Auditory cortex hyperconnectivity before rTMS is correlated with tinnitus improvement.

INTRODUCTION: Repetitive transcranial magnetic stimulation (rTMS) has been used as a potential treatment for tinnitus; however, its effectiveness is variable and unpredictable. We hypothesized that resting-state functional connectivity before rTMS may be correlated with rTMS treatment effectiveness. METHODS: We applied 1-Hz rTMS to the left primary auditory (A1) and dorsolateral prefrontal cortices (DLPFC) of 10 individuals with tinnitus and 10 age-matched controls. Resting-state functional magnetic resonance imaging (fMRI) studies were performed approximately one week before rTMS. Seed-based connectivity analyses were conducted for each individual, with seed regions as rTMS target areas. RESULTS: Compared to controls, the left superior temporal areas showed significantly increased positive connectivity with the left A1 and negative connectivity with the left DLPFC in the tinnitus group. The left frontoparietal and right cerebellar areas showed significantly increased negative connectivity with the left A1 and positive connectivity with the left DLPFC. Seed-based hyperconnectivity was correlated with tinnitus improvement (pre-rTMS vs. 2-week post-rTMS Tinnitus Handicap Inventory scores). Tinnitus improvement was significantly correlated with left A1 hyperconnectivity; however, no correlation was observed with left DLPFC connectivity. Positive rTMS outcomes were associated with significantly increased positive connectivity in bilateral superior temporal areas and significantly increased negative connectivity in bilateral frontal areas. CONCLUSIONS: Our results suggest that oversynchronisation of left A1 connectivity before rTMS of the left A1 and DLPFC is associated with treatment effectiveness.

Auditory cortex hyperconnectivity before rTMS is correlated with tinnitus improvement / Correlación entre hiperconectividad de la corteza auditiva antes del tratamiento con estimulación magnética transcraneal repetitiva y mejoría de los acúfenos

Introduction: Repetitive transcranial magnetic stimulation (rTMS) has been used as a potential treatment for tinnitus; however, its effectiveness is variable and unpredictable. We hypothesized that resting-state functional connectivity before rTMS may be correlated with rTMS treatment effectiveness. Methods: We applied 1-Hz rTMS to the left primary auditory (A1) and dorsolateral prefrontal cortices (DLPFC) of 10 individuals with tinnitus and 10 age-matched controls. Resting-state functional magnetic resonance imaging (fMRI) studies were performed approximately one week before rTMS. Seed-based connectivity analyses were conducted for each individual, with seed regions as rTMS target areas. Results: Compared to controls, the left superior temporal areas showed significantly increased positive connectivity with the left A1 and negative connectivity with the left DLPFC in the tinnitus group. The left frontoparietal and right cerebellar areas showed significantly increased negative connectivity with the left A1 and positive connectivity with the left DLPFC. Seed-based hyperconnectivity was correlated with tinnitus improvement (pre-rTMS vs. 2-week post-rTMS Tinnitus Handicap Inventory scores). Tinnitus improvement was significantly correlated with left A1 hyperconnectivity; however, no correlation was observed with left DLPFC connectivity. Positive rTMS outcomes were associated with significantly increased positive connectivity in bilateral superior temporal areas and significantly increased negative connectivity in bilateral frontal areas. Conclusions: Our results suggest that oversynchronisation of left A1 connectivity before rTMS of the left A1 and DLPFC is associated with treatment effectiveness.(AU)

Introducción: La estimulación magnética transcraneal repetitiva (EMTr) se ha utilizado como posible tratamiento para los acúfenos, aunque su efectividad es variable e impredecible. Planteamos la hipótesis de que existe una correlación entre la conectividad funcional en estado de reposo antes de aplicar EMTr y la efectividad de dicho tratamiento. Métodos: Aplicamos EMTr a 1 Hz sobre la corteza auditiva primaria (A1) y la corteza prefrontal dorsolateral (CPFDL) izquierdas de 10 pacientes con acúfenos y 10 controles del mismo rango de edad. Se realizaron estudios de resonancia magnética funcional (RMF) en estado de reposo de todos los pacientes aproximadamente una semana antes de la EMTr. En cada caso, se construyó un mapa de conectividad basado en las ROIs, en el que las ROIs eran las áreas que se tratarían con la EMTr. Resultados: La región temporal superior izquierda mostró una conectividad positiva significativamente mayor con el área A1 izquierda y mayor conectividad negativa con la CPFDL izquierda en los pacientes con acúfenos que en los controles. Además, las áreas frontoparietal izquierda y cerebelar derecha mostraron una conectividad negativa significativamente superior con el área A1 izquierda y mayor conectividad positiva con la CPFDL izquierda. La hiperconectividad de las ROIs se correlacionó con mejoría de los acúfenos según las puntuaciones pre-EMTr y 2 semanas post-EMTr en la escala Tinnitus Handicap Inventory. La mejoría de los acúfenos se correlacionó de manera significativa con la hiperconectividad del área A1 izquierda; sin embargo, no se encontró correlación con la conectividad de la CPFDL izquierda. El resultado favorable del tratamiento con EMTr se asocia con una mayor conectividad positiva en áreas temporales superiores de ambos hemisferios y con mayor conectividad negativa en áreas frontales bilaterales...(AU)

Epilepsia como una enfermedad de redes neuronales. Un punto de vista neurofisiológico / Epilepsy as a disease affecting neural networks: A neurophysiological perspective

Introducción: La epilepsia es un conjunto de redes de estructuras cerebrales representadas bilateralmente, que están funcional y anatómicamente conectadas; en la epilepsia, la actividad de cualquier parte del cerebro afecta la actividad de las demás. Esto es relevante para el entendimiento de la fisiopatología, la etiología, el diagnóstico y la prognosis de esta enfermedad.ObjetivoRevisar el estado del arte en cuanto al entendimiento de la visión neurofisiológica de la epilepsia como una enfermedad de redes neuronales.ResultadosSe describen los principios básicos y avanzados de la epilepsia como enfermedad de redes neuronales usando distintos métodos clínicos y matemáticos con una visión neurofisiológica, indicando las limitaciones de estos hallazgos en el contexto clínico.ConclusionesLa epilepsia es una enfermedad de redes neuronales complejas cuyo entendimiento permitirá mejorar los tratamientos disponibles y la certeza pronostica. (AU)

Introduction: The brain is a series of networks of functionally and anatomically connected, bilaterally represented structures; in epilepsy, activity of any part of the brain affects activity in the other parts. This is relevant for understanding the pathophysiology, diagnosis, and prognosis of the disease.ObjectiveIn this study, we present a state-of-the-art review of the neurophysiological view of epilepsy as a disease affecting neural networks.ResultsWe describe the basic and advanced principles of epilepsy as a disease affecting neural networks, based on the use of different clinical and mathematical techniques from a neurophysiological perspective, and signal the limitations of these findings in the clinical context.ConclusionsEpilepsy is a disease affecting complex neural networks. Understanding these will enable better management and prognostic confidence. (AU)

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.

Epilepsy as a disease affecting neural networks: a neurophysiological perspective.

INTRODUCTION: The brain is a series of networks of functionally and anatomically connected, bilaterally represented structures; in epilepsy, activity of any part of the brain affects activity in the other parts. This is relevant for understanding the pathophysiology, diagnosis, and prognosis of the disease. OBJECTIVES: In this study, we present a state-of-the-art review of the neurophysiological view of epilepsy as a disease affecting neural networks. RESULTS: We describe the basic and advanced principles of epilepsy as a disease affecting neural networks, based on the use of different clinical and mathematical techniques from a neurophysiological perspective, and signal the limitations of these findings in the clinical context. CONCLUSIONS: Epilepsy is a disease affecting complex neural networks. Understanding these will enable better management and prognostic confidence.

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.

Auditory cortex hyperconnectivity before rTMS is correlated with tinnitus improvement.

INTRODUCTION: Repetitive transcranial magnetic stimulation (rTMS) has been used as a potential treatment for tinnitus; however, its effectiveness is variable and unpredictable. We hypothesized that resting-state functional connectivity before rTMS may be correlated with rTMS treatment effectiveness. METHODS: We applied 1-Hz rTMS to the left primary auditory (A1) and dorsolateral prefrontal cortices (DLPFC) of 10 individuals with tinnitus and 10 age-matched controls. Resting-state functional magnetic resonance imaging (fMRI) studies were performed approximately one week before rTMS. Seed-based connectivity analyses were conducted for each individual, with seed regions as rTMS target areas. RESULTS: Compared to controls, the left superior temporal areas showed significantly increased positive connectivity with the left A1 and negative connectivity with the left DLPFC in the tinnitus group. The left frontoparietal and right cerebellar areas showed significantly increased negative connectivity with the left A1 and positive connectivity with the left DLPFC. Seed-based hyperconnectivity was correlated with tinnitus improvement (pre-rTMS vs. 2-week post-rTMS Tinnitus Handicap Inventory scores). Tinnitus improvement was significantly correlated with left A1 hyperconnectivity; however, no correlation was observed with left DLPFC connectivity. Positive rTMS outcomes were associated with significantly increased positive connectivity in bilateral superior temporal areas and significantly increased negative connectivity in bilateral frontal areas. CONCLUSIONS: Our results suggest that oversynchronisation of left A1 connectivity before rTMS of the left A1 and DLPFC is associated with treatment effectiveness.

Epilepsy as a disease affecting neural networks: A neurophysiological perspective. / Epilepsia como una enfermedad de redes neuronales. Un punto de vista neurofisiológico.

INTRODUCTION: The brain is a series of networks of functionally and anatomically connected, bilaterally represented structures; in epilepsy, activity of any part of the brain affects activity in the other parts. This is relevant for understanding the pathophysiology, diagnosis, and prognosis of the disease. OBJECTIVE: In this study, we present a state-of-the-art review of the neurophysiological view of epilepsy as a disease affecting neural networks. RESULTS: We describe the basic and advanced principles of epilepsy as a disease affecting neural networks, based on the use of different clinical and mathematical techniques from a neurophysiological perspective, and signal the limitations of these findings in the clinical context. CONCLUSIONS: Epilepsy is a disease affecting complex neural networks. Understanding these will enable better management and prognostic confidence.

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 humanoem 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 dasafasias, bem como de mecanismos de recuperação. (AU)

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. (AU)

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

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.