Time-varying phase synchronization of resting-state functional magnetic resonance imaging reveals a shift toward self-referential processes during sustained pain.

ABSTRACT: Growing evidence has suggested that time-varying functional connectivity between different brain regions might underlie the dynamic experience of pain. This study used a novel, data-driven framework to characterize the dynamic interactions of large-scale brain networks during sustained pain by estimating recurrent patterns of phase-synchronization. Resting-state functional magnetic resonance imaging signals were collected from 50 healthy participants before (once) and after (twice) the onset of sustained pain that was induced by topical application of capsaicin cream. We first decoded the instantaneous phase of neural activity and then applied leading eigenvector dynamic analysis on the time-varying phase-synchronization. We identified 3 recurrent brain states that show distinctive phase-synchronization. The presence of state 1, characterized by phase-synchronization between the default mode network and auditory, visual, and sensorimotor networks, together with transitions towards this brain state, increased during sustained pain. These changes can account for the perceived pain intensity and reported unpleasantness induced by capsaicin application. In contrast, state 3, characterized by phase-synchronization between the cognitive control network and sensory networks, decreased after the onset of sustained pain. These results are indicative of a shift toward internally directed self-referential processes (state 1) and away from externally directed cognitive control processes (state 3) during sustained pain.

Menstrually-related migraine shapes the structural similarity network integration of brain.

Menstrually-related migraine (MM) is a primary migraine in women of reproductive age. The underlying neural mechanism of MM was still unclear. In this study, we aimed to reveal the case-control differences in network integration and segregation for the morphometric similarity network of MM. Thirty-six patients with MM and 29 healthy females were recruited and underwent MRI scanning. The morphometric features were extracted in each region to construct the single-subject interareal cortical connection using morphometric similarity. The network topology characteristics, in terms of integration and segregation, were analyzed. Our results revealed that, in the absence of morphology differences, disrupted cortical network integration was found in MM patients compared to controls. The patients with MM showed a decreased global efficiency and increased characteristic path length compared to healthy controls. Regional efficiency analysis revealed the decreased efficiency in the left precentral gyrus and bilateral superior temporal gyrus contributed to the decreased network integration. The increased nodal degree centrality in the right pars triangularis was positively associated with the attack frequency in MM. Our results suggested MM would reorganize the morphology in the pain-related brain regions and reduce the parallel information processing capacity of the brain.

Aftereffects of alpha transcranial alternating current stimulation over the primary sensorimotor cortex on cortical processing of pain.

ABSTRACT: Transcranial alternating current stimulation (tACS) is believed to modulate brain oscillations in a frequency-specific manner. Given the correlation between sensorimotor α-oscillations and pain perception, tACS that targets sensorimotor α-oscillations has the potential to reduce pain. Therefore, this study sought to determine the aftereffects of α-tACS over unilateral primary sensorimotor cortex (SM1) on the perceptual and neural responses to noxious painful stimulation of the contralateral hand. Using a double-blinded and sham-controlled design, 60 healthy participants were recruited to receive either α-tACS or sham stimulation of unilateral SM1 through an electrode montage in a 4 × 1 ring configuration. Neural responses to laser nociceptive stimuli were assessed using functional magnetic resonance imaging immediately before and after α-tACS intervention. Perceptual reports were recorded simultaneously. Compared with sham stimulation, α-tACS attenuated bilateral SM1 responses to painful stimuli delivered to the contralateral hand. Although α-tACS did not exert direct effect on subjective pain perception, it can indirectly decrease ratings of pain perception by reducing brain activity within the targeted SM1. Moreover, α-tACS decreased the functional connectivity between the targeted SM1 and a network of regions that are crucially involved in pain processing, including the middle cingulate cortex, contralateral somatosensory cortex, and dorsolateral prefrontal cortex. These results demonstrated that after α-tACS applied over the unilateral SM1 does attenuate subsequent neural processing of pain within bilateral sensorimotor regions as well as sensorimotor functional connectivity. The findings provide evidence that sensorimotor α-oscillations directly affect pain processing and support the application of sensorimotor α-tACS for inducing pain analgesia.

Gyrus rectus asymmetry predicts trait alexithymia, cognitive empathy, and social function in neurotypical adults.

Reduced empathy and elevated alexithymia are observed in autism spectrum disorder (ASD), which has been linked to altered asymmetry in brain morphology. Here, we investigated whether trait autism, empathy, and alexithymia in the general population is associated with brain morphological asymmetry. We determined left-right asymmetry indexes for cortical thickness and cortical surface area (CSA) and applied these features to a support-vector regression model that predicted trait autism, empathy, and alexithymia. Results showed that less leftward asymmetry of CSA in the gyrus rectus (a subregion of the orbitofrontal cortex) predicted more difficulties in social functioning, as well as reduced cognitive empathy and elevated trait alexithymia. Meta-analytic decoding of the left gyrus rectus annotated functional items related to social cognition. Furthermore, the link between gyrus rectus asymmetry and social difficulties was accounted by trait alexithymia and cognitive empathy. These results suggest that gyrus rectus asymmetry could be a shared neural correlate among trait alexithymia, cognitive empathy, and social functioning in neurotypical adults. Left-right asymmetry of gyrus rectus influenced social functioning by affecting the cognitive processes of emotions in the self and others. Interventions that increase leftward asymmetry of the gyrus rectus might improve social functioning for individuals with ASD.

Ongoing first-hand pain facilitates somatosensory resonance but inhibits affective sharing in empathy for pain.

Alterations of empathy for others' pain among patients with chronic pain remained inconsistent. Here, applying a capsaicin-based ongoing pain model on healthy participants, this study investigated how ongoing first-hand pain influences empathic reactions to vicarious pain stimuli. Healthy participants were randomly treated with topical capsaicin cream (capsaicin group) or hand cream (control group) on the left forearm. Video clips showing limbs in painful and non-painful situations were used to induce empathic responses. The capsaicin group showed greater empathic neural responses in the right primary somatosensory cortex (S1) than the control group but smaller responses in the left anterior insula (AI) accompanied with smaller empathic pain-intensity ratings. Notably, the intensity of ongoing pain negatively correlated with empathy-related neural responses in the left AI. Inter-subject phase synchronization analysis was used to assess stimulus-dependent dynamic functional connectivity within or between brain regions engaged in pain empathy. The capsaicin group showed greater empathy-related neural synchronization within S1 and between S1 and AI, but less synchronization within AI and between AI and MCC. Behaviorally, the differential inter-subject pain-intensity rating alignment between painful and non-painful videos was more positive for the capsaicin group than for the control group, and this effect was partially mediated by the inter-subject neural synchronization between S1 and AI. These results suggest that ongoing first-hand pain facilitates neural activation and synchronization within brain regions associated with empathy-related somatosensory resonance at the cost of inhibiting activation and synchronization within brain regions engaged in empathy-related affective sharing.

Impact of anodal high-definition transcranial direct current stimulation of medial prefrontal cortex on stroop task performance and its electrophysiological correlates. A pilot study.

Medial prefrontal cortex (MPC) has been associated with a wide range of cognitive functions; however, its specific role in interference control is not fully understood. The current study investigates the role of MPC in interference control by externally stimulating it with an electric current and studying associated behavioral and neurophysiological markers. Participants randomly assigned to experimental and sham groups were administered with a high-definition transcranial direct current stimulation (HD-tDCS) of 2 mA for 15 min. They performed a classic color-word Stroop task before, during, and immediately after the stimulation, while electroencephalography (EEG) was acquired throughout the experiment. A decrease in reaction time (RT) for incongruent and neutral trials of the Stroop task was observed in the experimental group compared to the sham group with a significant reduction in the Stroop Effect after stimulation; however, no significant change was observed in the amplitude and latency of N200, P200, and N450 event related potentials. Furthermore, the resting state complexity of the neural signals in the medial frontal region was decreased in the experimental group with a decrease in theta frequency band during the Stroop task. We conclude that the stimulation of MPC increases its efficiency in resolving the conflict by reducing theta power during the Stroop task, which is also reflected in the reduced complexity in the resting state EEG. (ClinicalTrials.gov Identifier: NCT04318522).

Differential Effects of 10 and 20 Hz Brain Stimulation in Chronic Stroke: A tACS-fMRI Study.

Transcranial alternating current stimulation (tACS) is an emerging non-invasive neuromodulation technique, which could be potentially applied to enhance stroke rehabilitation. In this study, we aimed to characterize the frequency-specific effects of tACS in chronic stroke. Therefore, concurrent tACS and functional magnetic resonance imaging (fMRI) were conducted in 13 chronic stroke individuals. Resting-state and task-based fMRI were collected for each subject under different frequencies (10 Hz, 20 Hz, Sham). Task-based fMRI showed that increased activation was found in the ipsilesional precentral area during paretic hand movements after 10 Hz tACS, while increased activation was found in the contralesional precentral area during non-paretic hand movements after both 10 and 20 Hz tACS. Resting-state seed-based functional connectivity (FC) analysis showed that 10 Hz tACS mainly modulated FC within motor-related regions, while 20 Hz tACS also modulated regions beyond the motor-related areas. Graph theory analysis further demonstrated the functional interaction modulated by tACS in the whole-brain level. Taken together, our results showed that tACS might exhibit frequency-specific modulation in chronic stroke. 20 Hz tACS facilitates the functional interaction between the sensorimotor regions and brain regions involved in executive control, while 10 Hz and sham tACS has limited effect on motor-related brain activity. Our results reveal the neural response process under external current stimulation, providing new insight into the neuromodulation mechanism of tACS in a lesioned brain.

Analgesia induced by anodal tDCS and high-frequency tRNS over the motor cortex: Immediate and sustained effects on pain perception.

BACKGROUND: Many studies have shown effects of anodal transcranial direct current stimulation (a-tDCS) and high-frequency transcranial random noise stimulation (tRNS) on elevating cortical excitability. Moreover, tRNS with a direct current (DC)-offset is more likely to lead to increases in cortical excitability than solely tRNS. While a-tDCS over primary motor cortex (M1) has been shown to attenuate pain perception, tRNS + DC-offset may prove as an effective means for pain relief. OBJECTIVE: This study aimed to examine effects of a-tDCS and high-frequency tRNS + DC-offset over M1 on pain expectation and perception, and assess whether these effects could be influenced by the certainty of pain expectation. METHODS: Using a double-blinded and sham-controlled design, 150 healthy participants were recruited to receive a single-session a-tDCS, high-frequency tRNS + DC-offset, or sham stimulation over M1. The expectation and perception of electrical stimulation in certain and uncertain contexts were assessed at baseline, immediately after, and 30 min after stimulation. RESULTS: Compared with sham stimulation, a-tDCS induced immediate analgesic effects that were greater when the stimulation outcome was expected with uncertainty; tRNS induced immediate and sustained analgesic effects that were mediated by decreasing pain expectation. Nevertheless, we found no strong evidence for tRNS being more effective for attenuating pain than a-tDCS. CONCLUSIONS: The analgesic effects of a-tDCS and tRNS showed different temporal courses, which could be related to the more sustained effectiveness of high-frequency tRNS + DC-offset in elevating cortical excitability. Moreover, expectations of pain intensity should be taken into consideration to maximize the benefits of neuromodulation.

Suffer together, bond together: Brain-to-brain synchronization and mutual affective empathy when sharing painful experiences.

Previous behavioral studies have shown that sharing painful experiences can strengthen social bonds and promote mutual prosociality, yet the neural mechanisms underlying this phenomenon remain unclear. We hypothesized that sharing a painful experience induces brain-to-brain synchronization and mutual empathy for each other's pain between pain-takers and pain-observers, which then leads to enhanced social bonding. To test this hypothesis, we adopted an electroencephalographic (EEG) hyper-scanning technique to assess neuronal and behavioral activity during a Pain-Sharing task in which high- or low-intensity pain stimulation was randomly delivered to one participant of a dyad on different experimental trials. Single-brain analysis showed that sensorimotor α-oscillation power was suppressed more when expecting high-intensity pain than when expecting low-intensity pain similarly for self-directed or partner-directed pain. Dual-brain analysis revealed that expecting high-intensity pain induced greater brain-to-brain synchronization of sensorimotor α-oscillation phases between pain-takers and pain-observers than did expecting low-intensity pain. Mediation analysis further revealed that brain-to-brain synchronization of sensorimotor α-oscillations mediated the effects of pain-stimulation intensity on mutual affective sharing for partner-directed pain. This mutual affective empathy during the task predicted the social bonding, as indexed by prosocial inclinations measured after the task. These results support the hypothesis that sharing a painful experience triggers emotional resonance between pairs of individuals through brain-to-brain synchronization of neuronal α-oscillations recorded over the sensorimotor cortex, and this emotional resonance further strengthens social bonds and motivates prosocial behavior within pairs of individuals.

Hyperconnection and hyperperfusion of overlapping brain regions in patients with menstrual-related migraine: a multimodal neuroimaging study.

PURPOSE: Menstrual-related migraine (MRM) results in moderate to severe intensity headaches accompanied by physical and emotional disability over time in women. Neuroimaging methodologies have advanced our understanding of migraine; however, the neural mechanisms of MRM are not clearly understood. METHODS: In this study, fourteen MRM patients in the interictal phase and fifteen age- and education-matched healthy control females were recruited. Resting-state functional magnetic resonance imaging (fMRI) and pulsed arterial spin labeling (PASL) MRI were collected for both the subject groups outside of their menstrual periods. Eigenvector centrality mapping (ECM) was performed on resting-state fMRI, and the relative cerebral blood flow (relCBF) was assessed using PASL-MRI. RESULTS: MRM patients showed a significantly increased eigenvector centrality in the right medial frontal gyrus compared to healthy controls. Seed-based ECM analysis revealed that increased centrality was associated with the right medial frontal gyrus's hyperconnectivity with the left insula and the right supplementary motor area. The perfusion MRI revealed significantly increased relCBF in the hyperconnected regions. Furthermore, the hyperconnection positively correlated with the attack frequency, while the hyperperfusion showed a positive correlation with the disease duration. CONCLUSION: The results suggest that menstrual-related migraine is associated with cerebral hyperconnection and hyperperfusion in critical pain-processing brain regions. Furthermore, this elevated cerebral activity is correlated with different aspects of functional impairment in MRM patients suggesting that perfusion analysis, along with whole-brain connectivity analysis, can provide a comprehensive understanding of neural mechanisms of MRM.

Altered relation of resting-state alpha rhythm with blood oxygen level dependent signal in healthy aging: Evidence by EEG-fMRI fusion analysis.

OBJECTIVE: The goal of this study is to explore the changes of spatial correlates of alpha rhythm in the aged adults. METHODS: Electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI) data were simultaneously recorded from 27 young and 19 elderly adults at resting state with their eyes closed. Alpha rhythm power fluctuation was extracted from EEG signal of parietal-occipital region and was fused with fMRI data by correlating alpha rhythm with blood oxygen level dependent (BOLD) signal using general linear models. RESULTS: For both young adults and the elderly, the regions correlated with alpha rhythm power were widely distributed in cortical and subcortical regions. However, compared to young adults, correlations between alpha rhythm and the activity of thalamus and frontal regions were significantly reduced in the elderly. In addition, an increased correlation with alpha rhythm was found in frontal, insula and cingulate gyrus regions in the elderly. CONCLUSIONS: Changes in the roles of the above brain regions may be present in the generation or modulation of alpha rhythm due to age advancing. SIGNIFICANCE: This study provides novel insight into the alteration of the spatial correlates of alpha rhythm in the elderly by using simultaneous EEG-fMRI data fusion analysis.

Indoor incense burning impacts cognitive functions and brain functional connectivity in community older adults.

To investigate (1) the effects of indoor incense burning upon cognition over 3 years; (2) the associations between indoor incense burning with the brain's structure and functional connectivity of the default mode network (DMN); and (3) the interactions between indoor incense burning and vascular disease markers upon cognitive functions. Community older adults without stroke or dementia were recruited (n = 515). Indoor incense use was self-reported as having burnt incense at home ≥ weekly basis over the past 5 years. Detailed neuropsychological battery was administered at baseline (n = 227) and the Montreal Cognitive Assessment at baseline and year 3 (n = 515). MRI structural measures and functional connectivity of the DMN were recorded at baseline. Demographic and vascular risk factors and levels of outdoor pollutants were treated as covariates. Indoor incense burning was associated with reduced performance across multiple cognitive domains at baseline and year 3 as well as decreased connectivity in the DMN. It interacted with diabetes mellitus, hyperlipidemia and white matter hyperintensities to predict poorer cognitive performance. Indoor incense burning is (1) associated with poorer cognitive performance over 3 years; (2) related to decreased brain connectivity; and (3) it interacts with vascular disease to predispose poor cognitive performance.

Altered Brain Regional Homogeneity in First-Degree Relatives of Type 2 Diabetics: A functional MRI Study.

OBJECTIVE: This study aimed to investigate regional homogeneity in the first-: degree relatives of type 2 diabetes patients. METHODS: Seventy-eight subjects, including 26 type 2 diabetes patients, 26 first-: degree relatives, and 26 healthy controls, were assessed. All participants underwent resting-state functional magnetic resonance imaging scanning. The estimated regional homogeneity value was used to evaluate differences in brain activities. RESULTS: In first-: degree relatives, we observed significantly decreased regional homogeneity in the left anterior cingulate cortex, left insula, and bilateral temporal lobes, and increased regional homogeneity in the left superior frontal gyrus, right anterior cingulate cortex, and bilateral posterior cingulate cortex compared to healthy controls. In type 2 diabetes patients, we detected altered regional homogeneity in the left anterior cingulate cortex, left insula, bilateral posterior cingulate cortex, and several other brain regions compared to healthy controls. Both first-: degree relatives and type 2 diabetes patients showed decreased regional homogeneity in the left superior temporal gyrus, right middle temporal gyrus, left anterior cingulate cortex, left insula, and increased regional homogeneity in the left superior frontal gyrus and bilateral posterior cingulate cortex. CONCLUSION: These findings suggest that altered regional homogeneity in the left anterior cingulate cortex, left insula, left superior frontal gyrus, bilateral posterior cingulate cortex, and bilateral temporal lobes might be a neuroimaging biomarker of type 2 diabetes -: related brain dysfunction.

Mapping the patterns of cortical thickness in single- and multiple-domain amnestic mild cognitive impairment patients: a pilot study.

Amnestic mild cognitive impairment (aMCI) is considered as a transitional stage between the expected cognitive decline of normal aging and Alzheimer's disease (AD). Structural brain difference has shown the potential in cognitive related diagnosis, however cortical thickness patterns transferred from aMCI to AD, especially in the subtypes of aMCI, is still unclear. In this study, we investigated the cortical thickness discrepancies among AD, aMCI and normal control (NC) entities, especially for two subtypes of aMCI - multiple-domain aMCI (aMCI-m) and single-domain aMCI (aMCI-s). Both region of interest (ROI)-based and vertex-based statistical strategies were performed for group-level cortical thickness comparison. Spearman correlation was utilized to identify the correlation between cortical thickness and clinical neuropsychological scores. The result demonstrated that there was a significant cortical thickness decreasing tendency in fusiform gyrus from NC to aMCI-s to aMCI-m to finally AD in both left and right hemispheres. Meanwhile, the two subtypes of aMCI showed cortical thickness difference in middle temporal gyrus in left hemisphere. Spearman correlation indicated that neuropsychological scores had significant correlations with entorhinal, inferior temporal and middle temporal gyrus. The findings suggested that cortical thickness might serve as a potential imaging biomarker for the differential diagnosis of cognitive impairment.

Neuroimaging endophenotypes of type 2 diabetes mellitus: a discordant sibling pair study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is characterized by notable familial aggregation involving common variants of many genes, and its heritability leads to a high prevalence in the siblings of affected individuals compared with the general population. Endophenotypes are objective, heritable, quantitative traits that appear to reflect the genetic risk for polygenic disorders at more biologically tractable levels. Based on a sibling pair design, we aimed to find the neuroimaging endophenotypes of T2DM and investigate the role of inherent neurological disorders in the pathogenesis and deterioration of T2DM. METHODS: Twenty-six pairs of diagnosed T2DM patients with unaffected siblings and 26 unrelated controls were included in this study. Both high-resolution structural MRI and three-dimensional pseudo-continuous arterial spin labelling (3D-pCASL) MRI data were acquired with a 3.0 T MRI system. Voxel-based morphometry (VBM) analysis was performed on the structural T1W images, and cerebral blood flow (CBF) maps were obtained. All data were processed with the SPM8 package under the MATLAB 7.6 operation environment. RESULTS: The T2DM patients and their unaffected siblings shared significant atrophy in the right inferior/middle temporal gyrus, and left insula, in addition to elevated CBF in the right prefrontal lobe. Several regions with abnormal CBF in siblings, including the right inferior/middle temporal gyrus, left insula, left operculum, right supramarginal gyrus, right prefrontal lobe, and bilateral anterior cingulate cortex, also presented significant atrophy in T2DM patients. CONCLUSIONS: The shared brain regions with grey matter (GM) loss and CBF increases may serve as neuroimaging endophenotypes of T2DM, and the regions with abnormal CBF in siblings indicate an increased risk for T2DM.

Hyperexcitability of Cortical Oscillations in Patients with Somatoform Pain Disorder: A Resting-State EEG Study.

Patients with somatoform pain disorder (SPD) suffer from somatic pain that cannot be fully explained by specific somatic pathology. While the pain experience requires the integration of sensory and contextual processes, the cortical oscillations have been suggested to play a crucial role in pain processing and integration. The present study is aimed at identifying the abnormalities of spontaneous cortical oscillations among patients with SPD, thus for a better understanding of the ongoing brain states in these patients. Spontaneous electroencephalography data during a resting state with eyes open were recorded from SPD patients and healthy controls, and their cortical oscillations as well as functional connectivity were compared using both electrode-level and source-level analysis. Compared with healthy controls, SPD patients exhibited greater resting-state alpha oscillations (8.5-12.5 Hz) at the parietal region, as reflected by both electrode-level spectral power density and exact low-resolution brain electromagnetic tomography (eLORETA) cortical current density. A significant correlation between parietal alpha oscillation and somatization severity was observed in SPD patients, after accounting for the influence of anxiety and depression. Functional connectivity analysis further revealed a greater frontoparietal connectivity of the resting-state alpha oscillations in SPD patients, which was indexed by the coherence between pairs of electrodes and the linear connectivity between pairs of eLORETA cortical sources. The enhanced resting-state alpha oscillation in SPD patients could be relevant with attenuated sensory information gating and excessive integration of pain-related information, while the enhanced frontoparietal connectivity could be reflecting their sustained attention to bodily sensations and hypervigilance to somatic sensations.

Neural evidence for long-term marriage shaping the functional brain network organization between couples.

Long-term married couples have been reported to share personality and behavioural similarities, but whether long-term marriage would shape the brain is hitherto unknown. In this study, 35 pairs of long-term married couples, who have married and living together at least 30 years, were recruited, and resting state functional magnetic resonance imaging was used to examine the neural correlates of long-term marriage between couples. Seven intrinsic connectivity networks were extracted using spatially constrained group independent component analysis, and the spatial similarity of each network as well as functional connectome similarity between couples were investigated respectively. The significant spatial similarities in the salience and frontoparietal networks as well as marginally significant connectome similarity were observed in long-term married couples. In addition, the marital duration showed a significantly positive correlation with the spatial similarity in the frontoparietal network and connectome similarity. The results provide objective evidence that long-term marriage would shape brain network organization, and the combination of initial personality traits and long-term common experience of the couples may be potential factors that account for similar brain network organizations between couples.

Frequency-specific age-related decreased brain network diversity in cognitively healthy elderly: A whole-brain data-driven analysis.

Age-related changes in functional brain network have been well documented. However, recent studies have suggested the nonstationary properties of the functional connectivity of the brain, and little is known about the changes of functional connectivity dynamics during aging. In this study, a two-step singular value decomposition was introduced to capture the dynamic patterns of the time-varying functional connectivity in different frequency intervals, and the whole-brain and regional brain diversity were quantified by using Shannon entropy. The relationships between age and functional connectivity dynamics were investigated in a relatively large sample cohort of cognitively healthy elderly (N = 188, ages 65-80). The results showed an age-related decreased diversity in the whole brain as well as in the right inferior frontal gyrus, right amygdala, right hippocampus, left parahippocampal, and left inferior parietal gyrus in the frequency interval of 0.06-0.12 Hz. In addition, the whole-brain diversity during resting state could also reflect the general mental flexibility. This study provided the first evidence of frequency-specific age effects on the functional connectivity dynamics in cognitively healthy elderly, and may shed new light on the dynamic functional connectivity analysis of aging and neurodegenerative diseases.

Automatic Segmentation of Acute Ischemic Stroke From DWI Using 3-D Fully Convolutional DenseNets.

Acute ischemic stroke is recognized as a common cerebral vascular disease in aging people. Accurate diagnosis and timely treatment can effectively improve the blood supply of the ischemic area and reduce the risk of disability or even death. Understanding the location and size of infarcts plays a critical role in the diagnosis decision. However, manual localization and quantification of stroke lesions are laborious and time-consuming. In this paper, we propose a novel automatic method to segment acute ischemic stroke from diffusion weighted images (DWIs) using deep 3-D convolutional neural networks (CNNs). Our method can efficiently utilize 3-D contextual information and automatically learn very discriminative features in an end-to-end and data-driven way. To relieve the difficulty of training very deep 3-D CNN, we equip our network with dense connectivity to enable the unimpeded propagation of information and gradients throughout the network. We train our model with Dice objective function to combat the severe class imbalance problem in data. A DWI data set containing 242 subjects (90 for training, 62 for validation, and 90 for testing) with various types of acute ischemic stroke was constructed to evaluate our method. Our model achieved high performance on various metrics (Dice similarity coefficient: 79.13%, lesionwise precision: 92.67%, and lesionwise F1 score: 89.25%), outperforming the other state-of-the-art CNN methods by a large margin. We also evaluated the model on ISLES2015-SSIS data set and achieved very competitive performance, which further demonstrated its generalization capacity. The proposed method is fast and accurate, demonstrating a good potential in clinical routines.

The Spatial Associations of Cerebral Blood Flow and Spontaneous Brain Activities with White Matter Hyperintensities-An Exploratory Study Using Multimodal Magnetic Resonance Imaging.

White matter hyperintensities (WMHs) have been reported to be correlated with functional brain changes, but the association of the specific WMHs distribution pattern with regional functional changes remains uncertain. The aim of this study is to explore the possible spatial correlation of WMH with changes in cerebral blood flow (CBF) and spontaneous brain activities in elderly using a novel approach. The WMHs, CBF, and spontaneous brain activities measured by intrinsic connectivity contrast (ICC), were quantified using multimodal magnetic resonance imaging for 69 elderly subjects. Such approach enables us to expand our search for newly identified correlated areas by drawing strengths of different modes and provides a means for triangulation as well as complementary insights. The results showed significant positive correlations between WMH volumes in the right superior corona radiata and CBF in the left supplementary motor area, as well as between WMH volumes in left anterior limb internal capsule and CBF in the right putamen. Significant correlations of regional WMH volumes and ICC were also detected between the right anterior corona radiata and the left cuneus, and the right superior occipital cortex, as well as between the right superior corona radiata and the left superior occipital cortex. These findings may suggest a regional compensatory functional enhancement accounting for the maintenance of cognitively normal status, which can be supported by the widely observed phenomenon that mild to moderate WMH load could have little effect on global cognitive performance.