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1.
PLoS Comput Biol ; 17(6): e1009136, 2021 06.
Article in English | MEDLINE | ID: mdl-34181648

ABSTRACT

The white matter contains long-range connections between different brain regions and the organization of these connections holds important implications for brain function in health and disease. Tractometry uses diffusion-weighted magnetic resonance imaging (dMRI) to quantify tissue properties along the trajectories of these connections. Statistical inference from tractometry usually either averages these quantities along the length of each fiber bundle or computes regression models separately for each point along every one of the bundles. These approaches are limited in their sensitivity, in the former case, or in their statistical power, in the latter. We developed a method based on the sparse group lasso (SGL) that takes into account tissue properties along all of the bundles and selects informative features by enforcing both global and bundle-level sparsity. We demonstrate the performance of the method in two settings: i) in a classification setting, patients with amyotrophic lateral sclerosis (ALS) are accurately distinguished from matched controls. Furthermore, SGL identifies the corticospinal tract as important for this classification, correctly finding the parts of the white matter known to be affected by the disease. ii) In a regression setting, SGL accurately predicts "brain age." In this case, the weights are distributed throughout the white matter indicating that many different regions of the white matter change over the lifespan. Thus, SGL leverages the multivariate relationships between diffusion properties in multiple bundles to make accurate phenotypic predictions while simultaneously discovering the most relevant features of the white matter.


Subject(s)
Diffusion Tensor Imaging/statistics & numerical data , Neuroimaging/statistics & numerical data , White Matter/diagnostic imaging , Aging/pathology , Algorithms , Amyotrophic Lateral Sclerosis/diagnostic imaging , Case-Control Studies , Computational Biology , Connectome/statistics & numerical data , Humans , Models, Neurological , Multivariate Analysis , Nerve Net/diagnostic imaging , Principal Component Analysis , Regression Analysis , Software
2.
PLoS Comput Biol ; 17(8): e1009216, 2021 08.
Article in English | MEDLINE | ID: mdl-34339414

ABSTRACT

Retinotopic mapping, i.e., the mapping between visual inputs on the retina and neuronal activations in cortical visual areas, is one of the central topics in visual neuroscience. For human observers, the mapping is obtained by analyzing functional magnetic resonance imaging (fMRI) signals of cortical responses to slowly moving visual stimuli on the retina. Although it is well known from neurophysiology that the mapping is topological (i.e., the topology of neighborhood connectivity is preserved) within each visual area, retinotopic maps derived from the state-of-the-art methods are often not topological because of the low signal-to-noise ratio and spatial resolution of fMRI. The violation of topological condition is most severe in cortical regions corresponding to the neighborhood of the fovea (e.g., < 1 degree eccentricity in the Human Connectome Project (HCP) dataset), significantly impeding accurate analysis of retinotopic maps. This study aims to directly model the topological condition and generate topology-preserving and smooth retinotopic maps. Specifically, we adopted the Beltrami coefficient, a metric of quasiconformal mapping, to define the topological condition, developed a mathematical model to quantify topological smoothing as a constrained optimization problem, and elaborated an efficient numerical method to solve the problem. The method was then applied to V1, V2, and V3 simultaneously in the HCP dataset. Experiments with both simulated and real retinotopy data demonstrated that the proposed method could generate topological and smooth retinotopic maps.


Subject(s)
Brain Mapping/methods , Retina/physiology , Visual Cortex/physiology , Adult , Algorithms , Brain Mapping/statistics & numerical data , Computational Biology , Computer Simulation , Connectome/methods , Connectome/statistics & numerical data , Databases, Factual , Female , Functional Neuroimaging/statistics & numerical data , Humans , Magnetic Resonance Imaging/statistics & numerical data , Male , Models, Neurological , Photic Stimulation , Retina/diagnostic imaging , Signal-To-Noise Ratio , Visual Cortex/diagnostic imaging , Visual Pathways/diagnostic imaging , Visual Pathways/physiology , Young Adult
3.
Neuroimage ; 233: 117894, 2021 06.
Article in English | MEDLINE | ID: mdl-33737245

ABSTRACT

Statistical power is key for robust, replicable science. Here, we systematically explored how numbers of trials and subjects affect statistical power in MEG sensor-level data. More specifically, we simulated "experiments" using the MEG resting-state dataset of the Human Connectome Project (HCP). We divided the data in two conditions, injected a dipolar source at a known anatomical location in the "signal condition", but not in the "noise condition", and detected significant differences at sensor level with classical paired t-tests across subjects, using amplitude, squared amplitude, and global field power (GFP) measures. Group-level detectability of these simulated effects varied drastically with anatomical origin. We thus examined in detail which spatial properties of the sources affected detectability, looking specifically at the distance from closest sensor and orientation of the source, and at the variability of these parameters across subjects. In line with previous single-subject studies, we found that the most detectable effects originate from source locations that are closest to the sensors and oriented tangentially with respect to the head surface. In addition, cross-subject variability in orientation also affected group-level detectability, boosting detection in regions where this variability was small and hindering detection in regions where it was large. Incidentally, we observed a considerable covariation of source position, orientation, and their cross-subject variability in individual brain anatomical space, making it difficult to assess the impact of each of these variables independently of one another. We thus also performed simulations where we controlled spatial properties independently of individual anatomy. These additional simulations confirmed the strong impact of distance and orientation and further showed that orientation variability across subjects affects detectability, whereas position variability does not. Importantly, our study indicates that strict unequivocal recommendations as to the ideal number of trials and subjects for any experiment cannot be realistically provided for neurophysiological studies and should be adapted according to the brain regions under study.


Subject(s)
Brain Mapping/methods , Brain Mapping/statistics & numerical data , Brain/diagnostic imaging , Brain/physiology , Magnetoencephalography/methods , Magnetoencephalography/statistics & numerical data , Connectome/methods , Connectome/statistics & numerical data , Electroencephalography/methods , Electroencephalography/statistics & numerical data , Humans , Monte Carlo Method
4.
Philos Trans A Math Phys Eng Sci ; 379(2198): 20200236, 2021 May 31.
Article in English | MEDLINE | ID: mdl-33840216

ABSTRACT

The concept of resonance in nonlinear systems is crucial and traditionally refers to a specific realization of maximum response provoked by a particular external perturbation. Depending on the system and the nature of perturbation, many different resonance types have been identified in various fields of science. A prominent example is in neuroscience where it has been widely accepted that a neural system may exhibit resonances at microscopic, mesoscopic and macroscopic scales and benefit from such resonances in various tasks. In this context, the two well-known forms are stochastic and vibrational resonance phenomena which manifest that detection and propagation of a feeble information signal in neural structures can be enhanced by additional perturbations via these two resonance mechanisms. Given the importance of network architecture in proper functioning of the nervous system, we here present a review of recent studies on stochastic and vibrational resonance phenomena in neuronal media, focusing mainly on their emergence in complex networks of neurons as well as in simple network structures that represent local behaviours of neuron communities. From this perspective, we aim to provide a secure guide by including theoretical and experimental approaches that analyse in detail possible reasons and necessary conditions for the appearance of stochastic resonance and vibrational resonance in neural systems. This article is part of the theme issue 'Vibrational and stochastic resonance in driven nonlinear systems (part 2)'.


Subject(s)
Models, Neurological , Nerve Net/physiology , Neurons/physiology , Animals , Computer Simulation , Connectome/statistics & numerical data , Electrophysiological Phenomena , Functional Neuroimaging , Humans , Mathematical Concepts , Nonlinear Dynamics , Stochastic Processes , Synaptic Transmission/physiology , Vibration
5.
PLoS Comput Biol ; 15(12): e1007551, 2019 12.
Article in English | MEDLINE | ID: mdl-31841504

ABSTRACT

Dynamic communication and routing play important roles in the human brain in order to facilitate flexibility in task solving and thought processes. Here, we present a network perturbation methodology that allows investigating dynamic switching between different network pathways based on phase offsets between two external oscillatory drivers. We apply this method in a computational model of the human connectome with delay-coupled neural masses. To analyze dynamic switching of pathways, we define four new metrics that measure dynamic network response properties for pairs of stimulated nodes. Evaluating these metrics for all network pathways, we found a broad spectrum of pathways with distinct dynamic properties and switching behaviors. We show that network pathways can have characteristic timescales and thus specific preferences for the phase lag between the regions they connect. Specifically, we identified pairs of network nodes whose connecting paths can either be (1) insensitive to the phase relationship between the node pair, (2) turned on and off via changes in the phase relationship between the node pair, or (3) switched between via changes in the phase relationship between the node pair. Regarding the latter, we found that 33% of node pairs can switch their communication from one pathway to another depending on their phase offsets. This reveals a potential mechanistic role that phase offsets and coupling delays might play for the dynamic information routing via communication pathways in the brain.


Subject(s)
Connectome , Models, Neurological , Nerve Net/physiology , Brain/anatomy & histology , Brain/physiology , Communication , Computational Biology , Computer Simulation , Connectome/statistics & numerical data , Humans , Nerve Net/anatomy & histology , Neural Networks, Computer , Neural Pathways/anatomy & histology , Neural Pathways/physiology
6.
Biometrics ; 76(1): 257-269, 2020 03.
Article in English | MEDLINE | ID: mdl-31350904

ABSTRACT

The field of neuroimaging dedicated to mapping connections in the brain is increasingly being recognized as key for understanding neurodevelopment and pathology. Networks of these connections are quantitatively represented using complex structures, including matrices, functions, and graphs, which require specialized statistical techniques for estimation and inference about developmental and disorder-related changes. Unfortunately, classical statistical testing procedures are not well suited to high-dimensional testing problems. In the context of global or regional tests for differences in neuroimaging data, traditional analysis of variance (ANOVA) is not directly applicable without first summarizing the data into univariate or low-dimensional features, a process that might mask the salient features of high-dimensional distributions. In this work, we consider a general framework for two-sample testing of complex structures by studying generalized within-group and between-group variances based on distances between complex and potentially high-dimensional observations. We derive an asymptotic approximation to the null distribution of the ANOVA test statistic, and conduct simulation studies with scalar and graph outcomes to study finite sample properties of the test. Finally, we apply our test to our motivating study of structural connectivity in autism spectrum disorder.


Subject(s)
Biometry/methods , Connectome/statistics & numerical data , Adolescent , Analysis of Variance , Autism Spectrum Disorder/diagnostic imaging , Child , Computer Simulation , Data Interpretation, Statistical , Diffusion Tensor Imaging/statistics & numerical data , Humans
7.
Mol Psychiatry ; 23(10): 1974-1980, 2018 10.
Article in English | MEDLINE | ID: mdl-29203849

ABSTRACT

Working memory (WM) is a central construct in cognitive neuroscience because it comprises mechanisms of active information maintenance and cognitive control that underpin most complex cognitive behavior. Individual variation in WM has been associated with multiple behavioral and health features including demographic characteristics, cognitive and physical traits and lifestyle choices. In this context, we used sparse canonical correlation analyses (sCCAs) to determine the covariation between brain imaging metrics of WM-network activation and connectivity and nonimaging measures relating to sensorimotor processing, affective and nonaffective cognition, mental health and personality, physical health and lifestyle choices derived from 823 healthy participants derived from the Human Connectome Project. We conducted sCCAs at two levels: a global level, testing the overall association between the entire imaging and behavioral-health data sets; and a modular level, testing associations between subsets of the two data sets. The behavioral-health and neuroimaging data sets showed significant interdependency. Variables with positive correlation to the neuroimaging variate represented higher physical endurance and fluid intelligence as well as better function in multiple higher-order cognitive domains. Negatively correlated variables represented indicators of suboptimal cardiovascular and metabolic control and lifestyle choices such as alcohol and nicotine use. These results underscore the importance of accounting for behavioral-health factors in neuroimaging studies of WM and provide a neuroscience-informed framework for personalized and public health interventions to promote and maintain the integrity of the WM network.


Subject(s)
Brain/diagnostic imaging , Cognition/physiology , Memory, Short-Term/physiology , Adult , Brain/physiology , Computer Simulation , Connectome/methods , Connectome/statistics & numerical data , Data Interpretation, Statistical , Female , Humans , Magnetic Resonance Imaging/methods , Male , Neuroimaging/methods , Neuropsychological Tests
8.
PLoS Comput Biol ; 14(4): e1006120, 2018 04.
Article in English | MEDLINE | ID: mdl-29664910

ABSTRACT

Variation in cortical connectivity profiles is typically modeled as having a coarse spatial scale parcellated into interconnected brain areas. We created a high-dimensional common model of the human connectome to search for fine-scale structure that is shared across brains. Projecting individual connectivity data into this new common model connectome accounts for substantially more variance in the human connectome than do previous models. This newly discovered shared structure is closely related to fine-scale distinctions in representations of information. These results reveal a shared fine-scale structure that is a major component of the human connectome that coexists with coarse-scale, areal structure. This shared fine-scale structure was not captured in previous models and was, therefore, inaccessible to analysis and study.


Subject(s)
Connectome/statistics & numerical data , Models, Neurological , Acoustic Stimulation , Adult , Algorithms , Brain/anatomy & histology , Brain/physiology , Computational Biology , Computer Simulation , Female , Humans , Magnetic Resonance Imaging , Male , Motion Pictures , Photic Stimulation , Young Adult
9.
PLoS Comput Biol ; 14(8): e1006381, 2018 08.
Article in English | MEDLINE | ID: mdl-30148879

ABSTRACT

Functional-effective connectivity and network topology are nowadays key issues for studying brain physiological functions and pathologies. Inferring neuronal connectivity from electrophysiological recordings presents open challenges and unsolved problems. In this work, we present a cross-correlation based method for reliably estimating not only excitatory but also inhibitory links, by analyzing multi-unit spike activity from large-scale neuronal networks. The method is validated by means of realistic simulations of large-scale neuronal populations. New results related to functional connectivity estimation and network topology identification obtained by experimental electrophysiological recordings from high-density and large-scale (i.e., 4096 electrodes) microtransducer arrays coupled to in vitro neural populations are presented. Specifically, we show that: (i) functional inhibitory connections are accurately identified in in vitro cortical networks, providing that a reasonable firing rate and recording length are achieved; (ii) small-world topology, with scale-free and rich-club features are reliably obtained, on condition that a minimum number of active recording sites are available. The method and procedure can be directly extended and applied to in vivo multi-units brain activity recordings.


Subject(s)
Connectome/methods , Excitatory Postsynaptic Potentials/physiology , Inhibitory Postsynaptic Potentials/physiology , Action Potentials/physiology , Animals , Cerebral Cortex/physiology , Connectome/statistics & numerical data , Electrodes , Interneurons , Nerve Net/physiology , Neurons/physiology , Rats/embryology , Rats, Sprague-Dawley
10.
Stat Med ; 38(29): 5486-5496, 2019 12 20.
Article in English | MEDLINE | ID: mdl-31650580

ABSTRACT

Many neuroscientists are interested in how connectomes (graphical representations of functional connectivity between areas of the brain) change in relation to covariates. In statistics, changes like this are analyzed using regression, where the outcomes or dependent variables are regressed onto the covariates. However, when the outcome is a complex object, such as connectome graphs, classical regression models cannot be used. The regression approach developed here to work with complex graph outcomes combines recursive partitioning with the Gibbs distribution. We will only discuss the application to connectomes, but the method is generally applicable to any graphical outcome. The method, called Gibbs-RPart, partitions the covariate space into a set of nonoverlapping regions such that the connectomes within regions are more similar than they are to the connectomes in other regions. This paper extends the object-oriented data analysis paradigm for graph-valued data based on the Gibbs distribution, which we have applied previously to hypothesis testing to compare populations of connectomes from distinct groups (see the work of La Rosa et al).


Subject(s)
Connectome/statistics & numerical data , Biostatistics , Brain/diagnostic imaging , Computer Simulation , Data Analysis , Humans , Likelihood Functions , Magnetic Resonance Imaging/statistics & numerical data , Models, Neurological , Models, Statistical , Parkinson Disease/diagnostic imaging , Regression Analysis
11.
J Math Biol ; 79(5): 1639-1663, 2019 10.
Article in English | MEDLINE | ID: mdl-31338567

ABSTRACT

We provide an analysis of a randomly grown 2-d network which models the morphological growth of dendritic and axonal arbors. From the stochastic geometry of this model we derive a dynamic graph of potential synaptic connections. We estimate standard network parameters such as degree distribution, average shortest path length and clustering coefficient, considering all these parameters as functions of time. Our results show that even a simple model with just a few parameters is capable of representing a wide spectra of architecture, capturing properties of well-known models, such as random graphs or small world networks, depending on the time of the network development. The introduced model allows not only rather straightforward simulations but it is also amenable to a rigorous analysis. This provides a base for further study of formation of synaptic connections on such networks and their dynamics due to plasticity.


Subject(s)
Connectome , Models, Neurological , Nerve Net/growth & development , Animals , Computer Simulation , Connectome/statistics & numerical data , Humans , Mathematical Concepts , Nerve Net/physiology , Neuronal Plasticity , Stochastic Processes
12.
Neuroimage ; 167: 11-22, 2018 02 15.
Article in English | MEDLINE | ID: mdl-29122720

ABSTRACT

Connectome-based predictive modeling (CPM; Finn et al., 2015; Shen et al., 2017) was recently developed to predict individual differences in traits and behaviors, including fluid intelligence (Finn et al., 2015) and sustained attention (Rosenberg et al., 2016a), from functional brain connectivity (FC) measured with fMRI. Here, using the CPM framework, we compared the predictive power of three different measures of FC (Pearson's correlation, accordance, and discordance) and two different prediction algorithms (linear and partial least square [PLS] regression) for attention function. Accordance and discordance are recently proposed FC measures that respectively track in-phase synchronization and out-of-phase anti-correlation (Meskaldji et al., 2015). We defined connectome-based models using task-based or resting-state FC data, and tested the effects of (1) functional connectivity measure and (2) feature-selection/prediction algorithm on individualized attention predictions. Models were internally validated in a training dataset using leave-one-subject-out cross-validation, and externally validated with three independent datasets. The training dataset included fMRI data collected while participants performed a sustained attention task and rested (N = 25; Rosenberg et al., 2016a). The validation datasets included: 1) data collected during performance of a stop-signal task and at rest (N = 83, including 19 participants who were administered methylphenidate prior to scanning; Farr et al., 2014a; Rosenberg et al., 2016b), 2) data collected during Attention Network Task performance and rest (N = 41, Rosenberg et al., in press), and 3) resting-state data and ADHD symptom severity from the ADHD-200 Consortium (N = 113; Rosenberg et al., 2016a). Models defined using all combinations of functional connectivity measure (Pearson's correlation, accordance, and discordance) and prediction algorithm (linear and PLS regression) predicted attentional abilities, with correlations between predicted and observed measures of attention as high as 0.9 for internal validation, and 0.6 for external validation (all p's < 0.05). Models trained on task data outperformed models trained on rest data. Pearson's correlation and accordance features generally showed a small numerical advantage over discordance features, while PLS regression models were usually better than linear regression models. Overall, in addition to correlation features combined with linear models (Rosenberg et al., 2016a), it is useful to consider accordance features and PLS regression for CPM.


Subject(s)
Attention/physiology , Brain/physiology , Connectome/standards , Executive Function/physiology , Magnetic Resonance Imaging/standards , Models, Statistical , Psychomotor Performance/physiology , Adult , Attention Deficit Disorder with Hyperactivity/diagnostic imaging , Attention Deficit Disorder with Hyperactivity/physiopathology , Brain/diagnostic imaging , Connectome/methods , Connectome/statistics & numerical data , Datasets as Topic , Humans , Magnetic Resonance Imaging/methods , Magnetic Resonance Imaging/statistics & numerical data , Reproducibility of Results , Young Adult
13.
Proc Natl Acad Sci U S A ; 112(21): E2820-8, 2015 May 26.
Article in English | MEDLINE | ID: mdl-25964365

ABSTRACT

In vivo tractography based on diffusion magnetic resonance imaging (dMRI) has opened new doors to study structure-function relationships in the human brain. Initially developed to map the trajectory of major white matter tracts, dMRI is used increasingly to infer long-range anatomical connections of the cortex. Because axonal projections originate and terminate in the gray matter but travel mainly through the deep white matter, the success of tractography hinges on the capacity to follow fibers across this transition. Here we demonstrate that the complex arrangement of white matter fibers residing just under the cortical sheet poses severe challenges for long-range tractography over roughly half of the brain. We investigate this issue by comparing dMRI from very-high-resolution ex vivo macaque brain specimens with histological analysis of the same tissue. Using probabilistic tracking from pure gray and white matter seeds, we found that ∼50% of the cortical surface was effectively inaccessible for long-range diffusion tracking because of dense white matter zones just beneath the infragranular layers of the cortex. Analysis of the corresponding myelin-stained sections revealed that these zones colocalized with dense and uniform sheets of axons running mostly parallel to the cortical surface, most often in sulcal regions but also in many gyral crowns. Tracer injection into the sulcal cortex demonstrated that at least some axonal fibers pass directly through these fiber systems. Current and future high-resolution dMRI studies of the human brain will need to develop methods to overcome the challenges posed by superficial white matter systems to determine long-range anatomical connections accurately.


Subject(s)
Diffusion Tensor Imaging/methods , Macaca mulatta/anatomy & histology , White Matter/anatomy & histology , Animals , Cerebral Cortex/anatomy & histology , Connectome/methods , Connectome/statistics & numerical data , Databases, Factual , Diffusion Tensor Imaging/statistics & numerical data , Gray Matter/anatomy & histology , Humans , Imaging, Three-Dimensional , Male , Models, Neurological , Neural Pathways/anatomy & histology
14.
Mol Psychiatry ; 21(7): 894-902, 2016 07.
Article in English | MEDLINE | ID: mdl-26416545

ABSTRACT

Depressive symptoms are common in multiple psychiatric disorders and are frequent sequelae of trauma. A dimensional conceptualization of depression suggests that symptoms should be associated with a continuum of deficits in specific neural circuits. However, most prior investigations of abnormalities in functional connectivity have typically focused on a single diagnostic category using hypothesis-driven seed-based analyses. Here, using a sample of 105 adult female participants from three diagnostic groups (healthy controls, n=17; major depression, n=38; and post-traumatic stress disorder, n=50), we examine the dimensional relationship between resting-state functional dysconnectivity and severity of depressive symptoms across diagnostic categories using a data-driven analysis (multivariate distance-based matrix regression). This connectome-wide analysis identified foci of dysconnectivity associated with depression severity in the bilateral amygdala. Follow-up seed analyses using subject-specific amygdala segmentations revealed that depression severity was associated with amygdalo-frontal hypo-connectivity in a network of regions including bilateral dorsolateral prefrontal cortex, anterior cingulate and anterior insula. In contrast, anxiety was associated with elevated connectivity between the amygdala and the ventromedial prefrontal cortex. Taken together, these results emphasize the centrality of the amygdala in the pathophysiology of depressive symptoms, and suggest that dissociable patterns of amygdalo-frontal dysconnectivity are a critical neurobiological feature across clinical diagnostic categories.


Subject(s)
Connectome/statistics & numerical data , Depression/physiopathology , Stress Disorders, Post-Traumatic/physiopathology , Adult , Amygdala/metabolism , Amygdala/physiopathology , Anxiety/metabolism , Anxiety/physiopathology , Anxiety Disorders/physiopathology , Cerebral Cortex/physiopathology , Connectome/methods , Depression/metabolism , Depressive Disorder, Major/physiopathology , Female , Functional Neuroimaging , Gyrus Cinguli/physiopathology , Humans , Magnetic Resonance Imaging/methods , Middle Aged , Neural Pathways/physiopathology , Prefrontal Cortex/physiopathology , Stress Disorders, Post-Traumatic/metabolism
15.
Neuroimage ; 133: 468-476, 2016 06.
Article in English | MEDLINE | ID: mdl-27034025

ABSTRACT

Aging is associated with declines in cognitive performance and multiple changes in the brain, including reduced default mode functional connectivity (FC). However, conflicting results have been reported regarding age differences in FC between hippocampal and default mode regions. This discrepancy may stem from the variation in selection of hippocampal regions. We therefore examined the effect of age on resting state FC of anterior and posterior hippocampal regions in an adult life-span sample. Advanced age was associated with lower FC between the posterior hippocampus and three regions: the posterior cingulate cortex, medial prefrontal cortex, and lateral parietal cortex. In addition, age-related reductions of FC between the left and right posterior hippocampus, and bilaterally along the posterior to anterior hippocampal axis were noted. Age differences in medial prefrontal and inter-hemispheric FC significantly differed between anterior and posterior hippocampus. Older age was associated with lower performance in all cognitive domains, but we observed no associations between FC and cognitive performance after controlling for age. We observed a significant effect of gender and a linear effect of COMT val158met polymorphism on hippocampal FC. Females showed higher FC of anterior and posterior hippocampus and medial prefrontal cortex than males, and the dose of val allele was associated with lower posterior hippocampus - posterior cingulate FC, independent of age. Vascular and metabolic factors showed no significant effects on FC. These results suggest differential age-related reduction in the posterior hippocampal FC compared to the anterior hippocampus, and an age-independent effect of gender and COMT on hippocampal FC.


Subject(s)
Aging , Cardiovascular Diseases/physiopathology , Catechol O-Methyltransferase/genetics , Cerebral Cortex/physiopathology , Hippocampus/physiopathology , Metabolic Diseases/physiopathology , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Cardiovascular Diseases/epidemiology , Comorbidity , Connectome/statistics & numerical data , Female , Genetic Predisposition to Disease/epidemiology , Genetic Predisposition to Disease/genetics , Humans , Male , Metabolic Diseases/epidemiology , Michigan/epidemiology , Middle Aged , Nerve Net/physiopathology , Neural Pathways/physiopathology , Prevalence , Risk Factors , Sex Distribution , Sex Factors , Young Adult
16.
Hum Brain Mapp ; 36(11): 4664-80, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26493163

ABSTRACT

Network properties can be estimated using functional connectivity MRI (fcMRI). However, regional variation of the fMRI signal causes systematic biases in network estimates including correlation attenuation in regions of low measurement reliability. Here we computed the spatial distribution of fcMRI reliability using longitudinal fcMRI datasets and demonstrated how pre-estimated reliability maps can correct for correlation attenuation. As a test case of reliability-based attenuation correction we estimated properties of the default network, where reliability was significantly lower than average in the medial temporal lobe and higher in the posterior medial cortex, heterogeneity that impacts estimation of the network. Accounting for this bias using attenuation correction revealed that the medial temporal lobe's contribution to the default network is typically underestimated. To render this approach useful to a greater number of datasets, we demonstrate that test-retest reliability maps derived from repeated runs within a single scanning session can be used as a surrogate for multi-session reliability mapping. Using data segments with different scan lengths between 1 and 30 min, we found that test-retest reliability of connectivity estimates increases with scan length while the spatial distribution of reliability is relatively stable even at short scan lengths. Finally, analyses of tertiary data revealed that reliability distribution is influenced by age, neuropsychiatric status and scanner type, suggesting that reliability correction may be especially important when studying between-group differences. Collectively, these results illustrate that reliability-based attenuation correction is an easily implemented strategy that mitigates certain features of fMRI signal nonuniformity.


Subject(s)
Connectome/statistics & numerical data , Data Interpretation, Statistical , Magnetic Resonance Imaging/statistics & numerical data , Nerve Net/physiology , Adult , Connectome/methods , Connectome/standards , Female , Humans , Magnetic Resonance Imaging/methods , Magnetic Resonance Imaging/standards , Male , Middle Aged , Reproducibility of Results , Young Adult
17.
J Neurosci ; 33(15): 6380-7, 2013 Apr 10.
Article in English | MEDLINE | ID: mdl-23575836

ABSTRACT

There is increasing interest in topological analysis of brain networks as complex systems, with researchers often using neuroimaging to represent the large-scale organization of nervous systems without precise cellular resolution. Here we used graph theory to investigate the neuronal connectome of the nematode worm Caenorhabditis elegans, which is defined anatomically at a cellular scale as 2287 synaptic connections between 279 neurons. We identified a small number of highly connected neurons as a rich club (N = 11) interconnected with high efficiency and high connection distance. Rich club neurons comprise almost exclusively the interneurons of the locomotor circuits, with known functional importance for coordinated movement. The rich club neurons are connector hubs, with high betweenness centrality, and many intermodular connections to nodes in different modules. On identifying the shortest topological paths (motifs) between pairs of peripheral neurons, the motifs that are found most frequently traverse the rich club. The rich club neurons are born early in development, before visible movement of the animal and before the main phase of developmental elongation of its body. We conclude that the high wiring cost of the globally integrative rich club of neurons in the C. elegans connectome is justified by the adaptive value of coordinated movement of the animal. The economical trade-off between physical cost and behavioral value of rich club organization in a cellular connectome confirms theoretical expectations and recapitulates comparable results from human neuroimaging on much larger scale networks, suggesting that this may be a general and scale-invariant principle of brain network organization.


Subject(s)
Brain/physiology , Caenorhabditis elegans , Connectome/statistics & numerical data , Neurons/physiology , Animals , Brain/growth & development , Models, Neurological , Neural Pathways/physiology
18.
Neuroimage ; 84: 133-40, 2014 Jan 01.
Article in English | MEDLINE | ID: mdl-23994315

ABSTRACT

Interest has recently grown in multi-center studies, which have more power than smaller studies in conducting sophisticated evaluations of basic neuroanatomy and neurodegenerative disorders. The large number of subjects that result from pooling multi-center datasets increases sensitivity, but also introduces a between-center variance component. Taking sex differences as an example, we examined the effects of different ratios of cases to controls (males to females) between scanners in multi-scanner morphometric studies, using voxel-based morphometry and data obtained on two scanners of the exact same model. Each subject was scanned twice with both scanners. Using the image obtained on either of the two scanners for each subject, voxel-based analyses were repeated with different ratios of males to females for each scanner. As the ratio of males to females became more imbalanced between the scanners, the differences between the two scanners more strongly affected the results of analyses of sex differences. When the ratio of males to females was balanced, the inclusion of scanner as a covariate in the statistical analysis had almost no influence on the results of analyses of sex differences. When the ratio of males to females was ill-balanced, the inclusion of scanner as a covariate suppressed scanner effects on the results, but made sex differences less likely to become significant. The present results suggest that as long as the ratio of cases to controls is well-balanced across different scanners, it is not always necessary to include scanner as a covariate in the statistical analysis, and that when the ratio of cases to controls is ill-balanced across scanners, the inclusion of scanner as a covariate in the statistical analysis can suppress scanner effects, but may make differences less likely to be detected.


Subject(s)
Brain/anatomy & histology , Connectome/instrumentation , Connectome/statistics & numerical data , Diffusion Tensor Imaging/instrumentation , Diffusion Tensor Imaging/statistics & numerical data , Multicenter Studies as Topic/statistics & numerical data , Aged , Equipment Design , Equipment Failure Analysis/statistics & numerical data , Female , Humans , Japan , Male , Middle Aged , Reproducibility of Results , Sensitivity and Specificity , Sex Distribution
19.
Neuroimage ; 80: 246-62, 2013 Oct 15.
Article in English | MEDLINE | ID: mdl-23631983

ABSTRACT

As researchers increase their efforts to characterize variations in the functional connectome across studies and individuals, concerns about the many sources of nuisance variation present and their impact on resting state fMRI (R-fMRI) measures continue to grow. Although substantial within-site variation can exist, efforts to aggregate data across multiple sites such as the 1000 Functional Connectomes Project (FCP) and International Neuroimaging Data-sharing Initiative (INDI) datasets amplify these concerns. The present work draws upon standardization approaches commonly used in the microarray gene expression literature, and to a lesser extent recent imaging studies, and compares them with respect to their impact on relationships between common R-fMRI measures and nuisance variables (e.g., imaging site, motion), as well as phenotypic variables of interest (age, sex). Standardization approaches differed with regard to whether they were applied post-hoc vs. during pre-processing, and at the individual vs. group level; additionally they varied in whether they addressed additive effects vs. additive+multiplicative effects, and were parametric vs. non-parametric. While all standardization approaches were effective at reducing undesirable relationships with nuisance variables, post-hoc approaches were generally more effective than global signal regression (GSR). Across approaches, correction for additive effects (global mean) appeared to be more important than for multiplicative effects (global SD) for all R-fMRI measures, with the exception of amplitude of low frequency fluctuations (ALFF). Group-level post-hoc standardizations for mean-centering and variance-standardization were found to be advantageous in their ability to avoid the introduction of artifactual relationships with standardization parameters; though results between individual and group-level post-hoc approaches were highly similar overall. While post-hoc standardization procedures drastically increased test-retest (TRT) reliability for ALFF, modest reductions were observed for other measures after post-hoc standardizations-a phenomena likely attributable to the separation of voxel-wise from global differences among subjects (global mean and SD demonstrated moderate TRT reliability for these measures). Finally, the present work calls into question previous observations of increased anatomical specificity for GSR over mean centering, and draws attention to the near equivalence of global and gray matter signal regression.


Subject(s)
Brain/physiology , Connectome/statistics & numerical data , Connectome/standards , Magnetic Resonance Imaging/statistics & numerical data , Magnetic Resonance Imaging/standards , Animals , Brain/anatomy & histology , Data Interpretation, Statistical , Humans , Models, Anatomic , Models, Neurological , Nerve Net/anatomy & histology , Nerve Net/physiology , Reference Values , Reproducibility of Results , Sensitivity and Specificity
20.
Comput Math Methods Med ; 2022: 1124927, 2022.
Article in English | MEDLINE | ID: mdl-35273647

ABSTRACT

Substantial information related to human cerebral conditions can be decoded through various noninvasive evaluating techniques like fMRI. Exploration of the neuronal activity of the human brain can divulge the thoughts of a person like what the subject is perceiving, thinking, or visualizing. Furthermore, deep learning techniques can be used to decode the multifaceted patterns of the brain in response to external stimuli. Existing techniques are capable of exploring and classifying the thoughts of the human subject acquired by the fMRI imaging data. fMRI images are the volumetric imaging scans which are highly dimensional as well as require a lot of time for training when fed as an input in the deep learning network. However, the hassle for more efficient learning of highly dimensional high-level features in less training time and accurate interpretation of the brain voxels with less misclassification error is needed. In this research, we propose an improved CNN technique where features will be functionally aligned. The optimal features will be selected after dimensionality reduction. The highly dimensional feature vector will be transformed into low dimensional space for dimensionality reduction through autoadjusted weights and combination of best activation functions. Furthermore, we solve the problem of increased training time by using Swish activation function, making it denser and increasing efficiency of the model in less training time. Finally, the experimental results are evaluated and compared with other classifiers which demonstrated the supremacy of the proposed model in terms of accuracy.


Subject(s)
Brain Mapping/statistics & numerical data , Brain/diagnostic imaging , Deep Learning , Functional Neuroimaging/statistics & numerical data , Magnetic Resonance Imaging/statistics & numerical data , Computational Biology , Connectome/statistics & numerical data , Databases, Factual , Humans , Imaging, Three-Dimensional/statistics & numerical data , Neural Networks, Computer
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