Exploring clinical outcomes in patients with idiopathic/inherited isolated generalized dystonia and stimulation of the subthalamic region / Explorando os desfechos clínicos em pacientes com distonia idiopática/hereditária generalizada isolada submetidos a estimulação da região subtalâmica

Abstract Background Deep Brain Stimulation (DBS) is an established treatment option for refractory dystonia, but the improvement among the patients is variable. Objective To describe the outcomes of DBS of the subthalamic region (STN) in dystonic patients and to determine whether the volume of tissue activated (VTA) inside the STN or the structural connectivity between the area stimulated and different regions of the brain are associated with dystonia improvement. Methods The response to DBS was measured by the Burke-Fahn-Marsden Dystonia Rating Scale (BFM) before and 7 months after surgery in patients with generalized isolated dystonia of inherited/idiopathic etiology. The sum of the two overlapping STN volumes from both hemispheres was correlated with the change in BFM scores to assess whether the area stimulated inside the STN affects the clinical outcome. Structural connectivity estimates between the VTA (of each patient) and different brain regions were computed using a normative connectome taken from healthy subjects. Results Five patients were included. The baseline BFM motor and disability subscores were 78.30 ± 13.55 (62.00-98.00) and 20.60 ± 7.80 (13.00-32.00), respectively. Patients improved dystonic symptoms, though differently. No relationships were found between the VTA inside the STN and the BFM improvement after surgery (p = 0.463). However, the connectivity between the VTA and the cerebellum structurally correlated with dystonia improvement (p = 0.003). Conclusions These data suggest that the volume of the stimulated STN does not explain the variance in outcomes in dystonia. Still, the connectivity pattern between the region stimulated and the cerebellum is linked to outcomes of patients.

Resumo Antecedentes A estimulação cerebral profunda (ECP) é um tratamento estabelecido para distonias refratárias. Porém, a melhora dos pacientes é variável. Objetivo O objetivo do estudo foi descrever os desfechos da ECP da região do núcleo subtalâmico (NST) e determinar se o volume de tecido ativado (VTA) dentro do NST ou se a conectividade estrutural entre a área estimulada e diferentes regiões cerebrais estão associadas a melhora da distonia. Métodos A resposta da ECP em pacientes com distonia generalizada isolada de etiologia hereditária/idiopática foi mensurada pela escala de Burke-Fahr-Marsden Dystonia Rating Scale (BFM) antes e 7 meses após a cirurgia. A soma dos volumes do NST nos dois hemisférios foi correlacionada com a melhora nos escores do BFM para avaliar se a área estimulada dentro do NST afeta o desfecho clínico. A conectividade estrutural estimada entre o VTA de cada paciente e as diferentes regiões cerebrais foram computadas usando um conectoma normativo retirado de indivíduos saudáveis. Resultados Cinco pacientes com idade de 40,00 ± 7,30 anos foram incluídos. O BFM motor e de incapacidade basal eram de 78,30 ± 13,55 (62,00-98,00) e 20,60 ± 7,80 (13,00-32,00), respectivamente. Os pacientes melhoraram com a cirurgia, mas com variabilidade. Não houve relação entre o VTA dentro do NST e a melhora do BFM após a cirurgia (p = 0.463). Entretanto, a conectividade estrutural entre o VTA e o cerebelo correlacionaram com a melhora da distonia (p = 0.003). Conclusão Os dados sugerem que o VTA dentro do NST não explica a variabilidade do desfecho clínico na distonia. Porém, o padrão de conectividade entre a região estimulada e o cerebelo foi relacionada com o desfecho dos pacientes.

Whole-brain Optical Imaging: A Powerful Tool for Precise Brain Mapping at the Mesoscopic Level / 神经科学通报·英文版

The mammalian brain is a highly complex network that consists of millions to billions of densely-interconnected neurons. Precise dissection of neural circuits at the mesoscopic level can provide important structural information for understanding the brain. Optical approaches can achieve submicron lateral resolution and achieve "optical sectioning" by a variety of means, which has the natural advantage of allowing the observation of neural circuits at the mesoscopic level. Automated whole-brain optical imaging methods based on tissue clearing or histological sectioning surpass the limitation of optical imaging depth in biological tissues and can provide delicate structural information in a large volume of tissues. Combined with various fluorescent labeling techniques, whole-brain optical imaging methods have shown great potential in the brain-wide quantitative profiling of cells, circuits, and blood vessels. In this review, we summarize the principles and implementations of various whole-brain optical imaging methods and provide some concepts regarding their future development.

Neurocognitive Dysfunction After Treatment for Pediatric Brain Tumors: Subtype-Specific Findings and Proposal for Brain Network-Informed Evaluations / 神经科学通报·英文版

The increasing number of long-term survivors of pediatric brain tumors requires us to incorporate the most recent knowledge derived from cognitive neuroscience into their oncological treatment. As the lesion itself, as well as each treatment, can cause specific neural damage, the long-term neurocognitive outcomes are highly complex and challenging to assess. The number of neurocognitive studies in this population grows exponentially worldwide, motivating modern neuroscience to provide guidance in follow-up before, during and after treatment. In this review, we provide an overview of structural and functional brain connectomes and their role in the neuropsychological outcomes of specific brain tumor types. Based on this information, we propose a theoretical neuroscientific framework to apply appropriate neuropsychological and imaging follow-up for future clinical care and rehabilitation trials.

El cerebro ¿Una máquina analógica con funcionamiento cuántico? / The brain. An analogic machine with quantum functioning?

Resumen La neurociencia moderna aborda el problema de funcionamiento global del cerebro para poder comprender los procesos neurobiológicos que subyacen a las funciones mentales, y especialmente, a la consciencia. La actividad cerebral está basada en el intercambio de información entre neuronas a través de contactos llamados sinapsis. Las neuronas forman redes de conexión entre ellas (circuitos), que están dedicados a procesar una parcela específica de información (visual, auditiva, motora…). Los circuitos establecen redes entre ellos, combinando diferentes modalidades de información para generar lo que conocemos como actividad mental. El estudio de las conexiones entre regiones corticales, que se ha llamado conectoma, está siendo abordado mediante técnicas de neuroimagen como la resonancia magnética nuclear, que aportan datos sobre la densidad de conexiones del cerebro. La capacidad del cerebro de crear nuevas conexiones en función de la experiencia (plasticidad cerebral), sugiere que el conectoma es una estructura dinámica en constante interacción con estímulos externos e internos. La pregunta sobre si el conocimiento del conectoma de un individuo nos per mitiría predecir su conducta parece que todavía no tiene respuesta clara, porque no conocemos los parámetros físicos que ligan la complejidad de las conexiones del cerebro con la aparición de las funciones mentales y de la consciencia. Por el momento, parece que la compleja e impredecible conducta no es el simple resultado de procesos lineales de interacción neuronal. La incertidumbre prima al determinismo, lo que abre la puerta a la posibilidad de un mecanismo cuántico para explicar la consciencia.

Abstract Modern neuroscience addresses the problem of the global functioning of the brain in order to understand the neurobiological processes that underlie mental functions, and especially, consciousness. Brain activity is based on the exchange of infor mation between neurons through contacts or synapses. Neurons form networks of connection between them (circuits), which are dedicated to processing a specific type of information (visual, auditory, motor…). The circuits establish networks among themselves, combining different modalities of information to generate what we know as mental activity. The study of connections between cortical regions, which has been called connectome, is being approached through neuroimaging techniques such as nuclear magnetic resonance that provide data on the density of connections in the brain. The brain's ability to create new connections based on experience (brain plasticity) suggests that the connectome is a dynamic structure in constant interaction with external and internal stimuli. The question about whether knowledge of an individual's connectome would allow us to predict his or her behavior seems to have no clear answer yet, because we do not know the physical parameters that link the complexity of the brain's connections with the appearance of mental functions and consciousness. At the moment, it seems that the complex and unpredictable behavior is not the simple result of linear processes of neuronal interaction. Uncertainty prevails over determinism, which opens the door to the possibility of a quantum mechanism to explain consciousness.

Frequency-Resolved Connectome Hubs and Their Test-Retest Reliability in the Resting Human Brain / 神经科学通报·英文版

Functional hubs with disproportionately extensive connectivities play a crucial role in global information integration in human brain networks. However, most resting-state functional magnetic resonance imaging (R-fMRI) studies have identified functional hubs by examining spontaneous fluctuations of the blood oxygen level-dependent signal within a typical low-frequency band (e.g., 0.01-0.08 Hz or 0.01-0.1 Hz). Little is known about how the spatial distributions of functional hubs depend on frequency bands of interest. Here, we used repeatedly measured R-fMRI data from 53 healthy young adults and a degree centrality analysis to identify voxelwise frequency-resolved functional hubs and further examined their test-retest reliability across two sessions. We showed that a wide-range frequency band (0.01-0.24 Hz) accessible with a typical sampling rate (fsample = 0.5 Hz) could be classified into three frequency bands with distinct patterns, namely, low-frequency (LF, 0.01-0.06 Hz), middle-frequency (MF, 0.06-0.16 Hz), and high-frequency (HF, 0.16-0.24 Hz) bands. The functional hubs were mainly located in the medial and lateral frontal and parietal cortices in the LF band, and in the medial prefrontal cortex, superior temporal gyrus, parahippocampal gyrus, amygdala, and several cerebellar regions in the MF and HF bands. These hub regions exhibited fair to good test-retest reliability, regardless of the frequency band. The presence of the three frequency bands was well replicated using an independent R-fMRI dataset from 45 healthy young adults. Our findings demonstrate reliable frequency-resolved functional connectivity hubs in three categories, thus providing insights into the frequency-specific connectome organization in healthy and disordered brains.

Individual-Level Lesion-Network Mapping to Visualize the Effects of a Stroke Lesion on the Brain Network: Connectograms in Stroke Syndromes

Recent advances in the vascular brain injury of cognitive function network / 中国脑血管病杂志

Vascular cognitive impairment and dementia (VCID) , characterized with progressive worsening of executive function,learning and memory ability,is a clinical syndrome associated with vascular etiologies. Vascular injury leads to the compromise of integrity in the anatomical network connectivity and functional network connectivity within white matter, cortical gray matter and subcortical gray matter of the brain. Recent advances of VCID at different levels, from molecule and cell to brain structure, functional network and clinical disease,are summarized in this review.

VisConnectome: an independent and graph-theory based software for visualizing the human brain connectome / 生物医学工程学杂志

As a complex system, the topology of human's brain network has an important effect on further study of brain's structural and functional mechanism. Graph theory, a kind of sophisticated analytic strategies, is widely used for analyzing complex brain networks effectively and comparing difference of topological structure alteration in normal development and pathological condition. For the purpose of using this analysis methodology efficiently, it is necessary to develop graph-based visualization software. Thus, we developed VisConnectome, which displays analysis results of the brain network friendly and intuitively. It provides an original graphical user interface (GUI) including the tool window, tool bar and innovative double slider filter, brain region bar, runs in any Windows operating system and doesn't rely on any platform such as Matlab. When importing the user-defined script file that initializes the brain network, VisConnectome abstracts the brain network to the ball-and-stick model and render it. VisConnectome allows a series of visual operations, such as identifying nodes and connection, modifying properties of nodes and connection such as color and size with the color palette and size double slider, imaging the brain regions, filtering the brain network according to its size property in a specific domain as simplification and blending with the brain surface as a context of the brain network. Through experiment and analysis, we conclude that VisConnectome is an effective visualization software with high speed and quality, which helps researchers to visualize and compare the structural and functional brain networks flexibly.

Pivotal Role of Subcortical Structures as a Network Hub in Focal Epilepsy: Evidence from Graph Theoretical Analysis Based on Diffusion-Tensor Imaging

BACKGROUND AND PURPOSE: There is accumulating evidence that epilepsy is caused by network dysfunction. We evaluated the hub reorganization of subcortical structures in patients with focal epilepsy using graph theoretical analysis based on diffusion-tensor imaging (DTI). In addition, we investigated differences in the values of diffusion tensors and scalars, fractional anisotropy (FA), and mean diffusivity (MD) of subcortical structures between patients with focal epilepsy and healthy subjects. METHODS: One hundred patients with focal epilepsy and normal magnetic resonance imaging (MRI) findings and 80 age- and sex-matched healthy subjects were recruited prospectively. All subjects underwent DTI to obtain data suitable for graph theoretical analysis. We investigated the differences in the node strength, cluster coefficient, eigenvector centrality, page-rank centrality measures, FA, and MD of subcortical structures between patients with epilepsy and healthy subjects. RESULTS: After performing multiple corrections, the cluster coefficient and the eigenvector centrality of the globus pallidus were higher in patients with epilepsy than in healthy subjects (p=0.006 and p=0.008, respectively). In addition, the strength and the page-rank centrality of the globus pallidus tended to be higher in patients with epilepsy than in healthy subjects (p=0.092 and p=0.032, respectively). The cluster coefficient of the putamen was lower in patients with epilepsy than in healthy subjects (p=0.004). The FA values of the caudate nucleus and thalamus were significantly lower in patients with epilepsy than in healthy subjects (p=0.009 and p=0.007, respectively), whereas the MD value of the thalamus was higher than that in healthy subjects (p=0.005). CONCLUSIONS: We discovered the presence of hub reorganization of subcortical structures in focal epilepsy patients with normal MRI findings, suggesting that subcortical structures play a pivotal role as a hub in the epilepsy network. These findings further reinforce the idea that epilepsy is a network disease.

Descobertas nos estudos das afasias com imagens de Tensor de Difusão / Findings in studies of aphasia with Diffusion Tensor Images

Haja vista que as pesquisas sobre o conectoma estão causando uma mudança de paradigma no campo da neurobiologia da linguagem, esta revisão concentra-se em descobertas das neurociências sobre o conectoma humano em relação às afasias pós-trauma ao utilizar imagens de tensor de difusão. Esta pesquisa é qualitativa, do tipo exploratória, caracterizando-se por uma revisão de literatura que compreendeu 16 artigos em língua inglesa publicados nos períodos de 2011 a 2016. Os resultados apontaram para a relação entre melhora da afasia e lateralização hemisférica; confirmaram o fascículo arqueado como uma importante via para a função da linguagem, não só na produção, como na compreensão; evidenciaram o papel funcional do fascículo uncinado no controle semântico e também indicaram a importância dos tractos temporais principalmente na compreensão da linguagem. Percebe-se que as pesquisas ainda possuem limitações principalmente quanto ao número de sujeitos investigados. Ainda faltam estudos sobre previsão de prognóstico das afasias, bem como de mecanismos de recuperação.

Considering that research into the connectome are causing a paradigm shift in the field of neurobiology of language, this review focuses on findings of neuroscience on the human connectome in relation to post stroke aphasia using diffusion tensor imaging. This research is qualitative, exploratory, characterizedby a literature review that included 16 articles in English published in the periods 2011 to 2016. The results pointed to the relationship between aphasia improvement and hemispheric lateralization; confirmed the arcuate fasciculusas an important pathway for the function of language, not only in language production but also in understanding; evidenced the functional role of uncinatefasciculus in semantic control and indicated the importance of temporal tracts mainly in language comprehension. It is noticed that the researches still have limitations mainly regarding the number of subjects investigated. There is still alack of studies on prediction of aphasia prognosis, as well as mechanisms of recovery

Abnormal Effective Connectivity of the Anterior Forebrain Regions in Disorders of Consciousness / 神经科学通报·英文版

A number of studies have indicated that disorders of consciousness result from multifocal injuries as well as from the impaired functional and anatomical connectivity between various anterior forebrain regions. However, the specific causal mechanism linking these regions remains unclear. In this study, we used spectral dynamic causal modeling to assess how the effective connections (ECs) between various regions differ between individuals. Next, we used connectome-based predictive modeling to evaluate the performance of the ECs in predicting the clinical scores of DOC patients. We found increased ECs from the striatum to the globus pallidus as well as from the globus pallidus to the posterior cingulate cortex, and decreased ECs from the globus pallidus to the thalamus and from the medial prefrontal cortex to the striatum in DOC patients as compared to healthy controls. Prediction of the patients' outcome was effective using the negative ECs as features. In summary, the present study highlights a key role of the thalamo-basal ganglia-cortical loop in DOCs and supports the anterior forebrain mesocircuit hypothesis. Furthermore, EC could be potentially used to assess the consciousness level.

Topological Alterations of the Intrinsic Brain Network in Patients with Functional Dyspepsia

BACKGROUND/AIMS: Previous studies reported that integrated information in the brain ultimately determines the subjective experience of patients with chronic pain, but how the information is integrated in the brain connectome of functional dyspepsia (FD) patients remains largely unclear. The study aimed to quantify the topological changes of the brain network in FD patients. METHODS: Small-world properties, network efficiency and nodal centrality were utilized to measure the changes in topological architecture in 25 FD patients and 25 healthy controls based on functional magnetic resonance imaging. Pearson's correlation assessed the relationship of each topological property with clinical symptoms. RESULTS: FD patients showed an increase of clustering coefficients and local efficiency relative to controls from the perspective of a whole network as well as elevated nodal centrality in the right orbital part of the inferior frontal gyrus, left anterior cingulate gyrus and left hippocampus, and decreased nodal centrality in the right posterior cingulate gyrus, left cuneus, right putamen, left middle occipital gyrus and right inferior occipital gyrus. Moreover, the centrality in the anterior cingulate gyrus was significantly associated with symptom severity and duration in FD patients. Nevertheless, the inclusion of anxiety and depression scores as covariates erased the group differences in nodal centralities in the orbital part of the inferior frontal gyrus and hippocampus. CONCLUSIONS: The results suggest topological disruption of the functional brain networks in FD patients, presumably in response to disturbances of sensory information integrated with emotion, memory, pain modulation, and selective attention in patients.

Stroke Connectome and Its Implications for Cognitive and Behavioral Sequela of Stroke / 대한뇌졸중학회지

Systems-based approaches to neuroscience, using network analysis and the human connectome, have been adopted by many researchers by virtue of recent progress in neuroimaging and computational technologies. Various neurological disorders have been evaluated from a network perspective, including stroke, Alzheimer's disease, Parkinson's disease, and traumatic brain injury. Until now, dynamic processes after stroke and during recovery were investigated through multimodal neuroimaging techniques. Many studies have shown disruptions in structural and functional connectivity, including in large-scale neural networks, in patients with stroke sequela such as motor weakness, aphasia, hemianopia, neglect, and general cognitive dysfunction. A connectome-based approach might shed light on the underlying mechanisms of stroke sequela and the recovery process, and could identify candidates for individualized rehabilitation programs. In this review, we briefly outline the basic concepts of structural and functional connectivity, and the connectome. Then, we explore current evidence regarding how stroke lesions cause changes in connectivity and network architecture parameters. Finally, the clinical implications of perspectives on the connectome are discussed in relation to the cognitive and behavioral sequela of stroke.

"The ""small-world"" property of default mode network in relapsing-remitting multiple sclerosis:a graph theory resting-state functional network analysis" / 中华行为医学与脑科学杂志

Objective To investigate the small-world property of default mode network in relapsingremitting multiple sclerosis (RRMS) compared with the (matched) healthy control subjects,using a graph theory for resting-state functional network analysis.Methods Twenty four patients with RRMS and 24 age-,and sexmatched healthy controls were exanined with resting-state functional MRI (R-fMRI) and 3D-T1WI on Trio 3.0 Tesla.The R-fMRI data were preprocessed,then 20 regions of interest (ROIs) was defined and extracted from the default mode network.The functional connectivity between a pair of regions was defined as the Pearson's correlation coefficient in the time courses.Graph theoretical analysis was implemented and compared with the property of binary functional network.Further,the relationships were examined between the topological property of functional networks and the clinical parameters.Results In this study,functional network in the default mode network was conducted,and the small-world characteristics were observed in both RRMS and healthy control group.In the range of densities (Dmin:0.01∶0.48 ;Dmin =0.42),compared with healthy control group,RRMS groups had a slightly smaller normalized clustering coefficient (P＞0.05),a slightly larger normalized path length (P＞0.05),and a slightly decrease small-world index (P＞0.05).The left posterior cingulated cortex showed a significantly larger clustering coefficient in RRMS group (P=0.031) on the network threshold at Dmin.The area under a curve (AUC) for clustering coefficient measure curves of the left posterior cingulated cortex (density range of 0.42:0.01:0.48) between two groups were compared.The AUC result was similar to the Dmin result (P=0.031).Negative correlation was observed between the clustering coefficient of left posterior cingulated cortex and the Paced Auditory Serial Addition Test (PASAT) in both the Dmin(P=0.023) and the AUC (P=0.020).Conclusion The default mode network has small-world property in RRMS group.The significantly increased clustering coefficience is observed in the left posterior cingulated cortex,which may be a side effect.

La evolución del aprendizaje: más allá de las redes neuronales / The evolution of learning: beyond neural networks

El tema del aprendizaje, ha sido ampliamente estudiado desde distintas perspectivas y en años recientes gracias al avance tecnológico, ha sido parte de diversos estudios con redes neuronales artificiales, las cuales tienen un punto de engranaje con la evolución de sistemas complejos. El desarrollo de éstas ha permitido comprender cómo la naturaleza ha dotado a los sistemas con la habilidad para adaptarse al medio, que es la línea que permite la pervivencia de las especies, lo cual puede ser clave para la comprensión del aprendizaje, y su necesidad de desarrollarse como un sistema flexible. El presente artículo, centra la investigación en la pregunta: cómo es que el proceso de aprendizaje llegó al cerebro?, y analiza el papel de diversos factores evolutivos relacionados con dicho proceso, desde las proteínas que han heredado la capacidad de ser flexibles en el entorno y cómo este proceso se aplica a sistemas más complejos como las redes neuronales, las cuales han ido moldeando sus características para permitir procesos cognitivos de orden superior como la lectura y la escritura como respuesta evolutiva a la cultura, las cuales se han desarrollado hasta alojarse en la neocorteza, lo cual por supuesto permite el desarrollo del connectome, que se caracteriza por la aprehensión de toda acción capaz de crear una respuesta adaptativa al medio.

with artificial neural networks, which have a point of gear with the evolution of complex systems. The development of these processes have enabled to understand how nature has provided systems with the ability to adapt to the environment, which is the line that allows the survival of the species, which may be the key to understanding of learning and its need to develop as a flexible system. This article focus on the question: How did learning process arrive to the brain? So it discusses the role of diverse evolutionary factors related to learning, since the proteins which have inherited the ability to be flexible into the environment andhow this process is applied to complex systems such as neural networks, which have been shaping their characteristics to allow cognitive processes of a higher order such as reading and writing as the evolutionary response to culture and how this makes possible to net on the neocortex, which of course allows the development of the connectome, a network characterized by the apprehension of any action which is capable of creating an adaptive response to the environment.

Anatomical Brain Connectivity Map of Korean Children

PURPOSE: The purpose of this study is to establish the method generating human brain anatomical connectivity from Korean children and evaluating the network topological properties using small-world network analysis. MATERIALS AND METHODS: Using diffusion tensor images (DTI) and parcellation maps of structural MRIs acquired from twelve healthy Korean children, we generated a brain structural connectivity matrix for individual. We applied one sample t-test to the connectivity maps to derive a representative anatomical connectivity for the group. By spatially normalizing the white matter bundles of participants into a template standard space, we obtained the anatomical brain network model. Network properties including clustering coefficient, characteristic path length, and global/local efficiency were also calculated. RESULTS: We found that the structural connectivity of Korean children group preserves the small-world properties. The anatomical connectivity map obtained in this study showed that children group had higher intra-hemispheric connectivity than inter-hemispheric connectivity. We also observed that the neural connectivity of the group is high between brain stem and motorsensory areas. CONCLUSION: We suggested a method to examine the anatomical brain network of Korean children group. The proposed method can be used to evaluate the efficiency of anatomical brain networks in people with disease.