Contralateral interictal spikes are related to tapetum damage in left temporal lobe epilepsy.

OBJECTIVE: In temporal lobe epilepsy (TLE), the epileptogenic focus is focal and unilateral in the majority of patients. A key characteristic of focal TLE is the presence of subclinical epileptiform activity in both the ictal and contralateral healthy hemisphere. Such interictal activity is clinically important, as it may reflect the spread of pathology, potentially leading to secondary epileptogenesis. The role played by white matter pathways in this process is unknown. METHODS: We compared three interhemispheric white matter tracts (anterior commissure, fornix, and tapetum) to determine the pathway most associated with the presence of contralateral interictal spikes. Forty patients with unilateral left or right TLE were categorized based on the presence or absence of contralateral interictal spikes. Analyses of variance (ANOVAs) were run on diffusion properties from each tract. RESULTS: The analyses revealed that patients with left TLE and with bilateral interictal spikes had lower fractional anisotropy (FA) and higher mean diffusivity (MD) in the tapetum. Patients with right TLE did not show this effect. No significant associations with bilateral activity were observed for the other tracts. Blood oxygen level-dependent (BOLD) functional connectivity data revealed that homotopic lateral, not mesial, temporal areas were reliably correlated in bilateral patients, independent of ictal side. SIGNIFICANCE: Our results indicate that, among the tracts investigated, only the tapetum was associated with contralateral epileptiform activity, implicating this structure in seizures and possible secondary epileptogenesis. We describe two mechanisms that might explain this association (the interruption of inhibitory signals or the toxic effect of carrying epileptiform signals toward the healthy hemisphere), but also acknowledge other rival factors that may be at work. We also report that patients with TLE with bilateral spikes had increased lateral bitemporal lobe connectivity. Our current results can be seen as bringing together important functional and structural data to elucidate the basis of contralateral interictal activity in focal, unilateral epilepsy. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here

Computational Brain Connectivity Mapping: A Core Health and Scientific Challenge

International audienceOne third of the burden of all the diseases in Europe is due to problems caused by diseases affecting brain. Although exceptional progress have been obtained for exploring the brain during the past decades, it is still terra-incognita and calls for specific efforts in research to better understand its architecture and functioning. To take up this great challenge of modern science and to solve the limited view of the brain provided just by one imaging modality, this article advocates the idea developed in my research group of a global approach involving new generation of models for brain connectivity mapping and strong interactions between structural and functional connectivities. Capitalizing on the strengths of integrated and complementary non invasive imaging modalities such as diffusion Magnetic Resonance Imaging (dMRI) and Electro & Magneto-Encephalography (EEG & MEG) will contribute to achieve new frontiers for identifying and characterizing structural and functional brain connectivities and to provide a detailed mapping of the brain connectivity, both in space and time. Thus leading to an added clinical value for high impact diseases with new perspectives in computational neuro-imaging and cognitive neuroscience

Topological Learning for Brain Networks

This paper proposes a novel topological learning framework that can integrate networks of different sizes and topology through persistent homology. This is possible through the introduction of a new topological loss function that enables such challenging task. The use of the proposed loss function bypasses the intrinsic computational bottleneck associated with matching networks. We validate the method in extensive statistical simulations with ground truth to assess the effectiveness of the topological loss in discriminating networks with different topology. The method is further applied to a twin brain imaging study in determining if the brain network is genetically heritable. The challenge is in overlaying the topologically different functional brain networks obtained from the resting-state functional MRI (fMRI) onto the template structural brain network obtained through the diffusion MRI (dMRI)

사람에서 점멸광자극을 이용한 성공적인 감마뇌파동조 유도의 결정 요인

학위논문(박사) -- 서울대학교대학원 : 자연과학대학 뇌인지과학과, 2023. 2. 김기웅.Background and Objectives: Although gamma entrainment using flickering light stimulus (FLS) of 40Hz was effective in reducing pathologies and enhancing cognitive function in mouse models of Alzheimers disease (AD), its efficacy was controversial in AD patients. The conflicting results in AD patients may be attributable to a couple of key factors. First, the optimal parameters of FLS for gamma entrainment may be different between diurnal humans and nocturnal mice. Second, the response to optimal FLS may be different between AD patients due to inter-individual difference in the microstructural integrity of white matter (WM) tracts. This study aimed to find the optimal parameters (color, luminal intensity and flickering frequency) of FLS for entraining gamma rhythms in diurnal humans and to examine the effect of fractional anisotropy (FA) of WM tracts on the entrainment and propagation of gamma rhythms. Methods: We first investigated the optimal color (white, red, green, and blue), luminal intensity (10 cd/m2, 100 cd/m2, 400 cd/m2, and 700 cd/m2), and frequency (32 - 50 Hz) of FLS for entraining gamma rhythms in visual cortex using event-related desynchronization/event-related synchronization (ERD/ERS) and for propagating gamma rhythm entrained in visual cortex to other brain regions using spectral Granger Causality (sGC) in 16 cognitively normal young adults (24.0 ± 3.7 yrs) and 35 cognitively normal older adults (70.0 ± 2.4 yrs). We also examined the adverse effects of FLS in both younger and older adults. Then we examined the effect of the FA of posterior thalamic radiations on the ERS of gamma rhythms entrained in visual cortex and that of and middle and superior longitudinal fasciculi on the sGC of the connectivity from visual cortex to temporal and frontal regions in 26 cognitively normal older adults using analysis of variance and linear regression analyses. Results: The FLSs using the lights of longer wavelengths such as white (p < 0.05) and red (p < 0.01) entrained and propagated gamma rhythms better than those of shorter wavelengths such as green and blue. The FLSs using stronger lights such as 700 cd/m2 (p < 0.001) and 400 cd/m2 (p < 0.01) entrained and propagated gamma rhythms better than weaker lights of 100 cd/m2 and 10 cd/m2. The FLSs flickering at 34-38 Hz were best for entraining and propagating gamma rhythm in younger adults (entrainment at Pz: p < 0.05, propagation: p < 0.05) while those flickering at 32-34 Hz were best for older adults (entrainment at Pz: p < 0.05, propagation: p < 0.001). In older adults, white FLSs of 700 cd/m2 flickering at 32–34 Hz entrained the gamma rhythms most strongly at visual cortex (p < 0.05) and propagated them most widely to other brain regions (p < 0.05). The FLSs of 700 cd/m2 flickering at 32 Hz entrained gamma rhythms worse in the visual cortex of the older adults whose FA of left posterior thalamic radiation was low than in those whose FA of left posterior thalamic radiation was not low (p 0.05), and their severity of adverse effects was milder than that in younger adults. Conclusion: In diurnal human, optimal flickering frequency for gamma entrainment was about 20% lower than that in nocturnal mice. Although the FLSs of stronger luminal intensity and the longer wavelength may entrain gamma rhythms better, they may result in more and severe adverse effects. In older adults, white or red FLSs of 700 cd/m2 flickering at 32-34 Hz may be optimal for entraining and propagating gamma rhythms. Since gamma rhythms were not properly entrained by optimal FLS in the older adults whose microstructural integrity of the white matter tracts was impaired, the integrity of the white matter tracts involved in the entrainment and propagation of gamma rhythm should be measured and considered in determining the indication of gamma entrainment using visual stimulation.연구배경 및 목적: 40Hz 점멸광자극 (flickering light stimulation, FLS)을 사용한 감마뇌파동조는 알츠하이머병 (Alzheimers disease, AD) 모델 쥐에서 병리를 감소시키고 인지 기능을 향상시키는 데 효과적이었지만 알츠하이머병 환자에서는 그 효능에 대해 논란이 있다. 알츠하이머병 환자의 상충되는 결과는 몇 가지 주요 요인에 기인할 수 있다. 첫째, 감마뇌파동조를 위한 FLS의 최적 매개변수는 일주 동물인 인간과 야행성 동물인 쥐 간에 다를 수 있다. 둘째, 최적의 FLS에 대한 반응은 백질 (white matter, WM) 섬유 다발 미세 구조적 무결성의 개인 간 차이로 인해 알츠하이머병 환자 간에 다를 수 있다. 이 연구는 일주 동물인 인간에서 감마뇌파를 동반하기 위한 FLS의 최적 매개변수 (색상, 밝기 및 점멸 주파수)를 찾고 감마뇌파의 동반 및 전파에 대한 백질 섬유 다발의 확산비등방성 (fractional anisotropy, FA)의 영향을 조사하는 것을 목표로 했다. 연구방법: 인지기능이 정상인 젊은 성인 16명과 노인 35명을 대상으로, 시각피질에 감마뇌파동조를 유도하고, 동조 된 시각피질의 감마뇌파를 다른 뇌 영역으로의 전파시킬 수 있는 FLS의 최적 색상 (백색, 적색, 녹색 및 청색), 밝기 (10 cd/m2, 100 cd/m2, 400 cd/m2 및 700 cd/m2) 및 점멸 주파수 (32-50 Hz)를 사건 관련 비 동기화/사건 관련 동기화 (event-related desynchronization/event-related synchronization, ERD/ERS)와 스펙트럼 그랜저 인과성 (spectral Granger Causality, sGC) 분석을 이용하여 조사했다. 아울러 젊은 성인과 노인에서 FLS의 부작용을 조사했다. 이어서 감마뇌파가 FLS에 의해 시각피질에 적절하게 동조 된 인지기능이 정상인 노인 26명을 대상으로, 시각피질에서 동조 된 감마뇌파의 ERS와 시각피질과 측두 및 전두 영역들 간 연결성인 sGC에 후방시상방사와 중간 및 상부 세로다발들의 확산비등방성이 미치는 영향을 회귀분석과 분산분석을 이용하여 조사했다. 연구결과: 사람에서는 백색 (p < 0.05) 및 적색 (p < 0.01)과 같은 장파장 FLS가 녹색 및 청색과 같은 단파장 FLS보다 감마뇌파동조를 더 강하게 유발하고, 동조 된 감마뇌파를 더 넓은 뇌 영역으로 전파시켰다. 또 700 cd/m2 (p < 0.001) 및 400 cd/m2 (p < 0.01)와 같은 강한 휘도 FLS는 100 cd/m2 및 10 cd/m2와 같은 약한 휘도 FLS보다 감마뇌파동조를 더 강하게 유발하고, 동조 된 감마뇌파를 더 넓은 뇌 영역으로 전파시켰다. 34-38 Hz에서 점멸하는 FLS는 젊은 성인에서 감마뇌파를 동반하고 전파하는 데 가장 효과적이었고 (Pz에서 동반: p < 0.05, 전파: p < 0.05) 32-34 Hz에서 점멸하는 FLS는 노인에게 가장 효과적이었다 (Pz에서 동반: p < 0.05, 전파: p < 0.001). 노인에서 32-34 Hz에서 점멸하는 700 cd/m2의 백색 FLS는 시각 피질에서 가장 강하게 감마뇌파를 동반하고 (p < 0.05) 다른 뇌 영역으로 가장 널리 전파했다 (p < 0.05). 32 Hz에서 점멸하는 700 cd/m2의 FLS는 좌후시상방사선의 FA가 낮지 않은 노인보다 낮은 노인에서 감마뇌파가 시각피질에 덜 동반된다 (p 0.05), 부작용의 심각성은 젊은 성인보다 경미했다. 결론: 주행성인 인간에서 감마 동조를 위한 최적의 점멸 주파수는 야행성 쥐보다 약 20% 낮았다. 더 강한 휘도와 더 긴 파장의 FLS가 감마뇌파를 더 잘 동조 시킬 수 있지만 더 크고 심각한 부작용을 초래할 수 있다. 노인의 경우 32-34 Hz에서 점멸하는 700 cd/m2의 백색 또는 적색 FLS가 감마뇌파를 동조하고 전파하는 데 최적일 수 있다. 감마뇌파는 백질 섬유 다발의 미세 구조적 무결성이 손상된 노인에서는 최적의 FLS에 의해 적절하게 동조 되지 않았기 때문에, 감마뇌파의 동조 및 전파와 관련된 백질 영역의 무결성은 시각적 자극을 사용하여 감마뇌파동조 적용을 결정할 때 측정되고 고려되어야 한다.1. Introduction 1 1.1. Background 1 1.2. Purpose 4 2. Methods 6 2.1. Study design 6 2.1.1. Study 1. Investigation on the optimal parameters of FLS for gamma entrainment in humans 6 2.1.2. Study 2. Investigation on the effect of WM microstructural integrity on the gamma entrainment by FLS in humans 7 2.2. Participants 7 2.2.1. Study 1. Investigation on the optimal parameters of FLS for gamma entrainment in humans 7 2.2.2. Study 2. Investigation on the effect of WM microstructural integrity on the gamma entrainment by FLS in humans 8 2.2.3. Clinical evaluation of the participants 8 2.3. Research ethics 9 2.4. FLS 9 2.5. Recording, preprocessing and analysis of EEG 10 2.6. Acquisition, preprocessing and analysis of DTI 13 2.7. Statistical analyses 14 3. Results 16 3.1. Effects of the rsEEG spectral band power on cognitive function 16 3.2. Entrainment and propagation of the gamma rhythms by FLS 16 3.3. Effects of the FLS color on gamma entrainment and propagation 17 3.4. Effects of the FLS intensity on gamma entrainment and propagation 18 3.5. Effects of the FLS frequency on gamma entrainment and propagation 18 3.6. Effects of the microstructural integrity of WM tracts on the gamma entrainment and propagation 20 3.7. Adverse effects 21 4. Discussions 23 5. Conclusions 35 Bibliography 66 국문초록 81박

Cortical resting state circuits: connectivity and oscillations

Ongoing spontaneous brain activity patterns raise ever-growing interest in the neuroscience community. Complex spatiotemporal patterns that emerge from a structural core and interactions of functional dynamics have been found to be far from arbitrary in empirical studies. They are thought to compose the network structure underlying human cognitive architecture. In this thesis, we use a biophysically realistic computer model to study key factors in producing complex spatiotemporal activation patterns. For the first time, we present a model of decreased physiological signal complexity in aging and demonstrate that delays shape functional connectivity in an oscillatory spiking-neuron network model for MEG resting-state data. Our results show that the inclusion of realistic delays maximizes model performance. Furthermore, we propose embracing a datadriven, comparative stance on decomposing the system into subnetworks.Últimamente, el interés de la comunidad científica sobre los patrones de la continua actividad espontanea del cerebro ha ido en aumento. Complejos patrones espacio-temporales emergen a partir de interacciones de un núcleo estructural con dinámicas funcionales. Se ha encontrado que estos patrones no son aleatorios y que componen la red estructural en la que la arquitectura cognitiva humana se basa. En esta tesis usamos un modelo computacional detallado para estudiar los factores clave en producir los patrones emergentes. Por primera vez, presentamos un modelo simplificado de la actividad cerebral en envejecimiento. También demostramos que la inclusión del desfase de transmisión en un modelo para grabaciones magnetoencefalográficas del estado en reposo maximiza el rendimiento del modelo. Para ello, aplicamos un modelo con una red de neuronas pulsantes (’spiking-neurons’) y con dinámicas oscilatorias. Además, proponemos adoptar una posición comparativa basada en los datos para descomponer el sistema en subredes

Asymmetric projections of the arcuate fasciculus to the temporal cortex underlie lateralized language function in the human brain

The arcuate fasciculus (AF) in the human brain has asymmetric structural properties. However, the topographic organization of the asymmetric AF projections to the cortex and its relevance to cortical function remain unclear. Here we mapped the posterior projections of the human AF in the inferior parietal and lateral temporal cortices using surface-based structural connectivity analysis based on diffusion MRI and investigated their hemispheric differences. We then performed the cross-modal comparison with functional connectivity based on resting-state functional MRI (fMRI) and task-related cortical activation based on fMRI using a semantic classification task of single words. Structural connectivity analysis showed that the left AF connecting to Broca's area predominantly projected in the lateral temporal cortex extending from the posterior superior temporal gyrus to the mid part of the superior temporal sulcus and the middle temporal gyrus, whereas the right AF connecting to the right homolog of Broca's area predominantly projected to the inferior parietal cortex extending from the mid part of the supramarginal gyrus to the anterior part of the angular gyrus. The left-lateralized projection regions of the AF in the left temporal cortex had asymmetric functional connectivity with Broca's area, indicating structure-function concordance through the AF. During the language task, left-lateralized cortical activation was observed. Among them, the brain responses in the temporal cortex and Broca's area that were connected through the left-lateralized AF pathway were specifically correlated across subjects. These results suggest that the human left AF, which structurally and functionally connects the mid temporal cortex and Broca's area in asymmetrical fashion, coordinates the cortical activity in these remote cortices during a semantic decision task. The unique feature of the left AF is discussed in the context of the human capacity for language.National Institutes of Health (U.S.) (Grant R01NS069696)National Institutes of Health (U.S.) (Grant P41EB015896)National Institutes of Health (U.S.) (Grant S10ODRR031599)National Institutes of Health (U.S.) (Grant S10RR021110)National Science Foundation (U.S.) (Grant NFS-DMS-1042134)Uehara Memorial Foundation (Fellowship)Society of Nuclear Medicine and Molecular Imaging (Wagner-Torizuka Fellowship)United States. Dept. of Energy (Grant DE-SC0008430

Individual variation in brain network topology predicts emotional intelligence

BACKGROUND: Social cognitive ability is a significant determinant of functional outcome and deficits in social cognition are a disabling symptom of psychotic disorders. The neurobiological underpinnings of social cognition are not well understood, hampering our ability to ameliorate these deficits. Using ‘resting-state’ fMRI (functional magnetic resonance imaging) and a trans-diagnostic, data-driven analytic strategy, we sought to identify the brain network basis of emotional intelligence, a key domain of social cognition. METHODS: Subjects included 60 participants with a diagnosis of schizophrenia or schizoaffective disorder and 46 healthy comparison participants from three different sites: Beth Israel Deaconess Medical Center, Boston, MA, McLean Hospital, Belmont, MA, and University of Pittsburgh, Pittsburgh, PA. All participants underwent a structural T1/MPRAGE and resting-state fMRI scan. Emotional Intelligence was measured using the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). A connectome-wide analysis of brain connectivity examined how each individual brain voxel’s connectivity correlated with emotional intelligence using multivariate distance matrix regression (MDMR). RESULTS: We identified a region in the left superior parietal lobule (SPL) where individual network topology predicted emotional intelligence. Specifically, the association of this region with the Default Mode Network (DMN) predicted higher emotional intelligence (r = 0.424, p < 0.001) and association with the Dorsal Attention Network (DAN) predicted lower emotional intelligence (r = -0.504, p < 0.001). This correlation was observed in both schizophrenia and healthy comparison participants. These results held true despite corrections for sex, age, race, medication dosage (chlorpromazine equivalents), and full scale IQ (FSIQ), and was replicable per site. Post-hoc analyses showed that membership of the left SPL was entirely within the DMN in high scorers and within the DAN in low scorers. This relationship was also shown to be specific to the identified left SPL region when compared to adjacent regions. Sulcal depth analysis of the left SPL revealed a correlation to emotional intelligence (r = 0.269, p = 0.0075). CONCLUSIONS: Previous studies have demonstrated individual variance in brain network topology but the cognitive or behavioral relevance of these differences was undetermined. We observe that the left SPL, a region of high individual variance at the cytoarchitectonic level, also demonstrates individual variance in its association with large scale brain networks and that network topology predicts emotional intelligence. This is the first demonstration of a clinical phenotype in individual brain network topology.2019-07-03T00:00:00