Resting state functional connectome in breast cancer patients with fear of cancer recurrence.

This study aimed to investigate network-level brain functional changes in breast cancer patients and their relationship with fear of cancer recurrence (FCR). Resting-state functional MRI was collected from 43 patients with breast cancer and 40 healthy controls (HCs). Graph theory analyses, whole-brain voxel-wise functional connectivity strength (FCS) analyses and seed-based functional connectivity (FC) analyses were performed to identify connection alterations in breast cancer patients. Correlations between brain functional connections (i.e. FCS and FC) and FCR level were assessed to further reveal the neural mechanisms of FCR in breast cancer patients. Graph theory analyses indicated a decreased clustering coefficient in breast cancer patients compared to HCs (P = 0.04). Patients with breast cancer exhibited significantly higher FCS in both higher-order function networks (frontoparietal, default mode, and dorsal attention systems) and primary somatomotor networks. Among the hyperconnected regions in breast cancer, the left inferior frontal operculum demonstrated a significant positive correlation with FCR. Our findings suggest that breast cancer patients exhibit less segregation of brain function, and the left inferior frontal operculum is a key region associated with FCR. This study offers insights into the neural mechanisms of FCR in breast cancer patients at the level of brain connectome.

Combining CRISPR-Cas9 and brain imaging to study the link from genes to molecules to networks.

Receptors, transporters, and ion channels are important targets for therapy development in neurological diseases, but their mechanistic role in pathogenesis is often poorly understood. Gene editing and in vivo imaging approaches will help to identify the molecular and functional role of these targets and the consequence of their regional dysfunction on the whole-brain level. We combine CRISPR-Cas9 gene editing with in vivo positron emission tomography (PET) and functional MRI (fMRI) to investigate the direct link between genes, molecules, and the brain connectome. The extensive knowledge of the Slc18a2 gene encoding the vesicular monoamine transporter (VMAT2), involved in the storage and release of dopamine, makes it an excellent target for studying the gene network relationships while structurally preserving neuronal integrity and function. We edited the Slc18a2 in the substantia nigra pars compacta of adult rats and used in vivo molecular imaging besides behavioral, histological, and biochemical assessments to characterize the CRISPR-Cas9-mediated VMAT2 knockdown. Simultaneous PET/fMRI was performed to investigate molecular and functional brain alterations. We found that stage-specific adaptations of brain functional connectivity follow the selective impairment of presynaptic dopamine storage and release. Our study reveals that recruiting different brain networks is an early response to the dopaminergic dysfunction preceding neuronal cell loss. Our combinatorial approach is a tool to investigate the impact of specific genes on brain molecular and functional dynamics, which will help to develop tailored therapies for normalizing brain function.

Distance from main arteries influences microstructural and functional brain tissue characteristics.

Given the substantial dependence of neurons on continuous supply of energy, the distribution of major cerebral arteries opens a question whether the distance from the main supply arteries constitutes a modulating factor for the microstructural and functional properties of brain tissue. To tackle this question, multimodal MRI acquisitions of 102 healthy volunteers over the full adult age span were utilised. Relaxation along a fictitious field in the rotating frame of rank n = 4 (RAFF4), adiabatic T1ρ, T2ρ,  and intracellular volume fraction (fICVF) derived from diffusion-weighted imaging were implemented to quantify microstructural (cellularity, myelin density, iron concentration) tissue characteristics and degree centrality and fractional amplitude of low-frequency fluctuations to probe for functional metrics. Inverse correlation of arterial distance with robust homogeneity was detected for T1ρ, T2ρ and RAFF4 for cortical grey matter and white matter, showing substantial complex microstructural differences between brain tissue close and farther from main arterial trunks. Albeit with wider variability, functional metrics pointed to increased connectivity and neuronal activity in areas farther from main arteries. Surprisingly, multiple of these microstructural and functional distance-based gradients diminished with higher age, pointing to uniformization of brain tissue with ageing. All in all, this pilot study provides a novel insight on brain regionalisation based on artery distance, which merits further investigation to validate its biological underpinnings.

Prediction of anxious depression using multimodal neuroimaging and machine learning.

Anxious depression is a common subtype of major depressive disorder (MDD) associated with adverse outcomes and severely impaired social function. It is important to clarify the underlying neurobiology of anxious depression to refine the diagnosis and stratify patients for therapy. Here we explored associations between anxiety and brain structure/function in MDD patients. A total of 260 MDD patients and 127 healthy controls underwent three-dimensional T1-weighted structural scanning and resting-state functional magnetic resonance imaging. Demographic data were collected from all participants. Differences in gray matter volume (GMV), (fractional) amplitude of low-frequency fluctuation ((f)ALFF), regional homogeneity (ReHo), and seed point-based functional connectivity were compared between anxious MDD patients, non-anxious MDD patients, and healthy controls. A random forest model was used to predict anxiety in MDD patients using neuroimaging features. Anxious MDD patients showed significant differences in GMV in the left middle temporal gyrus and ReHo in the right superior parietal gyrus and the left precuneus than HCs. Compared with non-anxious MDD patients, patients with anxious MDD showed significantly different GMV in the left inferior temporal gyrus, left superior temporal gyrus, left superior frontal gyrus (orbital part), and left dorsolateral superior frontal gyrus; fALFF in the left middle temporal gyrus; ReHo in the inferior temporal gyrus and the superior frontal gyrus (orbital part); and functional connectivity between the left superior temporal gyrus(temporal pole) and left medial superior frontal gyrus. A diagnostic predictive random forest model built using imaging features and validated by 10-fold cross-validation distinguished anxious from non-anxious MDD with an AUC of 0.802. Patients with anxious depression exhibit dysregulation of brain regions associated with emotion regulation, cognition, and decision-making, and our diagnostic model paves the way for more accurate, objective clinical diagnosis of anxious depression.

Preventive effect of one-session brief focused attention meditation on state fatigue: Resting state functional magnetic resonance imaging study.

INTRODUCTION: The extended practice of meditation may reduce the influence of state fatigue by changing neurocognitive processing. However, little is known about the preventive effects of one-session brief focused attention meditation (FAM) on state fatigue in healthy participants or its potential neural mechanisms. This study examined the preventive effects of one-session brief FAM on state fatigue and its neural correlates using resting-state functional MRI (rsfMRI) measurements. METHODS: We randomly divided 56 meditation-naïve participants into FAM and control groups. After the first rsfMRI scan, each group performed a 10-minute each condition while wearing a functional near-infrared spectroscopy (fNIRS) device for assessing brain activity. Subsequently, following a second rsfMRI scan, the participants completed a fatigue-inducing task (a Go/NoGo task) for 60 min. We evaluated the temporal changes in the Go/NoGo task performance of participants as an indicator of state fatigue. We then calculated changes in the resting-state functional connectivity (rsFC) of the rsfMRI from before to after each condition and compared them between groups. We also evaluated neural correlates between the changes in rsFC and state fatigue. RESULTS AND DISCUSSION: The fNIRS measurements indicated differences in brain activity during each condition between the FAM and control groups, showing decreased medial prefrontal cortex activity and decreased functional connectivity between the medial prefrontal cortex and middle frontal gyrus. The control group exhibited a decrement in Go/NoGo task performance over time, whereas the FAM group did not. These results, thus, suggested that FAM could prevent state fatigue. Compared with the control group, the rsFC analysis revealed a significant increase in the connectivity between the left dorsomedial prefrontal cortex and right superior parietal lobule in the FAM group, suggesting a modification of attention regulation by cognitive effort. In the control group, increased connectivity was observed between the bilateral posterior cingulate cortex and left inferior occipital gyrus, which might be associated with poor attention regulation and reduced higher-order cognitive function. Additionally, the change in the rsFC of the control group was related to state fatigue. CONCLUSION: Our findings suggested that one session of 10-minute FAM could prevent behavioral state fatigue by employing cognitive effort to modify attention regulation as well as suppressing poor attention regulation and reduced higher-order cognitive function.

Altered dynamic amplitude of low-frequency fluctuation in individuals at high risk for Alzheimer's disease.

The brain's dynamic spontaneous neural activity is significant in supporting cognition; however, how brain dynamics go awry in subjective cognitive decline (SCD) and mild cognitive impairment (MCI) remains unclear. Thus, the current study aimed to investigate the dynamic amplitude of low-frequency fluctuation (dALFF) alterations in patients at high risk for Alzheimer's disease and to explore its correlation with clinical cognitive assessment scales, to identify an early imaging sign for these special populations. A total of 152 participants, including 72 SCD patients, 44 MCI patients and 36 healthy controls (HCs), underwent a resting-state functional magnetic resonance imaging and were assessed with various neuropsychological tests. The dALFF was measured using sliding-window analysis. We employed canonical correlation analysis (CCA) to examine the bi-multivariate correlations between neuropsychological scales and altered dALFF among multiple regions in SCD and MCI patients. Compared to those in the HC group, both the MCI and SCD groups showed higher dALFF values in the right opercular inferior frontal gyrus (voxel P < .001, cluster P < .05, correction). Moreover, the CCA models revealed that behavioural tests relevant to inattention correlated with the dALFF of the right middle frontal gyrus and right opercular inferior frontal gyrus, which are involved in frontoparietal networks (R = .43, P = .024). In conclusion, the brain dynamics of neural activity in frontal areas provide insights into the shared neural basis underlying SCD and MCI.

Macroscale neurovascular coupling and functional integration in end-stage renal disease patients with cognitive impairment: A multimodal MRI study.

End-stage renal disease (ESRD) is associated with vascular and neuronal dysfunction, causing neurovascular coupling (NVC) dysfunction, but how NVC dysfunction acts on the mechanism of cognitive impairment in ESRD patients from local to remote is still poorly understood. We recruited 48 ESRD patients and 35 demographically matched healthy controls to scan resting-state functional MRI and arterial spin labeling, then investigated the four types of NVC between amplitude of low-frequency fluctuation (ALFF), fractional ALFF, regional homogeneity, degree centrality, and cerebral blood perfusion (CBF), and associated functional networks. Our results indicated that ESRD patients showed NVC dysfunction in global gray matter and multiple brain regions due to the mismatch between CBF and neural activity, and associated disrupted functional connectivity (FC) within sensorimotor network (SMN), visual network (VN), default mode network (DMN), salience network (SN), and disrupted FC between them with limbic network (LN), while increased FC between SMN and DMN. Anemia may affect the NVC of middle occipital gyrus and precuneus, and increased pulse pressure may result in disrupted FC with SMN. The NVC dysfunction of the right precuneus, middle frontal gyrus, and parahippocampal gyrus and the FC between the right angular gyrus and the right anterior cingulate gyrus may reflect cognitive impairment in ESRD patients. Our study confirmed that ESRD patients may exist NVC dysfunction and disrupted functional integration in SMN, VN, DMN, SN and LN, serving as one of the mechanisms of cognitive impairment. Anemia and increased pulse pressure may be related risk factors.

Stepwise Functional Brain Architecture Correlates with Atrophy in Progressive Supranuclear Palsy.

BACKGROUND: Stepwise functional connectivity (SFC) detects whole-brain functional couplings of a selected region of interest at increasing link-step topological distances. OBJECTIVE: This study applied SFC to test the hypothesis that stepwise architecture propagating from the disease epicenter would shape patterns of brain atrophy in patients with progressive supranuclear palsy-Richardson's syndrome (PSP-RS). METHODS: Thirty-six patients with PSP-RS and 44 age-matched healthy control subjects underwent brain magnetic resonance imaging on a 3-T scanner. The disease epicenter was defined as the peak of atrophy observed in an independent cohort of 13 cases with postmortem confirmation of PSP pathology and used as seed region for SFC analysis. First, we explored SFC rearrangements in patients with PSP-RS, as compared with age-matched control subjects. Subsequently, we tested SFC architecture propagating from the disease epicenter as a determinant of brain atrophy distribution. RESULTS: The disease epicenter was identified in the left midbrain tegmental region. Compared with age-matched control subjects, patients with PSP-RS showed progressively widespread decreased SFC of the midbrain with striatal and cerebellar regions through direct connections and sensorimotor cortical regions through indirect connections. A correlation was found between average link-step distance from the left midbrain in healthy subjects and brain volumes in patients with PSP-RS (r = 0.38, P < 0.001). CONCLUSIONS: This study provides comprehensive insights into the topology of functional network rearrangements in PSP-RS and demonstrates that the brain architectural topology, as described by SFC propagating from the disease epicenter, shapes the pattern of atrophic changes in PSP-RS. Our findings support the view of a network-based pathology propagation in this primary tauopathy. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Abnormal Local Brain Activity and Cognitive Impairments in Young Non-Disabled Patients With Intracerebral Hemorrhage: A Resting-State Functional MRI Study.

BACKGROUND: Resting-state functional MRI (rs-fMRI) has identified static changes of local brain activity among patients with intracerebral hemorrhage (ICH). However, the dynamic and concordance-related characteristics of brain activity remain unclear. PURPOSE: To investigate static, dynamic, and concordance-related features of the regional brain activity of young non-disabled ICH patients. STUDY TYPE: Prospective. SUBJECTS: Thirty-three ICH patients (modified Rankin Scale score ≤2, 21% female, 46.36 ± 6.53) and 33 matched healthy controls (HCs) (21% female, 47.64 ± 6.16). FIELD STRENGTH/SEQUENCE: 3-T, rs-fMRI using gradient echo-planar imaging, T1-weighted imaging. ASSESSMENT: Neuropsychological and rs-fMRI data were acquired from all participants. Amplitude of low-frequency fluctuations (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), voxel-mirrored homotopic connectivity, global signal correlation (GSCorr) and degree centrality (DC), and their dynamic and concordance-related changes with sliding window analysis were calculated based on rs-fMRI data at a whole-brain level. The burden of cerebral small vascular diseases (cSVD) was assessed by cSVD scores. All hemorrhage lesions were delineated on normalized T1 images. STATISTICAL TESTS: Multiple regression models, a voxel-level uncorrected P < 0.001, a cluster-level false discovery rate (FDR) corrected q < 0.05, a re-corrected qFDR <0.05 were considered significant. Pearson or Spearman correlation analyses between fMRI data and neurocognitive performance were performed. RESULTS: Compared to HCs, ICH patients showed significant abnormal changes of ALFF, dynamic ALFF, fALFF, ReHo, dynamic ReHo, GSCorr, DC, and voxel-wise concordance in multiple brain regions mainly including the bilateral cerebellar hemispheres, ipsilesional thalamus, and bilateral middle cingulum gyrus. The ALFF in the cerebellar posterior lobe and thalamus were significantly associated with attention (r = -0.481) and executive function (rho = -0.521) in ICH patients. DATA CONCLUSION: Young non-disabled ICH patients exhibit static, dynamic, and concordance-related alterations of local brain activity, part of which shows associations with cognitive functions. These findings may help comprehensively understand the mechanism of cognitive impairment after ICH. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 3.

2.5-Year changes of connectivity dynamism are relevant for physical and cognitive deterioration in multiple sclerosis.

BACKGROUND: In MS, functional connectivity (FC) dynamism may influence disease evolution. OBJECTIVES: The objective is to assess time-varying functional connectivity (TVFC) changes over time at 2.5-year follow-up in MS patients according to physical and cognitive worsening. METHODS: We collected 3T magnetic resonance imaging (MRI) for TVFC assessment (performed using sliding-window analysis of centrality) and clinical evaluations at baseline and 2.5-year follow-up from 28 healthy controls and 129 MS patients. Of these, 79 underwent baseline and follow-up neuropsychological assessment. At 2.5 years, physical/cognitive worsening was defined according to disability/neuropsychological score changes. RESULTS: At follow-up, 25/129 (19.3%) MS patients worsened physically and 14/79 (17.7%) worsened cognitively. At baseline, MS patients showed reduced TVFC versus controls. At 2.5-year follow-up, no TVFC changes were detected in controls. Conversely, TVFC decreased over time in parieto-temporal regions in stable MS patients and in default-mode network in worsened MS. In physically worsened MS, basal ganglia TVFC reductions were also found. Reduced TVFC over time in the putamen in physically worsened and reduced TVFC in the precuneus in cognitively worsened were significant versus stable MS. DISCUSSION: At 2.5-year follow-up, default-mode network TVFC reductions were found in worsening MS. Moreover, reduced deep gray matter TVFC characterized physically worsened patients, whereas precuneus involvement characterized cognitively worsened MS patients.

Graph analysis uncovers an opposing impact of methylphenidate on connectivity patterns within default mode network sub-divisions.

BACKGROUND: The Default Mode Network (DMN) is a central neural network, with recent evidence indicating that it is composed of functionally distinct sub-networks. Methylphenidate (MPH) administration has been shown before to modulate impulsive behavior, though it is not yet clear whether these effects relate to MPH-induced changes in DMN connectivity. To address this gap, we assessed the impact of MPH administration on functional connectivity patterns within and between distinct DMN sub-networks and tested putative relations to variability in sub-scales of impulsivity. METHODS: Fifty-five right-handed healthy adults underwent two resting-state functional MRI (rs-fMRI) scans, following acute administration of either MPH (20 mg) or placebo, via a randomized double-blind placebo-controlled design. Graph modularity analysis was implemented to fractionate the DMN into distinct sub-networks based on the impact of MPH (vs. placebo) on DMN connectivity patterns with other neural networks. RESULTS: MPH administration led to an overall decreased DMN connectivity, particularly with the auditory, cinguloopercular, and somatomotor networks, and increased connectivity with the parietomedial network. Graph analysis revealed that the DMN could be fractionated into two distinct sub-networks, with one exhibiting MPH-induced increased connectivity and the other decreased connectivity. Decreased connectivity of the DMN sub-network with the cinguloopercular network following MPH administration was associated with elevated impulsivity and non-planning impulsiveness. CONCLUSION: Current findings highlight the intricate effects of MPH administration on DMN rs-fMRI connectivity, uncovering its opposing impact on distinct DMN sub-divisions. MPH-induced dynamics in DMN connectivity patterns with other neural networks may account for some of the effects of MPH administration on impulsive behavior.

Loneliness and Resting-State Functional Brain Connectivity Among Older Adults: A Proportional Correlation.

OBJECTIVE: Loneliness reportedly increases the risk of dementia, especially Alzheimer's disease (AD). The authors' previous study demonstrated associations between loneliness and structural abnormalities observed in early-stage AD. The present study examined associations between the brain's functional characteristics and loneliness among older adults with concerns about cognitive decline. METHODS: This single-center study included 43 participants (13 with amnestic mild cognitive impairment and 30 with normal cognition). Participants were assessed with the revised University of California Los Angeles (UCLA) Loneliness Scale and underwent resting-state functional MRI. Functional images were preprocessed with the CONN toolbox. The selected seeds were within brain regions reportedly associated with loneliness. One-sample general linear model analysis was performed to examine regressions of UCLA Loneliness Scale scores and functional connectivity between the seeds and regions of interest. RESULTS: The revised UCLA Loneliness Scale scores were positively correlated with functional connectivity between the right hippocampus and left lateral parietal lobe and were negatively correlated with functional connectivity between the left amygdala and left frontal operculum and between the left amygdala and right supramarginal gyrus. Analyses were adjusted for age, sex, and education and scores on the Mini-Mental State Examination and Clinical Dementia Rating scale. CONCLUSIONS: Loneliness was associated with abnormal function of the hippocampus, parts of the parietal lobe and frontal cortex, and the amygdala. These findings may suggest a possible correlation between loneliness and neurological changes associated with dementia.

Hippocampus and olfactory impairment in Parkinson disease: a comparative exploratory combined volumetric/functional MRI study.

INTRODUCTION: Patients with Parkinson's Disease (PD) commonly experience Olfactory Dysfunction (OD). Our exploratory study examined hippocampal volumetric and resting-state functional magnetic resonance imaging (rs-fMRI) variations in a Healthy Control (HC) group versus a cognitively normal PD group, further categorized into PD with No/Mild Hyposmia (PD-N/MH) and PD with Severe Hyposmia (PD-SH). METHODS: We calculated participants' relative Total Hippocampal Volume (rTHV) and performed Spearman's partial correlations, controlled for age and gender, to examine the correlation between rTHV and olfactory performance assessed by the Odor Stick Identification Test for the Japanese (OSIT-J) score. Mann-Whitney U tests assessed rTHV differences across groups and subgroups, rejecting the null hypothesis for p < 0.05. Furthermore, a seed-based rs-fMRI analysis compared hippocampal connectivity differences using a one-way ANCOVA covariate model with controls for age and gender. RESULTS: Spearman's partial correlations indicated a moderate positive correlation between rTHV and OSIT-J in the whole study population (ρ = 0.406; p = 0.007), PD group (ρ = 0.493; p = 0.008), and PD-N/MH subgroup (ρ = 0.617; p = 0.025). Mann-Whitney U tests demonstrated lower rTHV in PD-SH subgroup compared to both HC group (p = 0.013) and PD-N/MH subgroup (p = 0.029). Seed-to-voxel rsfMRI analysis revealed reduced hippocampal connectivity in PD-SH subjects compared to HC subjects with a single cluster of voxels. CONCLUSIONS: Although the design of the study do not allow to make firm conclusions, it is reasonable to speculate that the progressive involvement of the hippocampus in PD patients is associated with the progression of OD.

Resting-state functional connectivity in adults with 47,XXX: a 7 Tesla MRI study.

Triple X syndrome is a sex chromosomal aneuploidy characterized by the presence of a supernumerary X chromosome, resulting in a karyotype of 47,XXX in affected females. It has been associated with a variable cognitive, behavioral, and psychiatric phenotype, but little is known about its effects on brain function. We therefore conducted 7 T resting-state functional magnetic resonance imaging and compared data of 19 adult individuals with 47,XXX and 21 age-matched healthy control women using independent component analysis and dual regression. Additionally, we examined potential relationships between social cognition and social functioning scores, and IQ, and mean functional connectivity values. The 47,XXX group showed significantly increased functional connectivity of the fronto-parietal resting-state network with the right postcentral gyrus. Resting-state functional connectivity (rsFC) variability was not associated with IQ and social cognition and social functioning deficits in the participants with 47,XXX. We thus observed an effect of a supernumerary X chromosome in adult women on fronto-parietal rsFC. These findings provide additional insight into the role of the X chromosome on functional connectivity of the brain. Further research is needed to understand the clinical implications of altered rsFC in 47,XXX.

Genetic mechanisms underlying brain functional homotopy: a combined transcriptome and resting-state functional MRI study.

Functional homotopy, the high degree of spontaneous activity synchrony and functional coactivation between geometrically corresponding interhemispheric regions, is a fundamental characteristic of the intrinsic functional architecture of the brain. However, little is known about the genetic mechanisms underlying functional homotopy. Resting-state functional magnetic resonance imaging data from a discovery dataset (656 healthy subjects) and 2 independent cross-race, cross-scanner validation datasets (103 and 329 healthy subjects) were used to calculate voxel-mirrored homotopic connectivity (VMHC) indexing brain functional homotopy. In combination with the Allen Human Brain Atlas, transcriptome-neuroimaging spatial correlation analysis was conducted to identify genes linked to VMHC. We found 1,001 genes whose expression measures were spatially associated with VMHC. Functional enrichment analyses demonstrated that these VMHC-related genes were enriched for biological functions including protein kinase activity, ion channel regulation, and synaptic function as well as many neuropsychiatric disorders. Concurrently, specific expression analyses showed that these genes were specifically expressed in the brain tissue, in neurons and immune cells, and during nearly all developmental periods. In addition, the VMHC-associated genes were linked to multiple behavioral domains, including vision, execution, and attention. Our findings suggest that interhemispheric communication and coordination involve a complex interaction of polygenes with a rich range of functional features.

Altered functional connectivity of the thalamus and salience network in patients with cluster headache: a pilot study.

BACKGROUND AND OBJECTIVE: Previous studies have shown that the salience network (SN) and the thalamus are involved in cluster headache (CH) attacks. However, very little is known regarding the altered thalamus-SN functional connectivity in CH. The aim of this study was to explore alterations of functional connectivity between the thalamus and the SN in patients with CH to further gain insight into the pathophysiology of CH. MATERIALS AND METHODS: The resting-state functional MRI (rs-fMRI) data of 21 patients with CH in the headache attack remission state during in-bout periods and 21 age- and sex-matched normal controls were obtained. The rs-fMRI data were analyzed by the independent component analysis (ICA) method, and the thalamus-SN functional connectivity in patients with right-sided and left-sided CH was compared with that in normal controls. RESULTS: Decreased functional connectivity was found between the thalamus, both ipsilateral and contralateral to the headache side, and the SN during headache remission state in both right-sided CH patients and left-sided CH patients. CONCLUSIONS: The findings suggest that the decreased functional connectivity between the thalamus and SN might be one of the pathologies underpinning the CH. This helps us to understand better the nature of the brain dysfunction in CH and the basic pathologies of CH, which implies that this deserves further investigation.

Exploring the neural mechanisms underlying achalasia: A study of functional connectivity and regional brain activity.

BACKGROUND AND AIMS: The pathophysiology of achalasia, which involves central nuclei abnormalities, remains unknown. We investigated the resting-state functional MRI (rs-fMRI) features of patients with achalasia. METHODS: We applied resting-state functional MRI (rs-fMRI) to investigate the brain features in patients with achalasia (n = 27), compared to healthy controls (n = 29). Focusing on three regions of interest (ROIs): the dorsal motor nucleus of the vagus (DMV), the nucleus ambiguus (NA), and the nucleus of the solitary tract (NTS), we analyzed variations in resting-state functional connectivity (rs-FC), fractional amplitude of low-frequency fluctuations (fALFF), and regional homogeneity (ReHo). RESULTS: Achalasia patients demonstrated stronger functional connectivity between the NA and the right precentral gyrus, left postcentral gyrus, and left insula. No significant changes were found in the DMV or NTS. The fMRI analysis showed higher rs-FC values for NA-DMV and NA-NTS connections in achalasia patients. Achalasia patients exhibited decreased fALFF values in the NA, DMV, and NTS regions, as well as increased ReHo values in the NA and DMV regions. A positive correlation was observed between fALFF values in all six ROIs and the width of the barium meal. The NTS fALFF value and NA ReHo value displayed a positive correlation with integrated relaxation pressure (IRP), while the ReHo value in the right precentral gyrus showed an inverse correlation with the height of the barium meal. CONCLUSIONS: Abnormal rs-FC and regional brain activity was found in patients with achalasia. Our study provides new insights into the pathophysiology of achalasia and highlights the potential of rs-fMRI in improving the diagnosis and treatment of this condition.

Brain-wide mapping of resting-state networks in mice using high-frame rate functional ultrasound.

Functional ultrasound (fUS) imaging is a method for visualizing deep brain activity based on cerebral blood volume changes coupled with neural activity, while functional MRI (fMRI) relies on the blood-oxygenation-level-dependent signal coupled with neural activity. Low-frequency fluctuations (LFF) of fMRI signals during resting-state can be measured by resting-state fMRI (rsfMRI), which allows functional imaging of the whole brain, and the distributions of resting-state network (RSN) can then be estimated from these fluctuations using independent component analysis (ICA). This procedure provides an important method for studying cognitive and psychophysiological diseases affecting specific brain networks. The distributions of RSNs in the brain-wide area has been reported primarily by rsfMRI. RSNs using rsfMRI are generally computed from the time-course of fMRI signals for more than 5 min. However, a recent dynamic functional connectivity study revealed that RSNs are still not perfectly stable even after 10 min. Importantly, fUS has a higher temporal resolution and stronger correlation with neural activity compared with fMRI. Therefore, we hypothesized that fUS applied during the resting-state for a shorter than 5 min would provide similar RSNs compared to fMRI. High temporal resolution rsfUS data were acquired at 10 Hz in awake mice. The quality of the default mode network (DMN), a well-known RSN, was evaluated using signal-noise separation (SNS) applied to different measurement durations of rsfUS. The results showed that the SNS did not change when the measurement duration was increased to more than 210 s. Next, we measured short-duration rsfUS multi-slice measurements in the brain-wide area. The results showed that rsfUS with the short duration succeeded in detecting RSNs distributed in the brain-wide area consistent with RSNs detected by 11.7-T MRI under awake conditions (medial prefrontal cortex and cingulate cortex in the anterior DMN, retrosplenial cortex and visual cortex in the posterior DMN, somatosensory and motor cortexes in the lateral cortical network, thalamus, dorsal hippocampus, and medial cerebellum), confirming the reliability of the RSNs detected by rsfUS. However, bilateral RSNs located in the secondary somatosensory cortex, ventral hippocampus, auditory cortex, and lateral cerebellum extracted from rsfUS were different from the unilateral RSNs extracted from rsfMRI. These findings indicate the potential of rsfUS as a method for analyzing functional brain networks and should encourage future research to elucidate functional brain networks and their relationships with disease model mice.

Functional connectivity gradients of the insula to different cerebral systems.

The diverse functional roles of the insula may emerge from its heavy connectivity to an extensive network of cortical and subcortical areas. Despite several previous attempts to investigate the hierarchical organization of the insula by applying the recently developed gradient approach to insula-to-whole brain connectivity data, little is known about whether and how there is variability across connectivity gradients of the insula to different cerebral systems. Resting-state functional MRI data from 793 healthy subjects were used to discover and validate functional connectivity gradients of the insula, which were computed based on its voxel-wise functional connectivity profiles to distinct cerebral systems. We identified three primary patterns of functional connectivity gradients of the insula to distinct cerebral systems. The connectivity gradients to the higher-order transmodal associative systems, including the prefrontal, posterior parietal, temporal cortices, and limbic lobule, showed a ventroanterior-dorsal axis across the insula; those to the lower-order unimodal primary systems, including the motor, somatosensory, and occipital cortices, displayed radiating transitions from dorsoanterior toward both ventroanterior and dorsoposterior parts of the insula; the connectivity gradient to the subcortical nuclei exhibited an organization along the anterior-posterior axis of the insula. Apart from complementing and extending previous literature on the heterogeneous connectivity patterns of insula subregions, the presented framework may offer ample opportunities to refine our understanding of the role of the insula in many brain disorders.

Subsystem mechanisms of default mode network underlying white matter hyperintensity-related cognitive impairment.

Functional changes of default mode network (DMN) have been proven to be closely associated with white matter hyperintensity (WMH) related cognitive impairment (CI). However, subsystem mechanisms of DMN underlying WMH-related CI remain unclear. The present study recruited WMH patients (n = 206) with mild CI and normal cognition, as well as healthy controls (HC, n = 102). Static/dynamic functional connectivity (FC) of the DMN's three subsystems were calculated using resting-state functional MRI. K-means clustering analyses were performed to extract distinct dynamic connectivity states. Compared with the WMH-NC group, the WMH-MCI group displayed lower static FC within medial temporal lobe (MTL) and core subsystem, between core-MTL subsystem, as well as between core and dorsal medial prefrontal cortex subsystem. All these static alterations were positively associated with information processing speed (IPS). Regarding dynamic FC, the WMH-MCI group exhibited higher dynamic FC within MTL subsystem than the HC and WMH-NC groups. Altered dynamic FC within MTL subsystem mediated the relationship between WMH and memory span (indirect effect: -0.2251, 95% confidence interval [-0.6295, -0.0267]). Additionally, dynamic FCs of DMN subsystems could be clustered into two recurring states. For dynamic FCs within MTL subsystem, WMH-MCI subjects exhibited longer mean dwell time (MDT) and higher reoccurrence fraction (RF) in a sparsely connected state (State 2). Altered MDT and RF in State 2 were negatively associated with IPS. Taken together, these findings indicated static/dynamic FC of DMN subsystems can provide relevant information on cognitive decline from different aspects, which provides a comprehensive view of subsystem mechanisms of DMN underlying WMH-related CI.