State fMRI Research Articles

Prevalent and sex-biased breathing patterns modify functional connectivity MRI in young adults

Resting state functional connectivity magnetic resonance imaging (fMRI) is a tool for investigating human brain organization. Here we identify, visually and algorithmically, two prevalent influences on fMRI signals during 440 h of resting state scans in 440 healthy young adults, both caused by deviations from normal breathing which we term deep breaths and bursts. The two respiratory patterns have distinct influences on fMRI signals and signal covariance, distinct timescales, distinct cardiovascular correlates, and distinct tendencies to manifest by sex. Deep breaths are not sex-biased. Bursts, which are serial taperings of respiratory depth typically spanning minutes at a time, are more common in males. Bursts share features of chemoreflex-driven clinical breathing patterns that also occur primarily in males, with notable neurological, psychiatric, medical, and lifespan associations. These results identify common breathing patterns in healthy young adults with distinct influences on functional connectivity and an ability to differentially influence resting state fMRI studies.

Investigation of Functional Connectivity Differences between Voluntary Respirations via Mouth and Nose Using Resting State fMRI.

The problems of mouth breathing have been well-studied, but the neural correlates of functional connectivity (FC) still remain unclear. We examined the difference in FC between the two types of breathing. For our study, 21 healthy subjects performed voluntary mouth and nasal breathing conditions during a resting state functional magnetic resonance imaging (fMRI). The region of interest (ROI) analysis of FC in fMRI was conducted using a MATLAB-based imaging software. The resulting analysis showed that mouth breathing had widespread connections and more left lateralization. Left inferior temporal gyrus had the most left lateralized connections in mouth breathing condition. Furthermore, the central opercular cortex FC showed a significant relationship with mouth breathing. For nasal breathing, the sensorimotor area had symmetry FC pattern. These findings suggest that various FCs difference appeared between two breathing conditions. The impacts of these differences need to be more investigated to find out potential link with cognitive decline in mouth breathing syndrome.

Functional parcellation of the hippocampus by semi-supervised clustering of resting state fMRI data

Many unsupervised methods are widely used for parcellating the brain. However, unsupervised methods aren’t able to integrate prior information, obtained from such as exiting functional neuroanatomy studies, to parcellate the brain, whereas the prior information guided semi-supervised method can generate more reliable brain parcellation. In this study, we propose a novel semi-supervised clustering method for parcellating the brain into spatially and functionally consistent parcels based on resting state functional magnetic resonance imaging (fMRI) data. Particularly, the prior supervised and spatial information is integrated into spectral clustering to achieve reliable brain parcellation. The proposed method has been validated in the hippocampus parcellation based on resting state fMRI data of 20 healthy adult subjects. The experimental results have demonstrated that the proposed method could successfully parcellate the hippocampus into head, body and tail parcels. The distinctive functional connectivity patterns of these parcels have further demonstrated the validity of the parcellation results. The effects of aging on the three hippocampus parcels’ functional connectivity were also explored across the healthy adult subjects. Compared with state-of-the-art methods, the proposed method had better performance on functional homogeneity. Furthermore, the proposed method had good test–retest reproducibility validated by parcellating the hippocampus based on three repeated resting state fMRI scans from 24 healthy adult subjects.

Alteration of Resting-state Functional Connectivity in the Sensorimotor Network in Patients with Thalamic Infarction.

To explore changes in functional connectivity (FC) within the sensorimotor network (SMN) and the relationship between the SMN and bilateral thalamus in patients with thalamic infarction (TI) using resting state functional magnetic resonance imaging (rs-fMRI). Also determined was whether those measures are useful for monitoring the functional recovery of somatosensory deficits. The study included 31 patients with TI presenting somatosensory dysfunction and 31 controls who underwent clinical assessments and MRI scanning at 6 months after a stroke. An independent component analysis was used to identify the SMN. The mean time courses of SMN activity were extracted for each subject, and FC with the bilateral thalamus was assessed. Differences in connectivity strength were compared between groups. Finally, we correlated the altered FC values with clinical data from patients with TI. Compared to controls, patients with TI showed decreases in FC within SMN in the ipsilesional posterior central gyrus (PCG) (Z-score = -4.581, cluster size = 171), but presented increased FC within the SMN in the ipsilesional supplementary motor area (SMA) (Z-score = 4.648, cluster size = 46). The FC values of the ipsilesional SMA correlated with the somatosensory function score of patients with TI (r = 0.426, P = 0.027). Increased FC was observed between the SMN and bilateral thalamus in patients with TI. The region exhibiting increased FC was adjacent to the lesion in the affected thalamus, while the area with increased FC overlapped the location of the lesion when the lesion was mirrored onto the unaffected thalamus. The increased FC in the ipsilesional SMA and between the SMN and perilesional thalamus might reflect functional reorganization in patients with TI presenting somatosensory deficits.

Experimental trauma rapidly modifies functional connectivity

Traumatic events can produce emotional, cognitive and autonomous physical responses. This may ultimately lead to post-traumatic stress disorder (PTSD), a psychiatric syndrome which requires comprehensive treatment. Trauma exposure alters functional connectivity; however, onset and nature of these changes are unknown. Here, we explore functional connectivity changes at rest directly after experimental trauma exposure. Seventy-three healthy subjects watched either a trauma or a control film. Resting state functional magnetic resonance imaging measurements were conducted before and directly after the film. Seed-based analyses revealed trauma-related changes in functional connectivity, specifically including decreases of connectivity between amygdala and middle temporal gyrus and increases between hippocampus and precuneus. These central effects were accompanied by trauma-related increases in heart rate. Moreover, connectivity between the amygdala and middle temporal gyrus predicted subsequent trauma-related valence. Our results demonstrate rapid functional connectivity changes in memory-related brain regions at rest after experimental trauma, selectively relating to changes in emotions evoked by the trauma manipulation. Results could represent an early predictive biomarker for the development of trauma-related PTSD and thus provide an indication for the need of early targeted preventive interventions.

Characteristics of resting state functional magnetic resonance imaging in tinnitus patients with different degrees of affective disorder

Objective:To analyze the correlation of the degree of affective disorder and brain function changes by comparing the differences of resting-state functional Magnetic Resonance Imaging（rs-fMRI） between healthy volunteers without tinnitus and patients with tinnitus. Method:A analysis of 19 patients with tinnitus and 15 healthy volunteers without tinnitus. The patients were divided into mild group and severe group according to tinnitus handicap inventory（THI）. Rs-fMRI was collected and the regional homogeneity（ReHo） analysis, amplitude of low-frequency fluctuation（ALFF） analysis, and fractional amplitude of low frequency fluctuation（fALFF） analysis of rs-fMRI were performed by DPABI software. Two-sample t-test of the ReHo value, ALFF value and fALFF value between the mild group and the control group, the severe group and the control group, were performed respectively. Result:The fALFF value of the left occipital gyrus in the mild group was higher than that in the control group, the difference was statistically significant（P<0.05）, but there is no statistically significant difference of ALFF value and ReHo value between two groups. The ALFF value of the middle temporal gyrus（left）, superior frontal gyrus（right）, inferior frontal gyrus pars triangularis（left） and caudate nucleus（left） in the severe group were higher than those of the control group. But there was no significant difference in the fALFF value and the ReHo value. Conclusion:Different severity of affective disorder in patients with tinnitus have different areas of brain function abnormalities. Mild group was detected by fALFF analysis and the active brain area was the left middle occipital region. Severe group was detected by ALFF analysis. The active brain regions were left middle temporal gyrus, right superior frontal gyrus, left inferior frontal gyrus pars triangularis, and left caudate nucleus.

Alertness fluctuations when performing a task modulate cortical evoked responses to transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS) has been widely used in human cognitive neuroscience to examine the causal role of distinct cortical areas in perceptual, cognitive and motor functions. However, it is widely acknowledged that the effects of focal cortical stimulation can vary substantially between participants and even from trial to trial within individuals. Recent work from resting state functional magnetic resonance imaging (fMRI) studies has suggested that spontaneous fluctuations in alertness over a testing session can modulate the neural dynamics of cortical processing, even when participants remain awake and responsive to the task at hand. Here we investigated the extent to which spontaneous fluctuations in alertness during wake-to-sleep transition can account for the variability in neurophysiological responses to TMS. We combined single-pulse TMS with neural recording via electroencephalography (EEG) to quantify changes in motor and cortical reactivity with fluctuating levels of alertness defined objectively on the basis of ongoing brain activity. We observed rapid, non-linear changes in TMS-evoked responses with decreasing levels of alertness, even while participants remained responsive in the behavioural task. Specifically, we found that the amplitude of motor evoked potentials peaked during periods of EEG flattening, whereas TMS-evoked potentials increased and remained stable during EEG flattening and the subsequent occurrence of theta ripples that indicate the onset of NREM stage 1 sleep. Our findings suggest a rapid and complex reorganization of active neural networks in response to spontaneous fluctuations of alertness over relatively short periods of behavioural testing during wake-to-sleep transition.

Functional connectivity of the anterior cingulate cortex in Veterans with mild traumatic brain injury

BackgroundTraumatic brain injury (TBI) is one of the most prevalent injuries in the military with mild traumatic brain injury (mTBI) accounting for approximately 70–80 % of all TBI. TBI has been associated with diffuse and focal brain changes to structures and networks underlying cognitive-emotional processing. Although the anterior cingulate cortex (ACC) plays a critical role in emotion regulation and executive function and is susceptible to mTBI, studies focusing on ACC resting state functional connectivity (rs-fc) in Veterans are limited. MethodsVeterans with mTBI (n = 49) and with no history of TBI (n = 25), ages 20–54 completed clinical assessments and an 8-minute resting state functional magnetic resonance imaging (rs-fMRI) on a 3 T Siemens scanner. Imaging results were analyzed with left and right ACC as seed regions using SPM8. Regression analyses were performed with time since injury. ResultsSeed-based analysis showed increased connectivity of the left and right ACC with brain regions including middle and posterior cingulate regions, preceneus, and occipital regions in the mTBI compared to the non-TBI group. ConclusionsThe rs-fMRI results indicate hyperconnectivity in Veterans with mTBI. These results are consistent with previous studies of recently concussed athletes showing ACC hyperconnectivity. Enhanced top-down control of attention networks necessary to compensate for the microstructural damage following mTBI may explain ACC hyperconnectivity post-mTBI.

The migraineur's brain networks: Continuous resting state fMRI over 30 days.

The aim of the current study was to identify typical alterations in resting state connectivity within different stages of the migraine cycle and to thus explore task-free mechanisms of headache attack generation in migraineurs. Recent evidence in migraine pathophysiology suggests that hours and even days before headache certain changes in brain activity take place, ultimately leading to an attack. Here, we investigate changes before headache onset using resting state functional magnetic resonance imaging (fMRI). Nine episodic migraineurs underwent daily resting state functional magnetic resonance imaging for a minimum period of 30 consecutive days, leading to a cumulative number of 282 total days scanned. Thus, data from 15 spontaneous headache attacks were acquired. This allows analysing not only the ictal and the interictal phase of migraine but also the preictal phase. ROI-to-ROI (region of interest) and ROI-to-voxel connectivity was calculated over the migraine cycle. Within the ROI-to-ROI analysis, the right nucleus accumbens showed enhanced functional connectivity to the left amygdala, hippocampus and gyrus parahippocampalis in the preictal phase compared to the interictal phase. ROI-to-voxel connectivity of the right accumbens with the dorsal rostral pons was enhanced during the preictal phase compared to interictally. Regarding custom defined ROIs, the dorsal pons was ictally functionally more strongly coupled to the hypothalamic area than interictally. This unique data set suggests that particularly connectivity changes in dopaminergic centres and between the dorsal pons and the hypothalamus are important within migraine attack generation and sustainment.

Identifying the brain's connector hubs at the voxel level using functional connectivity overlap ratio

Neuroimaging studies have shown that the brain is functionally organized into several large-scale brain networks. Within these networks are regions that are widely connected to several other regions within and/or outside the network. Regions that connect to several other networks, known as connector hubs, are believed to be crucial for information transfer and between-network communication within the brain. To identify regions with high between-network connectivity at the voxel level, we introduced a novel metric called functional connectivity overlap ratio (FCOR), which quantifies the spatial extent of a region's connection to a given network. Using resting state functional magnetic resonance imaging data, FCOR maps were generated for several well-known large-scale resting state networks (RSNs) and used to examine the relevant associations among different RSNs, identify connector hub regions in the cerebral cortex, and elucidate the hierarchical functional organization of the brain. Constructed FCOR maps revealed a strong association among the core neurocognitive networks (default mode, salience, and executive control) as well as among primary processing networks (sensorimotor, auditory, and visual). Prominent connector hubs were identified in the bilateral middle frontal gyrus, posterior cingulate, lateral parietal, middle temporal, dorsal anterior cingulate, and anterior insula, among others, regions mostly associated with the core neurocognitive networks. Finally, clustering the whole brain using FCOR features yielded a topological organization that arranges brain regions into a hierarchy of information processing systems with the primary processing systems at one end and the heteromodal systems comprising connector hubs at the other end.

The effects of Alzheimer's disease related striatal pathologic changes on the fractional amplitude of low-frequency fluctuations

This paper aims to correlate Alzheimer's disease (AD) related striatal pathologic changes with the fractional amplitude of low-frequency fluctuations (fALLF) in the blood oxygenation level-dependent (BOLD) signal in the resting state functional Magnetic Resonance Imaging (rs-fMRI). A dopamine modulated Izikhevich neuron model based network of striatum region is constructed. Balloon–Windkessel hemodynamic model is used to obtain BOLD signals. fALFF differences between two frequency bands (slow-5:0.01–0.027 Hz; slow-4:0.027–0.073 Hz) are investigated in the case of dopamine depletion, decrease in the synaptic connectivity and the input from cortical and thalamic region, assumed that they are the degenerations occurring in AD.

Changes in Intrinsic Brain Connectivity in Family-Focused Therapy Versus Standard Psychoeducation Among Youths at High Risk for Bipolar Disorder

We compared intrinsic network connectivity in symptomatic youths at high risk (HR) for bipolar disorder (BD) and healthy comparison (HC) youths. In HR youths, we also investigated treatment-related changes in intrinsic connectivity after family-focused therapy for high-risk youths (FFT-HR) vs standardized family psychoeducation. HR youths (N= 34; age 9-17 years; mean 14 years, 56% girls and 44% boys) with depressive and/or hypomanic symptoms and at least 1 first- or second-degree relative with BD I or II were randomly assigned to 4 months of FFT-HR (12 sessions of psychoeducation, communication, and problem-solving skills training) or enhanced care (EC; 3 family and 3 individual psychoeducation sessions). Before and after 4 months of treatment, participants underwent resting state functional magnetic resonance imaging (rs-fMRI). A whole-brain independent component analysis compared rs-fMRI networks in HR youths and 30 age-matched HC youths at a pretreatment baseline. Then we identified pretreatment to posttreatment (4-month) changes in network connectivity in HR youths receiving FFT-HR (n= 16) or EC (n= 18) and correlated these changes with depression improvement. At baseline, HR youths had greater connectivity between the ventrolateral prefrontal cortex (VLPFC) and the anterior default mode network (aDMN) than did HCs (p= .004). Over 4 months of treatment, FFT-HR-assigned HR youths had increased VLPFC-aDMN connectivity from pre- to posttreatment (p= .003), whereas HR youths in EC showed no significant change over time (p= .11) (treatment by time interaction, t31= 3.33, 95% CI= 0.27-1.14, p= .002]. Reduction in depression severity over 4 months inversely correlated with enhanced anterior DMN (r=-0.71) connectivity in the FFT-HR but not in the EC (r=-0.07) group (z=-2.17, p= .015). Compared to standard psychoeducation, FFT-HR is associated with stronger connectivity between the VLPFC and aDMN, suggesting possible enhancements of self-awareness, illness awareness, and emotion regulation. Early Intervention for Youth at Risk for Bipolar Disorder; https://clinicaltrials.gov/; NCT01483391.

Cross-network interaction for diagnosis of major depressive disorder based on resting state functional connectivity

Previous studies have suggested that resting-state functional connectivity plays a central role in the physiopathology of major depressive disorder (MDD). However, the individualized diagnosis of MDD based on resting-state functional connectivity is still unclear, especially in first episode drug-naive patients with MDD. Resting state functional magnetic resonance imaging was enrolled from 30 first episode drug-naive patients with MDD and age- and gender-matched 31 healthy controls. Whole brain functional connectivity was computed and viewed as classification features. Multivariate pattern analysis (MVPA) was performed to discriminate patients with MDD from controls. The experimental results exhibited a correct classification rate of 82.25% (p < 0.001) with sensitivity of 83.87% and specificity of 80.64%. Almost all of the consensus connections (125/128) were cross-network interaction among default mode network (DMN), salience network (SN), central executive network (CEN), visual cortex network (VN), Cerebellum and Other. Moreover, the supramarginal gyrus exhibited high discriminative power in classification. Our findings suggested cross-network interaction can be used as an effective biomarker for MDD clinical diagnosis, which may reveal the potential pathological mechanism for major depression. The current study further confirmed reliable application of MVPA in discriminating MDD patients from healthy controls.

Brain functional connectivity during storage based on resting state functional magnetic resonance imaging with synchronous urodynamic testing in healthy volunteers.

The aim of the study was to elucidate the correlation between spatially distinct brain areas with a full bladder from the perspective of functional connectivity using resting-state functional magnetic resonance imaging (rs-fMRI) with simultaneous urodynamic testing in healthy volunteers. The brain regions with full and empty bladders were reported via rs-fMRI using a 3T magnetic resonance system. Then, we identified brain regions that are activated during bladder filling by calculating the amplitude of low-frequency fluctuation (ALFF) values using brain imaging software (DPABI and SPM8) and empirically derived six regions of interest (ROI) from analysis of activation were used as seeds for resting-state functional connectivity (rs-FC) analysis with the rest of the brain to examine differences in the two conditions. Statistical analysis was performed with a paired t-test and statistical significance was defined as a P < 0.01. Twenty-two healthy volunteers (11 men and 11 women) 35-64years of age were enrolled. The rs-fMRI scans of 22 healthy volunteers were analyzed. After motion correction, two subjects were excluded. Meaningful data were obtained on 20 of these subjects. Compared with an empty bladder, functional connection enhancement was noted mainly in the right inferior orbitofrontal cortex and bilateral calcarine gyrus, the left lingual gyrus, left fusiform gyrus, left superior occipital gyrus, right insula, right inferior temporal gyrus, superior parietal lobe, left insula, right lingual gyrus, right fusiform gyrus, left parahippocampal gyrus, right inferior temporal gyrus, superior parietal lobe, left calcarine gyrus, bilateral lingual gyrus, prefrontal cortex, including the middle frontal gyrus and superior frontal gyrus, the right middle temporal gyrus, bilateral posterior cingulate cortex, and right precuneus. The decrease in functional connection was mainly located in the right inferior orbitofrontal cortex, prefrontal cortex, including the superior frontal gyrus, orbitofrontal cortex, and anterior cingulate cortex, the left inferior orbitofrontal cortex, right insula, middle occipital gyrus, angular gyrus, inferior frontal gyrus, right insula, middle temporal gyrus, inferior parietal lobe, middle occipital gyrus, supplementary motor area, superior frontal gyrus, left insula, bilateral posterior cingulate cortex, bilateral precuneus, middle occipital gyrus, and right middle temporal lobe. There were significant changes in the functional connectivity of the brain between full and empty bladders in healthy volunteers, which suggests that the central neural processes involved in storage needs brain areas with integrated control. These findings are strong evidence for physicians to consider brain responses in urine storage and offer the provision of some normative data.

DACC Resting State Functional Connectivity as a Predictor of Pain Symptoms Following Motor Vehicle Crash: A Preliminary Investigation

There is significant heterogeneity in pain outcomes following motor vehicle crashes (MVCs), such that a sizeable portion of individuals develop symptoms of chronic pain months after injury while others recover. Despite variable outcomes, the pathogenesis of chronic pain is currently unclear. Previous neuroimaging work implicates the dorsal anterior cingulate cortex (dACC) in adaptive control of pain, while prior resting state functional magnetic resonance imaging studies find increased functional connectivity (FC) between the dACC and regions involved in pain processing in those with chronic pain. Hyper-connectivity of the dACC to regions that mediate pain response may therefore relate to pain severity. The present study completed rsfMRI scans on N = 22 survivors of MVCs collected within 2 weeks of the incident to test whole-brain dACC-FC as a predictor of pain severity 6 months later. At 2 weeks, pain symptoms were predicted by positive connectivity between the dACC and the premotor cortex. Controlling for pain symptoms at 2 weeks, pain symptoms at 6 months were predicted by negative connectivity between the dACC and the precuneus. Previous research implicates the precuneus in the individual subjective awareness of pain. Given a relatively small sample size, approximately half of which did not experience chronic pain at 6 months, findings warrant replication. Nevertheless, this study provides preliminary evidence of enhanced dACC connectivity with motor regions and decreased connectivity with pain processing regions as immediate and prospective predictors of pain following MVC. PerspectiveThis article presents evidence of distinct neural vulnerabilities that predict chronic pain in MVC survivors based on whole-brain connectivity with the dorsal anterior cingulate cortex.

Increased resting state functional irregularity of T2DM brains with high HbA1c: sign for impaired verbal memory function?

Glycosylated hemoglobin A1c (HbA1c) has been considered as a key contributor to impaired cognition in type 2 diabetes mellitus (T2DM) brains. However, how does it affect the brain and whether the glucose controlling can slow down the process are still unknown. In the current study, T2DM patients with high glycosylated hemoglobin level (HGL) and controls with normal glycosylated hemoglobin level (NGL) were enrolled to investigate the relationships between HbA1c, brain imaging characteristics and cognitive function. First, a series of cognitive tests including California Verbal Learning Test (CVLT) were conducted. Then, the functional irregularity based on resting state functional magnetic resonance imaging data was evaluated via a new data-driven brain entropy (BEN) mapping analysis method. We found that the HGLs exhibited significantly increased BEN in the right precentral gyrus (PreCG.R), the right middle frontal gyrus (MFG.R), the triangular and opercular parts of the right inferior frontal gyrus (IFGtriang.R and IFGoperc.R). The strengths of the functional connections of PreCG.R with the brainstem/cerebellum were decreased. Partial correlation analysis showed that HbA1c had a strong positive correlation to regional BEN and negatively correlated with some CVLT scores. Negative correlations also existed between the BEN of PreCG.R/IFGoperc.R and some CVLT scores, suggesting the correspondence between higher HbA1c, increased BEN and decreased verbal memory function. This study demonstrated the potential of BEN in exploring the functional alterations affected by HbA1c and interpreting the verbal memory function decline. It will help understanding the neurophysiological mechanism of T2DM-induced cognitive decline and taking effective prevention or treatment measures.

Greater Dynamic and Lower Static Functional Brain Connectivity Prospectively Predict Placebo Response in Pediatric Generalized Anxiety Disorder.

Objectives: Placebo response is one of the most significant barriers to detecting treatment effects in pediatric (and adult) clinical trials focusing on affective and anxiety disorders. We sought to identify neurofunctional predictors of placebo response in adolescents with generalized anxiety disorder (GAD) by examining dynamic and static functional brain connectivity. Methods: Before randomization to blinded placebo, adolescents, aged 12-17 years, with GAD (N = 25) underwent resting state functional magnetic resonance imaging. Whole brain voxelwise correlation analyses were used to determine the relationship between change in anxiety symptoms from baseline to week 8 and seed-based dynamic and static functional connectivity maps of regions in the salience and ventral attention networks (amygdala, dorsal anterior cingulate cortex [dACC], and ventrolateral prefrontal cortex [VLPFC]). Results: Greater dynamic functional connectivity variability in amygdala, dACC, VLPFC, and regions within salience, default mode, and frontoparietal networks was associated with greater placebo response. Lower static functional connectivity between amygdala and dorsolateral prefrontal cortex, amygdala and medial prefrontal cortex, dACC and posterior cingulate cortex and greater static functional connectivity between VLPFC and inferior parietal lobule were associated with greater placebo response. Conclusion: Placebo response is associated with a distinct dynamic and static connectivity fingerprint characterized by "variable" dynamic but "weak" static connectivity in the salience, default mode, frontoparietal, and ventral attention networks. These data provide granular evidence of how circuit-based biotypes mechanistically relate to placebo response. Finding biosignatures that predict placebo response is critically important in clinical psychopharmacology and to improve our ability to detect medication-placebo differences in clinical trials.

Altered dynamic parahippocampus functional connectivity in patients with post-traumatic stress disorder

Objectives This study investigated dynamic brain functional alterations in post-traumatic stress disorder (PTSD) patients with resting state functional magnetic resonance imaging. Methods Degree centrality (DC) and seed-based functional connectivity (FC) analyses were conducted among typhoon survivours with (n = 27) and without PTSD (n = 33) and healthy controls (HC) (n = 30) to assess the intrinsic dysconnectivity pattern and network-level brain function. Results Both the PTSD group and the trauma-exposed control (TEC) group had increased DC in the left parahippocampal gyrus relative to the HC group. More increased DC in the left parahippocampal gyrus was found in the PTSD group. Both traumatised groups exhibited decreased left parahippocampal gyrus dynamic FC with the bilateral middle frontal gyrus and superior frontal gyrus relative to the HC group. The Checklist-Civilian Version score was positively correlated with dynamic FC between the parahippocampal gyrus and left superior frontal gyrus but was negatively correlated with dynamic FC between the parahippocampal gyrus and right middle frontal gyrus. Conclusions Trauma exposure may lead to an altered dynamic FC in individuals with or without PTSD. An altered DC in the parahippocampal gyrus may be an important risk factor for PTSD development following trauma exposure. A more prominently increased DC in the parahippocampal gyrus might be a common trait in the PTSD group.

Improved dynamic connection detection power in estimated dynamic functional connectivity considering multivariate dependencies between brain regions.

To estimate dynamic functional connectivity (dFC), the conventional method of sliding window correlation (SWC) suffers from poor performance of dynamic connection detection. This stems from the equal weighting of observations, suboptimal time scale, nonsparse output, and the fact that it is bivariate. To overcome these limitations, we exploited the kernel‐reweighted logistic regression (KELLER) algorithm, a method that is common in genetic studies, to estimate dFC in resting state functional magnetic resonance imaging (rs‐fMRI) data. KELLER can estimate dFC through estimating both spatial and temporal patterns of functional connectivity between brain regions. This paper compares the performance of the proposed KELLER method with current methods (SWC and tapered‐SWC (T‐SWC) with different window lengths) based on both simulated and real rs‐fMRI data. Estimated dFC networks were assessed for detecting dynamically connected brain region pairs with hypothesis testing. Simulation results revealed that KELLER can detect dynamic connections with a statistical power of 87.35% compared with 70.17% and 58.54% associated with T‐SWC (p‐value = .001) and SWC (p‐value <.001), respectively. Results of these different methods applied on real rs‐fMRI data were investigated for two aspects: calculating the similarity between identified mean dynamic pattern and identifying dynamic pattern in default mode network (DMN). In 68% of subjects, the results of T‐SWC with window length of 100 s, among different window lengths, demonstrated the highest similarity to those of KELLER. With regards to DMN, KELLER estimated previously reported dynamic connection pairs between dorsal and ventral DMN while SWC‐based method was unable to detect these dynamic connections.

Identification of neural networks preferentially engaged by epileptogenic mass lesions through lesion network mapping analysis

Lesion network mapping (LNM) has been applied to true lesions (e.g., cerebrovascular lesions in stroke) to identify functionally connected brain networks. No previous studies have utilized LNM for analysis of intra-axial mass lesions. Here, we implemented LNM for identification of potentially vulnerable epileptogenic networks in mass lesions causing medically-refractory epilepsy (MRE). Intra-axial brain lesions were manually segmented in patients with MRE seen at our institution (EL_INST). These lesions were then normalized to standard space and used as seeds in a high-resolution normative resting state functional magnetic resonance imaging template. The resulting connectivity maps were first thresholded (pBonferroni_cor < 0.05) and binarized; the thresholded binarized connectivity maps were subsequently summed to produce overall group connectivity maps, which were compared with established resting-state networks to identify potential networks prone to epileptogenicity. To validate our data, this approach was also applied to an external dataset of epileptogenic lesions identified from the literature (EL_LIT). As an additional exploratory analysis, we also segmented and computed the connectivity of institutional non-epileptogenic lesions (NEL_INST), calculating voxel-wise odds ratios (VORs) to identify voxels more likely to be functionally-connected with EL_INST versus NEL_INST. To ensure connectivity results were not driven by anatomical overlap, the extent of lesion overlap between EL_INST, and EL_LIT and NEL_INST was assessed using the Dice Similarity Coefficient (DSC, lower index ~ less overlap). Twenty-eight patients from our institution were included (EL_INST: 17 patients, 17 lesions, 10 low-grade glioma, 3 cavernoma, 4 focal cortical dysplasia; NEL_INST: 11 patients, 33 lesions, all brain metastases). An additional 23 cases (25 lesions) with similar characteristics to the EL_INST data were identified from the literature (EL_LIT). Despite minimal anatomical overlap of lesions, both EL_INST and EL_LIT showed greatest functional connectivity overlap with structures in the Default Mode Network, Frontoparietal Network, Ventral Attention Network, and the Limbic Network—with percentage volume overlap of 19.5%, 19.1%, 19.1%, and 12.5%, respectively—suggesting them as networks consistently engaged by epileptogenic mass lesions. Our exploratory analysis moreover showed that the mesial frontal lobes, parahippocampal gyrus, and lateral temporal neocortex were at least twice as likely to be functionally connected with the EL_INST compared to the NEL_INST group (i.e. Peak VOR > 2.0); canonical resting-state networks preferentially engaged by EL_INSTs were the Limbic and the Frontoparietal Networks (Mean VOR > 1.5). In this proof of concept study, we demonstrate the feasibility of LNM for intra-axial mass lesions by showing that ELs have discrete functional connections and may preferentially engage in discrete resting-state networks. Thus, the underlying normative neural circuitry may, in part, explain the propensity of particular lesions toward the development of MRE. If prospectively validated, this has ramifications for patient counseling along with both approach and timing of surgery for lesions in locations prone to development of MRE.