Abnormal Functional Connectivity Research Articles

Chronic Δ9-tetrahydrocannabinol exposure in adolescent nonhuman primates: persistent abnormalities in economic demand and brain functional connectivity.

Although chronic cannabis use during adolescence can alter brain function and impair complex behavioral processes, it is unclear whether such deficits persist into adulthood. Using a coordinated awake neuroimaging and behavioral approach in nonhuman primates, we addressed this issue by examining the impact of chronic adolescent exposure to Δ9-tetrahydrocannabinol (THC) on brain functional connectivity and motivational processes during early adulthood. Female and male squirrel monkeys (n = 23) were treated daily for 6 months during adolescence with vehicle or either a low (0.32 mg/kg) or high dose (3.2 mg/kg) of THC. Regional homogeneity and seed-to-whole-brain functional connectivity were analyzed prior to, during, and following discontinuation of chronic treatment to examine changes in regions implicated in reward processing. Subsequently, motivation and reward sensitivity in these subjects, now young adults, were evaluated in economic demand studies by determining the relationship between escalating response requirements and consumption of differing magnitudes of a palatable food reinforcer. Results show that adolescent THC exposure led to persistent alterations in mOFC, caudate, and ventral striatum whole-brain connectivity. Moreover, subjects treated with vehicle during adolescence displayed an orderly and expected inverse relationship between reward magnitude and demand elasticity, whereas THC-treated subjects exhibited dosage-dependent disorder in reward sensitivity and motivational deficits. Changes in neural circuitry (local connectivity in ventral striatum and whole brain connectivity in mOFC) and economic demand were correlated with indices of reward sensitivity in vehicle- but not THC-treated subjects. Taken together, these data indicate that chronic adolescent THC exposure produced long-lasting neurocognitive abnormalities in reward processing.

Deriving comprehensive literature trends on multi-omics analysis studies in autism spectrum disorder using literature mining pipeline

Autism spectrum disorder (ASD) is characterized by highly heterogenous abnormalities in functional brain connectivity affecting social behavior. There is a significant progress in understanding the molecular and genetic basis of ASD in the last decade using multi-omics approach. Mining this large volume of biomedical literature for insights requires considerable amount of manual intervention for curation. Machine learning and artificial intelligence fields are advancing toward simplifying data mining from unstructured text data. Here, we demonstrate our literature mining pipeline to accelerate data to insights. Using topic modeling and generative AI techniques, we present a pipeline that can classify scientific literature into thematic clusters and can help in a wide array of applications such as knowledgebase creation, conversational virtual assistant, and summarization. Employing our pipeline, we explored the ASD literature, specifically around multi-omics studies to understand the molecular interplay underlying autism brain.

Modeling Functional Brain Networks for ADHD via Spatial Preservation-Based Neural Architecture Search.

Modeling functional brain networks (FBNs) for attention deficit hyperactivity disorder (ADHD) has sparked significant interest since the abnormal functional connectivity is discovered in certain functional magnetic resonance imaging (fMRI)-based brain regions compared to typical developmental control (TC) individuals. However, existing models for modeling FBNs generally use dimensionality reduction techniques to process the high dimensional input data, which results in confusion and an inaccurate representation of voxel interactions between spatially close brain regions, causing misdiagnosis of the disease. To address these issues, we propose a spatial preservation-based neural architecture search (SP-NAS) for FBNs modeling in ADHD. The main work includes three-fold: 1) A spatial preservation module is designed to embed original spatial information into dimensionality reduction data, addressing the challenge of a large number of parameters in the original data and mitigating disease misdiagnosis resulting from voxel confusion between different brain regions caused by dimensionality reduction. 2) A search space using more suitable search operations is constructed to efficiently extract spatial-temporal interaction characteristics of fMRI data in ADHD while narrowing the search space. 3) Cross-regional association differences between ADHD and TC groups are explored for ADHD auxiliary diagnosis since the abnormal activation regions of ADHD relative to TC on the brain regions and the abnormal connectivity between the lesion brain regions are identified. Model validation results on the ADHD-200 dataset show that the FBNs obtained from SP-NAS not only achieve competitive results in ADHD diagnosis but also reveal abnormal connections in the lesion regions of ADHD consistent with clinical diagnosis.

Identification of asymmetrical abnormalities in functional connectivity and brain network topology for migraine sufferers: A preliminary study based on resting-state fMRI data

Research on the neural mechanisms underlying brain asymmetry in patients with migraine patients using fMRI is insufficient. This study proposed using lateralized algorithms for functional connectivity and brain network topology and investigated changes in their lateralization in patients with migraine. In study 1, laterality indices of functional connectivity (LFunctionCorr) and brain network topological properties (LBetweennessCentrality, LDegree, and LStrength) were defined. Differences between migraineurs and normal subjects were compared at whole-brain, half-brain, and region levels. In study 2, laterality indices were used to classify migraine and were validated using independent samples and the segment method for repeatability. In study 3, abnormal brain regions related to migraine were extracted based on the classification results and differences analysis. Study 1 found no significant differences related to in for migraine at the whole-brain level; however, significant differences were identified at the half-brain level for the hemispheric lateralization of the LFunctionCorr, while 11 significantly different brain regions were also identified at the brain region level. Furthermore, the classification accuracy in study 2 was 0.9366. With repeated validation, the accuracy reached 0.8561. Furthermore, after extending the samples according to the segmentation strategy, the classification accuracies were improved to 0.9408 and 0.8585. Study 3 identified 10 crucial brain regions with asymmetrical specificity based on laterality indices distributed across the visual network, the frontoparietal control network, the default mode network, the salience/ventral attention network and the limbic system. The results revealed novel insights and avenues for research into the mechanisms of migraine asymmetry and showed that the laterality indices could be used as a potential diagnostic imaging marker for migraine.

Methylphenidate differentially alters corticostriatal connectivity after traumatic brain injury.

Traumatic brain injury commonly impairs attention and executive function, and disrupts the large-scale brain networks that support these cognitive functions. Abnormalities of functional connectivity are seen in corticostriatal networks, which are associated with executive dysfunction and damage to neuromodulatory catecholaminergic systems caused by head injury. Methylphenidate, a stimulant medication that increases extracellular dopamine and noradrenaline, can improve cognitive function following TBI. In this experimental medicine add-on study to a randomised, double-blind, placebo-controlled clinical trial, we test whether administration of methylphenidate alters corticostriatal network function and influences drug response. 43 moderate-severe traumatic brain injury patients received 0.3 mg/kg of methylphenidate or placebo twice a day in 2-week blocks. 28 patients were included in the neuropsychological and functional imaging analysis (4 females, mean age 40.9±12.7, range 20-65) and underwent functional MRI and neuropsychological assessment after each block. 123I-Ioflupane SPECT Dopamine Transporter (DAT) scans were performed, and specific binding ratios were extracted from caudate subdivisions. Functional connectivity and the relationship to cognition was compared between drug and placebo conditions. Methylphenidate increased caudate to anterior cingulate cortex functional connectivity compared to placebo and decreased connectivity from the caudate to default mode network. Connectivity within the default mode network was also decreased by methylphenidate administration and there was a significant relationship between caudate functional connectivity and DAT binding during methylphenidate administration. Methylphenidate significantly improved executive function in TBI patients, and this was associated with alterations in the relationship between executive function and right anterior caudate functional connectivity. Functional connectivity is strengthened to brain regions including the anterior cingulate that are activated when attention is focused externally. These results show that methylphenidate alters caudate interactions with cortical brain networks involved in executive control. In contrast, caudate functional connectivity reduces to default mode network regions involved in internally focused attention and that deactivate during tasks that require externally focused attention. These results suggest that the beneficial cognitive effects of methylphenidate may be mediated through its impact on the caudate. Methylphenidate differentially influences how the caudate interacts with large-scale functional brain networks that exhibit co-ordinated but distinct patterns of activity required for attentionally demanding tasks.

Reduced resting-state functional connectivity of default mode network subsystems in patients with obsessive-compulsive disorder

ObjectivesNeuroimaging studies have reported extensive resting-state functional connectivity (rsFC) abnormalities in the default mode network (DMN) in patients with obsessive-compulsive disorder (OCD), but findings are inconsistent. DMN can be divided into three subsystems: core, dorsal medial prefrontal cortex (dMPFC), and medial temporal lobe (MTL). This study aimed to explore abnormalities in rsFC strength within and between DMN subsystems in OCD patients, and their relationship with clinical symptoms. MethodsThis study recruited 39 OCD patients and 45 healthy controls (HCs). OCD symptoms were assessed using the Yale-Brown Obsessive-Compulsive Scale (YBOCS). The seed-to-seed method was used to construct rsFC matrix. The rsFC strength within and between the three DMN subsystems were calculated. ResultsCompared to the HC group, the OCD group exhibited reduced rsFC strength within core subsystem (F = 7.799, p = 0.007, Bonferroni corrected p = 0.042). Further, this reduction was also observed in the unmedicated OCD group (n = 19), but not in the medicated OCD group (n = 18). In addition, rsFC strength within core subsystem was negatively correlated with the obsession subscale of YBOCS in the OCD group (r = −0.512, p = 0.004, Bonferroni corrected p = 0.008). Further, this correlation was also significant in the unmedicated OCD group, but not in the medicated OCD group. ConclusionsOur findings suggest that reduced rsFC strength within core subsystem is a feature of OCD patients and may serve as a potential biomarker of obsession severity. Moreover, pharmacological treatments may affect rsFC strength in DMN.

Abnormal Interhemispheric Functional Connectivity in Acute Pericoronitis: A Resting-State MRI Study.

Acute pericoronitis (AP) is a prevalent cause of odontogenic toothache which can significantly impact brain function. Previous research has predominantly concentrated on localized brain activity. However, the synergistic changes between brain hemispheres induced by toothache and resulting abnormal functional connectivity across the brain have not been comprehensively studied. A total of 34 patients with AP and 34 healthy individuals, matched for age, sex, and education were recruited for this study. All participants underwent resting-state functional magnetic resonance imaging (rs-MRI) scans. The voxel mirror homotopic connectivity (VMHC) method was used to identify intergroup differences. Brain regions exhibiting statistically significant differences were selected as regions of interest for further functional connectivity analysis. The partial correlation method was utilized to assess the correlation between abnormal VMHC values in different regions and clinical parameters, with age and sex included as covariates. Patients with AP exhibited reduced VMHC values in the thalamus and elevated VMHC values in the inferior frontal gyrus compared with healthy controls. Subsequent functional connectivity analyses revealed extensive changes in functional networks, predominantly affecting the default, frontoparietal, cerebellar, and pain networks. Changes in functional patterns across these brain networks offer novel insights into the neurophysiological mechanisms underlying pain information processing.

Exploring causal association between functional/structural connectivity and major depression disorder: A bidirectional Mendelian randomization study

ObjectivesPrior observational studies have suggested a correlation between major depressive disorder (MDD) and communication imbalances within the resting-state brain network (RSN), but the causal relationship remains unclear. This research uses Mendelian randomization (MR) analysis to explore the potential causal effects between functional connectivity (FC), structural connectivity (SC) and MDD. MethodsTwo-sample bidirectional MR analysis was employed in this study. Inverse variance weighted (IVW) was used to explore the causal relationship between the FC/SC and MDD, with various methods such as MR-Egger to conduct sensitivity analyses. ResultsThe IVW analysis results showed that higher genetic predicted dorsal attention network FC, limbic network SC, and dorsal attention network SC were associated with an increased risk of MDD (β: 15.08, 95%CI: 5.89–24.27, p = 0.001; β: 3.79, 95%CI: −0.22-7.8, p = 0.034; β: 9.89, 95%CI: 0.88–18.90, p = 0.031). Reverse MR analysis demonstrated that a genetically predicted elevated risk of MDD was associated with reduced frontal parietal network FC (β: −0.00046, p = 0.041). ConclusionsThe study suggests a causal relationship between the FC and SC within specific RSNs and the risk of MDD. Abnormalities in the dorsal attention network FC/SC and the limbic network SC were risk factors for MDD. The FC abnormality of the frontal parietal network may be the downstream influence following the MDD onset. Further investigation is needed to determine the potential utility of these neuroimaging markers in the prevention of MDD or the evaluation of treatment efficacy.

Altered brain function in treatment-resistant depression patients: A resting-state functional magnetic resonance imaging study

BackgroundIt has been established that there are functional changes in the brain of treatment-resistant depression (TRD) patients, but previous studies of functional connectivity (FC) usually involved selection of regions of interest based on accumulated a priori knowledge of the disorder. In this study, we combine amplitude of low-frequency fluctuation (ALFF) and FC; this approach, based on the abnormal ALFF, may provide some insights into the neural basis of the disease in terms of fMRI signals of low-frequency fluctuations. MethodsA total of 16 TRD patients, who visited the Qingdao Mental Health Center, Shandong Province, China between March 2023 and January 2024, along with 16 normal subjects, were enrolled into this study for functional imaging. In this study, we first explored the ALFF changes of TRD patients at a baseline resting state. Second, we selected the regions that were significantly changed in the ALFF as seeds and calculated the regional activity and functional connectivity (FC) of these regions using a seed-based approach. We also calculated correlations between the percent change in the PDQ-5D scores and ALFF values in brain regions with differing activity for TRD patients. ResultsDuring the baseline resting state, by using the ALFF, we found a significantly decreased or increased ALFF in the TRD patients relative to the controls. These regions were located in the left/right postcentral gyrus (PoCG.L/PoCG.R), right cuneus(CUN.R). We found that the ALFF values of the right hippocampus (HIP.R) in the TRD group were negatively correlated with the PDQ-5D score. Then, we selected these brain regions as seeds to investigate the FC changes in brains of TRD patients. We found abnormal functional connectivity in left/right middle frontal gyrus(MFG.L/MFG.R), the right Inferior frontal gyrus, opercular part (IFGoperc.R), the left/right Anterior cingulate and paracingulate gyri (ACC.L/ACC.R), the right supramarginal gyrus (SMG.R), and the right Calcarine fissure and surrounding cortex (CAL.R). ConclusionWe found a larger range of altered brain regions in TRD patients compared to healthy controls, especially in the central executive network (CEN), salience network (SN) and default mode network (DMN).

Cerebellum and basal ganglia connectivity in isolated REM sleep behaviour disorder and Parkinson's disease: an exploratory study.

REM sleep behaviour disorder (RBD) is a parasomnia characterised by dream-enacting behaviour with loss of muscle atonia during REM sleep and is a prodromal feature of α-synucleinopathies like Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Although cortical-to-subcortical connectivity is well-studied in RBD, cerebellar and subcortical nuclei reciprocal connectivity is less established. Nonetheless, it could be relevant since RBD pathology involves brainstem structures with an ascending gradient. In this study, we utilised resting-state functional MRI to investigate 13 people with isolated RBD (iRBD), 17 with Parkinson's disease and 16 healthy controls. We investigated the connectivity between the basal ganglia, thalamus and regions of the cerebellum. The cerebellum was segmented using a functional atlas, defined by a resting-state network-based parcellation, rather than an anatomical one. Controlling for age, we found a significant group difference (F4,82 = 5.47, pFDR = 0.017) in cerebellar-thalamic connectivity, with iRBD significantly lower compared to both control and Parkinson's disease. Specifically, cerebellar areas involved in this connectivity reduction were related to the default mode, language and fronto-parietal resting-state networks. Our findings show functional connectivity abnormalities in subcortical structures that are specific to iRBD and may be relevant from a pathophysiological standpoint. Further studies are needed to investigate how connectivity changes progress over time and whether specific changes predict disease course or phenoconversion.

Abnormal resting-state functional connectivity of hippocampal subregions in type 2 diabetes mellitus-associated cognitive decline.

Type 2 diabetes mellitus (T2DM) over time predisposes to inflammatory responses and abnormalities in functional brain networks that damage learning, memory, or executive function. The hippocampus is a key region often reporting connectivity abnormalities in memory disorders. Here, we investigated peripheral inflammatory responses and resting-state functional connectivity (RSFC) changes characterized of hippocampal subregions in type 2 diabetes-associated cognitive decline (T2DACD). The study included 16 patients with T2DM, 16 patients with T2DACD and 25 healthy controls (HCs). Subjects were assessed for cognitive performance, tested for the expression of inflammatory factors IL-6, IL-10 and TNF-α in peripheral serum, underwent resting-state functional magnetic resonance imaging scans, and analyzed for RSFC using the hippocampal subregions as seeds. We also calculated the correlation between cognitive performance and RSFC of hippocampal subregion, and analyzed the significantly altered RSFC values of T2DACD for Receiver Operating Characteristic (ROC) analysis. T2DACD patients showed a decline in their ability to complete cognitive assessment scales and experimental paradigms, and T2DM did not show abnormal cognitive performance. IL-6 expression was increased in peripheral serum in both T2DACD and T2DM. Compared with HCs, T2DACD showed abnormalities RSFC of the left anterior hippocampus with left precentral gyrus and left angular gyrus. T2DM showed abnormalities RSFC of the left middle hippocampus with right medial frontal gyrus, right anterior and middle hippocampus with left precuneus, left anterior hippocampus with right precuneus and right posterior middle temporal gyrus. Compared with T2DM, T2DACD showed abnormalities RSFC of the left posterior hippocampus and right middle hippocampus with left precuneus. In addition, RSFC in the left posterior hippocampus with left precuneus of T2DACD was positively correlated with Flanker conflict response time (r=0.766, P=0.001). In the ROC analysis, the significantly altered RSFC values of T2DACD achieved significant performance. T2DACD showed a significant decrease in attentional inhibition and working memory, peripheral pro-inflammatory response increased, and abnormalities RSFC of the hippocampal subregions with default mode network and sensory-motor network. T2DM did not show a significant cognitive decline, but peripheral pro-inflammatory response increased and abnormalities RSFC of the hippocampus subregions occurred in the brain. In addition, the left precuneus may be a key brain region in the conversion of T2DM to T2DACD. The results of this study may provide a basis for the preliminary diagnosis of T2DACD.

A mega-analysis of functional connectivity and network abnormalities in youth depression

A mega-analysis of functional connectivity and network abnormalities in youth depression

Influence of panic disorder and paroxetine on brain functional hubs in drug-free patients.

The effects of panic disorder (PD) and pharmacotherapy on brain functional hubs in drug-free patients, and the utility of their degree centrality (DC) in diagnosing and predicting treatment response (TR) for PD, remained unclear. This study aimed to assess the effects of PD and paroxetine on brain functional hubs in drug-free patients and to identify neuroimaging biomarkers for diagnosing and predicting TR in patients with PD. Imaging data from 54 medication-free PD patients and 54 matched healthy controls (HCs) underwent DC and functional connectivity (FC) analyses before and after a 4-week paroxetine treatment. Diagnosis and prediction of TR models for PD were constructed using support vector machine (SVM) and support vector regression (SVR), with DC as features. Patients with PD showed aberrant DC and FC in the anterior cingulum, temporal, and occipital areas compared with HCs at baseline. After treatment, DC of the patients increased in the calcarine cortex, lingual gyrus, and cerebellum IV/V, along with improved clinical symptoms. Utilizing voxel-wise DC values at baseline, the SVM effectively distinguished patients with PD from HCs with an accuracy of 83.33%. In SVR, the predicted TR significantly correlated with the observed TR (correlation coefficient (r) = 0.893, Mean Squared Error = 0.009). Patients with PD exhibited abnormal DC and FC, notably in the limbic network, temporal, and occipital regions. Paroxetine ameliorated patients' symptoms while altering their brain FC. SVM and SVR models, utilizing baseline DC, effectively distinguished the patients from HCs and accurately predicted TR.

Evaluation of Intra- and Inter-Network Connectivity within Major Brain Networks in Drug-Resistant Depression Using rs-fMRI.

Background: Major Depressive Disorder (MDD) is a significant challenge in modern medicine due to its unclear underlying causes. Brain network dysfunction is believed to play a key role in its pathophysiology. Resting-state functional MRI (rs-fMRI), a neuroimaging technique, enables the in vivo assessment of functional connectivity (FC) between brain regions, offering insights into these network dysfunctions. The aim of this study was to evaluate abnormalities in FC within major brain networks in patients with drug-resistant MDD. Methods: The study group consisted of 26 patients with drug-resistant MDD and an age-matched control group (CG) of 26 healthy subjects. The rs-fMRI studies were performed on a 3T MR scanner (Philips, Ingenia) using a 32-channel head and neck coil. Imaging data were statistically analyzed, focusing on the intra- and inter-network FC of the following networks: default mode (DMN), sensorimotor (SMN), visual (VN), salience (SN), cerebellar (CN), dorsal attention (DAN), language (LN), and frontoparietal (FPN). Results: In patients with MDD, the intra-network analysis showed significantly decreased FC between nodes within VN compared to CG. In contrast, the inter-network analysis showed significantly increased FC between nodes from VN and SN or VN and DAN compared to CG. Decreased FC was found between SN and CN or SN and FPN as well as VN and DAN nodes compared to CG. Conclusions: Patients with MDD showed significant abnormalities in resting-state cortical activity, mainly regarding inter-network functional connectivity. These results contribute to the knowledge on the pathomechanism of MDD and may also be useful for developing new treatments.

Abnormal resting-state functional connectivity of the right anterior cingulate cortex in chronic ketamine users and its correlation with cognitive impairments

BackgroundChronic ketamine use leads to cognitive impairments, however, the neural mechanisms underpinning these impairments are still unclear. AimsMany studies showed Anterior cingulate cortex (ACC)is strongly involved in cognition and drug addiction, as supported by our previous studies. The objective of this study was to assess the variations in resting-state functional connectivity (FC) changes in the right anterior cingulate cortex (ACC) of chronic ketamine users (CKUs) and their relationship with cognitive performance. MethodsThe study enrolled 28 chronic ketamine users (CKUs) and 30 healthy controls (HCs). Resting-state functional magnetic resonance imaging (fMRI) data were gathered from both groups. Cognitive functions were evaluated using the MATRICS Consensus Cognitive Battery (MCCB). ResultsCKUs demonstrated significantly poorer cognitive performance than HCs in various cognitive domains, including Visual Learning, Speed of Processing, Working Memory, and the composite score of MCCB. Group-level comparisons revealed that CKUs exhibited enhanced functional connectivity between the right ACC and the right postcentral gyrus (PCG) compared to HCs. There was a positive relationship between the connectivity of right ACC-PCG and reasoning and problem-solving score, but there was no significant association with the characteristics of ketamine use. ConclusionCKUs showed enhanced connectivity between the right ACC and the right PCG. This enhanced functional connectivity may indicate functional compensation for cognitive deficits in CKUs, especially for reasoning and problem-solving impairments in CKUs.

Resting-state functional connectivity abnormalities in subjective cognitive decline: A 7T MRI study

Resting-state functional connectivity (FC) MRI is sensitive to brain changes in Alzheimer’s disease in preclinical stages, however studies in persons with subjective cognitive decline (SCD) have reported conflicting findings, and no study is available at 7T MRI. In this study, we investigated FC alterations in sixty-six participants recruited at the Geneva Memory Center (24 controls, 14 SCD, 28 cognitively impaired [CI]). Participants were classified as SCD if they reported cognitive complaints without objective cognitive deficits, and underwent 7T fMRI to assess FC in canonical brain networks and their association with cognitive/clinical features. SCD showed normal cognition, a trend for higher depressive symptoms, and normal AD biomarkers. Compared to the other two groups, SCD showed higher FC in frontal default mode network (DMN) and insular and superior temporal nodes of ventral attention network (VAN). Higher FC in the DMN and VAN was associated with worse cognition but not depression, suggesting that hyper-connectivity in these networks may be a signature of age-related cognitive decline in SCD at low risk of developing AD.

Compensation patterns and altered functional connectivity in alcohol use disorder with and without Korsakoff's syndrome.

Alcohol use disorder is a chronic disease characterized by an inappropriate pattern of drinking, resulting in negative consequences for the individual's physical, mental and social health. Korsakoff's syndrome is a complication of alcohol use disorder and is characterized by severe memory and executive deficits. The fronto-cerebellar and Papez circuits are structurally affected in patients with alcohol use disorder with and without Korsakoff's syndrome. The first objective of the present study was to measure the effect of chronic and excessive alcohol consumption on resting-state functional connectivity of these two functional brain networks. The second objective was to identify, for the first time, resting-state functional connectivity abnormalities specific to amnesic patients with Korsakoff's syndrome. In the present study, a neuropsychological assessment and a resting-state functional magnetic resonance imaging examination were conducted in 31 healthy controls (43.6 ± 6.1 years) and 46 patients (46.6 ± 9.1 years) with alcohol use disorder including 14 patients with Korsakoff's syndrome (55.5 ± 5.3 years) to examine the effect of chronic and heavy alcohol consumption on functional connectivity of the fronto-cerebellar and the Papez circuits at rest and the specificity of functional connectivity changes in Korsakoff's syndrome compared to alcohol use disorder without Korsakoff's syndrome. The resting-state functional connectivity analyses focused on the nodes of the fronto-cerebellar and Papez circuits and combined region of interest and graph theory approaches, and whether these alterations are associated with the neuropsychological profile. In patients pooled together compared to controls, lower global efficiency was observed in the fronto-cerebellar circuit. In addition, certain regions of the fronto-cerebellar and Papez circuits were functionally hyperconnected at rest, which positively correlated with executive functions. Patients with Korsakoff's syndrome showed lower resting-state functional connectivity, lower local and global efficiency within the Papez circuit compared to those without Korsakoff's syndrome. Resting-state functional connectivity positively correlated with several cognitive scores in patients with Korsakoff's syndrome. The fronto-cerebellar and Papez circuits, two normally well-segregated networks, are functionally altered by alcohol use disorder. The Papez circuit attempts to compensate for deficits in the fronto-cerebellar circuit, albeit insufficiently as evidenced by patients' overall lower cognitive performance. Korsakoff's syndrome is characterized by altered functional connectivity in the Papez circuit known to be centrally involved in memory.

The impact of indirect structure on functional connectivity in schizophrenia using a multiplex brain network

It is known that abnormal functional connectivity (FC) in schizophrenia (SZ) is closely related to structural connectivity (SC). We speculate that indirect SC also have an impact on FC in SZ patients. Conventional single-layer network has limitations for studying the relationship between indirect SC and FC. Thus, this study constructed a multiplex network based on structural connectivity and functional connectivity (SC-FC). The SC-FC bandwidth and SC-FC cost are used to analyze the impact of indirect SC on FC. Moreover, this paper proposed mediation ability, mediation cost, mediated strength and mediated cost to quantify the effects of mediator nodes and mediated nodes on indirect SC. The results show that SZ patients exhibit lower SC-FC bandwidth and SC-FC cost compared to healthy controls (HC), which could be caused by the limbic and subcortical network (LSN), default mode network (DMN) and visual network (VN). The mediator and mediated nodes in indirect SC of SZ patients also showed diminished effects. These findings suggest that functional communication ability and cost in SZ patients are influenced by indirect SC. This study provides new perspectives for understanding the relationship between indirect SC and FC, and provides strong evidence for interpreting the physiological mechanisms of SZ patients.

Transcriptional patterns of amygdala functional connectivity in first-episode, drug-naïve major depressive disorder

Previous research has established associations between amygdala functional connectivity abnormalities and major depressive disorder (MDD). However, inconsistencies persist due to limited sample sizes and poorly elucidated transcriptional patterns. In this study, we aimed to address these gaps by analyzing a multicenter magnetic resonance imaging (MRI) dataset consisting of 210 first-episode, drug-naïve MDD patients and 363 age- and sex-matched healthy controls (HC). Using Pearson correlation analysis, we established individualized amygdala functional connectivity patterns based on the Automated Anatomical Labeling (AAL) atlas. Subsequently, machine learning techniques were employed to evaluate the diagnostic utility of amygdala functional connectivity for identifying MDD at the individual level. Additionally, we investigated the spatial correlation between MDD-related amygdala functional connectivity alterations and gene expression through Pearson correlation analysis. Our findings revealed reduced functional connectivity between the amygdala and specific brain regions, such as frontal, orbital, and temporal regions, in MDD patients compared to HC. Importantly, amygdala functional connectivity exhibited robust discriminatory capability for characterizing MDD at the individual level. Furthermore, we observed spatial correlations between MDD-related amygdala functional connectivity alterations and genes enriched for metal ion transport and modulation of chemical synaptic transmission. These results underscore the significance of amygdala functional connectivity alterations in MDD and suggest potential neurobiological mechanisms and markers for these alterations.

Investigating changes of functional brain networks in major depressive disorder by graph theoretical analysis of resting-state fMRI

BackgroundMajor Depressive Disorder (MDD), as a chronic mental disorder, causes changes in mood, thoughts, and behavior. The pathophysiology of the disorder and its treatment are still unknown. One of the most notable changes observed in patients with MDD through fMRI is abnormal functional brain connectivity. MethodsPreprocessed data from 60 MDD patients and 60 normal controls (NCs) were selected, which has been performed using the DPARSF toolbox. The whole-brain functional networks and topologies were extracted using graph theory-based methods. A two-sample, two-tailed t-test was used to compare the topological features of functional brain networks between the MDD and NCs groups using the DPABI-Net/Statistical Analysis toolbox. ResultsThe obtained results showed a decrease in both global and local efficiency in MDD patients compared to NCs, and specifically, MDD patients showed significantly higher path length values. Acceptable p-values were obtained with a small sample size and less computational volume compared to the other studies on large datasets. At the node level, MDD patients showed decreased and relatively decreased node degrees in the sensorimotor network (SMN) and the dorsal attention network (DAN), respectively, as well as decreased node efficiency in the SMN, default mode network (DMN), and DAN. Also, MDD patients showed slightly decreased node efficiency in the visual networks (VN) and the ventral attention network (VAN), which were reported after FDR correction with Q < 0.05. LimitationsAll participants were Chinese. ConclusionsCollectively, increased path length, decreased global and local efficiency, and also decreased nodal degree and efficiency in the SMN, DAN, DAN, VN, and VAN were found in patients compared to NCs.