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1.
CNS Neurosci Ther ; 30(6): e14786, 2024 Jun.
Article En | MEDLINE | ID: mdl-38828694

PURPOSE: To investigate dynamic functional connectivity (dFC) within the cerebellar-whole brain network and dynamic topological properties of the cerebellar network in obstructive sleep apnea (OSA) patients. METHODS: Sixty male patients and 60 male healthy controls were included. The sliding window method examined the fluctuations in cerebellum-whole brain dFC and connection strength in OSA. Furthermore, graph theory metrics evaluated the dynamic topological properties of the cerebellar network. Additionally, hidden Markov modeling validated the robustness of the dFC. The correlations between the abovementioned measures and clinical assessments were assessed. RESULTS: Two dynamic network states were characterized. State 2 exhibited a heightened frequency, longer fractional occupancy, and greater mean dwell time in OSA. The cerebellar networks and cerebrocerebellar dFC alterations were mainly located in the default mode network, frontoparietal network, somatomotor network, right cerebellar CrusI/II, and other networks. Global properties indicated aberrant cerebellar topology in OSA. Dynamic properties were correlated with clinical indicators primarily on emotion, cognition, and sleep. CONCLUSION: Abnormal dFC in male OSA may indicate an imbalance between the integration and segregation of brain networks, concurrent with global topological alterations. Abnormal default mode network interactions with high-order and low-level cognitive networks, disrupting their coordination, may impair the regulation of cognitive, emotional, and sleep functions in OSA.


Cerebellum , Nerve Net , Sleep Apnea, Obstructive , Humans , Male , Sleep Apnea, Obstructive/physiopathology , Sleep Apnea, Obstructive/diagnostic imaging , Cerebellum/diagnostic imaging , Cerebellum/physiopathology , Middle Aged , Adult , Nerve Net/diagnostic imaging , Nerve Net/physiopathology , Magnetic Resonance Imaging , Connectome , Neural Pathways/physiopathology , Neural Pathways/diagnostic imaging , Default Mode Network/physiopathology , Default Mode Network/diagnostic imaging
2.
Cereb Cortex ; 34(6)2024 Jun 04.
Article En | MEDLINE | ID: mdl-38836288

Major depressive disorder demonstrated sex differences in prevalence and symptoms, which were more pronounced during adolescence. Yet, research on sex-specific brain network characteristics in adolescent-onset major depressive disorder remains limited. This study investigated sex-specific and nonspecific alterations in resting-state functional connectivity of three core networks (frontoparietal network, salience network, and default mode network) and subcortical networks in adolescent-onset major depressive disorder, using seed-based resting-state functional connectivity in 50 medication-free patients with adolescent-onset major depressive disorder and 56 healthy controls. Irrespective of sex, compared with healthy controls, adolescent-onset major depressive disorder patients showed hypoconnectivity between bilateral hippocampus and right superior temporal gyrus (default mode network). More importantly, we further found that females with adolescent-onset major depressive disorder exhibited hypoconnectivity within the default mode network (medial prefrontal cortex), and between the subcortical regions (i.e. amygdala, striatum, and thalamus) with the default mode network (angular gyrus and posterior cingulate cortex) and the frontoparietal network (dorsal prefrontal cortex), while the opposite patterns of resting-state functional connectivity alterations were observed in males with adolescent-onset major depressive disorder, relative to their sex-matched healthy controls. Moreover, several sex-specific resting-state functional connectivity changes were correlated with age of onset, sleep disturbance, and anxiety in adolescent-onset major depressive disorder with different sex. These findings suggested that these sex-specific resting-state functional connectivity alterations may reflect the differences in brain development or processes related to early illness onset, underscoring the necessity for sex-tailored diagnostic and therapeutic approaches in adolescent-onset major depressive disorder.


Brain , Depressive Disorder, Major , Magnetic Resonance Imaging , Nerve Net , Sex Characteristics , Humans , Depressive Disorder, Major/physiopathology , Depressive Disorder, Major/diagnostic imaging , Female , Adolescent , Male , Brain/physiopathology , Brain/diagnostic imaging , Nerve Net/diagnostic imaging , Nerve Net/physiopathology , Neural Pathways/physiopathology , Neural Pathways/diagnostic imaging , Young Adult , Age of Onset , Brain Mapping , Default Mode Network/physiopathology , Default Mode Network/diagnostic imaging
3.
Commun Biol ; 7(1): 689, 2024 Jun 05.
Article En | MEDLINE | ID: mdl-38839931

Advanced methods such as REACT have allowed the integration of fMRI with the brain's receptor landscape, providing novel insights transcending the multiscale organisation of the brain. Similarly, normative modelling has allowed translational neuroscience to move beyond group-average differences and characterise deviations from health at an individual level. Here, we bring these methods together for the first time. We used REACT to create functional networks enriched with the main modulatory, inhibitory, and excitatory neurotransmitter systems and generated normative models of these networks to capture functional connectivity deviations in patients with schizophrenia, bipolar disorder (BPD), and ADHD. Substantial overlap was seen in symptomatology and deviations from normality across groups, but these could be mapped into a common space linking constellations of symptoms through to underlying neurobiology transdiagnostically. This work provides impetus for developing novel biomarkers that characterise molecular- and systems-level dysfunction at the individual level, facilitating the transition towards mechanistically targeted treatments.


Magnetic Resonance Imaging , Schizophrenia , Humans , Schizophrenia/physiopathology , Schizophrenia/diagnostic imaging , Adult , Male , Brain/physiopathology , Brain/diagnostic imaging , Female , Bipolar Disorder/physiopathology , Attention Deficit Disorder with Hyperactivity/physiopathology , Attention Deficit Disorder with Hyperactivity/diagnostic imaging , Mental Disorders/physiopathology , Mental Disorders/diagnostic imaging , Young Adult , Models, Neurological , Middle Aged , Nerve Net/physiopathology , Nerve Net/diagnostic imaging
4.
CNS Neurosci Ther ; 30(6): e14779, 2024 Jun.
Article En | MEDLINE | ID: mdl-38828650

AIMS: Previous neuroimaging studies of vascular cognitive impairment, no dementia (VCIND), have reported functional alterations, but far less is known about the effects of cognitive training on functional connectivity (FC) of intrinsic connectivity networks (ICNs) and how they relate to intervention-related cognitive improvement. This study provides comprehensive research on the changes in intra- and inter-brain functional networks in patients with VCIND who received computerized cognitive training, with a focus on the underlying mechanisms and potential therapeutic strategies. METHODS: We prospectively collected 60 patients with VCIND who were randomly divided into the training group (N = 30) receiving computerized cognitive training and the control group (N = 30) receiving fixed cognitive training. Functional MRI scans and cognitive assessments were performed at baseline, at the 7-week training, and at the 6-month follow-up. Utilizing templates for ICNs, the study employed a linear mixed model to compare intra- and inter-network FC changes between the two groups. Pearson correlation was applied to calculate the relationship between FC and cognitive function. RESULTS: We found significantly decreased intra-network FC within the default mode network (DMN) following computerized cognitive training at Month 6 (p = 0.034), suggesting a potential loss of functional specialization. Computerized training led to increased functional coupling between the DMN and sensorimotor network (SMN) (p = 0.01) and between the language network (LN) and executive control network (ECN) at Month 6 (p < 0.001), indicating compensatory network adaptations in patients with VCIND. Notably, the intra-LN exhibited enhanced functional specialization after computerized cognitive training (p = 0.049), with significant FC increases among LN regions, which correlated with improvements in neuropsychological measures (p < 0.05), emphasizing the targeted impact of computerized cognitive training on language abilities. CONCLUSIONS: This study provides insights into neuroplasticity and adaptive changes resulting from cognitive training in patients with VCIND, with implications for potential therapeutic strategies.


Brain , Cognitive Dysfunction , Magnetic Resonance Imaging , Nerve Net , Humans , Male , Female , Aged , Cognitive Dysfunction/therapy , Cognitive Dysfunction/physiopathology , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/rehabilitation , Middle Aged , Nerve Net/diagnostic imaging , Nerve Net/physiopathology , Brain/diagnostic imaging , Brain/physiopathology , Therapy, Computer-Assisted/methods , Prospective Studies , Cognitive Training
5.
Cereb Cortex ; 34(6)2024 Jun 04.
Article En | MEDLINE | ID: mdl-38847535

Given the widespread use and relapse of methamphetamine (METH), it has caused serious public health burdens globally. However, the neurobiological basis of METH addiction remains poorly understood. Therefore, this study aimed to use magnetic resonance imaging (MRI) to investigate changes in brain networks and their connection to impulsivity and drug craving in abstinent individuals with METH use disorder (MUDs). A total of 110 MUDs and 55 age- and gender-matched healthy controls (HCs) underwent resting-state functional MRI and T1-weighted imaging scans, and completed impulsivity and cue-induced craving measurements. We applied independent component analysis to construct functional brain networks and multivariate analysis of covariance to investigate group differences in network connectivity. Mediation analyses were conducted to explore the relationships among brain-network functional connectivity (FC), impulsivity, and drug craving in the patients. MUDs showed increased connectivity in the salience network (SN) and decreased connectivity in the default mode network compared to HCs. Impulsivity was positively correlated with FC within the SN and played a completely mediating role between METH craving and FC within the SN in MUDs. These findings suggest alterations in functional brain networks underlying METH dependence, with SN potentially acting as a core neural substrate for impulse control disorders.


Amphetamine-Related Disorders , Brain , Craving , Cues , Impulsive Behavior , Magnetic Resonance Imaging , Methamphetamine , Humans , Male , Amphetamine-Related Disorders/diagnostic imaging , Amphetamine-Related Disorders/physiopathology , Amphetamine-Related Disorders/psychology , Adult , Craving/physiology , Impulsive Behavior/physiology , Female , Brain/diagnostic imaging , Brain/physiopathology , Methamphetamine/adverse effects , Nerve Net/diagnostic imaging , Nerve Net/physiopathology , Neural Pathways/physiopathology , Neural Pathways/diagnostic imaging , Young Adult
6.
BMC Pediatr ; 24(1): 318, 2024 May 08.
Article En | MEDLINE | ID: mdl-38720281

Reading learning disability (RLD) is characterized by a specific difficulty in learning to read that is not better explained by an intellectual disability, lack of instruction, psychosocial adversity, or a neurological disorder. According to the domain-general hypothesis, a working memory deficit is the primary problem. Working memory in this population has recently been linked to altered resting-state functional connectivity within the default mode network (DMN), salience network (SN), and frontoparietal network (FPN) compared to that in typically developing individuals. The main purpose of the present study was to compare the within-network functional connectivity of the DMN, SN, FPN, and reading network in two groups of children with RLD: a group with lower-than-average working memory (LWM) and a group with average working memory (AWM). All subjects underwent resting-state functional magnetic resonance imaging (fMRI), and data were analyzed from a network perspective using the network brain statistics framework. The results showed that the LWM group had significantly weaker connectivity in a network that involved brain regions in the DMN, SN, and FPN than the AWM group. Although there was no significant difference between groups in reading network in the present study, other studies have shown relationship of the connectivity of the angular gyrus, supramarginal gyrus, and inferior parietal lobe with the phonological process of reading. The results suggest that although there are significant differences in functional connectivity in the associated networks between children with LWM and AWM, the distinctive cognitive profile has no specific effect on the reading network.


Dyslexia , Magnetic Resonance Imaging , Memory, Short-Term , Humans , Memory, Short-Term/physiology , Child , Male , Female , Dyslexia/physiopathology , Dyslexia/diagnostic imaging , Brain/diagnostic imaging , Brain/physiopathology , Nerve Net/diagnostic imaging , Nerve Net/physiopathology , Reading , Case-Control Studies
7.
Hum Brain Mapp ; 45(7): e26694, 2024 May.
Article En | MEDLINE | ID: mdl-38727014

Schizophrenia (SZ) is a debilitating mental illness characterized by adolescence or early adulthood onset of psychosis, positive and negative symptoms, as well as cognitive impairments. Despite a plethora of studies leveraging functional connectivity (FC) from functional magnetic resonance imaging (fMRI) to predict symptoms and cognitive impairments of SZ, the findings have exhibited great heterogeneity. We aimed to identify congruous and replicable connectivity patterns capable of predicting positive and negative symptoms as well as cognitive impairments in SZ. Predictable functional connections (FCs) were identified by employing an individualized prediction model, whose replicability was further evaluated across three independent cohorts (BSNIP, SZ = 174; COBRE, SZ = 100; FBIRN, SZ = 161). Across cohorts, we observed that altered FCs in frontal-temporal-cingulate-thalamic network were replicable in prediction of positive symptoms, while sensorimotor network was predictive of negative symptoms. Temporal-parahippocampal network was consistently identified to be associated with reduced cognitive function. These replicable 23 FCs effectively distinguished SZ from healthy controls (HC) across three cohorts (82.7%, 90.2%, and 86.1%). Furthermore, models built using these replicable FCs showed comparable accuracies to those built using the whole-brain features in predicting symptoms/cognition of SZ across the three cohorts (r = .17-.33, p < .05). Overall, our findings provide new insights into the neural underpinnings of SZ symptoms/cognition and offer potential targets for further research and possible clinical interventions.


Cognitive Dysfunction , Connectome , Magnetic Resonance Imaging , Nerve Net , Schizophrenia , Humans , Schizophrenia/diagnostic imaging , Schizophrenia/physiopathology , Male , Adult , Female , Connectome/methods , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/physiopathology , Cohort Studies , Nerve Net/diagnostic imaging , Nerve Net/physiopathology , Young Adult , Middle Aged
8.
Hum Brain Mapp ; 45(7): e26698, 2024 May.
Article En | MEDLINE | ID: mdl-38726908

Mediation analysis assesses whether an exposure directly produces changes in cognitive behavior or is influenced by intermediate "mediators". Electroencephalographic (EEG) spectral measurements have been previously used as effective mediators representing diverse aspects of brain function. However, it has been necessary to collapse EEG measures onto a single scalar using standard mediation methods. In this article, we overcome this limitation and examine EEG frequency-resolved functional connectivity measures as a mediator using the full EEG cross-spectral tensor (CST). Since CST samples do not exist in Euclidean space but in the Riemannian manifold of positive-definite tensors, we transform the problem, allowing for the use of classic multivariate statistics. Toward this end, we map the data from the original manifold space to the Euclidean tangent space, eliminating redundant information to conform to a "compressed CST." The resulting object is a matrix with rows corresponding to frequencies and columns to cross spectra between channels. We have developed a novel matrix mediation approach that leverages a nuclear norm regularization to determine the matrix-valued regression parameters. Furthermore, we introduced a global test for the overall CST mediation and a test to determine specific channels and frequencies driving the mediation. We validated the method through simulations and applied it to our well-studied 50+-year Barbados Nutrition Study dataset by comparing EEGs collected in school-age children (5-11 years) who were malnourished in the first year of life with those of healthy classmate controls. We hypothesized that the CST mediates the effect of malnutrition on cognitive performance. We can now explicitly pinpoint the frequencies (delta, theta, alpha, and beta bands) and regions (frontal, central, and occipital) in which functional connectivity was altered in previously malnourished children, an improvement to prior studies. Understanding the specific networks impacted by a history of postnatal malnutrition could pave the way for developing more targeted and personalized therapeutic interventions. Our methods offer a versatile framework applicable to mediation studies encompassing matrix and Hermitian 3D tensor mediators alongside scalar exposures and outcomes, facilitating comprehensive analyses across diverse research domains.


Electroencephalography , Humans , Electroencephalography/methods , Child , Child, Preschool , Female , Male , Connectome/methods , Cognition/physiology , Malnutrition/physiopathology , Nerve Net/diagnostic imaging , Nerve Net/physiopathology , Nerve Net/physiology , Brain/physiopathology , Brain/diagnostic imaging , Brain/physiology , Infant
9.
Sci Rep ; 14(1): 10495, 2024 05 07.
Article En | MEDLINE | ID: mdl-38714807

Schizophrenia is a serious and complex mental disease, known to be associated with various subtle structural and functional deviations in the brain. Recently, increased attention is given to the analysis of brain-wide, global mechanisms, strongly altering the communication of long-distance brain areas in schizophrenia. Data of 32 patients with schizophrenia and 28 matched healthy control subjects were analyzed. Two minutes long 64-channel EEG recordings were registered during resting, eyes closed condition. Average connectivity strength was estimated with Weighted Phase Lag Index (wPLI) in lower frequencies: delta and theta, and Amplitude Envelope Correlation with leakage correction (AEC-c) in higher frequencies: alpha, beta, lower gamma and higher gamma. To analyze functional network topology Minimum Spanning Tree (MST) algorithms were applied. Results show that patients have weaker functional connectivity in delta and alpha frequency bands. Concerning network differences, the result of lower diameter, higher leaf number, and also higher maximum degree and maximum betweenness centrality in patients suggest a star-like, and more random network topology in patients with schizophrenia. Our findings are in accordance with some previous findings based on resting-state EEG (and fMRI) data, suggesting that MST network structure in schizophrenia is biased towards a less optimal, more centralized organization.


Brain , Electroencephalography , Schizophrenia , Humans , Schizophrenia/physiopathology , Electroencephalography/methods , Male , Female , Adult , Brain/physiopathology , Brain/diagnostic imaging , Nerve Net/physiopathology , Nerve Net/diagnostic imaging , Rest/physiology , Algorithms , Middle Aged , Magnetic Resonance Imaging/methods , Case-Control Studies , Young Adult
11.
Brain Behav ; 14(5): e3518, 2024 May.
Article En | MEDLINE | ID: mdl-38698619

OBJECTIVE: The objective of this study was to investigate the functional changes associated with mild cognitive impairment (MCI) using independent component analysis (ICA) with the word generation task functional magnetic resonance imaging (fMRI) and resting-state fMRI. METHODS: In this study 17 patients with MCI and age and education-matched 17 healthy individuals as control group are investigated. All participants underwent resting-state fMRI and task-based fMRI while performing the word generation task. ICA was used to identify the appropriate independent components (ICs) and their associated networks. The Dice Coefficient method was used to determine the relevance of the ICs to the networks of interest. RESULTS: IC-14 was found relevant to language network in both resting-state and task-based fMRI, IC-4 to visual, and IC-28 to dorsal attention network (DAN) in word generation task-based fMRI by Sorento-Dice Coefficient. ICA showed increased activation in language network, which had a larger voxel size in resting-state functional MRI than word generation task-based fMRI in the bilateral lingual gyrus. Right temporo-occipital fusiform cortex, right hippocampus, and right thalamus were also activated in the task-based fMRI. Decreased activation was found in DAN and visual network MCI patients in word generation task-based fMRI. CONCLUSION: Task-based fMRI and ICA are more sophisticated and reliable tools in evaluation cognitive impairments in language processing. Our findings support the neural mechanisms of the cognitive impairments in MCI.


Cognitive Dysfunction , Language , Magnetic Resonance Imaging , Humans , Cognitive Dysfunction/physiopathology , Cognitive Dysfunction/diagnostic imaging , Magnetic Resonance Imaging/methods , Male , Female , Aged , Middle Aged , Nerve Net/diagnostic imaging , Nerve Net/physiopathology , Brain Mapping/methods , Brain/physiopathology , Brain/diagnostic imaging , Rest/physiology
12.
Brain Behav ; 14(5): e3504, 2024 May.
Article En | MEDLINE | ID: mdl-38698583

BACKGROUND: Electroacupuncture (EA) has been shown to facilitate brain plasticity-related functional recovery following ischemic stroke. The functional magnetic resonance imaging technique can be used to determine the range and mode of brain activation. After stroke, EA has been shown to alter brain connectivity, whereas EA's effect on brain network topology properties remains unclear. An evaluation of EA's effects on global and nodal topological properties in rats with ischemia reperfusion was conducted in this study. METHODS AND RESULTS: There were three groups of adult male Sprague-Dawley rats: sham-operated group (sham group), middle cerebral artery occlusion/reperfusion (MCAO/R) group, and MCAO/R plus EA (MCAO/R + EA) group. The differences in global and nodal topological properties, including shortest path length, global efficiency, local efficiency, small-worldness index, betweenness centrality (BC), and degree centrality (DC) were estimated. Graphical network analyses revealed that, as compared with the sham group, the MCAO/R group demonstrated a decrease in BC value in the right ventral hippocampus and increased BC in the right substantia nigra, accompanied by increased DC in the left nucleus accumbens shell (AcbSh). The BC was increased in the right hippocampus ventral and decreased in the right substantia nigra after EA intervention, and MCAO/R + EA resulted in a decreased DC in left AcbSh compared to MCAO/R. CONCLUSION: The results of this study provide a potential basis for EA to promote cognitive and motor function recovery after ischemic stroke.


Electroacupuncture , Infarction, Middle Cerebral Artery , Magnetic Resonance Imaging , Rats, Sprague-Dawley , Reperfusion Injury , Animals , Electroacupuncture/methods , Male , Rats , Reperfusion Injury/physiopathology , Reperfusion Injury/therapy , Reperfusion Injury/diagnostic imaging , Infarction, Middle Cerebral Artery/therapy , Infarction, Middle Cerebral Artery/physiopathology , Infarction, Middle Cerebral Artery/diagnostic imaging , Brain/physiopathology , Brain/diagnostic imaging , Brain Ischemia/therapy , Brain Ischemia/physiopathology , Brain Ischemia/diagnostic imaging , Disease Models, Animal , Nerve Net/physiopathology , Nerve Net/diagnostic imaging , Ischemic Stroke/therapy , Ischemic Stroke/physiopathology , Ischemic Stroke/diagnostic imaging , Hippocampus/diagnostic imaging , Hippocampus/physiopathology
13.
PLoS One ; 19(5): e0302470, 2024.
Article En | MEDLINE | ID: mdl-38701101

Network oscillation in the anterior cingulate cortex (ACC) plays a key role in attention, novelty detection and anxiety; however, its involvement in cognitive impairment caused by acute systemic inflammation is unclear. To investigate the acute effects of systemic inflammation on ACC network oscillation and cognitive function, we analyzed cytokine level and cognitive performance as well as network oscillation in the mouse ACC Cg1 region, within 4 hours after lipopolysaccharide (LPS, 30 µg/kg) administration. While the interleukin-6 concentration in the serum was evidently higher in LPS-treated mice, the increases in the cerebral cortex interleukin-6 did not reach statistical significance. The power of kainic acid (KA)-induced network oscillation in the ACC Cg1 region slice preparation increased in LPS-treated mice. Notably, histamine, which was added in vitro, increased the oscillation power in the brain slices from LPS-untreated mice; for the LPS-treated mice, however, the effect of histamine was suppressive. In the open field test, frequency of entries into the center area showed a negative correlation with the power of network oscillation (0.3 µM of KA, theta band (3-8 Hz); 3.0 µM of KA, high-gamma band (50-80 Hz)). These results suggest that LPS-induced systemic inflammation results in increased network oscillation and a drastic change in histamine sensitivity in the ACC, accompanied by the robust production of systemic pro-inflammatory cytokines in the periphery, and that these alterations in the network oscillation and animal behavior as an acute phase reaction relate with each other. We suggest that our experimental setting has a distinct advantage in obtaining mechanistic insights into inflammatory cognitive impairment through comprehensive analyses of hormonal molecules and neuronal functions.


Cognition , Gyrus Cinguli , Histamine , Inflammation , Lipopolysaccharides , Animals , Gyrus Cinguli/metabolism , Gyrus Cinguli/physiopathology , Inflammation/metabolism , Mice , Male , Histamine/blood , Histamine/metabolism , Kainic Acid , Interleukin-6/blood , Interleukin-6/metabolism , Behavior, Animal , Nerve Net/physiopathology , Mice, Inbred C57BL
14.
Hum Brain Mapp ; 45(7): e26689, 2024 May.
Article En | MEDLINE | ID: mdl-38703095

Tau pathology and its spatial propagation in Alzheimer's disease (AD) play crucial roles in the neurodegenerative cascade leading to dementia. However, the underlying mechanisms linking tau spreading to glucose metabolism remain elusive. To address this, we aimed to examine the association between pathologic tau aggregation, functional connectivity, and cascading glucose metabolism and further explore the underlying interplay mechanisms. In this prospective cohort study, we enrolled 79 participants with 18F-Florzolotau positron emission tomography (PET), 18F-fluorodeoxyglucose PET, resting-state functional, and anatomical magnetic resonance imaging (MRI) images in the hospital-based Shanghai Memory Study. We employed generalized linear regression and correlation analyses to assess the associations between Florzolotau accumulation, functional connectivity, and glucose metabolism in whole-brain and network-specific manners. Causal mediation analysis was used to evaluate whether functional connectivity mediates the association between pathologic tau and cascading glucose metabolism. We examined 22 normal controls and 57 patients with AD. In the AD group, functional connectivity was associated with Florzolotau covariance (ß = .837, r = 0.472, p < .001) and glucose covariance (ß = 1.01, r = 0.499, p < .001). Brain regions with higher tau accumulation tend to be connected to other regions with high tau accumulation through functional connectivity or metabolic connectivity. Mediation analyses further suggest that functional connectivity partially modulates the influence of tau accumulation on downstream glucose metabolism (mediation proportion: 49.9%). Pathologic tau may affect functionally connected neurons directly, triggering downstream glucose metabolism changes. This study sheds light on the intricate relationship between tau pathology, functional connectivity, and downstream glucose metabolism, providing critical insights into AD pathophysiology and potential therapeutic targets.


Alzheimer Disease , Fluorodeoxyglucose F18 , Magnetic Resonance Imaging , Nerve Net , Positron-Emission Tomography , tau Proteins , Humans , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/metabolism , Alzheimer Disease/physiopathology , Male , Female , Aged , tau Proteins/metabolism , Middle Aged , Nerve Net/diagnostic imaging , Nerve Net/metabolism , Nerve Net/physiopathology , Glucose/metabolism , Connectome , Prospective Studies , Brain/diagnostic imaging , Brain/metabolism , Brain/physiopathology , Aged, 80 and over
15.
Hum Brain Mapp ; 45(7): e26691, 2024 May.
Article En | MEDLINE | ID: mdl-38703114

Verbal memory decline is a significant concern following temporal lobe surgeries in patients with epilepsy, emphasizing the need for precision presurgical verbal memory mapping to optimize functional outcomes. However, the inter-individual variability in functional networks and brain function-structural dissociations pose challenges when relying solely on group-level atlases or anatomical landmarks for surgical guidance. Here, we aimed to develop and validate a personalized functional mapping technique for verbal memory using precision resting-state functional MRI (rs-fMRI) and neurosurgery. A total of 38 patients with refractory epilepsy scheduled for surgical interventions were enrolled and 28 patients were analyzed in the study. Baseline 30-min rs-fMRI scanning, verbal memory and language assessments were collected for each patient before surgery. Personalized verbal memory networks (PVMN) were delineated based on preoperative rs-fMRI data for each patient. The accuracy of PVMN was assessed by comparing post-operative functional impairments and the overlapping extent between PVMN and surgical lesions. A total of 14 out of 28 patients experienced clinically meaningful declines in verbal memory after surgery. The personalized network and the group-level atlas exhibited 100% and 75.0% accuracy in predicting postoperative verbal memory declines, respectively. Moreover, six patients with extra-temporal lesions that overlapped with PVMN showed selective impairments in verbal memory. Furthermore, the lesioned ratio of the personalized network rather than the group-level atlas was significantly correlated with postoperative declines in verbal memory (personalized networks: r = -0.39, p = .038; group-level atlas: r = -0.19, p = .332). In conclusion, our personalized functional mapping technique, using precision rs-fMRI, offers valuable insights into individual variability in the verbal memory network and holds promise in precision verbal memory network mapping in individuals.


Brain Mapping , Magnetic Resonance Imaging , Humans , Female , Male , Adult , Young Adult , Brain Mapping/methods , Memory Disorders/etiology , Memory Disorders/diagnostic imaging , Memory Disorders/physiopathology , Middle Aged , Drug Resistant Epilepsy/surgery , Drug Resistant Epilepsy/diagnostic imaging , Drug Resistant Epilepsy/physiopathology , Adolescent , Nerve Net/diagnostic imaging , Nerve Net/physiopathology , Nerve Net/surgery , Postoperative Complications/diagnostic imaging , Neurosurgical Procedures , Verbal Learning/physiology , Epilepsy, Temporal Lobe/surgery , Epilepsy, Temporal Lobe/diagnostic imaging , Epilepsy, Temporal Lobe/physiopathology
16.
Neural Plast ; 2024: 8862647, 2024.
Article En | MEDLINE | ID: mdl-38715980

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder that is characterized by inattention, hyperactivity, and impulsivity. The neural mechanisms underlying ADHD remain inadequately understood, and current approaches do not well link neural networks and attention networks within brain networks. Our objective is to investigate the neural mechanisms related to attention and explore neuroimaging biological tags that can be generalized within the attention networks. In this paper, we utilized resting-state functional magnetic resonance imaging data to examine the differential functional connectivity network between ADHD and typically developing individuals. We employed a graph convolutional neural network model to identify individuals with ADHD. After classification, we visualized brain regions with significant contributions to the classification results. Our results suggest that the frontal, temporal, parietal, and cerebellar regions are likely the primary areas of dysfunction in individuals with ADHD. We also explored the relationship between regions of interest and attention networks, as well as the connection between crucial nodes and the distribution of positively and negatively correlated connections. This analysis allowed us to pinpoint the most discriminative brain regions, including the right orbitofrontal gyrus, the left rectus gyrus and bilateral insula, the right inferior temporal gyrus and bilateral transverse temporal gyrus in the temporal region, and the lingual gyrus of the occipital lobe, multiple regions of the basal ganglia and the upper cerebellum. These regions are primarily involved in the attention executive control network and the attention orientation network. Dysfunction in the functional connectivity of these regions may contribute to the underlying causes of ADHD.


Attention Deficit Disorder with Hyperactivity , Brain , Magnetic Resonance Imaging , Neural Networks, Computer , Humans , Attention Deficit Disorder with Hyperactivity/physiopathology , Attention Deficit Disorder with Hyperactivity/diagnostic imaging , Magnetic Resonance Imaging/methods , Male , Female , Brain/physiopathology , Brain/diagnostic imaging , Nerve Net/diagnostic imaging , Nerve Net/physiopathology , Adult , Brain Mapping/methods , Neural Pathways/physiopathology , Neural Pathways/diagnostic imaging , Young Adult , Adolescent , Child , Attention/physiology
17.
Addict Biol ; 29(5): e13395, 2024 May.
Article En | MEDLINE | ID: mdl-38709211

The brain mechanisms underlying the risk of cannabis use disorder (CUD) are poorly understood. Several studies have reported changes in functional connectivity (FC) in CUD, although none have focused on the study of time-varying patterns of FC. To fill this important gap of knowledge, 39 individuals at risk for CUD and 55 controls, stratified by their score on a self-screening questionnaire for cannabis-related problems (CUDIT-R), underwent resting-state functional magnetic resonance imaging. Dynamic functional connectivity (dFNC) was estimated using independent component analysis, sliding-time window correlations, cluster states and meta-state indices of global dynamics and were compared among groups. At-risk individuals stayed longer in a cluster state with higher within and reduced between network dFNC for the subcortical, sensory-motor, visual, cognitive-control and default-mode networks, relative to controls. More globally, at-risk individuals had a greater number of meta-states and transitions between them and a longer state span and total distance between meta-states in the state space. Our findings suggest that the risk of CUD is associated with an increased dynamic fluidity and dynamic range of FC. This may result in altered stability and engagement of the brain networks, which can ultimately translate into altered cortical and subcortical function conveying CUD risk. Identifying these changes in brain function can pave the way for early pharmacological and neurostimulation treatment of CUD, as much as they could facilitate the stratification of high-risk individuals.


Brain , Connectome , Magnetic Resonance Imaging , Marijuana Abuse , Humans , Male , Female , Marijuana Abuse/physiopathology , Marijuana Abuse/diagnostic imaging , Brain/physiopathology , Brain/diagnostic imaging , Young Adult , Adult , Case-Control Studies , Nerve Net/physiopathology , Nerve Net/diagnostic imaging , Default Mode Network/physiopathology , Default Mode Network/diagnostic imaging , Adolescent
18.
J Math Biol ; 89(1): 3, 2024 May 13.
Article En | MEDLINE | ID: mdl-38740613

Dynamical systems on networks typically involve several dynamical processes evolving at different timescales. For instance, in Alzheimer's disease, the spread of toxic protein throughout the brain not only disrupts neuronal activity but is also influenced by neuronal activity itself, establishing a feedback loop between the fast neuronal activity and the slow protein spreading. Motivated by the case of Alzheimer's disease, we study the multiple-timescale dynamics of a heterodimer spreading process on an adaptive network of Kuramoto oscillators. Using a minimal two-node model, we establish that heterogeneous oscillatory activity facilitates toxic outbreaks and induces symmetry breaking in the spreading patterns. We then extend the model formulation to larger networks and perform numerical simulations of the slow-fast dynamics on common network motifs and on the brain connectome. The simulations corroborate the findings from the minimal model, underscoring the significance of multiple-timescale dynamics in the modeling of neurodegenerative diseases.


Alzheimer Disease , Brain , Computer Simulation , Mathematical Concepts , Models, Neurological , Neurons , Humans , Alzheimer Disease/physiopathology , Neurons/physiology , Brain/physiopathology , Connectome , Neurodegenerative Diseases/physiopathology , Neurodegenerative Diseases/pathology , Nerve Net/physiopathology , Nerve Net/physiology
19.
Cereb Cortex ; 34(5)2024 May 02.
Article En | MEDLINE | ID: mdl-38741271

This study investigates abnormalities in cerebellar-cerebral static and dynamic functional connectivity among patients with acute pontine infarction, examining the relationship between these connectivity changes and behavioral dysfunction. Resting-state functional magnetic resonance imaging was utilized to collect data from 45 patients within seven days post-pontine infarction and 34 normal controls. Seed-based static and dynamic functional connectivity analyses identified divergences in cerebellar-cerebral connectivity features between pontine infarction patients and normal controls. Correlations between abnormal functional connectivity features and behavioral scores were explored. Compared to normal controls, left pontine infarction patients exhibited significantly increased static functional connectivity within the executive, affective-limbic, and motor networks. Conversely, right pontine infarction patients demonstrated decreased static functional connectivity in the executive, affective-limbic, and default mode networks, alongside an increase in the executive and motor networks. Decreased temporal variability of dynamic functional connectivity was observed in the executive and default mode networks among left pontine infarction patients. Furthermore, abnormalities in static and dynamic functional connectivity within the executive network correlated with motor and working memory performance in patients. These findings suggest that alterations in cerebellar-cerebral static and dynamic functional connectivity could underpin the behavioral dysfunctions observed in acute pontine infarction patients.


Brain Stem Infarctions , Cerebellum , Magnetic Resonance Imaging , Neural Pathways , Pons , Humans , Male , Female , Middle Aged , Cerebellum/physiopathology , Cerebellum/diagnostic imaging , Neural Pathways/physiopathology , Neural Pathways/diagnostic imaging , Pons/diagnostic imaging , Pons/physiopathology , Brain Stem Infarctions/physiopathology , Brain Stem Infarctions/diagnostic imaging , Aged , Adult , Cerebral Cortex/physiopathology , Cerebral Cortex/diagnostic imaging , Nerve Net/physiopathology , Nerve Net/diagnostic imaging
20.
Cereb Cortex ; 34(5)2024 May 02.
Article En | MEDLINE | ID: mdl-38752981

Adolescents are high-risk population for major depressive disorder. Executive dysfunction emerges as a common feature of depression and exerts a significant influence on the social functionality of adolescents. This study aimed to identify the multimodal co-varying brain network related to executive function in adolescent with major depressive disorder. A total of 24 adolescent major depressive disorder patients and 43 healthy controls were included and completed the Intra-Extra Dimensional Set Shift Task. Multimodal neuroimaging data, including the amplitude of low-frequency fluctuations from resting-state functional magnetic resonance imaging and gray matter volume from structural magnetic resonance imaging, were combined with executive function using a supervised fusion method named multimodal canonical correlation analysis with reference plus joint independent component analysis. The major depressive disorder showed more total errors than the healthy controls in the Intra-Extra Dimensional Set Shift task. Their performance on the Intra-Extra Dimensional Set Shift Task was negatively related to the 14-item Hamilton Rating Scale for Anxiety score. We discovered an executive function-related multimodal fronto-occipito-temporal network with lower amplitude of low-frequency fluctuation and gray matter volume loadings in major depressive disorder. The gray matter component of the identified network was negatively related to errors made in Intra-Extra Dimensional Set Shift while positively related to stages completed. These findings may help to deepen our understanding of the pathophysiological mechanisms of cognitive dysfunction in adolescent depression.


Depressive Disorder, Major , Executive Function , Magnetic Resonance Imaging , Multimodal Imaging , Humans , Depressive Disorder, Major/diagnostic imaging , Depressive Disorder, Major/physiopathology , Adolescent , Executive Function/physiology , Male , Female , Magnetic Resonance Imaging/methods , Multimodal Imaging/methods , Brain/diagnostic imaging , Brain/physiopathology , Gray Matter/diagnostic imaging , Gray Matter/pathology , Neuroimaging/methods , Cognition/physiology , Nerve Net/diagnostic imaging , Nerve Net/physiopathology , Neuropsychological Tests , Brain Mapping/methods
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