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.

Genetic Approaches for Neural Circuits Dissection in Non-human Primates / 神经科学通报·英文版

Genetic tools, which can be used for the morphology study of specific neurons, pathway-selective connectome mapping, neuronal activity monitoring, and manipulation with a spatiotemporal resolution, have been widely applied to the understanding of complex neural circuit formation, interactions, and functions in rodents. Recently, similar genetic approaches have been tried in non-human primates (NHPs) in neuroscience studies for dissecting the neural circuits involved in sophisticated behaviors and clinical brain disorders, although they are still very preliminary. In this review, we introduce the progress made in the development and application of genetic tools for brain studies on NHPs. We also discuss the advantages and limitations of each approach and provide a perspective for using genetic tools to study the neural circuits of NHPs.

Direction Selectivity of TmY Neurites in Drosophila / 神经科学通报·英文版

The perception of motion is an important function of vision. Neural wiring diagrams for extracting directional information have been obtained by connectome reconstruction. Direction selectivity in Drosophila is thought to originate in T4/T5 neurons through integrating inputs with different temporal filtering properties. Through genetic screening based on synaptic distribution, we isolated a new type of TmY neuron, termed TmY-ds, that form reciprocal synaptic connections with T4/T5 neurons. Its neurites responded to grating motion along the four cardinal directions and showed a variety of direction selectivity. Intriguingly, its direction selectivity originated from temporal filtering neurons rather than T4/T5. Genetic silencing and activation experiments showed that TmY-ds neurons are functionally upstream of T4/T5. Our results suggest that direction selectivity is generated in a tripartite circuit formed among these three neurons-temporal filtering, TmY-ds, and T4/T5 neurons, in which TmY-ds plays a role in the enhancement of direction selectivity in T4/T5 neurons.

Reading Argumentative Texts: Effects of the presence-absence of connectives in reading comprehension and cognitive effort / Leer Textos Argumentativos: efectos de la presencia-ausencia de conectores en la comprensión lectora y esfuerzo cognitivo

Recent studies prove a strong association between reading and eye movements. Few investigations report the role of connectors and prior knowledge during reading in Spanish, as well as their association with eye movements. The present study aims to evaluate the effects of the presence absence of connectors in two argumentative texts on cognitive effort and reading comprehension. Forty-one psychology undergraduate students participated in a reading comprehension task, while their eye movements were recorded. The condition with connectors was related to prior knowledge, the slide time fixation, the slide number fixations, and the slide return fixations. The condition without connectors was related to the return fixations, the time fixation, and the number of fixations. Prior knowledge was correlated with the total time fixation, the total return fixations, and comprehension. This suggests that during reading without connectors more cognitive effort is required, observed in the return fixations; moreover, prior knowledge has an important role in the visual strategies required to process and obtain a representation of text. But participant performance was still good as observed in the scores of the reading comprehension task

Estudios prueban una asociación entre lectura y movimientos oculares al reportar el efecto de los conectores en el procesamiento textual. Pocas investigaciones revelan el papel de los conectores, el conocimiento previo y los movimientos oculares en la lectura de textos en español. El objetivo fue evaluar los efectos de la presencia-ausencia de conectores en dos textos argumentativos sobre el esfuerzo cognitivo y la comprensión lectora. Participaron 41 universitarios en una tarea de lectura con registro de sus movimientos oculares. La comprensión en la condición con conectores estuvo relacionada con conocimiento previo, tiempo y número de fijaciones por diapositiva, además del número de regresos en la lectura por diapositiva. Mientras la comprensión de textos sin conectores estuvo relacionada con conocimiento previo, regresos, tiempo y número de fijaciones, el conocimiento previo se correlacionó con tiempo y número fijaciones, regresos en la lectura y la comprensión. Se sugiere que la lectura de un texto sin conectores requerirá mayor esfuerzo cognitivo observado en los regresos en la lectura; además, el conocimiento previo afecta las estrategias visuales para procesar y representar mentalmente un texto. Pero, el desempeño de los participantes sigue siendo bueno, según lo observado en los puntajes de la tarea de comprensión lectora.

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

Clinical Personal Connectomics Using Hybrid PET/MRI / 대한핵의학회잡지

Brain connectivity can now be studied with topological analysis using persistent homology. It overcame the arbitrariness of thresholding to make binary graphs for comparison between disease and normal control groups. Resting-state fMRI can yield personal interregional brain connectivity based on perfusion signal on MRI on individual subject bases and FDG PET produces the topography of glucose metabolism. Assuming metabolism perfusion coupling and disregarding the slight difference of representing time of metabolism (before image acquisition) and representing time of perfusion (during image acquisition), topography of brain metabolism on FDG PET and topologically analyzed brain connectivity on resting-state fMRI might be related to yield personal connectomics of individual subjects and even individual patients. The work of association of FDG PET/resting-state fMRI is yet to be warranted; however, the statistics behind the group comparison of connectivity on FDG PET or resting-state MRI was already developed. Before going further into the connectomics construction using directed weighted brain graphs of FDG PET or resting-state fMRI, I detailed in this review the plausibility of using hybrid PET/MRI to enable the interpretation of personal connectomics which can lead to the clinical use of brain connectivity in the near future.

Fear Network Model in Panic Disorder: The Past and the Future

The core concept for pathophysiology in panic disorder (PD) is the fear network model (FNM). The alterations in FNM might be linked with disturbances in the autonomic nervous system (ANS), which is a common phenomenon in PD. The traditional FNM included the frontal and limbic regions, which were dysregulated in the feedback mechanism for cognitive control of frontal lobe over the primitive response of limbic system. The exaggerated responses of limbic system are also associated with dysregulation in the neurotransmitter system. The neuroimaging studies also corresponded to FNM concept. However, more extended areas of FNM have been discovered in recent imaging studies, such as sensory regions of occipital, parietal cortex and temporal cortex and insula. The insula might integrate the filtered sensory information via thalamus from the visuospatial and other sensory modalities related to occipital, parietal and temporal lobes. In this review article, the traditional and advanced FNM would be discussed. I would also focus on the current evidences of insula, temporal, parietal and occipital lobes in the pathophysiology. In addition, the white matter and functional connectome studies would be reviewed to support the concept of advanced FNM. An emerging dysregulation model of fronto-limbic-insula and temporooccipito-parietal areas might be revealed according to the combined results of recent neuroimaging studies. The future delineation of advanced FNM model can be beneficial from more extensive and advanced studies focusing on the additional sensory regions of occipital, parietal and temporal cortex to confirm the role of advanced FNM in the pathophysiology of PD.

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.

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.

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.

Functional Connectivity-Based Modelling Simulates Subject-Specific Network Spreading Effects of Focal Brain Stimulation / 神经科学通报·英文版

Neurostimulation remarkably alleviates the symptoms in a variety of brain disorders by modulating the brain-wide network. However, how brain-wide effects on the direct and indirect pathways evoked by focal neurostimulation elicit therapeutic effects in an individual patient is unknown. Understanding this remains crucial for advancing neural circuit-based guidance to optimize candidate patient screening, pre-surgical target selection, and post-surgical parameter tuning. To address this issue, we propose a functional brain connectome-based modeling approach that simulates the spreading effects of stimulating different brain regions and quantifies the rectification of abnormal network topology in silico. We validated these analyses by pinpointing nuclei in the basal ganglia circuits as top-ranked targets for 43 local patients with Parkinson's disease and 90 patients from a public database. Individual connectome-based analysis demonstrated that the globus pallidus was the best choice for 21.1% and the subthalamic nucleus for 19.5% of patients. Down-regulation of functional connectivity (up to 12%) at these prioritized targets optimally maximized the therapeutic effects. Notably, the priority rank of the subthalamic nucleus significantly correlated with motor symptom severity (Unified Parkinson's Disease Rating Scale III) in the local cohort. These findings underscore the potential of neural network modeling for advancing personalized brain stimulation therapy, and warrant future experimental investigation to validate its clinical utility.

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.

Review of Recent Advancement of Ultra High Field Magnetic Resonance Imaging: from Anatomy to Tractography

PURPOSE: Advances of magnetic resonance imaging (MRI), especially that of the Ultra-High Field (UHF) MRI will be reviewed. MATERIALS AND METHODS: Diffusion MRI data was obtained from a healthy adult young male of age 30 using a 7.0T research MRI scanner (Magnetom, Siemens) with 40 mT/m maximum gradient field. The specific imaging parameters used for the data acquisition were a single shot DW echo planar imaging. RESULTS: Three areas of the imaging experiments are focused on for the study, namely the anatomy, angiography, and tractography. CONCLUSION: It is envisioned that, in near future, there will be more 7.0T MRIs for brain research and explosive clinical application research will also be developed, for example in the area of connectomics in neuroscience and clinical neurology and neurosurgery.

Quality of life of people living with HIV/AIDS treated by the specialized service in Vitória-ES, Brazil / Qualidade de vida de pessoas que vivem com HIV/AIDS assistidas no serviço especializado em Vitória (ES), Brasil

The aim of this study is to establish the factors that influence the quality of life of people living with HIV/AIDS being treated at a specialized public service. The participants answered the questionnaire on sociodemographic conditions, issues related to HIV and daily habits. The quality of life was analyzed using the HIV/AIDS-targeted quality of life (HAT-QoL) instrument with 42 items divided into 9 fields: General Activity, Sexual Activity, Confidentiality Concerns, Health Concerns, Financial Concerns, HIV Awareness, Satisfaction with Life, Issues related to Medication and Trust in the Physician. Bivariate and multiple linear regressions were performed. Of the participants, 53.1% were women and had a mean age of 42 years. In analyzing the quality of life, the HAT-QoL domain with the lowest average was Financial Concerns (39.4), followed by Confidentiality Concerns (43.2), Sexual Activity (55.2) and Health Concerns (62. 88). There was an association between the variables: not being gainfully employed (p < 0.001), being mulatto or black (p = 0.045) and alcohol consumption (p = 0.041) with the worst quality of life scores. Inadequate socioeconomic and health conditions had a negative impact on the quality of life of people with HIV/AIDS.

O objetivo do presente estudo é verificar os fatores que influenciam na qualidade de vida das pessoas que vivem com HIV/AIDS assistidas no serviço especializado. Os entrevistados responderam os questionários sobre condições sociodemográficas, aspectos relacionados ao HIV e hábitos. A qualidade de vida foi analisada por meio do instrumento HAT-QoL, com 42 itens divididos em nove domínios: Atividade Geral, Atividade Sexual, Preocupações com Sigilo, Preocupação com a Saúde, Preocupação Financeira, Conscientização sobre o HIV, Satisfação com a Vida, Questões relativas à medicação e Confiança no médico. Análises bivariadas e regressão linear múltipla foram realizadas. Dos entrevistados, 53,1% eram mulheres e tinham média de idade de 42 anos. Na análise da qualidade de vida, o domínio do HAT-QoL com menor média foi Preocupação financeira (39,4), seguido de Preocupação com sigilo (43,2), Atividades sexuais (55,2) e Preocupação com a saúde (62,88). Houve associação entre as variáveis não ter vínculo trabalhista (p < 0,001), ser pardo ou negro (p = 0,045) e consumir bebida alcoólica (p = 0,041), com piores escores da qualidade de vida. Condições socioeconômicas e de saúde inadequadas apresentaram impacto negativo na qualidade de vida das pessoas com HIV/AIDS.

Advances in Functional Connectomics in Neuroscience : A Focus on Post-Traumatic Stress Disorder

Recent breakthroughs in functional neuroimaging techniques have launched the quest of mapping the connections of the human brain, otherwise known as the human connectome. Imaging connectomics is an umbrella term that refers to the neuroimaging techniques used to generate these maps, which recently has enabled comprehensive brain mapping of network connectivity combined with graph theoretic methods. In this review, we present an overview of the key concepts in functional connectomics. Furthermore, we discuss articles that applied task-based and/or resting-state functional magnetic resonance imaging to examine network deficits in post-traumatic stress disorder (PTSD). These studies have provided important insights regarding the etiology of PTSD, as well as the overall organization of the brain network. Advances in functional connectomics are expected to provide insight into the pathophysiology and the development of biomarkers for diagnosis and treatment of PTSD.

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.

Organización de las redes cerebrales / Organization of brain networks

El procesamiento de información por el cerebro se basa en sistemas de redes (networks) que poseen propiedades estructurales y funcionales derivadas de su extrema complejidad. Al tratarse de sistemas complejos con propiedades dinámicos no lineares, las redes se auto organizan permanentemente para adecuarse tanto a los procesamientos rápidos, como en el caso de las funciones cognitivas o ejecutivas, como a las más lentas, derivadas de la capacidad de generar cambios plásticos para adaptarse a las situaciones cambiantes de los entornos externos e internos. El estudio de la conectividad en el SNC se ha sistematizado por teorías de gráficas, modelos simples de un sistema, basados en conjuntos de nodos y márgenes o bordes que poseen propiedades de pequeño mundo (ni azarística, ni regular) de modo tal que el conectoma se organiza en los pequeños volúmenes relativos del cerebro permietiendo una alta eficiencia a bajo costo dada la corta distancia ente nodos centrales que procesan gran cantidad de información. Las proyecciones largas entre regiones distantes del SNC si bien eficaces en las funciones integradoras son costosas en estructura y metabolismo, y por ello vulnerables tanto en el desarrollo como en patologías, como la enfermedad de Alzheimer, la esquizofreia, la epilepsia, el ADHD la esclerosis múltiple, etc. Se conceptualiza al conectoma como fenotipo intermedio o endofenotipo con características heredables modificables en las distintas etapas de la vida, desde el desarrollo pre y perinatal hasta el envejecimiento.

The processing of information by the brain is based on systems of networks that have both structural and functional properties, given their extreme complexity. Because they consist in complex systems with nonlinear dynamic properties, the networks organize themselves permanently to adjust either to quick processings, as is the case with cognitive or executive functions and to the slowest processings which result from the capability of generating plastic changes to adapt to the changing contexts of the external and internal environments. The study of connectivity in the CNS has been systematized by graphics theories, which consist in simple models of a system based on sets of nodes and margins or borders that have properties of a small-world network (neither at random nor regular), so that the connectome is organized in the small relative volumes of the brain, enabling a high efficiency at a low cost, given the short distance between central nodes that process a large amount of information. Although the long projections between the regions that are far from the CNS are efficacious in the integrative functions, they are costly in structure and metabolism, and therefore, vulnerable both in development as well as in pathologies such as Alzheimer's Disease, schizophrenia, epilepsy and ADHD in multiple sclerosis, etc. The author conceptualizes the connectome as an intermediate phenotype or endophenotype with modifying inheritable characteristics in the different stages of life, from the pre- and perinatal development until ageing.