Lower Functional Connectivity Research Articles

Limbic Connectivity Underlies Pain Treatment Response in Small-Fiber Neuropathy.

Small-fiber neuropathy (SFN) is characterized by neuropathic pain due to degeneration of small-diameter nerves in the skin. Given that brain reorganization occurs following chronic neuropathic pain, this study investigated the structural and functional basis of pain-related brain changes after skin nerve degeneration. Diffusion-weighted and resting-state functional MRI data were acquired from 53 pathologically confirmed SFN patients, and the structural and functional connectivity of the pain-related network was assessed using network-based statistic (NBS) analysis. Compared with age- and sex-matched controls, the SFN patients exhibited a robust and global reduction of functional connectivity, mainly across the limbic and somatosensory systems. Furthermore, lower functional connectivity was associated with skin nerve degeneration measured by reduced intraepidermal nerve fiber density and better therapeutic response to anti-neuralgia medications, particularly for the connectivity between the insula and the limbic areas including the anterior and middle cingulate cortices. Similar to the patterns of functional connectivity changes, the structural connectivity was robustly reduced among the limbic and somatosensory areas, and the cognition-integration areas including the inferior parietal lobule. There was shared reduction of structural and functional connectivity among the limbic, somatosensory, striatal, and cognition-integration systems: (1) between the middle cingulate cortex and inferior parietal lobule and (2) between the thalamus and putamen. These observations indicate the structural basis underlying altered functional connectivity in SFN. Our findings provide imaging evidence linking structural and functional brain dysconnectivity to sensory deafferentation caused by peripheral nerve degeneration and therapeutic responses for neuropathic pain in SFN. ANN NEUROL 2023;93:655-667.

Adaptive working memory training does not produce transfer effects in cognition and neuroimaging

Despite growing interest in cognitive interventions from academia and industry, it remains unclear if working memory (WM) training, one of the most popular cognitive interventions, produces transfer effects. Transfer effects are training-induced gains in performance in untrained cognitive tasks, while practice effects are improvements in trained task. The goal of this study was to evaluate potential transfer effects by comprehensive cognitive testing and neuroimaging. In this prospective, randomized-controlled, and single-blind study, we administered an 8-week n-back training to 55 healthy middle-aged (50–64 years) participants. State-of-the-art multimodal neuroimaging was used to examine potential anatomic and functional changes. Relative to control subjects, who performed non-adaptive WM training, no near or far transfer effects were detected in experimental subjects, who performed adaptive WM training. Equivalently, no training-related changes were observed in white matter integrity, amplitude of low frequency fluctuations, glucose metabolism, functional and metabolic connectivity. Exploratory within-group comparisons revealed some gains in transfer tasks, which, however, cannot be attributed to an increased WM capacity. In conclusion, WM training produces transfer effects neither at the cognitive level nor in terms of neural structure or function. These results speak against a common view that training-related gains reflect an increase in underlying WM capacity. Instead, the presently observed practice effects may be a result of optimized task processing strategies, which do not necessarily engage neural plasticity.

Mild behavioral impairment and functional connectivity in dementia‐free elderly

AbstractBackgroundMild Behavioral Impairment (MBI), characterized by de novo emergent and persistent neuropsychiatric symptoms in later life, may be used to improve early detection of neurodegenerative disease. While alterations in resting‐state networks have been demonstrated in early‐stage Alzheimer’s disease (AD), few studies have explored these networks in MBI. Here, we assessed activity in the default mode network (DMN) and the salience network (SN), using resting‐state functional magnetic resonance imaging (fMRI), in association with MBI. We hypothesized that the strength of functional connectivity (FC) within the DMN and SN would be reduced in dementia‐free persons with MBI (MBI+), relative to those without (MBI‐).MethodsData from dementia‐free participants in three prospective cohort studies were pooled. MBI+ status was determined using the MBI‐checklist. Imaging data were acquired using 3T MRI. Seed‐based connectivity analyses were performed using the CONN toolbox. The DMN included the posterior cingulate cortex (PCC), medial prefrontal cortex (MPFC), and lateral parietal (LP) regions, with the PCC as the seed. The SN included the anterior cingulate cortex (ACC), anterior insula (AI), rostral prefrontal cortex (RPFC), and supramarginal gyrus (SMG), with the ACC as the seed. FC maps of the DMN and SN were computed for each MBI group; difference maps were extracted to identify regions with significantly different connectivity across MBI groups. A threshold of p<0.05 was used with false discovery rate correction for multiple comparisons at the cluster level; a p<0.001 uncorrected for voxel level was used for group comparisons. All analyses were covaried for age, sex, years of education, and Montreal Cognitive Assessment scores.ResultsOf the 95 participants, 32 were MBI+ and 63 MBI‐ (mean age 71.7; 54.7% female). Within the DMN, MBI+ individuals had lower functional connectivity between the PCC and MPFC, compared to MBI‐ (β=‐0.15, p=0.004). Within the SN, MBI+ was associated with lower functional connectivity between the ACC and left AI (β=‐0.12, p=0.028).ConclusionOur findings suggest that in dementia‐free individuals, MBI is associated with decreased functional connectivity in networks disrupted in AD. This result lends additional support to MBI as a potential early marker of disease.

Altered functional connectivity: A possible reason for reduced performance during visual cognition involving scene incongruence and negative affect.

Object-context associations and valence are two unavoidable stimulus characteristics when it comes to the processing of natural visual scenes. In line with our previous studies exploring the parallel processing of context-congruity and valence, in the current study, we investigated the valence-specific differences in functional connectivity between congruent-incongruent picture pairs during binocular rivalry using high-density EEG. The functional connectivity measure was calculated using sLORETA during the perceptual dominance of congruent and incongruent stimuli in a time window of 400ms before the response and compared within and between positive, negative, and neutral valence categories (84 Brodmann's areas across 7 frequency bands) using t-tests. A significant difference in functional connectivity between congruent-incongruent picture pairs was seen only when associated with negative valence and a maximum number of area pairs showed differences in lower alpha 1 (7.1-9Hz), upper alpha (11.1-13Hz), and beta (13.1-30Hz) frequency bands. The functional connectivity was significantly lower during incongruent perception between the area pairs which process mainly emotion, attention, memory, and semantic relations compared to their corresponding congruent stimuli. Similarly, negative incongruent percepts were found to have significantly lower connectivity between areas processing attention, emotion, and incongruence in the lower alpha 2 (9.1-11Hz) band when compared to positive incongruent percepts. Together, these results suggest that the perception of negative incongruence is associated with lower functional connectivity and this could be a possible reason for the increased error rates when faced with incongruity and negative affect during visual tasks.

Default mode network and medial temporal lobe functional connectivity changes with Alzheimer’s disease severity and cognitive impairment in individuals with Down syndrome

AbstractBackgroundBy age 40, virtually all people with Down syndrome (DS) have sufficient beta‐amyloid and tau pathologies present to meet the criteria for pathological Alzheimer's disease (AD). Determining the timing and location of neurobiological changes caused by AD is critically important for effective intervention within this high‐risk population and more broadly in the general population, but little is known about the brain changes associated with clinical onset of AD in DS. Previous studies in sporadic AD suggest that functional connectivity of the default mode network (DMN) and medial temporal lobe (MTL) is vulnerable to AD pathology‐related impairment.MethodSeventy‐five individuals with DS (mean age 49.9±6.6, 36% women) from a subset of the Alzheimer’s Biomarkers Consortium ‐ Down Syndrome study underwent MRI, including an MPRAGE scan and a resting state functional scan. Participants completed a battery of neuropsychological tests and were assigned a consensus diagnosis for the presence or absence of mild cognitive impairment (MCI‐DS) or AD dementia. Forty‐eight participants were classified as cognitively stable (CS) (mean age 48±6.1, 42% women), 16 participants had MCI‐DS (mean age 50.8±4.2, 19% women), and 11 participants had dementia (mean age 57.2±6.6, 36% women).ResultParticipants with dementia had lower functional connectivity between the posterior DMN and the MTL relative to the CS and MCI‐DS groups. MCI‐DS participants had greater functional connectivity within the MTL relative to the CS group. Functional connectivity differences in these networks tracked with memory performance as well.ConclusionChanges in DMN and MTL functional connectivity are related to the progression of clinical symptoms of AD‐DS and may reflect synaptic changes stemming from AD pathology.

Differential effects of age and sex on medial temporal lobe networks revealed by longitudinal analyses across the adult lifespan

AbstractBackgroundThe medial temporal lobe (MTL) is extensively connected to the rest of the brain through two specific networks which are particularly affected in Alzheimer’s disease (AD): the anterior‐temporal (AT) and posterior‐medial (PM) systems. As the specific and respective effects of age and sex on the functional integrity of these networks are still largely unknown, we sought to fill this gap using longitudinal data spanning the entire adult life.MethodLongitudinal data from 215 cognitively unimpaired adults (aged 19‐85, including 113 females, followed‐up up to 47 months, 419 scans) were analysed. Seed‐based analyses were applied to resting‐state functional magnetic resonance imaging to generate connectivity maps (seeds: the perirhinal cortex for AT and the parahippocampal cortex for PM). The AT and PM networks were defined by comparing baseline maps from adults younger than 40 using a paired permutation t‐test with threshold‐free cluster enhancement (TFCE) and familywise error (FWE) correction (p<.05) (Figure 1). These masks were then used to extract the mean functional connectivity (FC) for each participant. The interaction effects between network, age and sex were investigated using linear mixed models.ResultThere was a significant interaction between age and networks (p<.001), with a decrease of FC with age in PM and an increase in AT (Figure 2). Sex differences were also observed within these two systems (p<.001), with males exhibiting higher FC than females in AT but lower FC in PM (Figure 3). Age‐related trajectories were not modulated by sex differences (p>.05) and were best described by a linear relationship according to model comparison testing different polynomials.ConclusionBy encompassing the entire adult lifespan and assessing longitudinal changes, our study provides strong support that the two MTL networks display differential alterations in the context of aging, as well as sex differences. Since MTL connectivity has been described as particularly affected in the early stages of AD, and age and sex are risk factors, these findings may be helpful to enhance the clinical utility of such biomarkers for the early detection of AD‐related changes.

Differential effects of age and sex on medial temporal lobe networks revealed by longitudinal analyses across the adult lifespan

AbstractBackgroundThe medial temporal lobe (MTL) is extensively connected to the rest of the brain through two specific networks which are particularly affected in Alzheimer’s disease (AD): the anterior‐temporal (AT) and posterior‐medial (PM) systems. As the specific and respective effects of age and sex on the functional integrity of these networks are still largely unknown, we sought to fill this gap using longitudinal data spanning the entire adult life.MethodLongitudinal data from 215 cognitively unimpaired adults (aged 19‐85, including 113 females, followed‐up up to 47 months, 419 scans) were analysed. Seed‐based analyses were applied to resting‐state functional magnetic resonance imaging to generate connectivity maps (seeds: the perirhinal cortex for AT and the parahippocampal cortex for PM). The AT and PM networks were defined by comparing baseline maps from adults younger than 40 using a paired permutation t‐test with threshold‐free cluster enhancement (TFCE) and familywise error (FWE) correction (p<.05) (Figure 1). These masks were then used to extract the mean functional connectivity (FC) for each participant. The interaction effects between network, age and sex were investigated using linear mixed models.ResultThere was a significant interaction between age and networks (p<.001), with a decrease of FC with age in PM and an increase in AT (Figure 2). Sex differences were also observed within these two systems (p<.001), with males exhibiting higher FC than females in AT but lower FC in PM (Figure 3). Age‐related trajectories were not modulated by sex differences (p>.05) and were best described by a linear relationship according to model comparison testing different polynomials.ConclusionBy encompassing the entire adult lifespan and assessing longitudinal changes, our study provides strong support that the two MTL networks display differential alterations in the context of aging, as well as sex differences. Since MTL connectivity has been described as particularly affected in the early stages of AD, and age and sex are risk factors, these findings may be helpful to enhance the clinical utility of such biomarkers for the early detection of AD‐related changes.

Correlations between Hippocampus and Cognitive Score in Patients with Carotid Artery Stenosis Based on Resting State Functional Magnetic Resonance Imaging

Objective To investigate the correlations among brain functional connectivity,hippocampal subregion volume and cognitive score in the patients with carotid artery stenosis(CAS)based on resting state functional magnetic resonance imaging.Methods Forty CAS patients treated in the Nanjing Drum Tower Hospital Affiliated to Medical School of Nanjing University from January to December in 2019 and 31 healthy volunteers were enrolled in this study.All the participants underwent cognitive assessment,structural MRI for the measurement of hippocampal volume,and resting state functional magnetic resonance imaging for the examination of brain functional connectivity(FC).We compared the cognitive function,hippocampal subregion volumes,and brain functional connectivity between the two groups and investigated the correlations between the three indicators.Results The CAS patients had lower mini-mental state examination(MMSE)(F=13.346,P=0.001)and Montreal cognitive assessment(MoCA)(F=52.005,P<0.001)scores than the healthy volunteers.Compared with healthy volunteers,CAS patients showed small whole hippocampus(right side:t=2.176,P=0.033;left side:t=2.881,P=0.005;especially on the left side),small hippocampal tail(right side:t=2.394,P=0.019;left side:t=3.158,P=0.002),small hippocampal body(right side:t=2.336,P=0.022;left side:t=3.165,P=0.002),small subiculum(right side:t=2.211,P=0.030;left side:t=2.430;P=0.018),and small molecular layer(right side:t=2.103,P=0.039;left side:t=2.702,P=0.009).The whole hippocampal volume was positively correlated with MoCA and MMSE scores(left MoCA:r=0.289,P=0.015;right MMSE:r=0.249,P=0.038;left MMSE:r=0.316,P=0.008).The volume changes in the subiculum,presubiculum,and left molecular layer were positively correlated with MoCA(right subiculum:r=0.290,P=0.015;left subiculum:r=0.382,P=0.001;right presubiculum:r=0.293,P=0.014;left presubiculum:r=0.440,P<0.001;left molecular layer:r=0.259,P=0.031)and MMSE scores(right subiculum:r=0.278,P=0.020;left subiculum:r=0.419,P<0.001;right presubiculum:r=0.296,P=0.013;left presubiculum:r=0.506,P<0.001;left molecular layer:r=0.298,P=0.012),while the volume changes in the remaining hippocampal subregions were not correlated with cognitive scores(all P>0.05).Compared with healthy volunteers,the CAS patients presented low FC values of the left hippocampus to the occipital lobe and frontal lobe and of right hippocampus to the occipital lobe,temporal lobe,prefrontal lobe,and middle frontal gyrus(Gaussian random field correction,voxel P<0.01,cluster P<0.05).The volume changes of the left whole hippocampus,hippocampal head,and cornu ammonis 1(CA1)were positively correlated with the FC value of right hippocampus to the temporal lobe(left whole hippocampus:r=0.358,P=0.025;right hippocampal head:r=0.325,P=0.044;left hippocampal head:r=0.360,P=0.024;right CA1:r=0.326,P=0.043;left CA1:r=0.341,P=0.034).MoCA and MMSE scores were positively correlated with the FC value of right hippocampus to the frontal lobe(MoCA middle frontal gyrus:r=0.389,P=0.014;MoCA prefrontal lobe:r=0.363,P=0.023;MMSE prefrontal lobe:r=0.321,P=0.046).Conclusions CAS patients have different levels of cognitive impairment.Hippocampal atrophy and a decline in the FC value of hippocampus to the occipital lobe may play a role in cognitive impairment in CAS patients.This discovery lays a foundation for the future research on the mechanism of cognitive dysfunction in CAS patients.

The effect of low-frequency rTMS on auditory hallucinations, EEG source localization and functional connectivity in schizophrenia

BackgroundLow-frequency repetitive transcranial magnetic stimulation (LF-rTMS) diminishes auditory hallucinations (AHs). The aims of our study were a) to assess the efficacy of LF-rTMS in a randomized, sham-controlled double-blind alignment, b) to identify the electrophysiological changes accompanying the LF-rTMS, and c) to identify the influence of LF-rTMS on brain functional connectivity (FC). MethodsNineteen schizophrenia patients with antipsychotic-resistant AHs were randomized to either active (n = 10) or sham (n = 9) LF-rTMS administered over the left temporo-parietal region for ten days. The clinical effect was assessed by the Auditory Hallucination Rating Scale (AHRS). The localization of the differences in electrical activity was identified by standardized low resolution brain electromagnetic tomography (sLORETA) and FC was measured by lagged phase synchronization. ResultsAHRS scores were significantly improved for patients receiving active rTMS compared to the sham (median reduction: 40 % vs 12 %; p = 0.01). sLORETA revealed a decrease of alpha-2, beta-1,-2 bands in the left hemisphere in the active group. Active rTMS led to a decrease of the lagged phase connectivity in beta bands originating in areas close to the site of stimulation, and to a prevailing increase of alpha-2 FC. No significant differences in current density or FC were observed in the sham group. LimitationsLimitations to our study included the small group sizes, and the disability of LORETA to assess subcortical neuronal activity. ConclusionsLF-rTMS attenuated AHs and induced a decrease of higher frequency bands on the left hemisphere. The FC changes support the assumption that LF-rTMS is linked to the modulation of cortico-cortical coupling.

Characterization of Resting-State Striatal Differences in First-Episode Depression and Recurrent Depression.

The presence of reward deficits in major depressive disorder is associated with abnormal striatal function. However, differences in striatal whole-brain functional between recurrent depressive episode (RDE) and first-episode depression (FDE) have not been elucidated. Thirty-three patients with RDE, 27 with FDE, and 35 healthy controls (HCs) were recruited for this study. A seed-based functional connectivity (FC) method was used to analyze abnormalities in six predefined striatal subregion circuits among the three groups of subjects and to further explore the correlation between abnormal FC and clinical symptoms. The results revealed that compared with the FDE group, the RDE group showed higher FC of the striatal subregion with the left middle occipital gyrus, left orbital area of the middle frontal gyrus, and bilateral posterior cerebellar gyrus, while showing lower FC of the striatal subregion with the right thalamus, left inferior parietal lobule, left middle cingulate gyrus, right angular gyrus, right cerebellum anterior lobe, and right caudate nucleus. In the RDE group, the HAMD-17 scores were positively correlated with the FC between the left dorsal rostral putamen and the left cerebellum posterior lobe. This study provides new insights into understanding the specificity of striatal circuits in the RDE group.

Altered functional connectivity pattern of hippocampal subfields in individuals with objectively-defined subtle cognitive decline and its association with cognition and cerebrospinal fluid biomarkers.

Recent studies have shown that in the preclinical phase of Alzheimer's disease (AD), subtle cognitive changes can be detected using sensitive neuropsychological measures, and have proposed the concept of objectively-defined subtle cognitive decline (Obj-SCD). We aimed to assess the functional alteration of hippocampal subfields in individuals with Obj-SCD and its association with cognition and pathological biomarkers. Forty-two participants with cognitively normal (CN), 29 with Obj-SCD, and 55 with mild cognitive impairment (MCI) were retrospectively collected from the ADNI database. Neuropsychological performance, functional MRI, and cerebrospinal fluid (CSF) data were obtained. We calculated the seed-based functional connectivity (FC) of hippocampal subfields (cornu ammonis1 [CA1], CA2/3/dentate gyrus [DG], and subiculum) with whole-brain voxels. Additionally, we analyzed the correlation between FC values of significantly altered regions and neuropsychological performance and CSF biomarkers. The Obj-SCD group showed lower FC between left CA1-CA2/3/DG and right thalamus and higher FC between right subiculum and right superior parietal gyrus (SPG) compared with the CN and MCI groups. In the Obj-SCD group, FC values between left CA2/3/DG and right thalamus were positively associated with Auditory Verbal Learning Test (AVLT) recognition (r = 0.395, p = 0.046) and CSF Aβ1-42 levels (r = 0.466, p = 0.019), and FC values between left CA1 and right thalamus were positively correlated with CSF Aβ1-42 levels (r = 0.530, p = 0.006). Taken together, dysfunction in CA1-CA2/3/DG subregions suggests subtle cognitive impairment and AD-specific pathological changes in individuals with Obj-SCD. Additionally, increased subiculum connectivity may indicate early functional compensation for subtle cognitive changes.

Mechanisms of imbalanced frontostriatal functional connectivity in obsessive-compulsive disorder.

The diagnosis of obsessive-compulsive disorder (OCD) has been linked with changes in frontostriatal resting-state connectivity. However, replication of prior findings is lacking, and the mechanistic understanding of these effects is incomplete. To confirm and advance knowledge on changes in frontostriatal functional connectivity in OCD, participants with OCD and matched healthy controls underwent resting-state functional, structural and diffusion neuroimaging. Functional connectivity changes in frontostriatal systems were here replicated in individuals with OCD (n = 52) compared with controls (n = 45). OCD participants showed greater functional connectivity (t = 4.3, PFWE = 0.01) between the nucleus accumbens (NAcc) and the orbitofrontal cortex (OFC) but lower functional connectivity between the dorsal putamen and lateral prefrontal cortex (t = 3.8, PFWE = 0.04) relative to controls. Computational modelling suggests that NAcc-OFC connectivity changes reflect an increased influence of NAcc over OFC activity and reduced OFC influence over NAcc activity (posterior probability, Pp > 0.66). Conversely, dorsal putamen showed reduced modulation over lateral prefrontal cortex activity (Pp > 0.90). These functional deregulations emerged on top of a generally intact anatomical substrate. We provide out-of-sample replication of opposite changes in ventro-anterior and dorso-posterior frontostriatal connectivity in OCD and advance the understanding of the neural underpinnings of these functional perturbations. These findings inform the development of targeted therapies normalizing frontostriatal dynamics in OCD.

Resting-state functional connectivity for determining outcomes in upper extremity function after stroke: A functional near-infrared spectroscopy study

Functional near-infrared spectroscopy (fNIRS) is a non-invasive and promising tool to map the brain functional networks in stroke recovery. Our study mainly aimed to use fNIRS to detect the different patterns of resting-state functional connectivity (RSFC) in subacute stroke patients with different degrees of upper extremity motor impairment defined by Fugl-Meyer motor assessment of upper extremity (FMA-UE). The second aim was to investigate the association between FMA-UE scores and fNIRS-RSFC among different regions of interest (ROIs) in stroke patients. Forty-nine subacute (2 weeks-6 months) stroke patients with subcortical lesions were enrolled and were classified into three groups based on FMA-UE scores: mild impairment (n = 17), moderate impairment (n = 13), and severe impairment (n = 19). All patients received FMA-UE assessment and 10-min resting-state fNIRS monitoring. The fNIRS signals were recorded over seven ROIs: bilateral dorsolateral prefrontal cortex (DLPFC), middle prefrontal cortex (MPFC), bilateral primary motor cortex (M1), and bilateral primary somatosensory cortex (S1). Functional connectivity (FC) was calculated by correlation coefficients between each channel and each ROI pair. To reveal the comprehensive differences in FC among three groups, we compared FC on the group level and ROI level. In addition, to determine the associations between FMA-UE scores and RSFC among different ROIs, Spearman's correlation analyses were performed with a significance threshold of p < 0.05. For easy comparison, we defined the left hemisphere as the ipsilesional hemisphere and flipped the lesional right hemisphere in MATLAB R2013b. For the group-level comparison, the one-way ANOVA and post-hoc t-tests (mild vs. moderate; mild vs. severe; moderate vs. severe) showed that there was a significant difference among three groups (F = 3.42, p = 0.04) and the group-averaged FC in the mild group (0.64 ± 0.14) was significantly higher than that in the severe group (0.53 ± 0.14, p = 0.013). However, there were no significant differences between the mild and moderate group (MD ± SE = 0.05 ± 0.05, p = 0.35) and between the moderate and severe group (MD ± SE = 0.07 ± 0.05, p = 0.16). For the ROI-level comparison, the severe group had significantly lower FC of ipsilesional DLPFC-ipsilesional M1 [p = 0.015, false discovery rate (FDR)-corrected] and ipsilesional DLPFC-contralesional M1 (p = 0.035, FDR-corrected) than those in the mild group. Moreover, the result of Spearman's correlation analyses showed that there were significant correlations between FMA-UE scores and FC of the ipsilesional DLPFC-ipsilesional M1 (r = 0.430, p = 0.002), ipsilesional DLPFC-contralesional M1 (r = 0.388, p = 0.006), ipsilesional DLPFC-MPFC (r = 0.365, p = 0.01), and ipsilesional DLPFC-contralesional DLPFC (r = 0.330, p = 0.021). Our findings indicate that different degrees of post-stroke upper extremity impairment reflect different RSFC patterns, mainly in the connection between DLPFC and bilateral M1. The association between FMA-UE scores and the FC of ipsilesional DLPFC-associated ROIs suggests that the ipsilesional DLPFC may play an important role in motor-related plasticity. These findings can help us better understand the neurophysiological mechanisms of upper extremity motor impairment and recovery in subacute stroke patients from different perspectives. Furthermore, it sheds light on the ipsilesional DLPFC-bilateral M1 as a possible neuromodulation target.

Inherent regional brain activity changes in male obstructive sleep apnea with mild cognitive impairment: A resting-state magnetic resonance study.

Obstructive sleep apnea (OSA) is the most common sleep disorder worldwide. Previous studies have shown that OSA patients are often accompanied by cognitive function loss, and the underlying neurophysiological mechanism is still unclear. This study aimed to determine whether there are differences in regional homogeneity (Reho) and functional connectivity (FC) across the brain between OSA patients with MCI (OSA-MCI) and those without MCI (OSA-nMCI) and whether such differences can be used to distinguish the two groups. Resting state magnetic resonance data were collected from 48 OSA-MCI patients and 47 OSA-nMCI patients. The brain regions with significant differences in Reho and FC between the two groups were identified, and the Reho and FC features were combined with machine learning methods for classification. Compared with OSA-nMCI patients, OSA-MCI patients showed significantly lower Reho in bilateral lingual gyrus and left superior temporal gyrus. OSA-MCI patients also showed significantly lower FC between the bilateral lingual gyrus and bilateral cuneus, left superior temporal gyrus and left middle temporal gyrus, middle frontal gyrus, and bilateral posterior cingulate/calcarine/cerebellar anterior lobe. Based on Reho and FC features, logistic regression classification accuracy was 0.87; sensitivity, 0.70; specificity, 0.89; and area under the curve, 0.85. Correlation analysis showed that MoCA scale score in OSA patients was significant positive correlation sleep efficiency and negatively correlation with neck circumference. In conclusion, our results showed that the OSA-MCI group showed decreased Reho and FC in specific brain regions compared with the OSA-nMCI group, which may help to understand the underlying neuroimaging mechanism of OSA leading to cognitive dysfunction and may serve as a potential biomarker to distinguish whether OSA is accompanied by cognitive impairment.

Hippocampal Network Dysfunction in Early Psychosis: A 2-Year Longitudinal Study

BackgroundHippocampal abnormalities are among the most consistent findings in schizophrenia. Numerous studies have reported deficits in hippocampal volume, function, and connectivity in the chronic stage of illness. While hippocampal volume and function deficits are also present in the early stage of illness, there is mixed evidence of both higher and lower functional connectivity. Here, we use graph theory to test the hypothesis that hippocampal network connectivity is broadly lowered in early psychosis and progressively worsens over 2 years. MethodsWe examined longitudinal resting-state functional connectivity in 140 participants (68 individuals in the early stage of psychosis, 72 demographically similar healthy control individuals). We used an anatomically driven approach to quantify hippocampal network connectivity at 2 levels: 1) a core hippocampal-medial temporal lobe cortex (MTLC) network; and 2) an extended hippocampal-cortical network. Group and time effects were tested in a linear mixed effects model. ResultsEarly psychosis patients showed elevated functional connectivity in the core hippocampal-MTLC network, but contrary to our hypothesis, did not show alterations within the broader hippocampal-cortical network. Hippocampal-MTLC network hyperconnectivity normalized longitudinally and predicted improvement in positive symptoms but was not associated with increasing illness duration. ConclusionsThese results show abnormally elevated functional connectivity in a core hippocampal-MTLC network in early psychosis, suggesting that selectively increased hippocampal signaling within a localized cortical circuit may be a marker of the early stage of psychosis. Hippocampal-MTLC hyperconnectivity could have prognostic and therapeutic implications.

Brain connectivity markers in degenerative cervical myelopathy patients with depression for predicting the prognosis following decompression surgery.

To determine if brain functional connectivity (FC) is associated with the prognosis in depressed degenerative cervical myelopathy patients (DCM) and to investigate the possible brain functional mechanism. Resting-state fMRI scans and peripheral blood cell counts from 33 depressed DCM patients, 33 age and gender-matched DCM patients without depression were analyzed. All patients were evaluated using Japanese Orthopedic Association score before and 6 weeks after decompression surgery. JOA recovery rate was calculated to assess the functional recovery for DCM patients. For each participant, seed-based functional connectivity maps based on sub-regions centered on the striatum were computed and compared between groups. Pearson correlations were performed to explore the relationships between clinical measures and brain alterations in depressed DCM patients. To further investigate the relationships between brain alterations and clinical measures in depressed DCM patients, mediation analyses were performed. Flow cytometry was also performed on the three of the 33 depressed DCM patients, and the results were analyzed. In comparison to patients without depression, DCM patients exhibited lower FC between the dorsal caudate (dC) and the inferior frontal operculum, which is located in the dorsal lateral prefrontal cortex (dlPFC). In depressed DCM patients, the altered dC-dlPFC FC was associated with inflammation as determined by the neutrophils/lymphocyte's ratio and prognosis. Furthermore, the mediation analysis demonstrated that the dC-dlPFC FC mediated the effect of inflammation on prognosis. The outcomes of our three cases followed a similar pattern to these findings. In conclusion, our findings imply that inflammation slowed the functional recovery in depressed DCM patients through the striatal-frontal FC pathway.

Resting-state functional connectivity alteration in elderly patients with knee osteoarthritis and declined cognition: An observational study.

This study is designed to investigate the brain function changed regions in elderly patients with knee osteoarthritis (KOA) and to explore the relationship between neuropsychological tests and resting-state functional magnetic resonance imaging (rs-fMRI) network to clarify the possible mechanism underlying cognitive changes in KOA patients. Fifty-two patients aged ≥ 65 with KOA and twenty-two healthy-matched controls were recruited in this study. All participants were given rs-fMRI check. We used graph theory analysis to characterize functional connectivity (FC) and topological organization of the brain structural network. The relationship between FC values, topological properties, and the neuropsychological test scores was analyzed. Compared with the controls, fourteen edges with lower functional connectivity were noted in the KOA group. Local efficiency and small-worldness of KOA patients decreased compared to the healthy controls. No significant alterations of nodal topological properties were found between the two groups. There was a significant positive correlation between the AVLT-H (L) and the internetwork of default mode network (DMN) (left/right orbitofrontal Superior cortex) and limbic/cortical areas (left/right caudate, right amygdala). AVLT-H(L) was positively correlated with small-worldness and local efficiency. The results indicated that for elderly KOA patients with declined cognition, topological properties, FC between DMN and subcortical limbic network related regions are significantly decreased compared to healthy controls. These alterations demonstrated a significant correlation with the neuropsychological test scores.

Association study between hypothalamic functional connectivity, early nutrition, and glucose levels in healthy children aged 6 years: The COGNIS study follow-up.

Breastfeeding (BF) is the gold standard in infant nutrition; knowing how it influences brain connectivity would help understand the mechanisms involved, which would help close the nutritional gap between infant formulas and breast milk. We analyzed potential long-term differences depending on the diet with an experimental infant formula (EF), compared to a standard infant formula (SF) or breastfeeding (BF) during the first 18 months of life on children's hypothalamic functional connectivity (FC) assessed at 6 years old. A total of 62 children participating in the COGNIS randomized clinical trial (Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02094547) were included in this study. They were randomized to receive an SF (n = 22) or a bioactive nutrient-enriched EF (n = 20). BF children were also included as a control study group (BF: n = 20). Brain function was evaluated using functional magnetic resonance imaging (fMRI) and mean glucose levels were collected through a 24-h continuous glucose monitoring (CGM) device at 6 years old. Furthermore, nutrient intake was also analyzed during the first 18 months of life and at 6 years old through 3-day dietary intake records. Groups fed with EF and BF showed lower FC between the medial hypothalamus (MH) and the anterior cingulate cortex (ACC) in comparison with SF-fed children. Moreover, the BF children group showed lower FC between the MH and the left putamen extending to the middle insula, and higher FC between the MH and the inferior frontal gyrus (IFG) compared to the EF-fed children group. These areas are key regions within the salience network, which is involved in processing salience stimuli, eating motivation, and hedonic-driven desire to consume food. Indeed, current higher connectivity found on the MH-IFG network in the BF group was associated with lower simple sugars acceptable macronutrient distribution ranges (AMDRs) at 6 months of age. Regarding linoleic acid intake at 12 months old, a negative association with this network (MH-IFG) only in the BF group was found. In addition, BF children showed lower mean glucose levels compared to SF-fed children at 6 years old. Our results may point out a possible relationship between diet during the first 18 months of life and inclined proclivity for hedonic eating later in life.Clinical trial registrationhttps://www.clinicaltrials.gov/, identifier NCT02094547.

The interplay between structural and functional connectivity in early stage Parkinson's disease patients

The mechanisms underlying cognitive disturbances in Parkinson's disease (PD) are poorly understood but likely to depend on the ongoing degenerative processes affecting structural and functional connectivity (FC). This pilot study examined patterns of FC alterations during a cognitive task using EEG and structural characteristics of white matter (WM) pathways connecting these activated regions in early-stage PD. Eleven PD patients and nine healthy controls (HCs) underwent EEG recording during an auditory oddball task and MRI scans. Source localization was performed and Gaussian mixture model was fitted to identify brain regions with high power during task performance. These areas served as seed regions for connectivity analysis. FC among these regions was assessed by measures of magnitude squared coherence (MSC), and phase-locking value (PLV), while structural connectivity was evaluated using fiber tracking based on diffusion tensor imaging (DTI). The paracentral lobule (PL), superior parietal lobule (SPL), superior and middle frontal gyrus (SMFG), parahippocampal gyrus, superior and middle temporal gyri (STG, MTG) demonstrated increased activation during task performance. Compared to HCs, PD showed lower FC between SMFG and PL and between SMFG and SPL in MSC (p = 0.012 and p = 0.036 respectively). No significant differences between the groups were observed in PLV and the measured DTI metrics along WM tracts. These findings demonstrate that in early PD, cognitive performance changes might be attributed to FC alterations, suggesting that FC is affected early on in the degenerative process, whereas structural damage is more prominent in advanced stages as a result of the disease burden accumulation.

Frontothalamic Circuit Abnormalities in Patients With Bipolar Depression and Suicide Attempts.

Objective: Suicide is the leading cause of premature death among patients with bipolar disorder (BD), so it is imperative to identify biological or psychometric markers for suicide risk. Previous functional neuroimaging studies of the general BD population have focused on abnormalities within cortical-subcortical circuits. The aim of the current study was to examine potential cortico-subcortical circuit abnormalities predictive of suicide attempt in patients with BD.Methods: We examined functional connectivity (FC) based on 5 regions of interest: bilateral anterior cingulate cortex (ACC), medial frontal cortex, inferior frontal cortex, amygdala, and thalamus, by resting-state functional magnetic resonance imaging (rs-fMRI) in 65 participants, including patients with BD and suicide attempts (SA group; n = 24), patients with BD and no suicide attempts (NSA group; n = 15), and healthy control subjects (HC group; n = 26). Patients met DSM-5 criteria for bipolar I disorder with current major depressive episode.Results: The total patient group (SA+NSA) exhibited significantly lower FC between bilateral thalamus and frontal cortex (F = 35.11, P < .01), and this deficit was most severe in the SA group. In addition, patients demonstrated significantly reduced FC values between bilateral inferior frontal gyrus and both inferior temporal gyrus (F = 20.68, P < .01) and fusiform gyrus (F = 20.98, P < .01), but FC was stronger in the SA group than the NSA group. Both patient groups also exhibited reduced FC based on these seeds including bilateral amygdala, medial frontal cortex, and ACC, but without significant differences between the SA and NSA groups.Conclusions: The results suggest that reduced FC within specific frontothalamic circuits may increase the vulnerability for suicidal behavior in patients with BD. These FC abnormalities might provide potential predictors of suicide attempt in BD.