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1.
Hum Brain Mapp ; 45(10): e26776, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38958131

ABSTRACT

Recent studies in Parkinson's disease (PD) patients reported disruptions in dynamic functional connectivity (dFC, i.e., a characterization of spontaneous fluctuations in functional connectivity over time). Here, we assessed whether the integrity of striatal dopamine terminals directly modulates dFC metrics in two separate PD cohorts, indexing dopamine-related changes in large-scale brain network dynamics and its implications in clinical features. We pooled data from two disease-control cohorts reflecting early PD. From the Parkinson's Progression Marker Initiative (PPMI) cohort, resting-state functional magnetic resonance imaging (rsfMRI) and dopamine transporter (DaT) single-photon emission computed tomography (SPECT) were available for 63 PD patients and 16 age- and sex-matched healthy controls. From the clinical research group 219 (KFO) cohort, rsfMRI imaging was available for 52 PD patients and 17 age- and sex-matched healthy controls. A subset of 41 PD patients and 13 healthy control subjects additionally underwent 18F-DOPA-positron emission tomography (PET) imaging. The striatal synthesis capacity of 18F-DOPA PET and dopamine terminal quantity of DaT SPECT images were extracted for the putamen and the caudate. After rsfMRI pre-processing, an independent component analysis was performed on both cohorts simultaneously. Based on the derived components, an individual sliding window approach (44 s window) and a subsequent k-means clustering were conducted separately for each cohort to derive dFC states (reemerging intra- and interindividual connectivity patterns). From these states, we derived temporal metrics, such as average dwell time per state, state attendance, and number of transitions and compared them between groups and cohorts. Further, we correlated these with the respective measures for local dopaminergic impairment and clinical severity. The cohorts did not differ regarding age and sex. Between cohorts, PD groups differed regarding disease duration, education, cognitive scores and L-dopa equivalent daily dose. In both cohorts, the dFC analysis resulted in three distinct states, varying in connectivity patterns and strength. In the PPMI cohort, PD patients showed a lower state attendance for the globally integrated (GI) state and a lower number of transitions than controls. Significantly, worse motor scores (Unified Parkinson's Disease Rating Scale Part III) and dopaminergic impairment in the putamen and the caudate were associated with low average dwell time in the GI state and a low total number of transitions. These results were not observed in the KFO cohort: No group differences in dFC measures or associations between dFC variables and dopamine synthesis capacity were observed. Notably, worse motor performance was associated with a low number of bidirectional transitions between the GI and the lesser connected (LC) state across the PD groups of both cohorts. Hence, in early PD, relative preservation of motor performance may be linked to a more dynamic engagement of an interconnected brain state. Specifically, those large-scale network dynamics seem to relate to striatal dopamine availability. Notably, most of these results were obtained only for one cohort, suggesting that dFC is impacted by certain cohort features like educational level, or disease severity. As we could not pinpoint these features with the data at hand, we suspect that other, in our case untracked, demographical features drive connectivity dynamics in PD. PRACTITIONER POINTS: Exploring dopamine's role in brain network dynamics in two Parkinson's disease (PD) cohorts, we unraveled PD-specific changes in dynamic functional connectivity. Results in the Parkinson's Progression Marker Initiative (PPMI) and the KFO cohort suggest motor performance may be linked to a more dynamic engagement and disengagement of an interconnected brain state. Results only in the PPMI cohort suggest striatal dopamine availability influences large-scale network dynamics that are relevant in motor control.


Subject(s)
Corpus Striatum , Dopamine Plasma Membrane Transport Proteins , Dopamine , Magnetic Resonance Imaging , Parkinson Disease , Positron-Emission Tomography , Tomography, Emission-Computed, Single-Photon , Humans , Parkinson Disease/diagnostic imaging , Parkinson Disease/metabolism , Parkinson Disease/physiopathology , Female , Male , Middle Aged , Aged , Dopamine/metabolism , Dopamine Plasma Membrane Transport Proteins/metabolism , Corpus Striatum/diagnostic imaging , Corpus Striatum/metabolism , Corpus Striatum/physiopathology , Cohort Studies , Dihydroxyphenylalanine/analogs & derivatives , Connectome , Nerve Net/diagnostic imaging , Nerve Net/metabolism , Nerve Net/physiopathology
3.
Commun Biol ; 7(1): 801, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38956310

ABSTRACT

Efficiency of evidence accumulation (EEA), an individual's ability to selectively gather goal-relevant information to make adaptive choices, is thought to be a key neurocomputational mechanism associated with cognitive functioning and transdiagnostic risk for psychopathology. However, the neural basis of individual differences in EEA is poorly understood, especially regarding the role of largescale brain network dynamics. We leverage data from 5198 participants from the Human Connectome Project and Adolescent Brain Cognitive Development Study to demonstrate a strong association between EEA and flexible adaptation to cognitive demand in the "task-positive" frontoparietal and dorsal attention networks. Notably, individuals with higher EEA displayed divergent task-positive network activation across n-back task conditions: higher activation under high cognitive demand (2-back) and lower activation under low demand (0-back). These findings suggest that brain networks' flexible adaptation to cognitive demands is a key neural underpinning of EEA.


Subject(s)
Brain , Cognition , Connectome , Humans , Brain/physiology , Male , Female , Cognition/physiology , Adolescent , Nerve Net/physiology , Young Adult , Adult , Magnetic Resonance Imaging , Adaptation, Physiological
4.
Hum Brain Mapp ; 45(10): e26726, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38949487

ABSTRACT

Resting-state functional connectivity (FC) is widely used in multivariate pattern analysis of functional magnetic resonance imaging (fMRI), including identifying the locations of putative brain functional borders, predicting individual phenotypes, and diagnosing clinical mental diseases. However, limited attention has been paid to the analysis of functional interactions from a frequency perspective. In this study, by contrasting coherence-based and correlation-based FC with two machine learning tasks, we observed that measuring FC in the frequency domain helped to identify finer functional subregions and achieve better pattern discrimination capability relative to the temporal correlation. This study has proven the feasibility of coherence in the analysis of fMRI, and the results indicate that modeling functional interactions in the frequency domain may provide richer information than that in the time domain, which may provide a new perspective on the analysis of functional neuroimaging.


Subject(s)
Connectome , Magnetic Resonance Imaging , Humans , Magnetic Resonance Imaging/methods , Connectome/methods , Adult , Male , Female , Machine Learning , Young Adult , Brain/physiology , Brain/diagnostic imaging , Nerve Net/diagnostic imaging , Nerve Net/physiology
5.
Proc Natl Acad Sci U S A ; 121(28): e2402624121, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38954543

ABSTRACT

The pial vasculature is the sole source of blood supply to the neocortex. The brain is contained within the skull, a vascularized bone marrow with a unique anatomical connection to the brain meninges. Recent developments in tissue clearing have enabled detailed mapping of the entire pial and calvarial vasculature. However, what are the absolute flow rate values of those vascular networks? This information cannot accurately be retrieved with the commonly used bioimaging methods. Here, we introduce Pia-FLOW, a unique approach based on large-scale transcranial fluorescence localization microscopy, to attain hemodynamic imaging of the whole murine pial and calvarial vasculature at frame rates up to 1,000 Hz and spatial resolution reaching 5.4 µm. Using Pia-FLOW, we provide detailed maps of flow velocity, direction, and vascular diameters which can serve as ground-truth data for further studies, advancing our understanding of brain fluid dynamics. Furthermore, Pia-FLOW revealed that the pial vascular network functions as one unit for robust allocation of blood after stroke.


Subject(s)
Connectome , Hemodynamics , Pia Mater , Animals , Mice , Hemodynamics/physiology , Pia Mater/blood supply , Cerebrovascular Circulation/physiology , Brain/blood supply , Brain/diagnostic imaging , Skull/diagnostic imaging , Skull/blood supply , Stroke/physiopathology , Stroke/diagnostic imaging , Male , Mice, Inbred C57BL
6.
Transl Psychiatry ; 14(1): 268, 2024 Jun 29.
Article in English | MEDLINE | ID: mdl-38951513

ABSTRACT

The urgency of addressing common mental disorders (bipolar disorder, attention-deficit hyperactivity disorder (ADHD), and schizophrenia) arises from their significant societal impact. Developing strategies to support psychiatrists is crucial. Previous studies focused on the relationship between these disorders and changes in the resting-state functional connectome's modularity, often using static functional connectivity (sFC) estimation. However, understanding the dynamic reconfiguration of resting-state brain networks with rich temporal structure is essential for comprehending neural activity and addressing mental health disorders. This study proposes an unsupervised approach combining spatial and temporal characterization of brain networks to classify common mental disorders using fMRI timeseries data from two cohorts (N = 408 participants). We employ the weighted stochastic block model to uncover mesoscale community architecture differences, providing insights into network organization. Our approach overcomes sFC limitations and biases in community detection algorithms by modelling the functional connectome's temporal dynamics as a landscape, quantifying temporal stability at whole-brain and network levels. Findings reveal individuals with schizophrenia exhibit less assortative community structure and participate in multiple motif classes, indicating less specialized network organization. Patients with schizophrenia and ADHD demonstrate significantly reduced temporal stability compared to healthy controls. This study offers insights into functional connectivity (FC) patterns' spatiotemporal organization and their alterations in common mental disorders, highlighting the potential of temporal stability as a biomarker.


Subject(s)
Attention Deficit Disorder with Hyperactivity , Brain , Connectome , Magnetic Resonance Imaging , Nerve Net , Schizophrenia , Humans , Schizophrenia/physiopathology , Schizophrenia/diagnostic imaging , Attention Deficit Disorder with Hyperactivity/physiopathology , Attention Deficit Disorder with Hyperactivity/diagnostic imaging , Female , Male , Adult , Brain/physiopathology , Brain/diagnostic imaging , Nerve Net/diagnostic imaging , Nerve Net/physiopathology , Bipolar Disorder/physiopathology , Bipolar Disorder/diagnostic imaging , Young Adult , Middle Aged , Mental Disorders/physiopathology , Mental Disorders/diagnostic imaging
7.
Commun Biol ; 7(1): 790, 2024 Jun 29.
Article in English | MEDLINE | ID: mdl-38951602

ABSTRACT

Neuroscience research has shown that specific brain patterns can relate to creativity during multiple tasks but also at rest. Nevertheless, the electrophysiological correlates of a highly creative brain remain largely unexplored. This study aims to uncover resting-state networks related to creative behavior using high-density electroencephalography (HD-EEG) and to test whether the strength of functional connectivity within these networks could predict individual creativity in novel subjects. We acquired resting state HD-EEG data from 90 healthy participants who completed a creative behavior inventory. We then employed connectome-based predictive modeling; a machine-learning technique that predicts behavioral measures from brain connectivity features. Using a support vector regression, our results reveal functional connectivity patterns related to high and low creativity, in the gamma frequency band (30-45 Hz). In leave-one-out cross-validation, the combined model of high and low networks predicts individual creativity with very good accuracy (r = 0.36, p = 0.00045). Furthermore, the model's predictive power is established through external validation on an independent dataset (N = 41), showing a statistically significant correlation between observed and predicted creativity scores (r = 0.35, p = 0.02). These findings reveal large-scale networks that could predict creative behavior at rest, providing a crucial foundation for developing HD-EEG-network-based markers of creativity.


Subject(s)
Brain , Creativity , Electroencephalography , Rest , Humans , Electroencephalography/methods , Male , Female , Adult , Brain/physiology , Young Adult , Rest/physiology , Connectome/methods
8.
Transl Psychiatry ; 14(1): 270, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38956035

ABSTRACT

Brain function is vulnerable to the consequences of inadequate sleep, an adverse trend that is increasingly prevalent. The REM sleep phase has been implicated in coordinating various brain structures and is hypothesized to have potential links to brain variability. However, traditional imaging research have encountered challenges in attributing specific brain region activity to REM sleep, remained understudied at the whole-brain connectivity level. Through the spilt-night paradigm, distinct patterns of REM sleep phases were observed among the full-night sleep group (n = 36), the early-night deprivation group (n = 41), and the late-night deprivation group (n = 36). We employed connectome-based predictive modeling (CPM) to delineate the effects of REM sleep deprivation on the functional connectivity of the brain (REM connectome) during its resting state. The REM sleep-brain connectome was characterized by stronger connectivity within the default mode network (DMN) and between the DMN and visual networks, while fewer predictive edges were observed. Notably, connections such as those between the cingulo-opercular network (CON) and the auditory network, as well as between the subcortex and visual networks, also made significant contributions. These findings elucidate the neural signatures of REM sleep loss and reveal common connectivity patterns across individuals, validated at the group level.


Subject(s)
Brain , Connectome , Magnetic Resonance Imaging , Sleep Deprivation , Sleep, REM , Humans , Male , Sleep Deprivation/physiopathology , Sleep Deprivation/diagnostic imaging , Sleep, REM/physiology , Female , Adult , Brain/physiopathology , Brain/diagnostic imaging , Young Adult , Nerve Net/physiopathology , Nerve Net/diagnostic imaging , Default Mode Network/diagnostic imaging , Default Mode Network/physiopathology
10.
Hum Brain Mapp ; 45(10): e26764, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38994667

ABSTRACT

Presurgical planning prior to brain tumor resection is critical for the preservation of neurologic function post-operatively. Neurosurgeons increasingly use advanced brain mapping techniques pre- and intra-operatively to delineate brain regions which are "eloquent" and should be spared during resection. Functional MRI (fMRI) has emerged as a commonly used non-invasive modality for individual patient mapping of critical cortical regions such as motor, language, and visual cortices. To map motor function, patients are scanned using fMRI while they perform various motor tasks to identify brain networks critical for motor performance, but it may be difficult for some patients to perform tasks in the scanner due to pre-existing deficits. Connectome fingerprinting (CF) is a machine-learning approach that learns associations between resting-state functional networks of a brain region and the activations in the region for specific tasks; once a CF model is constructed, individualized predictions of task activation can be generated from resting-state data. Here we utilized CF to train models on high-quality data from 208 subjects in the Human Connectome Project (HCP) and used this to predict task activations in our cohort of healthy control subjects (n = 15) and presurgical patients (n = 16) using resting-state fMRI (rs-fMRI) data. The prediction quality was validated with task fMRI data in the healthy controls and patients. We found that the task predictions for motor areas are on par with actual task activations in most healthy subjects (model accuracy around 90%-100% of task stability) and some patients suggesting the CF models can be reliably substituted where task data is either not possible to collect or hard for subjects to perform. We were also able to make robust predictions in cases in which there were no task-related activations elicited. The findings demonstrate the utility of the CF approach for predicting activations in out-of-sample subjects, across sites and scanners, and in patient populations. This work supports the feasibility of the application of CF models to presurgical planning, while also revealing challenges to be addressed in future developments. PRACTITIONER POINTS: Precision motor network prediction using connectome fingerprinting. Carefully trained models' performance limited by stability of task-fMRI data. Successful cross-scanner predictions and motor network mapping in patients with tumor.


Subject(s)
Connectome , Feasibility Studies , Magnetic Resonance Imaging , Preoperative Care , Humans , Connectome/methods , Magnetic Resonance Imaging/methods , Female , Male , Adult , Preoperative Care/methods , Brain Neoplasms/surgery , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/physiopathology , Motor Activity/physiology , Middle Aged , Brain/diagnostic imaging , Brain/physiology , Machine Learning , Young Adult
11.
JAMA Netw Open ; 7(7): e2420479, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38976268

ABSTRACT

Importance: Understanding the heterogeneity of neuropsychiatric symptoms (NPSs) and associated brain abnormalities is essential for effective management and treatment of dementia. Objective: To identify dementia subtypes with distinct functional connectivity associated with neuropsychiatric subsyndromes. Design, Setting, and Participants: Using data from the Open Access Series of Imaging Studies-3 (OASIS-3; recruitment began in 2005) and Alzheimer Disease Neuroimaging Initiative (ADNI; recruitment began in 2004) databases, this cross-sectional study analyzed resting-state functional magnetic resonance imaging (fMRI) scans, clinical assessments, and neuropsychological measures of participants aged 42 to 95 years. The fMRI data were processed from July 2022 to February 2024, with secondary analysis conducted from August 2022 to March 2024. Participants without medical conditions or medical contraindications for MRI were recruited. Main Outcomes and Measures: A multivariate sparse canonical correlation analysis was conducted to identify functional connectivity-informed NPS subsyndromes, including behavioral and anxiety subsyndromes. Subsequently, a clustering analysis was performed on obtained latent connectivity profiles to reveal neurophysiological subtypes, and differences in abnormal connectivity and phenotypic profiles between subtypes were examined. Results: Among 1098 participants in OASIS-3, 177 individuals who had fMRI and at least 1 NPS at baseline were included (78 female [44.1%]; median [IQR] age, 72 [67-78] years) as a discovery dataset. There were 2 neuropsychiatric subsyndromes identified: behavioral (r = 0.22; P = .002; P for permutation = .007) and anxiety (r = 0.19; P = .01; P for permutation = .006) subsyndromes from connectivity NPS-associated latent features. The behavioral subsyndrome was characterized by connections predominantly involving the default mode (within-network contribution by summed correlation coefficients = 54) and somatomotor (within-network contribution = 58) networks and NPSs involving nighttime behavior disturbance (R = -0.29; P < .001), agitation (R = -0.28; P = .001), and apathy (R = -0.23; P = .007). The anxiety subsyndrome mainly consisted of connections involving the visual network (within-network contribution = 53) and anxiety-related NPSs (R = 0.36; P < .001). By clustering individuals along these 2 subsyndrome-associated connectivity latent features, 3 subtypes were found (subtype 1: 45 participants; subtype 2: 43 participants; subtype 3: 66 participants). Patients with dementia of subtype 3 exhibited similar brain connectivity and cognitive behavior patterns to those of healthy individuals. However, patients with dementia of subtypes 1 and 2 had different dysfunctional connectivity profiles involving the frontoparietal control network (FPC) and somatomotor network (the difference by summed z values was 230 within the SMN and 173 between the SMN and FPC for subtype 1 and 473 between the SMN and visual network for subtype 2) compared with those of healthy individuals. These dysfunctional connectivity patterns were associated with differences in baseline dementia severity (eg, the median [IQR] of the total score of NPSs was 2 [2-7] for subtype 3 vs 6 [3-8] for subtype 1; P = .04 and 5.5 [3-11] for subtype 2; P = .03) and longitudinal progression of cognitive impairment and behavioral dysfunction (eg, the overall interaction association between time and subtypes to orientation was F = 4.88; P = .008; using the time × subtype 3 interaction item as the reference level: ß = 0.05; t = 2.6 for time × subtype 2; P = .01). These findings were further validated using a replication dataset of 193 participants (127 female [65.8%]; median [IQR] age, 74 [69-77] years) consisting of 154 newly released participants from OASIS-3 and 39 participants from ADNI. Conclusions and Relevance: These findings may provide a novel framework to disentangle the neuropsychiatric and brain functional heterogeneity of dementia, offering a promising avenue to improve clinical management and facilitate the timely development of targeted interventions for patients with dementia.


Subject(s)
Brain , Dementia , Magnetic Resonance Imaging , Humans , Female , Male , Aged , Middle Aged , Cross-Sectional Studies , Magnetic Resonance Imaging/methods , Aged, 80 and over , Brain/diagnostic imaging , Brain/physiopathology , Dementia/physiopathology , Dementia/diagnostic imaging , Dementia/psychology , Adult , Neuropsychological Tests/statistics & numerical data , Connectome/methods
12.
Hum Brain Mapp ; 45(10): e26778, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38980175

ABSTRACT

Brain activity continuously fluctuates over time, even if the brain is in controlled (e.g., experimentally induced) states. Recent years have seen an increasing interest in understanding the complexity of these temporal variations, for example with respect to developmental changes in brain function or between-person differences in healthy and clinical populations. However, the psychometric reliability of brain signal variability and complexity measures-which is an important precondition for robust individual differences as well as longitudinal research-is not yet sufficiently studied. We examined reliability (split-half correlations) and test-retest correlations for task-free (resting-state) BOLD fMRI as well as split-half correlations for seven functional task data sets from the Human Connectome Project to evaluate their reliability. We observed good to excellent split-half reliability for temporal variability measures derived from rest and task fMRI activation time series (standard deviation, mean absolute successive difference, mean squared successive difference), and moderate test-retest correlations for the same variability measures under rest conditions. Brain signal complexity estimates (several entropy and dimensionality measures) showed moderate to good reliabilities under both, rest and task activation conditions. We calculated the same measures also for time-resolved (dynamic) functional connectivity time series and observed moderate to good reliabilities for variability measures, but poor reliabilities for complexity measures derived from functional connectivity time series. Global (i.e., mean across cortical regions) measures tended to show higher reliability than region-specific variability or complexity estimates. Larger subcortical regions showed similar reliability as cortical regions, but small regions showed lower reliability, especially for complexity measures. Lastly, we also show that reliability scores are only minorly dependent on differences in scan length and replicate our results across different parcellation and denoising strategies. These results suggest that the variability and complexity of BOLD activation time series are robust measures well-suited for individual differences research. Temporal variability of global functional connectivity over time provides an important novel approach to robustly quantifying the dynamics of brain function. PRACTITIONER POINTS: Variability and complexity measures of BOLD activation show good split-half reliability and moderate test-retest reliability. Measures of variability of global functional connectivity over time can robustly quantify neural dynamics. Length of fMRI data has only a minor effect on reliability.


Subject(s)
Brain , Connectome , Magnetic Resonance Imaging , Humans , Magnetic Resonance Imaging/standards , Magnetic Resonance Imaging/methods , Reproducibility of Results , Brain/physiology , Brain/diagnostic imaging , Connectome/standards , Connectome/methods , Oxygen/blood , Male , Female , Rest/physiology , Adult , Image Processing, Computer-Assisted/methods , Image Processing, Computer-Assisted/standards , Brain Mapping/methods , Brain Mapping/standards
13.
Hum Brain Mapp ; 45(10): e26749, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38989605

ABSTRACT

The cerebellum has been involved in social abilities and autism. Given that the cerebellum is connected to the cortex via the cerebello-thalamo-cortical loop, the connectivity between the cerebellum and cortical regions involved in social interactions, that is, the right temporo-parietal junction (rTPJ) has been studied in individuals with autism, who suffer from prototypical deficits in social abilities. However, existing studies with small samples of categorical, case-control comparisons have yielded inconsistent results due to the inherent heterogeneity of autism, suggesting that investigating how clinical dimensions are related to cerebellar-rTPJ functional connectivity might be more relevant. Therefore, our objective was to study the functional connectivity between the cerebellum and rTPJ, focusing on its association with social abilities from a dimensional perspective in a transdiagnostic sample. We analyzed structural magnetic resonance imaging (MRI) and functional MRI (fMRI) scans obtained during naturalistic films watching from a large transdiagnostic dataset, the Healthy Brain Network (HBN), and examined the association between cerebellum-rTPJ functional connectivity and social abilities measured with the social responsiveness scale (SRS). We conducted univariate seed-to-voxel analysis, multivariate canonical correlation analysis (CCA), and predictive support vector regression (SVR). We included 1404 subjects in the structural analysis (age: 10.516 ± 3.034, range: 5.822-21.820, 506 females) and 414 subjects in the functional analysis (age: 11.260 ± 3.318 years, range: 6.020-21.820, 161 females). Our CCA model revealed a significant association between cerebellum-rTPJ functional connectivity, full-scale IQ (FSIQ) and SRS scores. However, this effect was primarily driven by FSIQ as suggested by SVR and univariate seed-to-voxel analysis. We also demonstrated the specificity of the rTPJ and the influence of structural anatomy in this association. Our results suggest that there is a complex relationship between cerebellum-rTPJ connectivity, social performance and IQ. This relationship is specific to the cerebellum-rTPJ connectivity, and is largely related to structural anatomy in these two regions. PRACTITIONER POINTS: We analyzed cerebellum-right temporoparietal junction (rTPJ) connectivity in a pediatric transdiagnostic sample. We found a complex relationship between cerebellum and rTPJ connectivity, social performance and IQ. Cerebellum and rTPJ functional connectivity is related to structural anatomy in these two regions.


Subject(s)
Cerebellum , Magnetic Resonance Imaging , Humans , Cerebellum/diagnostic imaging , Cerebellum/physiopathology , Cerebellum/pathology , Male , Female , Young Adult , Adult , Connectome/methods , Social Skills , Adolescent , Nerve Net/diagnostic imaging , Nerve Net/physiopathology , Parietal Lobe/diagnostic imaging , Parietal Lobe/physiopathology , Temporal Lobe/diagnostic imaging , Temporal Lobe/physiopathology , Neural Pathways/physiopathology , Neural Pathways/diagnostic imaging
14.
J Psychiatry Neurosci ; 49(4): E218-E232, 2024.
Article in English | MEDLINE | ID: mdl-38960625

ABSTRACT

BACKGROUND: Childhood trauma plays a crucial role in the dysfunctional reward circuitry in major depressive disorder (MDD). We sought to explore the effect of abnormalities in the globus pallidus (GP)-centric reward circuitry on the relationship between childhood trauma and MDD. METHODS: We conducted seed-based dynamic functional connectivity (dFC) analysis among people with or without MDD and with or without childhood trauma. We explored the relationship between abnormal reward circuitry, childhood trauma, and MDD. RESULTS: We included 48 people with MDD and childhood trauma, 30 people with MDD without childhood trauma, 57 controls with childhood trauma, and 46 controls without childhood trauma. We found that GP subregions exhibited abnormal dFC with several regions, including the inferior parietal lobe, thalamus, superior frontal gyrus (SFG), and precuneus. Abnormal dFC in these GP subregions showed a significant correlation with childhood trauma. Moderation analysis revealed that the dFC between the anterior GP and SFG, as well as between the anterior GP and the precentral gyrus, modulated the relationship between childhood abuse and MDD severity. We observed a negative correlation between childhood trauma and MDD severity among patients with lower dFC between the anterior GP and SFG, as well as higher dFC between the anterior GP and precentral gyrus. This suggests that reduced dFC between the anterior GP and SFG, along with increased dFC between the anterior GP and precentral gyrus, may attenuate the effect of childhood trauma on MDD severity. LIMITATIONS: Cross-sectional designs cannot be used to infer causality. CONCLUSION: Our findings underscore the pivotal role of reward circuitry abnormalities in MDD with childhood trauma. These abnormalities involve various brain regions, including the postcentral gyrus, precentral gyrus, inferior parietal lobe, precuneus, superior frontal gyrus, thalamus, and middle frontal gyrus. CLINICAL TRIAL REGISTRATION: ChiCTR2300078193.


Subject(s)
Adverse Childhood Experiences , Depressive Disorder, Major , Globus Pallidus , Adult , Female , Humans , Male , Middle Aged , Young Adult , Connectome , Depressive Disorder, Major/physiopathology , Depressive Disorder, Major/diagnostic imaging , Globus Pallidus/diagnostic imaging , Globus Pallidus/physiopathology , Magnetic Resonance Imaging , Nerve Net/diagnostic imaging , Nerve Net/physiopathology , Neural Pathways/physiopathology , Neural Pathways/diagnostic imaging , Reward
15.
Nat Commun ; 15(1): 5698, 2024 Jul 07.
Article in English | MEDLINE | ID: mdl-38972924

ABSTRACT

The arthropod mushroom body is well-studied as an expansion layer representing olfactory stimuli and linking them to contingent events. However, 8% of mushroom body Kenyon cells in Drosophila melanogaster receive predominantly visual input, and their function remains unclear. Here, we identify inputs to visual Kenyon cells using the FlyWire adult whole-brain connectome. Input repertoires are similar across hemispheres and connectomes with certain inputs highly overrepresented. Many visual neurons presynaptic to Kenyon cells have large receptive fields, while interneuron inputs receive spatially restricted signals that may be tuned to specific visual features. Individual visual Kenyon cells randomly sample sparse inputs from combinations of visual channels, including multiple optic lobe neuropils. These connectivity patterns suggest that visual coding in the mushroom body, like olfactory coding, is sparse, distributed, and combinatorial. However, the specific input repertoire to the smaller population of visual Kenyon cells suggests a constrained encoding of visual stimuli.


Subject(s)
Connectome , Drosophila melanogaster , Mushroom Bodies , Visual Pathways , Animals , Mushroom Bodies/physiology , Mushroom Bodies/cytology , Drosophila melanogaster/physiology , Visual Pathways/physiology , Neurons/physiology , Interneurons/physiology , Optic Lobe, Nonmammalian/cytology , Optic Lobe, Nonmammalian/physiology , Neuropil/physiology , Neuropil/cytology
16.
J Headache Pain ; 25(1): 99, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38862883

ABSTRACT

Migraine is a complex neurological condition characterized by recurrent headaches, which is often accompanied by various neurological symptoms. Magnetic resonance imaging (MRI) is a powerful tool for investigating whole-brain connectivity patterns; however, systematic assessment of structural connectome organization has rarely been performed. In the present study, we aimed to examine the changes in structural connectivity in patients with episodic migraines using diffusion MRI. First, we computed structural connectivity using diffusion MRI tractography, after which we applied dimensionality reduction techniques to the structural connectivity and generated three low-dimensional eigenvectors. We subsequently calculated the manifold eccentricity, defined as the Euclidean distance between each data point and the center of the data in the manifold space. We then compared the manifold eccentricity between patients with migraines and healthy controls, revealing significant between-group differences in the orbitofrontal cortex, temporal pole, and sensory/motor regions. Between-group differences in subcortico-cortical connectivity further revealed significant changes in the amygdala, accumbens, and caudate nuclei. Finally, supervised machine learning effectively classified patients with migraines and healthy controls using cortical and subcortical structural connectivity features, highlighting the importance of the orbitofrontal and sensory cortices, in addition to the caudate, in distinguishing between the groups. Our findings confirmed that episodic migraine is related to the structural connectome changes in the limbic and sensory systems, suggesting its potential utility as a diagnostic marker for migraine.


Subject(s)
Connectome , Migraine Disorders , Humans , Migraine Disorders/diagnostic imaging , Migraine Disorders/pathology , Connectome/methods , Female , Adult , Male , Limbic System/diagnostic imaging , Limbic System/pathology , Diffusion Tensor Imaging/methods , Young Adult
17.
Hum Brain Mapp ; 45(8): e26750, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38853710

ABSTRACT

The triple-network model has been widely applied in neuropsychiatric disorders including autism spectrum disorder (ASD). However, the mechanism of causal regulations within the triple-network and their relations with symptoms of ASD remains unclear. 81 male ASD and 80 well matched typically developing control (TDC) were included in this study, recruited from Autism Brain Image Data Exchange-I datasets. Spatial reference-based independent component analysis was used to identify the anterior and posterior part of default-mode network (aDMN and pDMN), salience network (SN), and bilateral executive-control network (ECN) from resting-state functional magnetic resonance imaging data. Spectral dynamic causal model and parametric empirical Bayes with Bayesian model reduction/average were adopted to explore the effective connectivity (EC) within triple-network and the relationship between EC and autism diagnostic observation schedule (ADOS) scores. After adjusting for age and site effect, ASD and TDC groups both showed inhibition patterns. Compared with TDC, ASD group showed weaker self-inhibition in aDMN and pDMN, stronger inhibition in pDMN→aDMN, weaker inhibition in aDMN→LECN, pDMN→SN, LECN→SN, and LECN→RECN. Furthermore, negative relationships between ADOS scores and pDMN self-inhibition strength, as well as with the EC of pDMN→aDMN were observed in ASD group. The present study reveals imbalanced effective connections within triple-networks in ASD children. More attentions should be focused at the pDMN, which modulates the core symptoms of ASD and may serve as an important region for ASD diagnosis and the target region for ASD treatments.


Subject(s)
Autism Spectrum Disorder , Default Mode Network , Magnetic Resonance Imaging , Humans , Autism Spectrum Disorder/diagnostic imaging , Autism Spectrum Disorder/physiopathology , Male , Child , Default Mode Network/diagnostic imaging , Default Mode Network/physiopathology , Connectome , Nerve Net/diagnostic imaging , Nerve Net/physiopathology , Executive Function/physiology , Adolescent , Bayes Theorem
18.
Hum Brain Mapp ; 45(8): e26710, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38853713

ABSTRACT

Cross-situational inconsistency is common in the expression of honesty traits; yet, there is insufficient emphasis on behavioral dishonesty across multiple contexts. The current study aimed to investigate behavioral dishonesty in various contexts and reveal the associations between trait honesty, behavioral dishonesty, and neural patterns of observing others behave honestly or dishonestly in videos (abbr.: (dis)honesty video-watching). First, the results revealed limitations in using trait honesty to reflect variations in dishonest behaviors and predict behavioral dishonesty. The finding highlights the importance of considering neural patterns in understanding and predicting dishonest behaviors. Second, by comparing the predictive performance of seven types of data across three neural networks, the results showed that functional connectivity in the hypothesis-driven network during (dis)honesty video-watching provided the highest predictive power in predicting multitask behavioral dishonesty. Last, by applying the feature elimination method, the midline self-referential regions (medial prefrontal cortex, posterior cingulate cortex, and anterior cingulate cortex), anterior insula, and striatum were identified as the most informative brain regions in predicting behavioral dishonesty. In summary, the study offered insights into individual differences in deception and the intricate connections among trait honesty, behavioral dishonesty, and neural patterns during (dis)honesty video-watching.


Subject(s)
Deception , Magnetic Resonance Imaging , Nerve Net , Humans , Male , Female , Adult , Young Adult , Nerve Net/physiology , Nerve Net/diagnostic imaging , Connectome , Cerebral Cortex/physiology , Cerebral Cortex/diagnostic imaging , Video Recording , Social Behavior
19.
Elife ; 122024 Jun 10.
Article in English | MEDLINE | ID: mdl-38857169

ABSTRACT

Understanding how different neuronal types connect and communicate is critical to interpreting brain function and behavior. However, it has remained a formidable challenge to decipher the genetic underpinnings that dictate the specific connections formed between neuronal types. To address this, we propose a novel bilinear modeling approach that leverages the architecture similar to that of recommendation systems. Our model transforms the gene expressions of presynaptic and postsynaptic neuronal types, obtained from single-cell transcriptomics, into a covariance matrix. The objective is to construct this covariance matrix that closely mirrors a connectivity matrix, derived from connectomic data, reflecting the known anatomical connections between these neuronal types. When tested on a dataset of Caenorhabditis elegans, our model achieved a performance comparable to, if slightly better than, the previously proposed spatial connectome model (SCM) in reconstructing electrical synaptic connectivity based on gene expressions. Through a comparative analysis, our model not only captured all genetic interactions identified by the SCM but also inferred additional ones. Applied to a mouse retinal neuronal dataset, the bilinear model successfully recapitulated recognized connectivity motifs between bipolar cells and retinal ganglion cells, and provided interpretable insights into genetic interactions shaping the connectivity. Specifically, it identified unique genetic signatures associated with different connectivity motifs, including genes important to cell-cell adhesion and synapse formation, highlighting their role in orchestrating specific synaptic connections between these neurons. Our work establishes an innovative computational strategy for decoding the genetic programming of neuronal type connectivity. It not only sets a new benchmark for single-cell transcriptomic analysis of synaptic connections but also paves the way for mechanistic studies of neural circuit assembly and genetic manipulation of circuit wiring.


Subject(s)
Caenorhabditis elegans , Connectome , Neurons , Animals , Caenorhabditis elegans/genetics , Caenorhabditis elegans/physiology , Mice , Neurons/physiology , Single-Cell Analysis , Models, Neurological
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