Altered Connectivity Research Articles

Impaired topology and connectivity of grey matter structural networks in major depressive disorder: evidence from a multi-site neuroimaging data-set.

Major depressive disorder (MDD) has been increasingly understood as a disruption of brain connectome. Investigating grey matter structural networks with a large sample size can provide valuable insights into the structural basis of network-level neuropathological underpinnings of MDD. Using a multisite MRI data-set including nearly 2000 individuals, this study aimed to identify robust topology and connectivity abnormalities of grey matter structural network linked to MDD and relevant clinical phenotypes. A total of 955 MDD patients and 1009 healthy controls were included from 23 sites. Individualised structural covariance networks (SCN) were established based on grey matter volume maps. Following data harmonisation, network topological metrics and focal connectivity were examined for group-level comparisons, individual-level classification performance and association with clinical ratings. Various validation strategies were applied to confirm the reliability of findings. Compared with healthy controls, MDD individuals exhibited increased global efficiency, abnormal regional centralities (i.e. thalamus, precentral gyrus, middle cingulate cortex and default mode network) and altered circuit connectivity (i.e. ventral attention network and frontoparietal network). First-episode drug-naive and recurrent patients exhibited different patterns of deficits in network topology and connectivity. In addition, the individual-level classification of topological metrics outperforms that of structural connectivity. The thalamus-insula connectivity was positively associated with the severity of depressive symptoms. Based on this high-powered data-set, we identified reliable patterns of impaired topology and connectivity of individualised SCN in MDD and relevant subtypes, which adds to the current understanding of neuropathology of MDD and might guide future development of diagnostic and therapeutic markers.

Higher-order functional brain networks and anterior cingulate glutamate + glutamine (Glx) in antipsychotic-naïve first episode psychosis patients

Human connectome studies have provided abundant data consistent with the hypothesis that functional dysconnectivity is predominant in psychosis spectrum disorders. Converging lines of evidence also suggest an interaction between dorsal anterior cingulate cortex (dACC) cortical glutamate with higher-order functional brain networks (FC) such as the default mode (DMN), dorsal attention (DAN), and executive control networks (ECN) in healthy controls (HC) and this mechanism may be impaired in psychosis. Data from 70 antipsychotic-medication naïve first-episode psychosis (FEP) and 52 HC were analyzed. 3T Proton magnetic resonance spectroscopy (1H-MRS) data were acquired from a voxel in the dACC and assessed correlations (positive FC) and anticorrelations (negative FC) of the DMN, DAN, and ECN. We then performed regressions to assess associations between glutamate + glutamine (Glx) with positive and negative FC of these same networks and compared them between groups. We found alterations in positive and negative FC in all networks (HC > FEP). A relationship between dACC Glx and positive and negative FC was found in both groups, but when comparing these relationships between groups, we found contrasting associations between these variables in FEP patients compared to HC. We demonstrated that both positive and negative FC in three higher-order resting state networks are already altered in antipsychotic-naïve FEP, underscoring the importance of also considering anticorrelations for optimal characterization of large-scale functional brain networks as these represent biological processes as well. Our data also adds to the growing body of evidence supporting the role of dACC cortical Glx as a mechanism underlying alterations in functional brain network connectivity. Overall, the implications for these findings are imperative as this particular mechanism may differ in untreated or chronic psychotic patients; therefore, understanding this mechanism prior to treatment could better inform clinicians.Clinical trial registration: Trajectories of Treatment Response as Window into the Heterogeneity of Psychosis: A Longitudinal Multimodal Imaging Study, NCT03442101. Glutamate, Brain Connectivity and Duration of Untreated Psychosis (DUP), NCT02034253.

Dysconnectivity of the Nucleus Accumbens and Amygdala in Youths with Thought Problems: A Dimensional Approach.

Background: Youths with thought problems (TP) are at risk to develop psychosis and obsessive-compulsive disorder (OCD). Yet, the pathophysiological mechanisms underpinning TP are still unclear. Functional magnetic resonance imaging (fMRI) studies have shown that striatal and limbic alterations are associated with psychosis-like and obsessive-like symptoms in individuals at clinical risk for psychosis, schizophrenia, and OCD. More specifically, nucleus accumbens (NAcc) and amygdala are mainly involved in these associations. The current study aims to investigate the neural correlates of TP in youth populations using a dimensional approach and explore potential cognitive functions and neurotransmitters associated with it. Methods: Seed-to-voxels functional connectivity analyses using NAcc and amygdala as regions-of-interest were conducted with resting-state fMRI data obtained from 1360 young individuals, and potential confounders related to TP such as anxiety and cognitive functions were included as covariates in multiple regression analyses. Replicability was tested in using an adult cohort. In addition, functional decoding and neurochemical correlation analyses were performed to identify the associated cognitive functions and neurotransmitters. Results: The altered functional connectivities between the right NAcc and posterior parahippocampal gyrus, between the right amygdala and lateral prefrontal cortex, and between the left amygdala and the secondary visual area were the best predictors of TP in multiple regression model. These functional connections are mainly involved in social cognition and reward processing. Conclusions: The results show that alterations in the functional connectivity of the NAcc and the amygdala in neural pathways involved in social cognition and reward processing are associated with severity of TP in youths.

Functional connectivity changes in neurodegenerative biomarker-positive athletes with repeated concussions.

Multimodal biomarkers may identify former contact sports athletes with repeated concussions and at risk for dementia. Our study aims to investigate whether biomarker evidence of neurodegeneration in former professional athletes with repetitive concussions (ExPro) is associated with worse cognition and mood/behavior, brain atrophy, and altered functional connectivity. Forty-one contact sports athletes with repeated concussions were divided into neurodegenerative biomarker-positive (n = 16) and biomarker-negative (n = 25) groups based on positivity of serum neurofilament light-chain. Six healthy controls (negative for biomarkers) with no history of concussions were also analyzed. We calculated cognitive and mood/behavior composite scores from neuropsychological assessments. Gray matter volume maps and functional connectivity of the default mode, salience, and frontoparietal networks were compared between groups using ANCOVAs, controlling for age, and total intracranial volume. The association between the connectivity networks and sports characteristics was analyzed by multiple regression analysis in all ExPro. Participants presented normal-range mean performance in executive function, memory, and mood/behavior tests. The ExPro groups did not differ in professional years played, age at first participation in contact sports, and number of concussions. There were no differences in gray matter volume between groups. The neurodegenerative biomarker-positive group had lower connectivity in the default mode network (DMN) compared to the healthy controls and the neurodegenerative biomarker-negative group. DMN disconnection was associated with increased number of concussions in all ExPro. Biomarkers of neurodegeneration may be useful to detect athletes that are still cognitively normal, but with functional connectivity alterations after concussions and at risk of dementia.

Multi-modal Neuroimaging Phenotyping of Mnemonic Anosognosia in the Aging Brain

BackgroundUnawareness is a behavioral condition characterized by a lack of self-awareness of objective memory decline. In the context of Alzheimer’s Disease (AD), unawareness may develop in predementia stages and contributes to disease severity and progression. Here, we use in-vivo multi-modal neuroimaging to profile the brain phenotype of individuals presenting altered self-awareness of memory during aging.MethodsAmyloid- and tau-PET (N = 335) and resting-state functional MRI (N = 713) imaging data of individuals from the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease (A4)/Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) Study were used in this research. We applied whole-brain voxel-wise and region-of-interest analyses to characterize the cortical intersections of tau, amyloid, and functional connectivity networks underlying unawareness in the aging brain compared to aware, complainer and control groups.ResultsIndividuals with unawareness present elevated amyloid and tau burden in midline core regions of the default mode network compared to aware, complainer or control individuals. Unawareness is characterized by an altered network connectivity pattern featuring hyperconnectivity in the medial anterior prefrontal cortex and posterior occipito-parietal regions co-locating with amyloid and tau deposition.ConclusionsUnawareness is an early behavioral biomarker of AD pathology. Failure of the self-referential system in unawareness of memory decline can be linked to amyloid and tau burden, along with functional network connectivity disruptions, in several medial frontal and parieto-occipital areas of the human brain.

Aberrant Brain Triple-Network Effective Connectivity Patterns in Type2 Diabetes Mellitus.

Aberrant brain functional connectivity network is thought to be related to cognitive impairment in patients with type2 diabetes mellitus (T2DM). This study aims to investigate the triple-network effective connectivity patterns in patients with T2DM within and between the default mode network (DMN), salience network (SN), and executive control network (ECN) and their associations with cognitive declines. In total, 92 patients with T2DM and 98 matched healthy controls (HCs) were recruited and underwent resting-state functional magnetic resonance imaging (rs-fMRI). Spectral dynamic causal modeling (spDCM) was used for effective connectivity analysis within the triple network. The posterior cingulate cortex (PCC), medial prefrontal cortex (mPFC), lateral prefrontal cortex (LPFC), supramarginal gyrus (SMG), and anterior insula (AINS) were selected as the regions of interest. Group comparisons were performed for effective connectivity calculated using the fully connected model, and the relationships between effective connectivity alterations and cognitive impairment as well as clinical parameters were detected. Compared to HCs, patients with T2DM exhibited increased or decreased effective connectivity patterns within the triple network. Furthermore, diabetes duration was significantly negatively correlated with increased effective connectivity from the r-LPFC to the mPFC, while body mass index (BMI) was significantly positively correlated with increased effective connectivity from the l-LPFC to the l-AINS (r = - 0.353, p = 0.001; r = 0.377, p = 0.004). These results indicate abnormal effective connectivity patterns within the triple network model in patients with T2DM and provide new insight into the neurological mechanisms of T2DM and related cognitive dysfunction.

Differential modulation of resting-state functional connectivity between amygdala and precuneus after acute physical exertion of varying intensity: indications for a role in affective regulation.

Physical activity influences psychological well-being. This study aimed to determine the impact of exercise intensity on psychological well-being and alterations in emotion-related brain functional connectivity (FC). Twenty young, healthy, trained athletes performed a low- and high-intensity interval exercise (LIIE and HIIE) as well as a control condition in a within-subject crossover design. Before and after each condition, Positive And Negative Affect Scale (PANAS) was assessed as well as resting-state functional MRI (rs-fMRI). Voxel-wise FC was examined for bilateral amygdala seed region to whole-brain and emotion-related anatomical regions (e.g., insula, temporal pole, precuneus). Data analyses were performed using linear mixed-effect models with fixed factors condition and time. The PANAS Positive Affect scale showed a significant increase after LIIE and HIIE and a significant reduction in Negative Affect after the control condition. In rs-fMRI, no significant condition-by-time interactions were observed between the amygdala and whole brain. Amygdala-precuneus FC analysis showed an interaction effect, suggesting reduced post-exercise anticorrelation after the control condition, but stable, or even slightly enhanced anticorrelation for the exercise conditions, especially HIIE. In conclusion, both LIIE and HIIE had positive effects on mood and concomitant effects on amygdala-precuneus FC, particularly after HIIE. Although no significant correlations were found between amygdala-precuneus FC and PANAS, results should be discussed in the context of affective disorders in whom abnormal amygdala-precuneus FC has been observed.

Weakened effective connectivity between salience network and default mode network during resting state in adolescent depression.

Adolescent major depressive disorder (MDD) is associated with altered resting-state connectivity between the default mode network (DMN) and the salience network (SN), which are involved in self-referential processing and detecting and filtering salient stimuli, respectively. Using spectral dynamical causal modelling, we investigated the effective connectivity and input sensitivity between key nodes of these networks in 30 adolescents with MDD and 32 healthy controls while undergoing resting-state fMRI. We found that the DMN received weaker inhibition from the SN and that the medial prefrontal cortex and the anterior cingulate cortex showed reduced self-inhibition in MDD, making them more prone to external influences. Moreover, we found that selective serotonin reuptake inhibitor (SSRI) intake was associated with decreased and increased self-inhibition of the SN and DMN, respectively, in patients. Our findings suggest that adolescent MDD is characterized by a hierarchical imbalance between the DMN and the SN, which could affect the integration of emotional and self-related information. We propose that SSRIs may help restore network function by modulating excitatory/inhibitory balance in the DMN and the SN. Our study highlights the potential of prefrontal-amygdala interactions as a biomarker and a therapeutic target for adolescent depression.

Brain and cognitive changes in patients with long COVID compared with infection-recovered control subjects.

Between 2.5% and 28% of people infected with SARS-CoV-2 suffer long COVID or persistence of symptoms for months after acute illness. Many symptoms are neurological, but the brain changes underlying the neuropsychological impairments remain unclear. This study aimed to provide a detailed description of the cognitive profile, the pattern of brain alterations in long COVID and the potential association between them. To address these objectives, 83 patients with persistent neurological symptoms after COVID-19 were recruited, and 22 now healthy control subjects chosen because they had suffered COVID-19 but did not experience persistent neurological symptoms. Patients and controls were matched for age, sex and educational level. All participants were assessed by clinical interview, comprehensive standardized neuropsychological tests and structural MRI. The mean global cognitive function of patients with long COVID assessed by Addenbrooke's Cognitive Examination-III screening test [overall cognitive level (OCLz) = -0.39 ± 0.12] was significantly below the infection recovered-controls (OCLz = +0.32 ± 0.16, P < 0.01). We observed that 48% of patients with long COVID had episodic memory deficit, with 27% also with impaired overall cognitive function, especially attention, working memory, processing speed and verbal fluency. The MRI examination included grey matter morphometry and whole brain structural connectivity analysis. Compared to infection recovered controls, patients had thinner cortex in a specific cluster centred on the left posterior superior temporal gyrus. In addition, lower fractional anisotropy and higher radial diffusivity were observed in widespread areas of the patients' cerebral white matter relative to these controls. Correlations between cognitive status and brain abnormalities revealed a relationship between altered connectivity of white matter regions and impairments of episodic memory, overall cognitive function, attention and verbal fluency. This study shows that patients with neurological long COVID suffer brain changes, especially in several white matter areas, and these are associated with impairments of specific cognitive functions.

Literature review and protocol for a prospective multicentre cohort study on multimodal prediction of seizure recurrence after unprovoked first seizure

IntroductionEpilepsy is a common neurological disorder characterised by recurrent seizures. Almost half of patients who have an unprovoked first seizure (UFS) have additional seizures and develop epilepsy. No current predictive...

Alterations in brain functional connectivity in patients with mild cognitive impairment: A systematic review and meta-analysis of functional near-infrared spectroscopy studies.

Emerging evidences suggest that cognitive deficits in individuals with mild cognitive impairment (MCI) are associated with disruptions in brain functional connectivity (FC). This systematic review and meta-analysis aimed to comprehensively evaluate alterations in FC between MCI individuals and healthy control (HC) using functional near-infrared spectroscopy (fNIRS). Thirteen studies were included in qualitative analysis, with two studies synthesized for quantitative meta-analysis. Overall, MCI patients exhibited reduced resting-state FC, predominantly in the prefrontal, parietal, and occipital cortex. Meta-analysis of two studies revealed a significant reduction in resting-state FC from the right prefrontal to right occipital cortex (standardized mean difference [SMD]=-.56; p<.001), left prefrontal to left occipital cortex (SMD=-.68; p<.001), and right prefrontal to left occipital cortex (SMD=-.53; p<.001) in MCI patients compared to HC. During naming animal-walking task, MCI patients exhibited enhanced FC in the prefrontal, motor, and occipital cortex, whereas a decrease in FC was observed in the right prefrontal to left prefrontal cortex during calculating-walking task. In working memory tasks, MCI predominantly showed increased FC in the medial and left prefrontal cortex. However, a decreased in prefrontal FC and a shifted in distribution from the left to the right prefrontal cortex were noted in MCI patients during a verbal frequency task. In conclusion, fNIRS effectively identified abnormalities in FC between MCI and HC, indicating disrupted FC as potential markers for the early detection of MCI. Future studies should investigate the use of task- and region-specific FC alterations as a sensitive biomarker for MCI.

Distinct Functional Connectivity Patterns for Intermittent Vs Constant Neuropathic Pain Phenotypes in Persistent Spinal Pain Syndrome Type 2 Patients.

Chronic low backpain (cLBP) has been associated with alterations in brain functional connectivity (FC) butbased upon heterogeneous populations and single network analyses. Our goal is to study a more homogeneous cLBP population and focus on multiple cross-network (CN) connectivity analysis. We hypothesize that within this population: 1) altered CNFC, involving emotion and reward/aversion functions are related to their pain levels and 2) altered relationships are dependent upon pain phenotype (constant neuropathic vs intermittent pain). In this case series, resting state fcMRI scans were obtained over a study duration of 60 months from 23 patients (13 constant neuropathic and 10 intermittent pain) with Persistent Spinal Pain Syndrome (PSPS Type 2) being considered for spinal cord stimulation (SCS) therapy at a single academic center. Images were acquired using a Discovery MR750 GE scanner. During the resting state acquisitions, they were asked to close their eyes and relax. The CNanalysis was performed on 7 brain networksand compared to age-matched controls. Linear regression was used to test the correlation between CN connectivity and pain scores. CNFCinvolving emotion networks (STM: striatum network index) was significantly lower than controls in all patients, regardless of pain phenotype (P < 0.003). Pain levels were positively correlated with emotional FCfor intermittent painbut negatively correlated for constant pain. This is thefirst report of 1) altered CN FCinvolving emotion/reward brain circuitry in 2) a homogeneous population of cLBPpatients with 3) two different pain phenotypes (constant vs intermittent) in PSPS Type 2 patients being considered for SCS. FC patterns were altered in cLBPpatients as compared to controls and were characteristic for each pain phenotype. Thesedata supportfcMRI as a potential and objective tool in assessing pain levels in cLBP patients with different painphenotypes.

38. Alterations In Functional Connectivity Of Pain-Relevant Brain Regions After Peripheral Nerve Injury

38. Alterations In Functional Connectivity Of Pain-Relevant Brain Regions After Peripheral Nerve Injury

The contribution of EEG to assess and treat motor disorders in multiple sclerosis

ObjectiveElectroencephalography (EEG) can highlight significant changes in spontaneous electrical activity of the brain produced by altered brain network connectivity linked to inflammatory demyelinating lesions and neuronal loss occurring in multiple sclerosis (MS). In this review, we describe the main EEG findings reported in the literature to characterize motor network alteration in term of local activity or functional connectivity changes in patients with MS (pwMS). MethodsA comprehensive literature search was conducted to include articles with quantitative analyses of resting-state EEG recordings (spectrograms or advanced methods for assessing spatial and temporal dynamics, such as coherence, theory of graphs, recurrent quantification, microstates) or dynamic EEG recordings during a motor task, with or without connectivity analyses. ResultsIn this systematic review, we identified 26 original articles using EEG in the evaluation of MS-related motor disorders. Various resting or dynamic EEG parameters could serve as diagnostic biomarkers of motor control impairment to differentiate pwMS from healthy subjects or be related to a specific clinical condition (fatigue) or neuroradiological aspects (lesion load). ConclusionsWe highlight some key EEG patterns in pwMS at rest and during movement, both suggesting an alteration or disruption of brain connectivity, more specifically involving sensorimotor networks. SignificanceSome of these EEG biomarkers of motor disturbance could be used to design future therapeutic strategies in MS based on neuromodulation approaches, or to predict the effects of motor training and rehabilitation in pwMS.

Clinical, psychological and brain imaging investigation of first episode psychosis patients treated at Semmelweis University, Department of Psychiatry and Psychotherapy, Budapest, Hungary

IntroductionFirst episode psychosis (FEP) is the first manifestation of psychotic disorders lasting at least one week, but not longer than 2 years, causing personal suffering and decreased functional outcome of patients. The early intervention in FEP is crucial. Published results on early intervention programmes indicate that during the first 5-10 years relapse prevention and functional outcomes can be improved and mental health care costs can be reduced, compared to treatment as usual.ObjectivesOur objective was to examine FEP patients at the Department of Psychiatry and Psychotherapy. Our aim was to create a homogeneous sample and identify factors that can help in early differential diagnosis and therapy. Our goal was to compare the neuropsychological performance and MRI results of patients and healthy controls.MethodsMale and female inpatients hospitalized at our department due to a first psychotic episode and consenting to participate were included, since 2019 October. Cases with drug induced psychosis and organic background in the etiology of the psychotic episode were excluded. Male and female healthy controls were matched by age and education. Including healthy controls is still in progress. The duration of the project is 36 months, 24 months for recruiting patients and healthy controls, 12 month for analyzing data. The investigation includes detailed clinical, neuropsychological examination (baseline, 6th, 12th, 18th, 24th month) and MRI (baseline and in the 24th month).ResultsForty patients and sixteen healthy controls were included. 60% of the patients were rehospitalized due to relapses. Neuropsychological tests (RBANS, faux pas, Baron-Cohen eyes test) indicate cognitive dysfunction compared to healthy subjects. Using resting state fMRI second level analysis we found alterations in thalamo-cortical connectivity. We found significant differences in the connectivity of the thalamus and frontal lobe, postcentral gyrus, insula and cerebellum.ConclusionsOur FEP research, although limited by the COVID-19 pandemic, shows promising results that can help in better understanding of the underlying factors of psychotic disorders.Disclosure of InterestNone Declared

The Role of the Insula in Chronic Pain and Associated Structural Changes: An Integrative Review.

Chronic pain affects a substantial portion of the global population, significantly impacting quality of life and well-being. This condition involves complex mechanisms, including dysfunction of the autonomic nervous system, which plays a crucial role in pain perception.The insula, a key brain region involved in pain processing, plays a critical role in pain perception and modulation. Lesions in the insula can result in pain asymbolia, where pain perception remains intact but emotional responses are inappropriate. The insula is anatomically and functionally divided into anterior and posterior regions, with the posterior insula processing nociceptive input based on intensity and location before relaying it to the anterior insula for emotional mediation. Understanding the insula's intricate role in pain processing is crucial, as it is involved in encoding prediction errors and mediating emotional dimensions of pain perception.The focus of this review wason synthesizing existing literature on the role of the insula in chronic pain and associated structural changes. The goal was to integrate findings from various sources to provide a comprehensive overview of the topic.The search strategy included a combination of Medical Subject Headings (MeSH) and relevant keywords related to insulaand chronic pain. The following databases were surveyed: PubMed, Embase, Scopus, and Web of Science. We identified a total of 2515 articles, and after following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline based on eligibility criteria, 46 articles were used to synthesize this review. Our study highlights the pivotal role of the insula in chronic pain processing and associated structural changes, integrating findings from diverse studies and neuroimaging investigations. Beyond mere pain sensation, the insula contributes to emotional awareness, attention, and salience detection within the pain network.Various chronic pain conditions reveal alterations in insular activity and connectivity, accompanied by changes in gray matter volume and neurochemical profiles. Interventions targeting the insula show promise in alleviating chronic pain symptoms. However, further research is needed to understand underlying mechanisms, which can aid in developing more effective therapeutic interventions for pain.

Functional connectivity subtypes of MDD and their associations with gene expression profile, neurotransmitter, and cognition

IntroductionThere’s large heterogeneity present in major depressive disorder (MDD) and controversial evidence on alterations of brain functional connectivity (FC), making it hard to elucidate the neurobiological basis of MDD. Subtyping is one promising solution to characterize this heterogeneity.ObjectivesTo identify neurophysiological subtypes of MDD based on FC derived from resting-state functional magnetic resonance imaging using large multisite data and investigate the differences in genetic mechanisms and neurotransmitter basis of FC alterations, and the differences of FC-related cognition between each subtype.MethodsConsensus clustering of FC patterns was applied to a population of 829 MDD patients from REST-Meta-MDD database after data cleaning and image quality control. Gene transcriptomic data derived from Allen Human Brain Atlas and neurotransmitter receptor/transporter density data acquired by using neuromap toolbox were used to characterize the molecular mechanism underlying each FC-based subtype by identifying the gene set and neurotransmitters/transporters showing high spatial similarity with the profiles of FC alterations between each subtype and 770 healthy controls. The FC-related cognition in each subtype was also selected by lasso regression.ResultsTwo stable neurophysiological MDD subtypes were found and labeled as hypoconnectivity (n=527) and hyperconnectivity (n=299) characterized by the FC differences in each subtype relative to controls, respectively. The two subtypes did not differ in age, sex, and scores of Hamilton Depression/Anxiety Scale.The genes related to FC alterations were enriched in ion transmembrane transport, synaptic transmission/organization, axon development, and regulation of neurotransmitter level for both subtypes, but specifically enriched in glial cell differentiation for hypoconnectivity subtype, while enriched in regulation of presynaptic membrane and regulation of neuron differentiation for hyperconnectivity subtype.FC alterations were associated with the density of 5-HT2a receptor in both subtypes. For hyperconnectivity subtype, FC alterations were also correlated with the density of norepinephrine transporter, glutamate receptor, GABA receptor, 5-HT1b receptor, and cannabinoid receptor.Both subtypes showed correlations between FC and categorization, motor inhibition, and localization. The FC in hypoconnectivity subtype correlated with response inhibition, selective attention, face recognition, sleep, empathy, expertise, uncertainty, and anticipation, while that was related to inference, speech perception, and reward anticipation in hyperconnectivity subtype.ConclusionsOur findings suggested the presence of two neuroimaging subtypes of MDD characterized by hypo or hyper-connectivity. The two subtypes had both shared and distinct genetic mechanisms, neurotransmitter receptor/transporter profiles, and cognition types.Disclosure of InterestNone Declared

A Multiscale Closed-Loop Neurotoxicity Model of Alzheimer's Disease Progression Explains Functional Connectivity Alterations.

The accumulation of amyloid-β (Aβ) and hyperphosphorylated-tau (hp-tau) are two classical histopathological biomarkers in Alzheimer's disease (AD). However, their detailed interactions with the electrophysiological changes at the meso- and macroscale are not yet fully understood. We developed a mechanistic multiscale model of AD progression, linking proteinopathy to its effects on neural activity and vice-versa. We integrated a heterodimer model of prion-like protein propagation and a brain network model of Jansen-Rit neural masses derived from human neuroimaging data whose parameters varied due to neurotoxicity. Results showed that changes in inhibition guided the electrophysiological alterations found in AD, and these changes were mainly attributed to Aβ effects. Additionally, we found a causal disconnection between cellular hyperactivity and interregional hypersynchrony contrary to previous beliefs. Finally, we demonstrated that early Aβ and hp-tau depositions' location determine the spatiotemporal profile of the proteinopathy. The presented model combines the molecular effects of both Aβ and hp-tau together with a mechanistic protein propagation model and network effects within a closed-loop model. This holds the potential to enlighten the interplay between AD mechanisms on various scales, aiming to develop and test novel hypotheses on the contribution of different AD-related variables to the disease evolution.

Assessing resting-state brain functional connectivity in adolescents and young adults with narcolepsy using functional near-infrared spectroscopy.

This study aimed to elucidate the alterations in the prefrontal cortex's functional connectivity and network topology in narcolepsy patients using functional near-infrared spectroscopy (fNIRS). Twelve narcolepsy-diagnosed patients from Guangxi Zhuang Autonomous Region's People's Hospital Sleep Medicine Department and 11 matched healthy controls underwent resting fNIRS scans. Functional connectivity and graph theory analyses were employed to assess the prefrontal cortex network's properties and their correlation with clinical features. Results indicated increased functional connectivity in these adolescent and young adult patients with narcolepsy, with significant variations in metrics like average degree centrality and node efficiency, particularly in the left middle frontal gyrus. These alterations showed correlations with clinical symptoms, including depression and sleep efficiency. However, the significance of these findings was reduced post False Discovery Rate adjustment, suggesting a larger sample size is needed for validation. In conclusion, the study offers initial observations that alterations in the prefrontal cortex's functional connectivity may potentially act as a neurobiological indicator of narcolepsy, warranting further investigation with a larger cohort to substantiate these findings and understand the underlying mechanisms.

Frequency-dependent alterations in functional connectivity in patients with Alzheimer's Disease spectrum disorders.

In the spectrum of Alzheimer's Disease (AD) and related disorders, the resting-state functional magnetic resonance imaging (rs-fMRI) signals within the cerebral cortex may exhibit distinct characteristics across various frequency ranges. Nevertheless, this hypothesis has not yet been substantiated within the broader context of whole-brain functional connectivity. This study aims to explore potential modifications in degree centrality (DC) and voxel-mirrored homotopic connectivity (VMHC) among individuals with amnestic mild cognitive impairment (aMCI) and AD, while assessing whether these alterations differ across distinct frequency bands. This investigation encompassed a total of 53 AD patients, 40 aMCI patients, and 40 healthy controls (HCs). DC and VMHC values were computed within three distinct frequency bands: classical (0.01-0.08 Hz), slow-4 (0.027-0.073 Hz), and slow-5 (0.01-0.027 Hz) for the three respective groups. To discern differences among these groups, ANOVA and subsequent post hoc two-sample t-tests were employed. Cognitive function assessment utilized the mini-mental state examination (MMSE) and Montreal Cognitive Assessment (MoCA). Pearson correlation analysis was applied to investigate the associations between MMSE and MoCA scores with DC and VMHC. Significant variations in degree centrality (DC) were observed among different groups across diverse frequency bands. The most notable differences were identified in the bilateral caudate nucleus (CN), bilateral medial superior frontal gyrus (mSFG), bilateral Lobule VIII of the cerebellar hemisphere (Lobule VIII), left precuneus (PCu), right Lobule VI of the cerebellar hemisphere (Lobule VI), and right Lobule IV and V of the cerebellar hemisphere (Lobule IV, V). Likewise, disparities in voxel-mirrored homotopic connectivity (VMHC) among groups were predominantly localized to the posterior cingulate gyrus (PCG) and Crus II of the cerebellar hemisphere (Crus II). Across the three frequency bands, the brain regions exhibiting significant differences in various parameters were most abundant in the slow-5 frequency band. This study enhances our understanding of the pathological and physiological mechanisms associated with AD continuum. Moreover, it underscores the importance of researchers considering various frequency bands in their investigations of brain function.