting-State fMRI Study in Schizophrenia.

Resting-state functional connectivity studies in schizophrenia evaluating average connectivity over the entire experiment have reported aberrant network integration, but findings are variable. Examining time-varying (dynamic) functional connectivity may help explain some inconsistencies. We assessed dynamic network connectivity using resting-state functional MRI in patients with schizophrenia, while unmedicated (n = 34), after 1 week (n = 29) and 6 weeks of treatment with risperidone (n = 24), as well as matched controls at baseline (n = 35) and after 6 weeks (n = 19). After identifying 41 independent components (ICs) comprising resting-state networks, sliding window analysis was performed on IC timecourses using an optimal window size validated with linear support vector machines. Windowed correlation matrices were then clustered into three discrete connectivity states (a relatively sparsely connected state, a relatively abundantly connected state, and an intermediately connected state). In unmedicated patients, static connectivity was increased between five pairs of ICs and decreased between two pairs of ICs when compared to controls, dynamic connectivity showed increased connectivity between the thalamus and somatomotor network in one of the three states. State statistics indicated that, in comparison to controls, unmedicated patients had shorter mean dwell times and fraction of time spent in the sparsely connected state, and longer dwell times and fraction of time spent in the intermediately connected state. Risperidone appeared to normalize mean dwell times after 6 weeks, but not fraction of time. Results suggest that static connectivity abnormalities in schizophrenia may partly be related to altered brain network temporal dynamics rather than consistent dysconnectivity within and between functional networks and demonstrate the importance of implementing complementary data analysis techniques.

Connectivity of precuneus to the default mode and dorsal attention networks: A possible invariant marker of long-term tinnitus.

Resting state functional connectivity studies of tinnitus have provided inconsistent evidence concerning its neural bases. This may be due to differences in the methodology used, but it is also likely related to the heterogeneity of the tinnitus population. In this study, our goal was to identify resting state functional connectivity alterations that consistently appear across tinnitus subgroups. We examined two sources of variability in the subgroups: tinnitus severity and the length of time a person has had chronic tinnitus (referred to as tinnitus duration). Data for the current large-scale analysis of variance originated partly from our earlier investigations (Schmidt et al., 2013; Carpenter-Thompson et al., 2015) and partly from previously unpublished studies. Decreased correlations between seed regions in the default mode network and the precuneus were consistent across individuals with long-term tinnitus (who have had tinnitus for greater than one year), with more bothersome tinnitus demonstrating stronger decreases. In the dorsal attention network, patients with moderately severe tinnitus showed increased correlations between seeds in the network and the precuneus, with this effect also present in only some patients with mild tinnitus. The same effects were not seen in patients with mild tinnitus and tinnitus duration between 6 and 12 months. Our results are promising initial steps towards identifying invariant neural correlates of tinnitus and indexing differences between subgroups.

State-dependent modulation of functional connectivity in early blind individuals

Resting-state functional connectivity (RSFC) studies have provided strong evidences that visual deprivation influences the brain's functional architecture. In particular, reduced RSFC coupling between occipital (visual) and temporal (auditory) regions has been reliably observed in early blind individuals (EB) at rest. In contrast, task-dependent activation studies have repeatedly demonstrated enhanced co-activation and connectivity of occipital and temporal regions during auditory processing in EB. To investigate this apparent discrepancy, the functional coupling between temporal and occipital networks at rest was directly compared to that of an auditory task in both EB and sighted controls (SC). Functional brain clusters shared across groups and cognitive states (rest and auditory task) were defined. In EBs, we observed higher occipito-temporal correlations in activity during the task than at rest. The reverse pattern was observed in SC. We also observed higher temporal variability of occipito-temporal RSFC in EB suggesting that occipital regions in this population may play the role of a multiple demand system. Our study reveals how the connectivity profile of sighted and early blind people is differentially influenced by their cognitive state, bridging the gap between previous task-dependent and RSFC studies. Our results also highlight how inferring group-differences in functional brain architecture solely based on resting-state acquisition has to be considered with caution.

Abnormal resting-state functional connectivity study in unilateral pulsatile tinnitus patients with single etiology: A seed-based functional connectivity study

ObjectivePrevious studies demonstrated altered regional neural activations in several brain areas in patients with pulsatile tinnitus (PT), especially indicating an important role of posterior cingulate cortex (PCC). However, few studies focused on the degree of functional connectivity (FC) of this area in PT patients. In this study, we will compare the FC of PCC in patients affected with this condition and normal controls by using resting-state functional magnetic resonance imaging (fMRI). MethodsStructural and functional MRI data were obtained from 36 unilateral PT patients with single etiology and 36 matched healthy controls. FC feature of the region of interest (PCC) were characterized using a seed-based correlation method with the voxels in the whole-brain. ResultsCompared with healthy controls, patients showed significant decreased FC to the right middle temporal gyrus (MTG), right thalamus and bilateral insula. By contrast, PCC demonstrated increased functional connectivity between the precuneus, bilateral inferior parietal lobule and middle occipital gyrus. We also found correlations between the disease duration of PT and FC of PCC-right MTG (r=−0.616, p<0.001). ConclusionsUnilateral PT patients could have abnormal FC to the PCC bilaterally in the brain. PCC, as a highly integrated brain area, is an example of nucleus that was involved in mediation between different neural networks. It might be a modulation core between visual network and auditory network. The decreased FC of MTG to PCC may indicate a down regulation of activity between PCC and auditory associated brain cortex. Decreased FC between limbic system (bilateral AI) and PCC may reflect the emotional message control in patient group. This study facilitated understanding of the underlying neuropathological process in patients with pulsatile tinnitus.