A watershed algorithm GUI for personalized fMRI-guided rTMS target.

Unprecedented 4D spatiotemporal infant regional cerebral blood flow framework and region-specific physiology–function coupling across infancy were elucidated, highlighting strong physiology–function coupling specifically at the default-mode network to meet extraneuronal metabolic demand for network emergence.

To investigate the functional connectivity of the default-mode network (DMN) in patients with end-stage renal disease (ESRD) by using independent component analysis of resting-state functional magnetic resonance (MR) imaging and to correlate these DMN connectivity changes with neuropsychological test results and clinical biomarkers. Medical research ethics committee approval and written informed consent were obtained. Forty-six patients with ESRD, including 22 with minimal nephrotic encephalopathy (MNE) and 24 without nephrotic encephalopathy, and 23 healthy control subjects underwent resting-state functional MR imaging. All patients were asymptomatic and without history of neurologic or psychiatric disease. Independent component analysis was used to isolate the DMN. To display the voxels that contributed most strongly to an independent component, the intensity values in each spatial map were converted to z scores, which indirectly provided a measurement of functional connectivity in the DMN. Maps of the DMN were compared among the groups. Pearson correlation analysis was performed to correlate abnormal DMN functional connectivity with serum urea, creatinine, duration of dialysis, duration of disease, and neuropsychological test scores. Patients with ESRD showed significantly less functional connectivity in the posterior cingulate cortex, precuneus, and medial prefrontal cortex (MPFC) (P < .01) than did control subjects. Comparison of the two patient groups showed significantly reduced functional connectivity in the superior and MPFC in the MNE group (P < .01). The functional connectivity of the MPFC was positively correlated with digital symbol test score (R = 0.293, P = .048). Serum creatinine level was negatively correlated with functional connectivity of the posterior cingulate cortex and precuneus in patients with ESRD (R = -0.51, P = .002). Functional connectivity in the DMN was impaired in patients with ESRD, with further reduction in the MPFC with the development of MNE, which might explain the reduced performance of these patients on neurocognitive tests. Serum creatinine level might be associated with impairment of the DMN in patients with ESRD.

Reading is a fundamental human capacity and yet it can easily be derailed by the simple act of mind-wandering. A large-scale brain network, referred to as the default mode network (DMN), has been shown to be involved in both mind-wandering and reading, raising the question as to how the same neural system could be implicated in processes with both costs and benefits to narrative comprehension. Resting-state functional magnetic resonance imaging (rs-fMRI) was used to explore whether the intrinsic functional connectivity of the two key midline hubs of the DMN—the posterior cingulate cortex (PCC) and anterior medial prefrontal cortex (aMPFC)—was predictive of individual differences in reading comprehension and task focus recorded outside of the scanner. Worse comprehension was associated with greater functional connectivity between the PCC and a region of the ventral striatum. Better comprehension was associated with greater functional connectivity with a region of the right insula. By contrast reports of increasing task focus were associated with functional connectivity from the aMPFC to clusters in the PCC, the left parietal and temporal cortex, and the cerebellum. Our results suggest that the DMN has both costs (such as poor comprehension) and benefits to reading (such as an on-task focus) because its midline core can couple its activity with other regions to form distinct functional communities that allow seemingly opposing mental states to occur. This flexible coupling allows the DMN to participate in cognitive states that complement the act of reading as well as others that do not.

PurposeWhether the intrinsic functional connectivity pattern of the default mode network (DMN) is involved in the progression of cognitive decline in Parkinson’s disease (PD) remains unclear. This study aimed to investigate the intrinsic functional connectivity (FC) pattern of the DMN anchored on the posterior cingulate cortex (PCC) in patients with PD by resting-state functional magnetic resonance imaging (fMRI).MethodsFifty patients with PD and 50 healthy controls (HCs) were included for resting-state fMRI scanning. A seed-based FC method was used to reveal FC patterns in the DMN with region of interest (ROI) in the PCC. Relationships between FC patterns and disease severity (UPDRS-III) were detected.ResultsCompared with the HCs, the patients with PD showed increased FC between the PCC and the right precuneus, left cuneus, and right angular gyrus. In the PD group, the increased FC values in the right precuneus were significantly and positively correlated with motor severity as assessed with UPDRS-III scores (rho = 0.337, p = 0.02).ConclusionOur result highlights that the patients with PD showed increased FC between the PCC and the right precuneus, left cuneus, and right angular gyrus in the DMN. The altered connectivity pattern in the DMN may play a crucial role in the neurophysiological mechanism of cognitive decline in patients with PD. These findings might provide new insights into neural mechanisms of cognitive decline in PD.

Objective To provide a new approach to further elucidate the underlying pathogenesis of major depressive disorder by using resting-state functional connectivity strengths(FCS) in unmedicated patients with major depressive disorder(MDD). Methods Thirty-three unmedicated patients with MDD and thirty-three normal controls underwent the resting-state functional magnetic resonance imaging(rs-fMRI).After preprocessing of rs-fMRI, the whole brain FCS values were constructed. Two-sample t-test was used to compare the FCS values of both groups to locate the regions with significant change. And correlation analysis was performed between the FCS values extracted from significantly different brain regions and Hamilton Depression Scale (HAMD24) scores. Results One sample t test had shown that high FCS values brain areas (hubs) of MDD patients and normal controls were mainly located in the default mode network (the prefrontal cortex, anterior cingulate gyrus, posterior cingulate gyrus, precuneus/cuneus, angular gyrus) and parietal cortex, lateral temporal cortex as well as occipital cortex. In comparison to the normal controls, the MDD patients had FCS values significantly decreased in the bilateral posterior cerebellar lobe (right posterior cerebellar t=-4.57, P<0.05; left posterior cerebellar t=-3.40,P<0.05), and FCS values increased in the right superior temporal gyrus (t=3.71,P<0.05) and left anterior insular lobe (t=3.91, P<0.05). There were no significant correlations between the HAMD24 scores and the FCS values in right/left posterior cerebellar (r=0.081, P=0.654; r=-0.028, P=0.877), right superior temporal gyrus (r=0.211, P=0.239) and left anterior insular lobe (r=-0.017,P=0.924). Conclusions These findings suggest abnormal functional connectivity in the bilateral posterior cerebellar lobe, right temporal lobe and left insular lobe in MDD. The FCS analysis may be used as a new research method to explore the pathogenesis of MDD. Key words: Depressive disorder; Resting state; Functional connectivity strengths

目的 探讨精神分裂症患者脑静息态默认网络、中心执行网络及突显网络的网络内及网络间的功能连接特点.方法 对74例精神分裂症患者(患者组)和79名相匹配的健康者(对照组)进行静息态fMRI扫描.采取功能连接分析方法,以内侧前额叶皮质及右侧前岛叶为感兴趣区域分别提取默认网络、中心执行网络及突显网络,分析3个网络内及网络间静息态功能连接情况;并对有差异的功能连接与精神症状及病程等进行偏相关分析.结果 与对照组相比,患者组内侧前额叶皮质与双侧背外侧前额叶皮质(左侧-0.02±0.18与-0.12±0.12,t=4.25,P＜0.01;右侧-0.02±0.11与-0.10±0.10,t=5.40,P＜0.01)、双侧豆状壳核(左侧0.14±0.12与0.04±0.10,t=5.03,P＜0.01;右侧0.13±0.11与0.03±0.98,t=4.96,P＜0.01)的功能连接增强;右侧前岛叶与左侧额中回(-0.05±0.17与-0.07±0.17,t=4.60,P＜0.01)及楔前叶/后扣带回(0.01±0.13与-0.09±0.14,t=4.01,P＜0.01)的功能连接增强(均采用高斯随机场理论校正,体素水平P＜0.01,簇水平P＜0.05);默认网络与中心执行网络、突显网络间的负向功能连接减小甚至消失(Bonferroni校正P＜0.05).患者组PANSS阳性症状分与右侧前岛叶与楔前叶/后扣带回皮质间的功能连接呈正相关(r=0.232,P=0.025);患者组病程与右侧前岛叶与左侧额中回(r=0.288,P=0.007)、楔前叶/后扣带回(r=0.196,P=0.049)间的功能连接呈正相关.结论 精神分裂症患者存在静息态默认网络、中心执行网络及突显网络3个网络间的连接异常,可能与精神分裂症的病理机制有关.

The neural substrates of posttraumatic stress disorder (PTSD) are still not fully elucidated. Hence, this study is to explore topological alterations of the default mode network (DMN) in victims with PTSD after a magnitude of 8.0 earthquake using resting-state functional magnetic resonance imaging (rs-fMRI).This study was approved by the local ethical review board, and all participants signed written informed consent. Sixty-two PTSD victims from the 2008 Sichuan earthquake and 62 matched exposed controls underwent rs-fMRI. PTSD was diagnosed by Clinician-Administered PTSD Scale, and underwent PTSD Checklist-Civilian Version for symptom scoring. The DMN was analyzed by using graph theoretical approaches. Further, Pearson correlation analysis was performed to correlate neuroimaging metrics to neuropsychological scores in victims with PTSD.Victims with PTSD showed decreased DMN functional connectivity strength between the right superior frontal gyrus and left inferior parietal lobule (IPL), and showed increased functional connectivity between the right IPL and precuneus or left posterior cingulate cortex. It was also found that victims with PTSD exhibited decreased nodal efficiency in right superior frontal gyrus and precuneus, and increased nodal efficiency in right hippocampus/parahippocampus. Apart from that, PTSD showed higher nodal degree in bilateral hippocampus/parahippocampus. In addition, the functional connectivity strength between the right IPL and precuneus correlated negatively to the avoid scores (r = -0.26, P = .04).This study implicates alteration of topological features on the DMN in PTSD victims after major earthquake, and provides new insights into DMN malfunction in PTSD based on graph theory.

Patients with schizophrenia exhibit impairments in working memory that often appear in attenuated form in persons at high risk for the illness. The authors hypothesized that deviations in task-related brain activation and deactivation would occur in persons with an at-risk mental state performing a working memory task that entailed the maintenance and manipulation of letters. Participants at ultra high risk for developing psychosis (N=60), identified using the Comprehensive Assessment of At-Risk Mental States, and healthy comparison subjects (N=38) 14 to 29 years of age underwent functional MRI while performing a verbal working memory task. Group differences in brain activation were identified using analysis of covariance. The two groups did not show significant differences in speed or accuracy of performance, even after accounting for differences in education. Irrespective of task condition, at-risk participants exhibited significantly less activation than healthy comparison subjects in the left anterior insula. During letter manipulation, at-risk persons exhibited greater task-related deactivation within the default-mode network than comparison subjects. Region-of-interest analysis in the at-risk group revealed significantly greater right dorsolateral prefrontal cortex activation during manipulation of letters. Despite comparable behavioral performance, at-risk participants performing a verbal working memory task exhibited altered brain activation compared with healthy subjects. These findings demonstrate an altered pattern of brain activation in at-risk persons that contains elements of reduced function as well as compensation.

Obsessive-compulsive disorder (OCD) is a chronic psychiatric illness with complex clinical manifestations. Cognitive dysfunction may underlie OC symptoms. The frontoparietal network (FPN) is a key region involved in cognitive control. However, the findings of impaired FPN regions have been inconsistent. We employed meta-analysis to identify the fMRI-specific abnormalities of the FPN in OCD. PubMed, Web of Science, Scopus, and EBSCOhost were searched to screen resting-state functional magnetic resonance imaging (rs-fMRI) studies exploring dysfunction in the FPN of OCD patients using three indicators: the amplitude of low-frequency fluctuation/fractional amplitude of low-frequency fluctuation (ALFF/fALFF), regional homogeneity (ReHo) and functional connectivity (FC). We compared all patients with OCD and control group in a primary analysis, and divided the studies by medication in secondary meta-analyses with the activation likelihood estimation (ALE) algorithm. A total of 31 eligible studies with 1359 OCD patients (756 men) and 1360 healthy controls (733 men) were included in the primary meta-analysis. We concluded specific changes in brain regions of FPN, mainly in the left dorsolateral prefrontal cortex (DLPFC, BA9), left inferior frontal gyrus (IFG, BA47), left superior temporal gyrus (STG, BA38), right posterior cingulate cortex (PCC, BA29), right inferior parietal lobule (IPL, BA40) and bilateral caudate. Additionally, altered connectivity within- and between-FPN were observed in the bilateral DLPFC, right cingulate gyrus and right thalamus. The secondary analyses showed improved convergence relative to the primary analysis. OCD patients showed dysfunction FPN, including impaired local important nodal brain regions and hypoconnectivity within the FPN (mainly in the bilateral DLPFC), during the resting state. Moreover, FPN appears to interact with the salience network (SN) and default mode network (DMN) through pivotal brain regions. Consistent with the hypothesis of fronto-striatal circuit dysfunction, especially in the dorsal cognitive circuit, these findings provide strong evidence for integrating two pathophysiological models of OCD.

Neuroimaging studies have demonstrated that irritable bowel syndrome (IBS)—a relapsing functional bowel disorder—presents with disrupted brain connections. However, little is known about the alterations of interhemispheric functional connectivity and underlying structural connectivity in IBS. This study combined resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI) to investigate changes in interhemispheric coordination in IBS patients. Resting-state functional and structural magnetic resonance images were acquired from 65 IBS patients and 67 healthy controls (HCs; matched for age, sex and educational level). Interhemispheric voxel-mirrored homotopic connectivity (VMHC) was calculated and compared between groups. Homotopic regions showing abnormal VMHC in patients were targeted as regions of interest (ROIs) for analysis of DTI tractography. The fractional anisotropy (FA), fiber number and fiber length were compared between groups. Statistical analysis was also performed by including anxiety and depression as covariates to evaluate their effect. A Pearson correlation analysis between abnormal interhemispheric connectivity and clinical indices of IBS patients was performed. Compared to HCs, IBS patients had higher interhemispheric functional connectivity between bilateral thalami, cuneus, posterior cingulate cortices (PCC), lingual gyri and inferior occipital/cerebellum lobes, as well as lower interhemispheric functional connectivity between bilateral ventral anterior cingulate cortices (vACC) and inferior parietal lobules (IPL). The inclusion of anxiety and depression as covariates abolished VMHC difference in vACC. Microstructural features of white matter tracts connecting functionally abnormal regions did not reveal any differences between the groups. VMHC values in vACC negatively correlated with the quality of life (QOL) scores of patients. In conclusion, this study provides preliminary evidence of the disrupted functional coordination rather than anatomic coordination between interhemispheric regions within the cortex-thalamus circuit in IBS patients, which could partly account for the enhanced visceral information processing and impaired endogenous pain or emotion inhibition associated with IBS.

Functional neuroimaging studies of epilepsy patients often show, at the time of epileptic activity, deactivation in default mode network (DMN) regions, which is hypothesized to reflect altered consciousness. We aimed to study the metabolic and electrophysiological correlates of these changes in the DMN regions. We studied six epilepsy patients that underwent scalp EEG-fMRI and later stereotaxic intracerebral EEG (SEEG) sampling regions of DMN (posterior cingulate cortex, Pre-cuneus, inferior parietal lobule, medial prefrontal cortex and dorsolateral frontal cortex) as well as non-DMN regions. SEEG recordings were subject to frequency analyses comparing sections with interictal epileptic discharges (IED) to IED-free baselines in the IED-generating region, DMN and non-DMN regions. EEG-fMRI and SEEG were obtained at rest. During IEDs, EEG-fMRI demonstrated deactivation in various DMN nodes in 5 of 6 patients, most frequently the pre-cuneus and inferior parietal lobule, and less frequently the other DMN nodes. SEEG analyses demonstrated decrease in gamma power (50–150 Hz), and increase in the power of lower frequencies (<30 Hz) at times of IEDs, in at least one DMN node in all patients. These changes were not apparent in the non-DMN regions. We demonstrate that, at the time of IEDs, DMN regions decrease their metabolic demand and undergo an EEG change consisting of decreased gamma and increased lower frequencies. These findings, specific to DMN regions, confirm in a pathological condition a direct relationship between DMN BOLD activity and EEG activity. They indicate that epileptic activity affects the DMN, and therefore may momentarily reduce the consciousness level and cognitive reserve.

SEE BIGLER DOI101093/AWW277 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Post-traumatic amnesia is very common immediately after traumatic brain injury. It is characterized by a confused, agitated state and a pronounced inability to encode new memories and sustain attention. Clinically, post-traumatic amnesia is an important predictor of functional outcome. However, despite its prevalence and functional importance, the pathophysiology of post-traumatic amnesia is not understood. Memory processing relies on limbic structures such as the hippocampus, parahippocampus and parts of the cingulate cortex. These structures are connected within an intrinsic connectivity network, the default mode network. Interactions within the default mode network can be assessed using resting state functional magnetic resonance imaging, which can be acquired in confused patients unable to perform tasks in the scanner. Here we used this approach to test the hypothesis that the mnemonic symptoms of post-traumatic amnesia are caused by functional disconnection within the default mode network. We assessed whether the hippocampus and parahippocampus showed evidence of transient disconnection from cortical brain regions involved in memory processing. Nineteen patients with traumatic brain injury were classified into post-traumatic amnesia and traumatic brain injury control groups, based on their performance on a paired associates learning task. Cognitive function was also assessed with a detailed neuropsychological test battery. Functional interactions between brain regions were investigated using resting-state functional magnetic resonance imaging. Together with impairments in associative memory, patients in post-traumatic amnesia demonstrated impairments in information processing speed and spatial working memory. Patients in post-traumatic amnesia showed abnormal functional connectivity between the parahippocampal gyrus and posterior cingulate cortex. The strength of this functional connection correlated with both associative memory and information processing speed and normalized when these functions improved. We have previously shown abnormally high posterior cingulate cortex connectivity in the chronic phase after traumatic brain injury, and this abnormality was also observed in patients with post-traumatic amnesia. Patients with post-traumatic amnesia showed evidence of widespread traumatic axonal injury measured using diffusion magnetic resonance imaging. This change was more marked within the cingulum bundle, the tract connecting the parahippocampal gyrus to the posterior cingulate cortex. These findings provide novel insights into the pathophysiology of post-traumatic amnesia and evidence that memory impairment acutely after traumatic brain injury results from altered parahippocampal functional connectivity, perhaps secondary to the effects of axonal injury on white matter tracts connecting limbic structures involved in memory processing.

To explore the spatial patterns of the amplitude of low-frequency fluctuation (ALFF) in patients with hepatic encephalopathy (HE) of varying severity and to correlate these fluctuations with clinical markers of HE. This study was approved by the local ethics committee, and written informed consent was obtained from all participants. Twenty-nine patients with HE (15 with overt and 14 with minimal HE) and 17 healthy control subjects underwent resting-state functional magnetic resonance (MR) imaging. The ALFF, an index reflecting the amplitudes of spontaneous brain activity, was compared among patients with overt HE, patients with minimal HE, and control subjects with analysis of variance tests and t tests between each pair. Pearson correlation analysis was performed between the ALFF and the venous blood ammonia level and Child-Pugh score of all patients with HE. Compared with control subjects, patients with overt and minimal HE showed decreased ALFF mainly in regions within the default-mode network (DMN) and increased ALFF in the cerebellum and middle temporal gyrus. Compared with patients with minimal HE, those with overt HE showed decreased ALFF in DMN regions and increased ALFF in the posterior insular cortex (P<.05, corrected for multiple comparisons). Both the venous blood ammonia levels and Child-Pugh scores of individual patients with HE showed negative correlation with ALFF within some DMN regions, whereas they showed positive correlation with ALFF in the posterior insular cortex (P<.05, corrected for multiple comparisons). Patients with HE have diffuse abnormalities in intrinsic brain activity. The levels of decreased ALFF in the DMN and increased ALFF in the posterior insular cortex are dependent on the severity of HE, suggesting continuous impairment of the DMN and a compensatory role of the insula during the progression of HE. Resting-state functional MR imaging with ALFF analysis may be a noninvasive modality with which to detect the progression of HE.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder usually presenting as reduced social interaction, lessened verbal communication, and repetitive behavior. Diagnosing autism spectrum disorder is extremely difficult because of its wide variety of symptoms, so it can only be diagnosed through behavioral tests and analysis of developmental history. Resting-state functional magnetic resonance imaging (rs-fMRI) can help researchers discover a neural substrate for autism spectrum disorder to diagnose it earlier. One prominent fMRI database for autism spectrum disorder research is the Autism Brain Imaging Data Exchange, a large-scale collection of anonymized functional MRI scans subdivided by age, gender, handedness, and scores on behavioral assessments. This analysis focused on two brain networks: the default mode network (DMN), which is active when minds wander, and the executive network, which is active during the performance of tasks. The medial prefrontal cortex (mPFC), posterior cingulate cortex (PCC), and angular gyrus are nodes of the default mode network, and the dorsolateral prefrontal cortex (DLPFC) is the main node in the executive network. Both networks are affected by autism spectrum disorder. This research used preprocessed resting-state fMRI data to establish neurocognitive phenotypes for autism spectrum disorder. Bivariate correlation was used to compare connectivity in the default mode network and dorsolateral prefrontal cortex between autism spectrum disorder fMRI scans and control fMRI scans, and these differences were analyzed for correlations with each patient’s assessment scores. After the Benjamini-Hochberg procedure was applied to reduce the false discovery rate, analysis of these metrics revealed that in autism spectrum disorder patients there was underconnectivity between the right posterior cingulate cortex and the right medial prefrontal cortex, while in control patients there was overconnectivity between the right angular gyrus and left dorsolateral prefrontal cortex. Autism spectrum disorder is extremely heritable, so phenotypic research is absolutely necessary for discovering more about the genetic causes of autism spectrum disorder, which will speed up autism spectrum disorder diagnosis and help researchers develop more targeted treatments for autism spectrum disorder.

Objective: To study resting-state functional connectivity (FC) of default mode network (DMN) in adolescent patients with first-episode drug-naive major depressive disorder (MDD). Methods: We enrolled thirty first-episode and drug-naive adolescent MDD patients and twenty-nine adolescent healthy control (HC) participants in the First Affiliated Hospital of Zhengzhou University. There were no differences in age, sex, and education between the MDD and HC group. Resting-state functional magnetic resonance images (fMRI) was performed. We selected posterior cingulate cortex (PCC) and medial prefrontal cortex (MPFC) of DMN as regions of interests (ROI). The differences of these regions from the whole brain functional connectivity were analyzed. The relations between abnormalities in FCs of DMN and clinical variables were further investigated. Results: Compared to the HCs, the MDD patients had congruently reduced FCs between the PCC and cerebellum, temporal cortices, occipital cortices, fusiform, dorsolateral prefrontal cortex. MPFC not only had reduced FCs with fusiform, temporal cortices, anterior cingulate cortex, but also had enhanced FCs with occipital cortices, parietal cortices, and precentral gyrus. In addition, the increased FC between the right MPFC and right precentral gyrus was positive correlated with Hamilton Rating Scale for Depression (HAMD) scores (r=0.38, P=0.04). The reduced FC between the left middle temporal gyrus and left PCC as well as the enhanced FC between the right middle cingulum and right MPFC were positive correlated with the duration of depression since onset (r=0.39, P=0.03; r=0.38, P=0.04). Conclusions: These findings show dysfunctional DMN connectivity of adolescent MDD patients. Neurodevelopmental abnormalities in DMN may present in adolescent MDD.