Altered Functional Connectivity Research Articles

Classification of recurrent major depressive disorder using a residual denoising autoencoder framework: Insights from large-scale multisite fMRI data

Background and objectiveRecurrent major depressive disorder (rMDD) has a high recurrence rate, and symptoms often worsen with each episode. Classifying rMDD using functional magnetic resonance imaging (fMRI) can enhance understanding of brain activity and aid diagnosis and treatment of this disorder. MethodsWe developed a Residual Denoising Autoencoder (Res-DAE) framework for the classification of rMDD. The functional connectivity (FC) was extracted from fMRI data as features. The framework addresses site heterogeneity by employing the Combat method to harmonize feature distribution differences. A feature selection method based on Fisher scores was used to reduce redundant information in the features. A data augmentation strategy using a Synthetic Minority Over-sampling Technique algorithm based on Extended Frobenius Norm measure was incorporated to increase the sample size. Furthermore, a residual module was integrated into the autoencoder network to preserve important features and improve the classification accuracy. ResultsWe tested our framework on a large-scale, multisite fMRI dataset, which includes 189 rMDD patients and 427 healthy controls. The Res-DAE achieved an average accuracy of 75.1 % (sensitivity = 69 %, specificity = 77.8 %) in cross-validation, thereby outperforming comparison methods. In a larger dataset that also includes first-episode depression (comprising 832 MDD patients and 779 healthy controls), the accuracy reached 70 %. ConclusionsWe proposed a deep learning framework that can effectively classify rMDD and 33 identify the altered FC associated with rMDD. Our study may reveal changes in brain function 34 associated with rMDD and provide assistance for the diagnosis and treatment of rMDD.

Alterations of functional brain activity and connectivity in female nurses working on long-term shift.

To investigate the alterations of functional brain activity and connectivity in female nurses working on long-term shifts and explore their correlations with work-related psychological traits. An exploratory cross-sectional study. Thirty-five female nurses working on long-term shifts (shift nurses) and 35 female nurses working on fixed days (fixed nurses) were enrolled. After assessing the work-related psychological traits, including burnout, perceived stress, anxiety, and depression of nurses, the fractional amplitude of low-frequency fluctuations (fALFF) and region of interest (ROI)-based functional connectivity (FC) analyses were performed to investigate the differences of brain spontaneous activity and functional connectivity between these two groups of nurses. Thereafter, correlations between the functional brain parameters (fALFF and FC) and clinical metrics were investigated among the shift nurses. Compared to fixed nurses, shift nurses had higher burnout, perceived stress and depression scores, lower fALFF in the right dorsolateral prefrontal cortex (dlPFC), left and right superior parietal lobule (SPL), bilateral anterior cingulate cortex (ACC), and higher fALFF in the right superior/middle temporal gyrus, as well as decreased FC between the right dlPFC (the selected ROI) and bilateral ACC, left and right inferior frontal/orbitofrontal gyrus (IFG/IOFG), right SPL, and left middle occipital gyrus (voxel-level p < 0.001, cluster level p < 0.05, GRF correction). Correlation analyses demonstrated that the fALFF value of the right dlPFC was significantly correlated with the burnout and anxiety scores, the FC value of the right dlPFC-right SPL was correlated with the perceived stress and burnout scores, the FC value of the right dlPFC-right IFG/IOFG was correlated with the burnout score in shift nurses (p < 0.05). Shift nurses had work-related altered functional activity and connectivity in the right frontoparietal network, which provided objective and visualised evidence to clarify the hazards of long-term shift work on female nurses. Seventy nurses participated deeply as subjects in this study. These findings are expected to draw managers' attention to the harmful influences of shift work on nurses.

Altered resting-state brain function in endurance athletes.

Previous research has confirmed significant differences in regional brain activity and functional connectivity between endurance athletes and non-athletes. However, no studies have investigated the differences in topological efficiency of the brain functional network between endurance athletes and non-athletes. Here, we compared differences in regional activities, functional connectivity, and topological properties to explore the functional basis associated with endurance training. The results showed significant correlations between Regional Homogeneity in the motor cortex, visual cortex, cerebellum, and the training intensity parameters. Alterations in functional connectivity among the motor cortex, visual cortex, cerebellum, and the inferior frontal gyrus and cingulate gyrus were significantly correlated with training intensity parameters. In addition, the graph theoretical analysis results revealed a significant reduction in global efficiency among athletes. This decline is mainly caused by decreased nodal efficiency and nodal local efficiency of the cerebellar regions. Notably, the sensorimotor regions, such as the precentral gyrus and supplementary motor areas, still exhibit increased nodal efficiency and nodal local efficiency. This study not only confirms the improvement of regional activity in brain regions related to endurance training, but also offers novel insights into the mechanisms through which endurance athletes undergo changes in the topological efficiency of the brain functional network.

Resting-state brain network remodeling after different nerve reconstruction surgeries: a functional magnetic resonance imaging study in brachial plexus injury rats.

JOURNAL/nrgr/04.03/01300535-202505000-00031/figure1/v/2024-07-28T173839Z/r/image-tiff Distinct brain remodeling has been found after different nerve reconstruction strategies, including motor representation of the affected limb. However, differences among reconstruction strategies at the brain network level have not been elucidated. This study aimed to explore intra-network changes related to altered peripheral neural pathways after different nerve reconstruction surgeries, including nerve repair, end-to-end nerve transfer, and end-to-side nerve transfer. Sprague-Dawley rats underwent complete left brachial plexus transection and were divided into four equal groups of eight: no nerve repair, grafted nerve repair, phrenic nerve end-to-end transfer, and end-to-side transfer with a graft sutured to the anterior upper trunk. Resting-state brain functional magnetic resonance imaging was obtained 7 months after surgery. The independent component analysis algorithm was utilized to identify group-level network components of interest and extract resting-state functional connectivity values of each voxel within the component. Alterations in intra-network resting-state functional connectivity were compared among the groups. Target muscle reinnervation was assessed by behavioral observation (elbow flexion) and electromyography. The results showed that alterations in the sensorimotor and interoception networks were mostly related to changes in the peripheral neural pathway. Nerve repair was related to enhanced connectivity within the sensorimotor network, while end-to-side nerve transfer might be more beneficial for restoring control over the affected limb by the original motor representation. The thalamic-cortical pathway was enhanced within the interoception network after nerve repair and end-to-end nerve transfer. Brain areas related to cognition and emotion were enhanced after end-to-side nerve transfer. Our study revealed important brain networks related to different nerve reconstructions. These networks may be potential targets for enhancing motor recovery.

Altered functional connectivity of brainstem nuclei in new daily persistent headache: Evidence from resting-state functional magnetic resonance imaging.

The new daily persistent headache (NDPH) is a rare primary headache disorder. However, the underlying mechanisms of NDPH remain incompletely understood. This study aims to apply seed-based analysis to explore the functional connectivity (FC) of brainstem nuclei in patients with NDPH using resting-state functional magnetic resonance imaging (MRI). The FC analysis from the region of interest (ROI) to whole brain voxels was used to investigate 29 patients with NDPH and 37 well-matched healthy controls (HCs) with 3.0 Tesla MRI. The 76 nuclei in the brainstem atlas were defined as ROIs. Furthermore, we explored the correlations between FC and patients' clinical characteristics and neuropsychological evaluations. Patients with NDPH exhibited reduced FC in multiple brainstem nuclei compared to HCs (including right inferior medullary reticular formation, right mesencephalic reticular formation, bilateral locus coeruleus, bilateral laterodorsal tegmental nucleus-central gray of the rhombencephalon, median raphe, left medial parabrachial nucleus, periaqueductal gray, and bilateral ventral tegmental area-parabrachial pigmented nucleus complex) and increased FC in periaqueductal gray. No significant correlations were found between the FC of these brain regions and clinical characteristics or neuropsychological evaluations after Bonferroni correction (p > 0.00016). Our results demonstrated that patients with NDPH have abnormal FC of brainstem nuclei involved in the perception and regulation of pain and emotions.

Compensatory increase in ipsilesional supplementary motor area and premotor connectivity is associated with greater gait impairments: a personalized fMRI analysis in chronic stroke.

Balance and mobility impairments are prevalent post-stroke and a large number of survivors require walking assistance at 6 months post-stroke which diminishes their overall quality of life. Personalized interventions for gait and balance rehabilitation are crucial. Recent evidence indicates that stroke lesions in primary motor pathways, such as corticoreticular pathways (CRP) and corticospinal tract (CST), may lead to reliance on alternate motor pathways as compensation, but the current evidence lacks comprehensive knowledge about the underlying neural mechanisms. In this study, we investigate the functional connectivity (FC) changes within the motor network derived from an individualized cortical parcellation approach in 33 participants with chronic stroke compared to 17 healthy controls. The correlations between altered motor FC and gait deficits (i.e., walking speed and walking balance) were then estimated in the stroke population to understand the compensation mechanism of the motor network in motor function rehabilitation post-stroke. Our results demonstrated significant FC increases between ipsilesional medial supplementary motor area (SMA) and premotor in stroke compared to healthy controls. Furthermore, we also revealed a negative correlation between ipsilesional SMA-premotor FC and self-selected walking speed, as well as the Functional Gait Assessment (FGA) scores. The increased FC between the ipsilesional SMA and premotor regions could be a compensatory mechanism within the motor network following a stroke when the individual can presumably no longer rely on the more precise CST modulation of movements to produce a healthy walking pattern. These findings enhance our understanding of individualized motor network FC changes and their connection to gait and walking balance impairments post-stroke, improving stroke rehabilitation interventions.

Convergent and divergent genes expression profiles associated with brain-wide functional connectome dysfunction in deficit and non-deficit schizophrenia.

Deficit schizophrenia (DS) is a subtype of schizophrenia characterized by the primary and persistent negative symptoms. Previous studies have identified differences in brain functions between DS and non-deficit schizophrenia (NDS) patients. However, the genetic regulation features underlying these abnormal changes are still unknown. This study aimed to detect the altered patterns of functional connectivity (FC) in DS and NDS and investigate the gene expression profiles underlying these abnormal FC. The study recruited 82 DS patients, 96 NDS patients, and 124 healthy controls (CN). Voxel-based unbiased brain-wide association study was performed to reveal altered patterns of FC in DS and NDS patients. Machine learning techniques were used to access the utility of altered FC for diseases diagnosis. Weighted gene co-expression network analysis (WGCNA) was employed to explore the associations between altered FC and gene expression of 6 donated brains. Enrichment analysis was conducted to identify the genetic profiles, and the spatio-temporal expression patterns of the key genes were further explored. Comparing to CN, 23 and 20 brain regions with altered FC were identified in DS and NDS patients. The altered FC among these regions showed significant correlations with the SDS scores and exhibited high efficiency in disease classification. WGCNA revealed associations between DS/NDS-related gene expression and altered FC. Additionally, 22 overlapped genes, including 12 positive regulation genes and 10 negative regulation genes, were found between NDS and DS. Enrichment analyses demonstrated relationships between identified genes and significant pathways related to cellular response, neuro regulation, receptor binding, and channel activity. Spatial and temporal gene expression profiles of SCN1B showed the lowest expression at the initiation of embryonic development, while DPYSL3 exhibited rapid increased in the fetal. The present study revealed different altered patterns of FC in DS and NDS patients and highlighted the potential value of FC in disease classification. The associations between gene expression and neuroimaging provided insights into specific and common genetic regulation underlying these brain functional changes in DS and NDS, suggesting a potential genetic-imaging pathogenesis of schizophrenia.

Differences in the expression of cortex-wide neural dynamics are related to behavioral phenotype

Behavior differs across individuals, ranging from typical to atypical phenotypes.1 Understanding how differences in behavior relate to differences in neural activity is critical for developing treatments of neuropsychiatric and neurodevelopmental disorders. One hypothesis is that differences in behavior reflect individual differences in the dynamics of how information flows through the brain. In support of this, the correlation of neural activity between brain areas, termed "functional connectivity," varies across individuals2 and is disrupted in autism,3 schizophrenia,4 and depression.5 However, the changes in neural activity that underlie altered behavior and functional connectivity remain unclear. Here, we show that individual differences in the expression of different patterns of cortical neural dynamics explain variability in both functional connectivity and behavior. Using mesoscale imaging, we recorded neural activity across the dorsal cortex of behaviorally "typical" and "atypical" mice. All mice shared the same recurring cortex-wide spatiotemporal motifs of neural activity, and these motifs explained the large majority of variance in cortical activity (>75%). However, individuals differed in how frequently different motifs were expressed. These differences in motif expression explained differences in functional connectivity and behavior across both typical and atypical mice. Our results suggest that differences in behavior and functional connectivity are due to changes in the processes that select which pattern of neural activity is expressed at each moment in time.

Aberrant dynamic functional connectivity of thalamocortical circuitry in major depressive disorder.

Thalamocortical circuitry has a substantial impact on emotion and cognition. Previous studies have demonstrated alterations in thalamocortical functional connectivity (FC), characterized by region-dependent hypo- or hyper-connectivity, among individuals with major depressive disorder (MDD). However, the dynamical reconfiguration of the thalamocortical system over time and potential abnormalities in dynamic thalamocortical connectivity associated with MDD remain unclear. Hence, we analyzed dynamic FC (dFC) between ten thalamic subregions and seven cortical subnetworks from resting-state functional magnetic resonance images of 48 patients with MDD and 57 healthy controls (HCs) to investigate time-varying changes in thalamocortical FC in patients with MDD. Moreover, dynamic laterality analysis was conducted to examine the changes in functional lateralization of the thalamocortical system over time. Correlations between the dynamic measures of thalamocortical FC and clinical assessment were also calculated. We identified four dynamic states of thalamocortical circuitry wherein patients with MDD exhibited decreased fractional time and reduced transitions within a negative connectivity state that showed strong correlations with primary cortical networks, compared with the HCs. In addition, MDD patients also exhibited increased fluctuations in functional laterality in the thalamocortical system across the scan duration. The thalamo-subnetwork analysis unveiled abnormal dFC variability involving higher-order cortical networks in the MDD cohort. Significant correlations were found between increased dFC variability with dorsal attention and default mode networks and the severity of symptoms. Our study comprehensively investigated the pattern of alteration of the thalamocortical dFC in MDD patients. The heterogeneous alterations of dFC between the thalamus and both primary and higher-order cortical networks may help characterize the deficits of sensory and cognitive processing in MDD.

Effect of high-definition transcranial direct current stimulation among late-subacute and chronic stroke survivors with fatigue: A randomized-controlled crossover trial protocol

Post-stroke fatigue (PSF) is a commonly overlooked symptom that impacts daily functioning and quality of life. It is caused by altered functional connectivity within the brain networks, which can potentially be influenced by neuromodulation. Multiple cortical regions have been targeted to reduce PSF, but the most efficient ones remain uncertain. Therefore, we aim to identify the most appropriate cortical stimulation site to reduce PSF. Twenty participants with PSF will be included in this cross-over trial. Each participant will receive one session of active anodal high definition- transcranial direct current stimulation (HD-tDCS) over three different cortical areas and one session of sham tDCS in a cross-over manner, with a two-week of washout period in between. Pre- and post- fatigue will be assessed using Fatigue Severity Scale and fatigability using electromyography by determining the time to task failure. Resting-state electroencephalography will be performed before and after each stimulation session to determine the functional connectivity of the cortical areas stimulated.

Functional connectivity alterations in PTSD patients with suicidal ideation

Post-traumatic stress disorder (PTSD) is a highly prevalent psychological disorder characterized by intense feelings of fear or helplessness after experiencing a traumatic event. PTSD is highly comorbid with mood disorders and patients are at increased risk for suicide. The present study aimed to identify neural connectivity alterations associated with suicidal ideation (SI) in PTSD patients by using resting-state functional magnetic resonance imaging. Voxel-to-voxel intrinsic connectivity was compared between PTSD patients with no (N-SI; N = 26) and high (H-SI; N = 7) SI. Region-to-voxel functional connectivity analysis was performed to identify the regions that contributed to intrinsic connectivity changes. H-SI patients had increased connectivity to various brain regions representing the central executive network, salience network, and default mode network in the frontal, temporal, and occipital lobes as well as subcortical structures involved in executive and limbic functioning, and motor systems. These results suggest SI is associated with large network-level alterations in PTSD patients and is not the result of neuronal abnormalities in any one specific area.

Compressed cerebellar functional connectome hierarchy in spinocerebellar ataxia type 3.

Spinocerebellar ataxia type 3 (SCA3) is an inherited movement disorder characterized by a progressive decline in motor coordination. Despite the extensive functional connectivity (FC) alterations reported in previous SCA3 studies in the cerebellum and cerebellar-cerebral pathways, the influence of these FC disturbances on the hierarchical organization of cerebellar functional regions remains unclear. Here, we compared 35 SCA3 patients with 48 age- and sex-matched healthy controls using a combination of voxel-based morphometry and resting-state functional magnetic resonance imaging to investigate whether cerebellar hierarchical organization is altered in SCA3. Utilizing connectome gradients, we identified the gradient axis of cerebellar hierarchical organization, spanning sensorimotor to transmodal (task-unfocused) regions. Compared to healthy controls, SCA3 patients showed a compressed hierarchical organization in the cerebellum at both voxel-level (p < .05, TFCE corrected) and network-level (p < .05, FDR corrected). This pattern was observed in both intra-cerebellar and cerebellar-cerebral gradients. We observed that decreased intra-cerebellar gradient scores in bilateral Crus I/II both negatively correlated with SARA scores (left/right Crus I/II: r = -.48/-.50, p = .04/.04, FDR corrected), while increased cerebellar-cerebral gradients scores in the vermis showed a positive correlation with disease duration (r = .48, p = .04, FDR corrected). Control analyses of cerebellar gray matter atrophy revealed that gradient alterations were associated with cerebellar volume loss. Further FC analysis showed increased functional connectivity in both unimodal and transmodal areas, potentially supporting the disrupted cerebellar functional hierarchy uncovered by the gradients. Our findings provide novel evidence regarding alterations in the cerebellar functional hierarchy in SCA3.

Cerebellar and thalamic connector hubs facilitate the involvement of visual and cognitive networks in essential tremor

IntroductionConnector hubs are specialized brain regions that connect multiple brain networks and therefore have the potential to affect the functions of multiple systems. This study aims to examine the involvement of connector hub regions in essential tremor. MethodsWe examined whole-brain functional connectivity alterations across multiple brain networks in 27 patients with essential tremor and 27 age- and sex-matched healthy controls to identify affected hub regions using a network metric called functional connectivity overlap ratio estimated from resting-state functional MRI. We also evaluated the relationships of affected hubs with cognitive and tremor scores in all patients and with motor function improvement scores in 15 patients who underwent postoperative follow-up evaluations after focused ultrasound thalamotomy. ResultsWe have identified affected connector hubs in the cerebellum and thalamus. Specifically, the dentate nucleus in the cerebellum and the dorsomedial thalamus exhibited more extensive connections with the sensorimotor network in patients. Moreover, the connections of the thalamic pulvinar with the visual network were also significantly widespread in the patient group. The connections of these connector hub regions with cognitive networks were negatively associated (FDR q < 0.05) with cognitive, tremor, and motor function improvement scores. ConclusionIn patients with essential tremor, connector hub regions within the cerebellum and thalamus exhibited widespread functional connections with sensorimotor and visual networks, leading to alternative pathways outside the classical tremor axis. Their connections with cognitive networks also affect patients’ cognitive function.

Exploring global and local processes underlying alterations in resting-state functional connectivity and dynamics in schizophrenia.

We examined changes in large-scale functional connectivity and temporal dynamics and their underlying mechanisms in schizophrenia (ScZ) through measurements of resting-state functional magnetic resonance imaging (rs-fMRI) data and computational modelling. The rs-fMRI measurements from patients with chronic ScZ (n=38) and matched healthy controls (n=43), were obtained through the public schizConnect repository. Computational models were constructed based on diffusion-weighted MRI scans and fit to the experimental rs-fMRI data. We found decreased large-scale functional connectivity across sensory and association areas and for all functional subnetworks for the ScZ group. Additionally global synchrony was reduced in patients while metastability was unaltered. Perturbations of the computational model revealed that decreased global coupling and increased background noise levels both explained the experimentally found deficits better than local changes to the GABAergic or glutamatergic system. The current study suggests that large-scale alterations in ScZ are more likely the result of global rather than local network changes.

From Software to Hardware: A Case Series of Functional Neurological Symptoms and Cerebrovascular Disease.

Neuroimaging studies have identified alterations in both brain structure and functional connectivity in patients with functional neurological disorder (FND). For many patients, FND emerges from physical precipitating events. Nevertheless, there are a limited number of case series in the literature that describe the clinical presentation and neuroimaging correlates of FND following cerebrovascular disease. The authors collected data from two clinics in the United Kingdom on 14 cases of acute, improving, or delayed functional neurological symptoms following cerebrovascular events. Most patients had functional neurological symptoms that were localized to cerebrovascular lesions, and the lesions mapped onto regions known to be part of functional networks disrupted in FND, including the thalamus, anterior cingulate gyrus, insula, and temporoparietal junction. The findings demonstrate that structural lesions can lead to FND symptoms, possibly explained through changes in relevant mechanistic functional networks.

Brain network centrality and connectivity are associated with clinical subtypes and disease progression in Parkinson's disease.

To investigate brain network centrality and connectivity alterations in different Parkinson's disease (PD) clinical subtypes using resting-state functional magnetic resonance imaging (RS-fMRI), and to explore the correlation between baseline connectivity changes and the clinical progression. Ninety-two PD patients were enrolled at baseline, alongside 38 age- and sex-matched healthy controls. Of these, 85 PD patients underwent longitudinal assessments with a mean of 2.75 ± 0.59 years. Two-step cluster analysis integrating comprehensive motor and non-motor manifestations was performed to define PD subtypes. Degree centrality (DC) and secondary seed-based functional connectivity (FC) were applied to identify brain network centrality and connectivity changes among groups. Regression analysis was used to explore the correlation between baseline connectivity changes and clinical progression. Cluster analysis identified two main PD subtypes: mild PD and moderate PD. Two different subtypes within the mild PD were further identified: mild motor-predominant PD and mild-diffuse PD. Accordingly, the disrupted DC and seed-based FC in the left inferior frontal orbital gyrus and left superior occipital gyrus were severe in moderate PD. The DC and seed-based FC alterations in the right gyrus rectus and right postcentral gyrus were more severe in mild-diffuse PD than in mild motor-predominant PD. Moreover, disrupted DC were associated with clinical manifestations at baseline in patients with PD and predicted motor aspects progression over time. Our study suggested that brain network centrality and connectivity changes were different among PD subtypes. RS-fMRI holds promise to provide an objective assessment of subtype-related connectivity changes and predict disease progression in PD.

Increased functional connectivity within the salience network in patients with insomnia.

Insomnia is a common sleep disorder with significant negative impacts on emotional states; however, the underlying mechanism of insomnia with comorbid emotional dysregulation remains largely unknown. The salience network (SN) plays an important role in both sleep and emotional regulation. The study aimed to explore the specific alterations in functional connectivity (FC) within the SN in insomnia patients. A total of 30 eligible patients with insomnia disorder (ID group) and 30 healthy controls (HC group) underwent resting-state functional magnetic resonance imaging (fMRI) scanning and psychometric assessments. Differences in FC within the SN were examined using seed-based region-to-region connectivity analysis. Compared with healthy controls, patients with insomnia showed increased FC within the SN, mainly between the anterior cingulate cortex (ACC) and right superior frontal gyrus (SFG), the right SFG and right supramarginal gyrus (SMG), and between the right insular (INS) and left SMG (P<0.05). Additionally, significant correlations were observed between increased FC and the Hamilton Depression Rating Scale (HAMD), Pittsburgh Sleep Quality Index (PSQI), and Hamilton Anxiety Rating Scale (HAMA) scores (P<0.05, after Bonferroni correction). These results suggest that increased FC within the SN may be related to poor sleep quality and negative emotions, highlighting the importance of the SN in the pathophysiological mechanisms of insomnia with comorbid emotional dysregulation.

Structural and Functional Alterations of Hippocampal Subfields in Patients With Adult-Onset Primary Hypothyroidism.

Hypothyroidism is often associated with cognitive and emotional dysregulation; however, the underlying neuropathological mechanisms remain elusive. The study aimed to characterize abnormal alterations in hippocampal subfield volumes and functional connectivity (FC) in patients with subclinical hypothyroidism (SCH) and overt hypothyroidism (OH). This cross-sectional observational study comprised 47 and 40 patients with newly diagnosed adult-onset primary SCH and OH, respectively, and 53 well-matched healthy controls (HCs). The demographics, clinical variables, and neuropsychological scale scores were collected. Next, the hippocampal subfield volumes and seed-based FC were compared between the groups. Finally, correlation analyses were performed. SCH and OH exhibited significant alterations in cognitive and emotional scale scores. Specifically, the volumes of the right granule cell molecular layer of the dentate gyrus (GC-ML-DG) head, cornu ammonis (CA) 4, and CA3 head were reduced in the SCH and OH groups. Moreover, the volumes of the right molecular layer head, CA1 body, left GC-ML-DG head, and CA4 head were lower in SCH. In addition, the hippocampal subfield volumes decreased more significantly in SCH than OH. The seed-based FC decreased in SCH but increased in OH compared with HCs. Correlation analyses revealed thyroid hormone was negatively correlated with FC values in hypothyroidism. Patients with SCH and OH might be at risk of cognitive decline, anxiety, or depression, and exhibited alterations in volume and FC in specific hippocampal subfields. Furthermore, the reduction in volume was more pronounced in SCH. This study provides novel insights into the neuropathological mechanisms of brain impairment in hypothyroidism.

Altered resting-state functional connectivity in newborns with hypoxic ischemic encephalopathy assessed using high-density functional near-infrared spectroscopy

Hypoxic-ischemic encephalopathy (HIE) results from a lack of oxygen to the brain during the perinatal period. HIE can lead to mortality and various acute and long-term morbidities. Improved bedside monitoring methods are needed to identify biomarkers of brain health. Functional near-infrared spectroscopy (fNIRS) can assess resting-state functional connectivity (RSFC) at the bedside. We acquired resting-state fNIRS data from 21 neonates with HIE (postmenstrual age [PMA] = 39.96), in 19 neonates the scans were acquired post-therapeutic hypothermia (TH), and from 20 term-born healthy newborns (PMA = 39.93). Twelve HIE neonates also underwent resting-state functional magnetic resonance imaging (fMRI) post-TH. RSFC was calculated as correlation coefficients amongst the time courses for fNIRS and fMRI data, respectively. The fNIRS and fMRI RSFC maps were comparable. RSFC patterns were then measured with graph theory metrics and compared between HIE infants and healthy controls. HIE newborns showed significantly increased clustering coefficients, network efficiency and modularity compared to controls. Using a support vector machine algorithm, RSFC features demonstrated good performance in classifying the HIE and healthy newborns in separate groups. Our results indicate the utility of fNIRS-connectivity patterns as potential biomarkers for HIE and fNIRS as a new bedside tool for newborns with HIE.

Effects of childhood maltreatment and major depressive disorder on functional connectivity in hippocampal subregions.

Major Depressive Disorder (MDD) with childhood maltreatment is a prevalent clinical phenotype. Prior studies have observed abnormal hippocampal activity in MDD patients, considering the hippocampus as a single nucleus. However, there is limited research investigating the static and dynamic changes in hippocampal subregion functional connectivity (FC) in MDD patients with childhood maltreatment. Therefore, we employed static and dynamic FC analyses using hippocampal subregions, including the anterior hippocampus and posterior hippocampus, as seed regions to investigate the neurobiological alterations associated with MDD resulting from childhood maltreatment. This study involved four groups: MDD with (n = 48) and without childhood maltreatment (n = 30), as well as healthy controls with (n = 57) and without (n = 46) childhood maltreatment. Compared to MDD patients without childhood maltreatment, those with childhood maltreatment exhibit altered FC between the hippocampal subregion and multiple brain regions, including the anterior cingulate gyrus, superior frontal gyrus, putamen, calcarine gyrus, superior temporal gyrus, angular gyrus, and supplementary motor area. Additionally, dynamic FC between the right medial-2 hippocampal head and the right calcarine gyrus shows a positive correlation with childhood maltreatment across all its subtypes. Moreover, dFC between the right hippocampal tail and the left angular gyrus moderates the relationship between childhood maltreatment and the depression severity. Our findings of distinct FC patterns within hippocampal subregions provide new clues for understanding the neurobiological basis of MDD with childhood maltreatment.