RESUMEN
Temporal lobe epilepsy (TLE) is the most common epilepsy syndrome that empirically represents a network disorder, which makes graph theory (GT) a practical approach to understand it. Multi-shell diffusion-weighted imaging (DWI) was obtained from 89 TLE and 50 controls. GT measures extracted from harmonized DWI matrices were used as factors in a support vector machine (SVM) analysis to discriminate between groups, and in a k-means algorithm to find intrinsic structural phenotypes within TLE. SVM was able to predict group membership (mean accuracy = 0.70, area under the curve (AUC) = 0.747, Brier score (BS) = 0.264) using 10-fold cross-validation. In addition, k-means clustering identified 2 TLE clusters: 1 similar to controls, and 1 dissimilar. Clusters were significantly different in their distribution of cognitive phenotypes, with the Dissimilar cluster containing the majority of TLE with cognitive impairment (χ2 = 6.641, P = 0.036). In addition, cluster membership showed significant correlations between GT measures and clinical variables. Given that SVM classification seemed driven by the Dissimilar cluster, SVM analysis was repeated to classify Dissimilar versus Similar + Controls with a mean accuracy of 0.91 (AUC = 0.957, BS = 0.189). Altogether, the pattern of results shows that GT measures based on connectome DWI could be significant factors in the search for clinical and neurobehavioral biomarkers in TLE.
Asunto(s)
Conectoma , Epilepsia del Lóbulo Temporal , Humanos , Epilepsia del Lóbulo Temporal/diagnóstico por imagen , Conectoma/métodos , Imagen de Difusión por Resonancia Magnética , Cognición , Imagen por Resonancia Magnética/métodosRESUMEN
Persistent homology offers a powerful tool for extracting hidden topological signals from brain networks. It captures the evolution of topological structures across multiple scales, known as filtrations, thereby revealing topological features that persist over these scales. These features are summarized in persistence diagrams, and their dissimilarity is quantified using the Wasserstein distance. However, the Wasserstein distance does not follow a known distribution, posing challenges for the application of existing parametric statistical models. To tackle this issue, we introduce a unified topological inference framework centered on the Wasserstein distance. Our approach has no explicit model and distributional assumptions. The inference is performed in a completely data driven fashion. We apply this method to resting-state functional magnetic resonance images (rs-fMRI) of temporal lobe epilepsy patients collected from two different sites: the University of Wisconsin-Madison and the Medical College of Wisconsin. Importantly, our topological method is robust to variations due to sex and image acquisition, obviating the need to account for these variables as nuisance covariates. We successfully localize the brain regions that contribute the most to topological differences. A MATLAB package used for all analyses in this study is available at https://github.com/laplcebeltrami/PH-STAT.
Asunto(s)
Epilepsia del Lóbulo Temporal , Humanos , Epilepsia del Lóbulo Temporal/diagnóstico por imagen , Red Nerviosa/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Modelos EstadísticosRESUMEN
OBJECTIVE: Social determinants of health, including the effects of neighborhood disadvantage, impact epilepsy prevalence, treatment, and outcomes. This study characterized the association between aberrant white matter connectivity in temporal lobe epilepsy (TLE) and disadvantage using a US census-based neighborhood disadvantage metric, the Area Deprivation Index (ADI), derived from measures of income, education, employment, and housing quality. METHODS: Participants including 74 TLE patients (47 male, mean age = 39.2 years) and 45 healthy controls (27 male, mean age = 31.9 years) from the Epilepsy Connectome Project were classified into ADI-defined low and high disadvantage groups. Graph theoretic metrics were applied to multishell connectome diffusion-weighted imaging (DWI) measurements to derive 162 × 162 structural connectivity matrices (SCMs). The SCMs were harmonized using neuroCombat to account for interscanner differences. Threshold-free network-based statistics were used for analysis, and findings were correlated with ADI quintile metrics. A decrease in cross-sectional area (CSA) indicates reduced white matter integrity. RESULTS: Sex- and age-adjusted CSA in TLE groups was significantly reduced compared to controls regardless of disadvantage status, revealing discrete aberrant white matter tract connectivity abnormalities in addition to apparent differences in graph measures of connectivity and network-based statistics. When comparing broadly defined disadvantaged TLE groups, differences were at trend level. Sensitivity analyses of ADI quintile extremes revealed significantly lower CSA in the most compared to least disadvantaged TLE group. SIGNIFICANCE: Our findings demonstrate (1) the general impact of TLE on DWI connectome status is larger than the association with neighborhood disadvantage; however, (2) neighborhood disadvantage, indexed by ADI, revealed modest relationships with white matter structure and integrity on sensitivity analysis in TLE. Further studies are needed to explore this relationship and determine whether the white matter relationship with ADI is driven by social drift or environmental influences on brain development. Understanding the etiology and course of the disadvantage-brain integrity relationship may serve to inform care, management, and policy for patients.
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Conectoma , Epilepsia del Lóbulo Temporal , Sustancia Blanca , Humanos , Masculino , Adulto , Epilepsia del Lóbulo Temporal/diagnóstico por imagen , Epilepsia del Lóbulo Temporal/epidemiología , Conectoma/métodos , Sustancia Blanca/diagnóstico por imagen , Imagen de Difusión Tensora/métodos , Encéfalo/diagnóstico por imagenRESUMEN
Temporal lobe epilepsy (TLE) has been conceptualized as focal disease with a discrete neurobiological focus and can respond well to targeted resection or ablation. In contrast, the neuro-cognitive deficits resulting from TLE can be widespread involving regions beyond the primary epileptic network. We hypothesize that this seemingly paradoxical findings can be explained by differences in connectivity between the primary epileptic region which is hyper-connected and its secondary influence on global connectome organization. This hypothesis is tested using regional and global graph theory metrics where we anticipate that regional mesial-temporal hyperconnectivity will be found and correlate with seizure frequency while global networks will be disorganized and be more closely associated with neuro-cognitive deficits. Resting-state fMRI was used to examine temporal lobe regional connectivity and global functional connectivity from 102 patients with TLE and 55 controls. Connectivity matrices were calculated for subcortical volumes and cortical parcellations. Graph theory metrics (global clustering coefficient (GCC), degree, closeness) were compared between groups and in relation to neuropsychological profiles and disease covariates using permutation testing and causal analysis. In TLE there was a decrease in GCC (pâ¯=â¯0.0345) associated with a worse neuropsychological profile (pâ¯=â¯0.0134). There was increased connectivity in the left hippocampus/amygdala (degree pâ¯=â¯0.0103, closeness pâ¯=â¯0.0104) and a decrease in connectivity in the right lateral temporal lobe (degree pâ¯=â¯0.0186, closeness pâ¯=â¯0.0122). A ratio between the hippocampus/amygdala and lateral temporal lobe-temporal lobe connectivity ratio (TLCR) revealed differences between TLE and controls for closeness (left pâ¯=â¯0.00149, right pâ¯=â¯0.0494) and for degree on left pâ¯=â¯0.00169; with trend on right pâ¯=â¯0.0567. Causal analysis suggested that "Epilepsy Activity" (seizure frequency, anti-seizure medications) was associated with increase in TLCR but not in GCC, while cognitive decline was associated with decreased GCC. These findings support the hypothesis that in TLE there is hyperconnectivity in the hippocampus/amygdala and hypoconnectivity in the lateral temporal lobe associated with "Epilepsy Activity." While, global connectome disorganization was associated with worse neuropsychological phenotype.
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Conectoma , Epilepsia del Lóbulo Temporal , Epilepsia del Lóbulo Temporal/diagnóstico por imagen , Lateralidad Funcional , Hipocampo , Humanos , Imagen por Resonancia Magnética , Red Nerviosa/diagnóstico por imagen , Lóbulo TemporalRESUMEN
Retinotopic organization is a fundamental feature of visual cortex thought to play a vital role in encoding spatial information. One important aspect of normal retinotopy is the representation of the right and left hemifields in contralateral visual cortex. However, in human albinism, many temporal retinal afferents decussate aberrantly at the optic chiasm resulting in partially superimposed representations of opposite hemifields in each hemisphere of visual cortex. Previous functional magnetic resonance imaging (fMRI) studies in human albinism suggest that the right and left hemifield representations are superimposed in a mirror-symmetric manner. This should produce imaging voxels which respond to two separate locations mirrored across the vertical meridian. However, it is not yet clear how retino-cortical miswiring in albinism manifests at the level of single voxel population receptive fields (pRFs). Here, we used pRF modeling to fit both single and dual pRF models to the visual responses of voxels in visual areas V1 to V3 of five subjects with albinism. We found that subjects with albinism (but not controls) have sizable clusters of voxels with unequivocal dual pRFs consistently corresponding to, but not fully coextensive with, regions of hemifield overlap. These dual pRFs were typically positioned at locations roughly mirrored across the vertical meridian and were uniquely clustered within a portion of the visual field for each subject.
Asunto(s)
Albinismo , Corteza Visual , Mapeo Encefálico , Humanos , Imagen por Resonancia Magnética , Quiasma Óptico , Corteza Visual/diagnóstico por imagen , Campos Visuales , Vías VisualesRESUMEN
Neuroticism, a core personality trait characterized by a tendency towards experiencing negative affect, has been reported to be higher in people with temporal lobe epilepsy (TLE) compared with healthy individuals. Neuroticism is a known predictor of depression and anxiety, which also occur more frequently in people with TLE. The purpose of this study was to identify abnormalities in whole-brain resting-state functional connectivity in relation to neuroticism in people with TLE and to determine the degree of unique versus shared patterns of abnormal connectivity in relation to elevated symptoms of depression and anxiety. Ninety-three individuals with TLE (55 females) and 40 healthy controls (18 females) from the Epilepsy Connectome Project (ECP) completed measures of neuroticism, depression, and anxiety, which were all significantly higher in people with TLE compared with controls. Resting-state functional connectivity was compared between controls and groups with TLE with high and low neuroticism using analysis of variance (ANOVA) and t-test. In secondary analyses, the same analytics were performed using measures of depression and anxiety and the unique variance in resting-state connectivity associated with neuroticism independent of symptoms of depression and anxiety identified. Increased neuroticism was significantly associated with hyposynchrony between the right hippocampus and Brodmann area (BA) 9 (region of prefrontal cortex (PFC)) (pâ¯<â¯0.005), representing a unique relationship independent of symptoms of depression and anxiety. Hyposynchrony of connection between the right hippocampus and BA47 (anterior frontal operculum) was associated with high neuroticism and with higher depression and anxiety scores (pâ¯<â¯0.05), making it a shared abnormal connection for the three measures. In conclusion, increased neuroticism exhibits both unique and shared patterns of abnormal functional connectivity with depression and anxiety symptoms between regions of the mesial temporal and frontal lobe.
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Epilepsia del Lóbulo Temporal/diagnóstico por imagen , Lóbulo Frontal/diagnóstico por imagen , Sistema Límbico/diagnóstico por imagen , Red Nerviosa/diagnóstico por imagen , Neuroticismo/fisiología , Lóbulo Temporal/diagnóstico por imagen , Adulto , Conectoma/métodos , Epilepsia del Lóbulo Temporal/fisiopatología , Femenino , Lóbulo Frontal/fisiopatología , Lateralidad Funcional/fisiología , Humanos , Sistema Límbico/fisiopatología , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Red Nerviosa/fisiopatología , Descanso/fisiología , Lóbulo Temporal/fisiopatologíaRESUMEN
The human fovea lies at the center of the retina and supports high-acuity vision. In normal visual system development, the highest acuity is correlated with both a high density of cone photoreceptors in the fovea and a magnified retinotopic representation of the fovea in the visual cortex. Both cone density and the cortical area dedicated to each degree of visual space-the latter describing cortical magnification (CM)-steadily decrease with increasing eccentricity from the fovea. In albinism, peak cone density at the fovea and visual acuity are decreased, but seem to be within normal limits in the periphery, thus providing a model to explore the correlation between retinal structure, cortical structure, and behavior. Here, we used adaptive optics scanning light ophthalmoscopy to assess retinal cone density and functional magnetic resonance imaging to measure CM in the primary visual cortex of normal controls and individuals with albinism. We find that retinotopic organization is more varied among individuals with albinism than previously appreciated. Additionally, CM outside the fovea is similar to that in controls, but also more variable. CM in albinism and controls exceeds that which might be predicted based on cone density alone, but is more accurately predicted by retinal ganglion cell density. This finding suggests that decreased foveal cone density in albinism may be partially counteracted by nonuniform connectivity between cones and their downstream signaling partners. Together, these results emphasize that central as well as retinal factors must be included to provide a complete picture of aberrant structure and function in albinism.
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Albinismo/fisiopatología , Células Fotorreceptoras Retinianas Conos/fisiología , Corteza Visual/fisiología , Adolescente , Adulto , Recuento de Células , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Oftalmoscopía/métodos , Óptica y Fotónica , Retina/fisiología , Células Fotorreceptoras Retinianas Conos/citología , Células Ganglionares de la Retina/fisiología , Agudeza Visual/fisiología , Adulto JovenRESUMEN
Behavioral and personality disorders in temporal lobe epilepsy (TLE) have been a topic of interest and controversy for decades, with less attention paid to alterations in normal personality structure and traits. In this investigation, core personality traits (the Big 5) and their neurobiological correlates in TLE were explored using the Neuroticism Extraversion Openness-Five Factor Inventory (NEO-FFI) and structural magnetic resonance imaging (MRI) through the Epilepsy Connectome Project (ECP). NEO-FFI scores from 67 individuals with TLE (34.6⯱â¯9.5â¯years; 67% women) were compared to 31 healthy controls (32.8⯱â¯8.9â¯years; 41% women) to assess differences in the Big 5 traits (agreeableness, openness, conscientiousness, neuroticism, and extraversion). Individuals with TLE showed significantly higher neuroticism, with no significant differences on the other traits. Neural correlates of neuroticism were then determined in participants with TLE including cortical and subcortical volumes. Distributed reductions in cortical gray matter volumes were associated with increased neuroticism. Subcortically, hippocampal and amygdala volumes were negatively associated with neuroticism. These results offer insight into alterations in the Big 5 personality traits in TLE and their brain-related correlates.
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Encéfalo/diagnóstico por imagen , Conectoma/métodos , Epilepsia del Lóbulo Temporal/diagnóstico por imagen , Neuroticismo , Inventario de Personalidad , Adulto , Amígdala del Cerebelo/diagnóstico por imagen , Amígdala del Cerebelo/fisiología , Encéfalo/fisiología , Epilepsia del Lóbulo Temporal/psicología , Femenino , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/fisiología , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Neuroticismo/fisiología , Personalidad/fisiologíaRESUMEN
It remains unclear to what extent retinotopic maps can undergo large-scale plasticity following damage to human visual cortex. The literature has predominately focused on retinotopic changes in patients with retinal pathologies or congenital brain malformations. Yet, damage to the adult visual cortex itself is common in cases such as stroke, tumor, or trauma. To address this issue, we used a unique database of fMRI vision maps in patients with adult-onset (n=25) and congenital (n=2) pathology of the visual cortex. We identified atypical retinotopic organization in three patients (two with adult-onset, and one with congenital pathology) consisting of an expanded ipsilateral field representation that was on average 3.2 times greater than healthy controls. The expanded representations were located at the vertical meridian borders between visual areas such as V1/V2. Additionally, two of the three patients had apparently an ectopic (topographically inconsistent) representation of the ipsilateral field within lateral occipital cortex that is normally associated with visual areas V3/V3A (and possibly other areas). Both adult-onset cases had direct damage to early visual cortex itself (rather than to the afferent drive only), resulting in a mostly nonfunctional hemisphere. The congenital case had severe cortical malformation of the visual cortex and was acallosal. Our results are consistent with a competitive model in which unilateral damage to visual cortex or disruption of the transcallosal connections removes interhemispheric suppression from retino-geniculate afferents in intact visual cortex that represent the vertical meridian and ipsilateral visual field.
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Daño Encefálico Crónico/congénito , Daño Encefálico Crónico/patología , Mapeo Encefálico , Retina/patología , Corteza Visual/patología , Vías Visuales/patología , Adulto , Anciano , Daño Encefálico Crónico/fisiopatología , Femenino , Lateralidad Funcional , Humanos , Procesamiento de Imagen Asistido por Computador , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Modelos Neurológicos , Oxígeno/sangre , Tomografía de Coherencia Óptica , Corteza Visual/irrigación sanguínea , Pruebas del Campo Visual , Campos Visuales/fisiología , Vías Visuales/irrigación sanguínea , Adulto JovenRESUMEN
Recent studies have demonstrated significant regional variability in the hemodynamic response function (HRF), highlighting the difficulty of correctly interpreting functional MRI (fMRI) data without proper modeling of the HRF. The focus of this study was to investigate the HRF variability within visual cortex. The HRF was estimated for a number of cortical visual areas by deconvolution of fMRI blood oxygenation level dependent (BOLD) responses to brief, large-field visual stimulation. Significant HRF variation was found across visual areas V1, V2, V3, V4, VO-1,2, V3AB, IPS-0,1,2,3, LO-1,2, and TO-1,2. Additionally, a subpopulation of voxels was identified that exhibited an impulse response waveform that was similar, but not identical, to an inverted version of the commonly described and modeled positive HRF. These voxels were found within the retinotopic confines of the stimulus and were intermixed with those showing positive responses. The spatial distribution and variability of these HRFs suggest a vascular origin for the inverted waveforms. We suggest that the polarity of the HRF is a separate factor that is independent of the suppressive or activating nature of the underlying neuronal activity. Correctly modeling the polarity of the HRF allows one to recover an estimate of the underlying neuronal activity rather than discard the responses from these voxels on the assumption that they are artifactual. We demonstrate this approach on phase-encoded retinotopic mapping data as an example of the benefits of accurately modeling the HRF during the analysis of fMRI data.
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Hemodinámica/fisiología , Corteza Visual/irrigación sanguínea , Corteza Visual/fisiología , Vías Visuales/irrigación sanguínea , Vías Visuales/fisiología , Adulto , Mapeo Encefálico , Circulación Cerebrovascular , Lateralidad Funcional , Humanos , Interpretación de Imagen Asistida por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Oxígeno/sangre , Estimulación Luminosa , Tiempo de Reacción/fisiologíaRESUMEN
Albinism is an inherited disorder characterized by disrupted melanin production in the eye, and often in the skin and hair. This retinal hypopigmentation is accompanied by pathological decussation of many temporal retinal afferents at the optic chiasm during development, ultimately resulting in partially superimposed representations of opposite visual hemifields in each cortical hemisphere. Within these aberrant regions of hemifield overlap, individual voxels have been shown to have bilateral, dual population receptive fields (pRFs) responding to roughly mirror-image locations across the vertical meridian. Nonetheless, how these two conflicting inputs combine to determine a voxel's response to image contrast is still unknown. To address this, we stimulated the right and left hemifields with separately controlled sinusoidal gratings, each having a variety of contrasts (0, 8, 20, 45, 100%), and extracted voxel-wise BOLD response amplitudes to each contrast combination in visual areas V1-V3. We then compared voxels' responses to each hemifield stimulated individually with conditions when both hemifields were stimulated simultaneously. We hypothesized that simultaneous stimulation of the two pRF components will result in either a suppressive or facilitative interaction. However, we found that BOLD responses to simultaneous stimulation appeared to reflect simple summation of the neural activity from the individual hemifield conditions. This suggests that the superimposed opposite hemifield representations do not interact. Thus, dual pRFs in albinism likely reflect two co-localized, but functionally independent populations of neurons each of which respond to a single hemifield. This finding is commensurate with psychophysical studies which have shown no clear perceptual interaction between opposite visual hemifields in human albinism.
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We introduce a novel, data-driven topological data analysis (TDA) approach for embedding brain networks into a lower-dimensional space in quantifying the dynamics of temporal lobe epilepsy (TLE) obtained from resting-state functional magnetic resonance imaging (rs-fMRI). This embedding facilitates the orthogonal projection of 0D and 1D topological features, allowing for the visualization and modeling of the dynamics of functional human brain networks in a resting state. We then quantify the topological disparities between networks to determine the coordinates for embedding. This framework enables us to conduct a coherent statistical inference within the embedded space. Our results indicate that brain network topology in TLE patients exhibits increased rigidity in 0D topology but more rapid flections compared to that of normal controls in 1D topology.
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INTRODUCTION: Emerging evidence illustrates that temporal lobe epilepsy (TLE) involves network disruptions represented by hyperexcitability and other seizure-related neural plasticity. However, these associations are not well-characterized. Our study characterizes the whole brain white matter connectome abnormalities in TLE patients compared to healthy controls (HCs) from the prospective Epilepsy Connectome Project study. Furthermore, we assessed whether aberrant white matter connections are differentially related to cognitive impairment and a history of focal-to-bilateral tonic-clonic (FBTC) seizures. METHODS: Multi-shell connectome MRI data were preprocessed using the DESIGNER guidelines. The IIT Destrieux gray matter atlas was used to derive the 162 × 162 structural connectivity matrices (SCMs) using MRTrix3. ComBat data harmonization was applied to harmonize the SCMs from pre- and post-scanner upgrade acquisitions. Threshold-free network-based statistics were used for statistical analysis of the harmonized SCMs. Cognitive impairment status and FBTC seizure status were then correlated with these findings. RESULTS: We employed connectome measurements from 142 subjects, including 92 patients with TLE (36 males, mean age = 40.1 ± 11.7 years) and 50 HCs (25 males, mean age = 32.6 ± 10.2 years). Our analysis revealed overall significant decreases in cross-sectional area (CSA) of the white matter tract in TLE group compared to controls, indicating decreased white matter tract integrity and connectivity abnormalities in addition to apparent differences in graph theoretic measures of connectivity and network-based statistics. Focal and generalized cognitive impaired TLE patients showcased higher trend-level abnormalities in the white matter connectome via decreased CSA than those with no cognitive impairment. Patients with a positive FBTC seizure history also showed trend-level findings of association via decreased CSA. CONCLUSIONS: Widespread global aberrant white matter connectome changes were observed in TLE patients and characterized by seizure history and cognitive impairment, laying a foundation for future studies to expand on and validate the novel biomarkers and further elucidate TLE's impact on brain plasticity.
Asunto(s)
Conectoma , Epilepsia del Lóbulo Temporal , Imagen por Resonancia Magnética , Sustancia Blanca , Humanos , Epilepsia del Lóbulo Temporal/diagnóstico por imagen , Epilepsia del Lóbulo Temporal/fisiopatología , Epilepsia del Lóbulo Temporal/patología , Masculino , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Femenino , Adulto , Persona de Mediana Edad , Disfunción Cognitiva/fisiopatología , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/etiología , Disfunción Cognitiva/patología , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/fisiopatología , Red Nerviosa/patología , Estudios Prospectivos , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Encéfalo/fisiopatologíaRESUMEN
Persistent homology offers a powerful tool for extracting hidden topological signals from brain networks. It captures the evolution of topological structures across multiple scales, known as filtrations, thereby revealing topological features that persist over these scales. These features are summarized in persistence diagrams, and their dissimilarity is quantified using the Wasserstein distance. However, the Wasserstein distance does not follow a known distribution, posing challenges for the application of existing parametric statistical models. To tackle this issue, we introduce a unified topological inference framework centered on the Wasserstein distance. Our approach has no explicit model and distributional assumptions. The inference is performed in a completely data driven fashion. We apply this method to resting-state functional magnetic resonance images (rs-fMRI) of temporal lobe epilepsy patients collected from two different sites: the University of Wisconsin-Madison and the Medical College of Wisconsin. Importantly, our topological method is robust to variations due to sex and image acquisition, obviating the need to account for these variables as nuisance covariates. We successfully localize the brain regions that contribute the most to topological differences. A MATLAB package used for all analyses in this study is available at https://github.com/laplcebeltrami/PH-STAT.
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Short-range functional connectivity in the limbic network is increased in patients with temporal lobe epilepsy (TLE), and recent studies have shown that cortical myelin content correlates with fMRI connectivity. We thus hypothesized that myelin may increase progressively in the epileptic network. We compared T1w/T2w gray matter myelin maps between TLE patients and age-matched controls and assessed relationships between myelin and aging. While both TLE patients and healthy controls exhibited increased T1w/T2w intensity with age, we found no evidence for significant group-level aberrations in overall myelin content or myelin changes through time in TLE.
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Epilepsia del Lóbulo Temporal , Sustancia Gris , Humanos , Sustancia Gris/diagnóstico por imagen , Epilepsia del Lóbulo Temporal/diagnóstico por imagen , Envejecimiento , Imagen por Resonancia Magnética , Vaina de MielinaRESUMEN
Machine learning analyses were performed on graph theory (GT) metrics extracted from brain functional and morphological data from temporal lobe epilepsy (TLE) patients in order to identify intrinsic network phenotypes and characterize their clinical significance. Participants were 97 TLE and 36 healthy controls from the Epilepsy Connectome Project. Each imaging modality (i.e., Resting-state functional Magnetic Resonance Imaging (RS-fMRI), and structural MRI) rendered 2 clusters: one comparable to controls and one deviating from controls. Participants were minimally overlapping across the identified clusters, suggesting that an abnormal functional GT phenotype did not necessarily mean an abnormal morphological GT phenotype for the same subject. Morphological clusters were associated with a significant difference in the estimated lifetime number of generalized tonic-clonic seizures and functional cluster membership was associated with age. Furthermore, controls exhibited significant correlations between functional GT metrics and cognition, while for TLE participants morphological GT metrics were linked to cognition, suggesting a dissociation between higher cognitive abilities and GT-derived network measures. Overall, these findings demonstrate the existence of clinically meaningful minimally overlapping phenotypes of morphological and functional GT networks. Functional network properties may underlie variance in cognition in healthy brains, but in the pathological state of epilepsy the cognitive limits might be primarily related to structural cerebral network properties.
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Conectoma , Epilepsia del Lóbulo Temporal , Encéfalo/diagnóstico por imagen , Conectoma/métodos , Epilepsia del Lóbulo Temporal/diagnóstico por imagen , Humanos , Aprendizaje Automático , Imagen por Resonancia Magnética/métodos , FenotipoRESUMEN
Functional magnetic resonance imaging for presurgical brain mapping enables neurosurgeons to identify viable tissue near a site of operable pathology which might be at risk of surgery-induced damage. However, focal brain pathology (e.g., tumors) may selectively disrupt neurovascular coupling while leaving the underlying neurons functionally intact. Such neurovascular uncoupling can result in false negatives on brain activation maps thereby compromising their use for surgical planning. One way to detect potential neurovascular uncoupling is to map cerebrovascular reactivity using either an active breath-hold challenge or a passive resting-state scan. The equivalence of these two methods has yet to be fully established, especially at a voxel level of resolution. To quantitatively compare breath-hold and resting-state maps of cerebrovascular reactivity, we first identified threshold settings that optimized coverage of gray matter while minimizing false responses in white matter. When so optimized, the resting-state metric had moderately better gray matter coverage and specificity. We then assessed the spatial correspondence between the two metrics within cortical gray matter, again, across a wide range of thresholds. Optimal spatial correspondence was strongly dependent on threshold settings which if improperly set tended to produce statistically biased maps. When optimized, the two CVR maps did have moderately good correspondence with each other (mean accuracy of 73.6%). Our results show that while the breath-hold and resting-state maps may appear qualitatively similar they are not quantitatively identical at a voxel level of resolution.
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This study explored the taxonomy of cognitive impairment within temporal lobe epilepsy and characterized the sociodemographic, clinical and neurobiological correlates of identified cognitive phenotypes. 111 temporal lobe epilepsy patients and 83 controls (mean ages 33 and 39, 57% and 61% female, respectively) from the Epilepsy Connectome Project underwent neuropsychological assessment, clinical interview, and high resolution 3T structural and resting-state functional MRI. A comprehensive neuropsychological test battery was reduced to core cognitive domains (language, memory, executive, visuospatial, motor speed) which were then subjected to cluster analysis. The resulting cognitive subgroups were compared in regard to sociodemographic and clinical epilepsy characteristics as well as variations in brain structure and functional connectivity. Three cognitive subgroups were identified (intact, language/memory/executive function impairment, generalized impairment) which differed significantly, in a systematic fashion, across multiple features. The generalized impairment group was characterized by an earlier age at medication initiation (P < 0.05), fewer patient (P < 0.001) and parental years of education (P < 0.05), greater racial diversity (P < 0.05), and greater number of lifetime generalized seizures (P < 0.001). The three groups also differed in an orderly manner across total intracranial (P < 0.001) and bilateral cerebellar cortex volumes (P < 0.01), and rate of bilateral hippocampal atrophy (P < 0.014), but minimally in regional measures of cortical volume or thickness. In contrast, large-scale patterns of cortical-subcortical covariance networks revealed significant differences across groups in global and local measures of community structure and distribution of hubs. Resting-state fMRI revealed stepwise anomalies as a function of cluster membership, with the most abnormal patterns of connectivity evident in the generalized impairment group and no significant differences from controls in the cognitively intact group. Overall, the distinct underlying cognitive phenotypes of temporal lobe epilepsy harbor systematic relationships with clinical, sociodemographic and neuroimaging correlates. Cognitive phenotype variations in patient and familial education and ethnicity, with linked variations in total intracranial volume, raise the question of an early and persisting socioeconomic-status related neurodevelopmental impact, with additional contributions of clinical epilepsy factors (e.g., lifetime generalized seizures). The neuroimaging features of cognitive phenotype membership are most notable for disrupted large scale cortical-subcortical networks and patterns of functional connectivity with bilateral hippocampal and cerebellar atrophy. The cognitive taxonomy of temporal lobe epilepsy appears influenced by features that reflect the combined influence of socioeconomic, neurodevelopmental and neurobiological risk factors.
Asunto(s)
Conectoma , Epilepsia del Lóbulo Temporal , Adulto , Cognición , Epilepsia del Lóbulo Temporal/diagnóstico por imagen , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Pruebas Neuropsicológicas , FenotipoRESUMEN
The Epilepsy Connectome Project examines the differences in connectomes between temporal lobe epilepsy (TLE) patients and healthy controls. Using these data, the effective connectivity of the default mode network (DMN) in patients with left TLE compared with healthy controls was investigated using spectral dynamic causal modeling (spDCM) of resting-state functional magnetic resonance imaging data. Group comparisons were made using two parametric empirical Bayes (PEB) models. The first level of each PEB model consisted of each participant's spDCM. Two different second-level models were constructed: the first comparing effective connectivity of the groups directly and the second using the Rey Auditory Verbal Learning Test (RAVLT) delayed free recall index as a covariate at the second level to assess effective connectivity controlling for the poor memory performance of left TLE patients. After an automated search over the nested parameter space and thresholding parameters at 95% posterior probability, both models revealed numerous connections in the DMN, which lead to inhibition of the left hippocampal formation. Left hippocampal formation inhibition may be an inherent result of the left temporal epileptogenic focus as memory differences were controlled for in one model and the same connections remained. An excitatory connection from the posterior cingulate cortex to the medial prefrontal cortex was found to be concomitant with left hippocampal formation inhibition in TLE patients when including RAVLT delayed free recall at the second level.
Asunto(s)
Conectoma/métodos , Epilepsia del Lóbulo Temporal/fisiopatología , Epilepsia/fisiopatología , Adulto , Teorema de Bayes , Encéfalo/fisiopatología , Epilepsia del Lóbulo Temporal/diagnóstico por imagen , Femenino , Lateralidad Funcional/fisiología , Hipocampo/fisiopatología , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Red Nerviosa/fisiopatología , Vías Nerviosas/fisiopatología , Corteza Prefrontal/fisiopatología , Lóbulo Temporal/fisiopatologíaRESUMEN
The Rat Genome Database (RGD) (http://rgd.mcw.edu) aims to meet the needs of its community by providing genetic and genomic infrastructure while also annotating the strengths of rat research: biochemistry, nutrition, pharmacology and physiology. Here, we report on RGD's development towards creating a phenome database. Recent developments can be categorized into three groups. (i) Improved data collection and integration to match increased volume and biological scope of research. (ii) Knowledge representation augmented by the implementation of a new ontology and annotation system. (iii) The addition of quantitative trait loci data, from rat, mouse and human to our advanced comparative genomics tools, as well as the creation of new, and enhancement of existing, tools to enable users to efficiently browse and survey research data. The emphasis is on helping researchers find genes responsible for disease through the use of rat models. These improvements, combined with the genomic sequence of the rat, have led to a successful year at RGD with over two million page accesses that represent an over 4-fold increase in a year. Future plans call for increased annotation of biological information on the rat elucidated through its use as a model for human pathobiology. The continued development of toolsets will facilitate integration of these data into the context of rat genomic sequence, as well as allow comparisons of biological and genomic data with the human genomic sequence and of an increasing number of organisms.