A lombalgia mecânica comum (LMC) representa um problema particularmente importante no ambiente ocupacional, muitas vezes associado a incapacidade, afastamento do trabalho e alto custo socioeconômico. O surgimento da neuroimagem funcional permitiu novos conhecimentos sobre a estrutura cerebral e a fisiologia da dor crônica. Embora os aspectos relacionados ao trabalho sejam importantes fatores de risco para a cronicidade, existem poucos estudos que abordam especificamente a fisiopatologia da LMC em indivíduos afastados do trabalho. A esse respeito, questionamos se um fator como a atenção, conhecida como um importante modulador da dor, poderia desempenhar um papel distintivo na modulação da dor nos indivíduos com LMC afastados do trabalho. Objetivos: comparar os correlatos neuronais entre indivíduos com lombalgia mecânica comum com afastamento do trabalho, com indivíduos lombálgicos sem afastamento. Métodos: Foram selecionados 74 indivíduos com LMC crônica, divididos em três grupos: indivíduos com LMC e afastamento do trabalho (LMC/A); indivíduos com LMC sem afastamento do trabalho (LMC) e indivíduos sem qualquer tipo de dor crônica e sem afastamento do trabalho (Controle). O estudo foi realizado no Hospital Israelita Albert Einstein (HIAE). A ressonância magnética funcional (RMf) foi utilizada durante o desempenho de dois paradigmas (dor e atenção). Resultados: Após a estimulação dolorosa, na comparação entre os grupos, verificamos diferença significativa na condição estimulação > repouso, sendo que o contraste LMC > LMC/A mostrou maior resposta hemodinâmica (efeito BOLD) no córtex cingulado anterior e giro frontal superior e médio direito (p < 0,001). No contraste controles > LMC/A, o grupo controle apresentou maior efeito BOLD em região do polo frontal e paracingulado (p = 0,002). Conclusão: Nosso estudo corrobora o conceito de que a presença de dor crônica está associada a uma alteração na plasticidade neuronal em áreas cerebrais que se estendem além das regiões somatossensoriais, para incluir áreas que processam emoções / Chronic low back pain (CLBP) is a particularly important problem in the occupational environment, often associated with incapacity, sick leave and high socioeconomic cost. The emergence of functional neuroimaging allowed new insights into the brain structure and physiology of chronic pain. Although work-related aspects are important risk factors for chronicity, there are few studies that specifically address the pathophysiology of CLBP in individuals with sick leave. In this regard, we questioned whether a factor such as the attention known as an important pain modulator could play a distinctive role in modulating pain in individuals with CLBP with sick leave. Objective The overall objective of this study is to compare the neuronal correlates between groups of individuals CLBP with or without sick leave. Methods We selected 74 individuals, divided into three groups: individuals with CLBP, functional incapacity and sick leave (CLBP_L); individuals with CLBP, functional disability without sick leave (CLBP_NL); individuals without any form of chronic pain and without sick leave (Control). Functional magnetic resonance imaging (fMRI) was used during the performance of two paradigms (pain and attention).Results After painful stimulation, a significant difference was observed in the stimulation > rest condition, while the CLBP > CLBP_L contrast showed a higher hemodynamic response in the anterior cingulate cortex and the right medium /superior frontal gyrus (p < 0.001) and in contrast controls > CLBP_L, the control group presented higher hemodynamic response in the frontal pole and paracingulate region (p = 0.002).Conclusions Our study corroborates the idea that the presence of chronic pain is associated with an alteration in neuronal plasticity involving brain areas linked to emotions and not just somatosensory areas

INTRODUÇÃO: O distúrbio fonológico é uma alteração na fala, que pode ocorrer em um ou mais níveis responsáveis pelo desenvolvimento do sistema fonológico, sendo três os níveis: produção e percepção da fala e organização de regras. Para ocorrer o desenvolvimento adequado do sistema fonológico, assim como dos outros aspectos da linguagem, são necessários a integridade e o funcionamento adequado do sistema auditivo, tanto na sua porção periférica, quanto na central. OBJETIVO: avaliar crianças com distúrbio fonológico, caracterizando os potenciais evocados auditivos de curta, média, e longa latências, além de verificar a evolução dos resultados dos potenciais evocados auditivos frente à terapia fonoaudiológica. MÉTODO: foram avaliadas 24 crianças sem distúrbio fonológico (grupo controle) e 23 crianças com distúrbio fonológico (grupo estudo), estas últimas divididas em dois subgrupos: 12 crianças submetidas à terapia fonoaudiológica (subgrupo IA) e 11 crianças não submetidas à terapia fonoaudiológica (subgrupo IB). Todas as crianças encontraram-se na faixa etária de oito a 11 anos, e foram submetidas ao ABFW Teste de Linguagem Infantil, audiometrias tonal e vocal, medidas de imitância acústica, potencial evocado auditivo de tronco encefálico, potencial evocado auditivo de média latência, e potencial cognitivo. As crianças com distúrbio fonológico submetidas à terapia fonoaudiológica foram reavaliadas após 12 sessões, e as crianças com distúrbio fonológico e não submetidas à terapia fonoaudiológica, após três meses da avaliação inicial. RESULTADOS: os resultados da análise quantitativa demonstraram que crianças com distúrbio fonológico, antes da terapia fonoaudiológica, apresentam diferença estatisticamente significante na latência da onda III e nos interpicos I-III e I-V do potencial evocado auditivo de tronco encefálico e na latência do potencial cognitivo, não sendo observada tal diferença para o potencial evocado auditivo de média latência. Na comparação dos resultados normais e alterados (análise qualitativa), entre os grupos controle e estudo, observou- se que o grupo estudo apresentou maior porcentagem de resultados alterados. Após terapia fonoaudiológica, observou-se melhora nos resultados do potencial evocado auditivo de tronco encefálico e do potencial cognitivo. CONCLUSÕES: crianças com distúrbio fonológico apresentam alterações no potencial evocado auditivo de tronco encefálico e no potencial cognitivo, sugerindo comprometimento da via auditiva em tronco encefálico e regiões corticais, apresentando melhora nos resultados destes potenciais frente à terapia fonoaudiológica. / INTRODUCTION: the phonological disorder is a speech disorder that may occur in one or more levels that are responsible for the development of the phonological system. Such levels are: speech production and perception, and rules organization. For a normal development of the phonological system, as well as of other aspects of language, it is necessary the integrity and the adequate functioning of the auditory system, either in its peripheral or central portion. AIM: to evaluate children with phonological disorder, characterizing the auditory evoked potentials of short, middle and long latencies, and to verify the auditory evoked potential results improvement after speech therapy. METHOD: 24 children without phonological disorder (control group) and 23 children with phonological disorder (study group) were evaluated; the study group was divided in two subgroups: 12 children attending speech therapy (subgroup IA) and 11 children not attending speech therapy (subgroup IB). Children?s age ranged from eight to 11 years, and all of them underwent the ABFW Child Language Test, pure tone and speech audiometry, acoustic immitance measures, brainstem auditory evoked potential, middle latency response, and cognitive potential. Children with phonological disorder who attended speech therapy were re-evaluated after 12 sessions, and children with phonological disorder who did not attend speech therapy were re-evaluated 3 months after the initial evaluation. RESULTS: the quantitative analysis of the results showed that children with phonological disorder presented statistical difference in the latency of wave III and in the interpeaks I-III and I-V of the brainstem auditory evoked potential, and in the latency of the cognitive potential; no statistical difference was found concerning the middle latency response. Comparing the normal and altered results (qualitative analysis) between the control and study groups, it was observed that the study group presented higher percentage of altered results. After the speech therapy, it was observed results improvement of the brainstem auditory evoked potential and of the cognitive potential. CONCLUSIONS: children with phonological disorder present alteration in the brainstem auditory evoked potential and in the cognitive potential, suggesting prejudice in the brainstem auditory pathway and cortical regions, showing improvement of these potentials? results with speech therapy.

A lombalgia mecânica comum (LMC) representa um problema particularmente importante no ambiente ocupacional, muitas vezes associado a incapacidade, afastamento do trabalho e alto custo socioeconômico. O surgimento da neuroimagem funcional permitiu novos conhecimentos sobre a estrutura cerebral e a fisiologia da dor crônica. Embora os aspectos relacionados ao trabalho sejam importantes fatores de risco para a cronicidade, existem poucos estudos que abordam especificamente a fisiopatologia da LMC em indivíduos afastados do trabalho. A esse respeito, questionamos se um fator como a atenção, conhecida como um importante modulador da dor, poderia desempenhar um papel distintivo na modulação da dor nos indivíduos com LMC afastados do trabalho. Objetivos: comparar os correlatos neuronais entre indivíduos com lombalgia mecânica comum com afastamento do trabalho, com indivíduos lombálgicos sem afastamento. Métodos: Foram selecionados 74 indivíduos com LMC crônica, divididos em três grupos: indivíduos com LMC e afastamento do trabalho (LMC/A); indivíduos com LMC sem afastamento do trabalho (LMC) e indivíduos sem qualquer tipo de dor crônica e sem afastamento do trabalho (Controle). O estudo foi realizado no Hospital Israelita Albert Einstein (HIAE). A ressonância magnética funcional (RMf) foi utilizada durante o desempenho de dois paradigmas (dor e atenção). Resultados: Após a estimulação dolorosa, na comparação entre os grupos, verificamos diferença significativa na condição estimulação > repouso, sendo que o contraste LMC > LMC/A mostrou maior resposta hemodinâmica (efeito BOLD) no córtex cingulado anterior e giro frontal superior e médio direito (p < 0,001). No contraste controles > LMC/A, o grupo controle apresentou maior efeito BOLD em região do polo frontal e paracingulado (p = 0,002). Conclusão: Nosso estudo corrobora o conceito de que a presença de dor crônica está associada a uma alteração na plasticidade neuronal em áreas cerebrais que se estendem além das regiões somatossensoriais, para incluir áreas que processam emoções / Chronic low back pain (CLBP) is a particularly important problem in the occupational environment, often associated with incapacity, sick leave and high socioeconomic cost. The emergence of functional neuroimaging allowed new insights into the brain structure and physiology of chronic pain. Although work-related aspects are important risk factors for chronicity, there are few studies that specifically address the pathophysiology of CLBP in individuals with sick leave. In this regard, we questioned whether a factor such as the attention known as an important pain modulator could play a distinctive role in modulating pain in individuals with CLBP with sick leave. Objective The overall objective of this study is to compare the neuronal correlates between groups of individuals CLBP with or without sick leave. Methods We selected 74 individuals, divided into three groups: individuals with CLBP, functional incapacity and sick leave (CLBP_L); individuals with CLBP, functional disability without sick leave (CLBP_NL); individuals without any form of chronic pain and without sick leave (Control). Functional magnetic resonance imaging (fMRI) was used during the performance of two paradigms (pain and attention).Results After painful stimulation, a significant difference was observed in the stimulation > rest condition, while the CLBP > CLBP_L contrast showed a higher hemodynamic response in the anterior cingulate cortex and the right medium /superior frontal gyrus (p < 0.001) and in contrast controls > CLBP_L, the control group presented higher hemodynamic response in the frontal pole and paracingulate region (p = 0.002).Conclusions Our study corroborates the idea that the presence of chronic pain is associated with an alteration in neuronal plasticity involving brain areas linked to emotions and not just somatosensory areas

Para caracterizar os potenciais evocados auditivos de crianças com distúrbio fonológico e verificar a evolução dos resultados destes potenciais frente à terapia fonoaudiológica, foram avaliadas por meio do potencial evocado auditivo de tronco encefálico, potencial evocado auditivo de média latência e potencial cognitivo, 24 crianças sem distúrbio fonológico e 23 crianças com distúrbio fonológico. Os resultados demonstraram que crianças com distúrbio fonológico apresentam diferença estatisticamente significante no potencial evocado auditivo de tronco encefálico e no potencial cognitivo antes da terapia fonoaudiológica, observando melhora nestes potenciais pós terapia fonoaudiológica / In order to characterize the auditory evoked potentials of children with phonological disorder and to verify these potentials results improvement after speech therapy, 24 children without phonological disorder and 23 children with phonological disorder were evaluated through brainstem auditory evoked potential, middle latency response and cognitive potential. The results showed that children with phonological disorder present a statistically significant difference in the brainstem auditory evoked potential and in the cognitive potential before the speech therapy, with an improvement of those potential after speech therapy

INTRODUÇÃO: O transtorno fonológico é uma alteração na fala que ocasiona um grau variável de inteligibilidade de fala. A gravidade deste transtorno pode ser medida por meio do Percentage of Consonants Correct-Revised, que verifica o número de consoantes corretas em uma amostra de fala em relação ao número total de consoantes desta amostra. A literatura relata sete subtipos do transtorno fonológico, dentre eles a relacionada à otite média com efusão. Os Potenciais Evocados Auditivos também são utilizados para avaliar indivíduos com alteração de linguagem, pois esta população pode apresentar um déficit na via auditiva central. OBJETIVO: caracterizar os resultados dos potenciais evocados auditivos de longa latência N1, P2, N2 e P300 obtidos em crianças com transtorno fonológico, e verificar a evolução dos resultados destes potenciais frente à terapia fonoaudiológica, correlacionando esta evolução ao histórico de otite e a gravidade deste transtorno. MÉTODOS: Participaram da pesquisa 66 crianças, 25 sem transtorno fonológico (grupo controle) e 41 com transtorno fonológico (grupo estudo). As crianças do grupo estudo foram divididas em dois subgrupos: 22 formaram o subgrupo estudo A e 19 formaram o subgrupo estudo B. Todas as crianças foram submetidas à avaliação audiológica básica e aos potencias evocados auditivos de longa latência. Após a avaliação audiológica completa, as crianças do subgrupo estudo A foram submetidas a 12 sessões de terapia fonoaudiológica e reavaliadas audiologicamente após este período e, as crianças do subgrupo estudo B, crianças que aguardavam terapia em fila de espera, foram reavaliadas após três meses da avaliação inicial. RESULTADOS: os resultados demonstraram, na análise dos dados quantitativos, que o grupo estudo, antes da terapia fonoaudiológica, apresentou diferença estatisticamente significante para as latências dos componentes P2 e P300 e para a amplitude do P300, quando comparado com o grupo controle. Na comparação das latências não foram observadas diferenças estatisticamente significantes entre a primeira e segunda avaliações audiológicas, tanto para o subgrupo estudo A como para o subgrupo estudo B. Verificou-se diferença estatisticamente significante para as amplitudes do P300 e do P2/N2 na comparação entre a primeira e segunda avaliações audiológicas para os subgrupos estudo A e B, respectivamente. Na análise dos dados qualitativos, verificou-se que o P300 apresentou maior porcentagem de resultados alterados no grupo estudo quando comparado ao grupo controle, sendo que o tipo de alteração mais freqüentemente encontrado foi o aumento de latência. Após terapia fonoaudiológica, observou-se maior ocorrência de melhora nos resultados para todos os componentes estudados. Os resultados demonstraram, também, que não existiu associação entre a evolução dos resultados dos potenciais evocados auditivos de longa latência e o histórico de otite, bem como correlação com o Percentage of Consonants Correct-Revised. CONCLUSÕES: crianças com transtorno fonológico apresentam alterações no P300, sugerindo comprometimento da via auditiva central, provavelmente decorrente de alteração no processamento auditivo, apresentando melhora nos resultados de todos os componentes dos potenciais evocados auditivos de longa latência frente à terapia fonoaudiológica. Não existe associação entre a evolução dos resultados e histórico de otite, bem como correlação entre a evolução dos resultados e Percentage of Consonants Correct-Revised. / INTRODUCTION: Phonological disorder is a speech disorder that causes a varying degree of speech intelligibility. The severity of this disorder may be measured by the Percentage of Consonants Corrects-Revised, which verifies the number of correct consonants in a speech sample in relation to the total number of consonants in the sample. Literature reports seven subtypes of phonological disorder, amongst them the one related to otitis media with effusion. Auditory evoked potentials are also used to assess individuals with language disorder since this population may present deficit in the central auditory pathway. AIM: to characterize the long latency auditory evoked potentials results N1, P2, N2 and P300 of children with phonological disorder and to verify the improvement of such potentials results with the speech therapy, correlating this improvement to the background of otitis and the severity of this disorder. METHODS: Sixty six children took part in this study, 25 without phonological disorder (control group) and 41 with phonological disorder (study group). Children of the study group were divided into two subgroups: study subgroup A, composed by 22 children and study subgroup B composed by 19 children. All children underwent a basic audiological evaluation and long latency auditory evoked potentials. After the complete audiological assessment, children from study subgroup A underwent 12 sessions of speech therapy and were audiologically re-assessed after this period; children from study subgroup B were re-assessed three months after the initial assessment. RESULTS: the analysis of quantitative data revealed that the study group presented significant statistical difference, before the speech therapy, for the latencies of components P2 and P300 and for the amplitude of P300 when compared to the control group. Comparing the latencies, no significant statistical differences were observed between the first and the second audiological evaluations, either for the study subgroup A or B. A significant statistical difference was verified for the amplitudes of P300 and P2/N2 in the comparison between the first and the second audiological evaluations for subgroups A and B respectively. The analysis of qualitative data revealed that the P300 presented higher percentage of altered results in the study group when compared to the control group, and the most frequent type of alteration found was increased latency. After the speech therapy, the results of all components analyzed improved. Results also showed that there was no association between the improvement of long latency auditory evoked potentials results with the background of otitis, as well as with the Percentage of Consonants Corrects-Revised. CONCLUSIONS: children with phonological disorder present altered P300 suggesting involvement of the central auditory pathway probably due to alterations in the auditory processing, presenting improvement in all components of long latency auditory evoked potentials results after speech therapy. There is no association between the improvement of results and the background of otitis, as well as no correlation between the improvement of results and the Percentage of Consonants Corrects-Revised.

Introdução: A esclerose mesial temporal (EMT) é a principal causa de epilepsia resistente ao tratamento medicamentoso. Pacientes com EMT apresentam dificuldades no processamento semântico e fonológico de linguagem e maior incidência de reorganização cerebral da linguagem (bilateral ou à direita) em relação à população geral. A ressonância magnética funcional (RMf) permite avaliar a reorganização cerebral das redes de linguagem, comparando padrões de ativação cerebral entre diversas regiões cerebrais. Objetivo: Investigar o desempenho linguístico de pacientes com EMT unilateral esquerda e direita e a ocorrência de reorganização das redes de linguagem com RMf para avaliar se a reorganização foi benéfica para a linguagem nestes pacientes. Métodos: Utilizamos provas clínicas de linguagem e paradigmas de nomeação visual e responsiva para RMf, desenvolvidos para este estudo. Foram avaliados 24 pacientes com EMTe, 22 pacientes com EMTd e 24 controles saudáveis, submetidos a provas de linguagem (fluência semântica e fonológica, nomeação de objetos, verbos, nomes próprios e responsiva, e compreensão de palavras) e a três paradigmas de linguagem por RMf [nomeação por confrontação visual (NCV), nomeação responsiva à leitura (NRL) e geração de palavras (GP)]. Seis regiões cerebrais de interesse (ROI) foram selecionadas (giro frontal inferior, giro frontal médio, giro frontal superior, giro temporal inferior, giro temporal médio e giro temporal superior). Índices de Lateralidade (ILs) foram calculados com dois métodos: bootstrap, do programa LI-Toolbox, independe de limiar, e PSC, que indica a intensidade da ativação cerebral de cada voxel. Cada grupo de pacientes (EMTe e EMTd) foi dividido em dois subgrupos, de acordo com o desempenho em relação aos controles na avaliação clinica de linguagem. O <= -1,5 foi utilizado como nota de corte para dividir os grupos em pacientes com bom e com mau desempenho de linguagem. Em seguida, comparou-se o desempenho linguístico dos subgrupos ao índices IL-boot. Resultados: Pacientes com EMT esquerda e direita mostraram pior desempenho que controles nas provas clínicas de nomeação de verbos, nomeação de nomes próprios, nomeação responsiva e fluência verbal. Os mapas de ativação cerebral por RMf mostraram efeito BOLD em regiões frontais e temporoparietais de linguagem. Os mapas de comparação de ativação cerebral entre os grupos revelaram que pacientes com EMT esquerda e direita apresentam maior ativação em regiões homólogas do hemisfério direito em relação aos controles. Os ILs corroboraram estes resultados, mostrando valores médios menores para os pacientes em relação aos controles e, portanto, maior simetria na representação da linguagem. A comparação entre o IL-boot e o desempenho nas provas clínicas de linguagem indicou que, no paradigma de nomeação responsiva à leitura, a reorganização funcional no giro temporal médio, e possivelmente, nos giros temporal inferior e superior associou-se a desempenho preservado em provas de nomeação. Conclusão: Pacientes com EMT direita e esquerda apresentam comprometimento de nomeação e fluência verbal e reorganização da rede cerebral de linguagem. A reorganização funcional de linguagem em regiões temporais, especialmente o giro temporal médio associou-se a desempenho preservado em provas de nomeação em pacientes com EMT esquerda no paradigma de RMf de nomeação responsiva à leitura / Introduction: Mesial temporal sclerosis (MTS) is the commonest cause of drug resistant epilepsy. MTS patients experience phonological and semantic processing difficulties, and increased prevalence of atypical (bilateral or right hemisphere) language dominance compared to the general population. Language reorganization can be studied with functional magnetic resonance imaging (fMRI), which allows comparison of brain activation patterns in different brain regions. Objective: To investigate performance on language tasks in patients with unilateral left and right MTS, and occurrence of atypical language dominance to determine if reorganization of language networks is beneficial to \' f . : W w y-four left MTS, 22 right MTS patients and 24 healthy controls. Subjects underwent language tasks (semantic and phonological fluency, object, verb, proper noun, and responsive naming, and word comprehension), and fMRI language paradigms [visual confrontation naming (VCN), reading responsive reading (RRN) and word generation (WG)]. Six regions of interest (ROI) (inferior frontal, middle frontal, superior frontal, inferior temporal, middle temporal and superior temporal gyri) were defined. Two language lateralization indexes (LI) were obtained for each ROI, one with a threshold-independent method using a bootstrap algorithm (LI-boot), and one that measures brain activation intensity in each voxel (Percentage Signal Change - PSC). Each patient group (left MTS and right MTS) was divided into two subgroups according to performance relative to controls in the language tasks. Z- <= -1.5 was used as a cut-off to divide patients in good and poor language performance groups. LI-boot indexes were compared between language performance subgroups. Left and right MTS patients showed worse performance than controls in verb, proper noun, and responsive naming, and verbal fluency language tasks. fMRI activation maps showed increased BOLD signal in frontal and temporoparietal language regions. Group comparison activation maps revealed that left and right MTS patients showed increased activation in homologous right hemisphere regions compared to controls. These results were corroborated by lower LI mean values for patients compared to controls, indicating greater hemispheric language representation symmetry. Comparison between LI-boot indexes and performance in language tasks showed that functional reorganization in the middle temporal, and, possibly, inferior and superior temporal gyri was associated with preserved naming performance. Conclusion: Left and right MTS patients display impaired naming and verbal fluency, as well as reorganization of the language network. Language network reorganization in the temporal regions, specially middle temporal gyrus, was associated with preserved naming in left MTS patients, in the responsive reading naming fMRI paradigm

Local field potentials (LFPs), extracellular potentials that reflect localized electrical activity, have long been used as a window to understand the behavioural dependence and mechanistic aspects of brain physiology. A principal premise that has driven the interpretation of LFPs is that they largely reflect the synaptic drive that impinges on neurons located in the vicinity of the recording microelectrode. An implicit, yet critical, assumption that led to the emergence of this premise is that dendrites, the structures onto which most synaptic inputs project, are purely passive compartments. However, there is a growing body of evidence demonstrating that dendrites express a plethora of active conductance, like voltage-gated ion channels, several of which are active in the subthreshold regime. These subthreshold-activated ion channels and their intra-neuronal localization profiles play widely acknowledged regulatory roles in the physiology, plasticity and pathophysiology of synapses and neurons. Despite this, the implications for the existence of these subthreshold conductances on constituent oscillatory patterns in LFPs and on the phase of neuronal spiking with reference to oscillating LFPs have surprisingly remained unexplored. The aim of this thesis is to examine if there exists a role of subthreshold conductances in regulating LFPs and the phase of spikes with reference to these LFPs. To address this, we chose to study LFPs and spikes from the CA1 region of the rat hippocampus, with hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels forming the specific subthreshold conductance of focus. The reasons behind these choices were manifold. First, CA1 pyramidal neurons are arranged in a laminar open-field configuration, making the interpretation of the source-sink formation in this region relatively tractable. Second, the dendrites of these neurons are endowed with a multitude of subthreshold conductances whose expression profiles, physiology and plasticity have been characterized in great detail. Third, this brain region has been implicated in coding for episodic and spatial memories. The phase of the spikes of the CA1 pyramidal neurons, with reference to the LFP, is believed to serve as a code that can be used to decode the location of the animal. Given that the most dominant LFP pattern seen in the CA1 region during such active exploration (and possibly encoding of spatial memories) consists of oscillations in the 4–10 Hz theta frequency band, we decided to focus our study on theta-frequency LFPs. Finally, consistent with the choice of the specific band of LFP frequencies, we focused on HCN channels because of their predominantly dendritic expression and their ability to bestow resonance and impedance phase lead, both in the theta-frequency range, on CA1 pyramidal neurons. In exploring the role of HCN channels on LFPs, we used a multi-compartmental morphologically realistic CA1 pyramidal neuron model and introduced an HCN channel conductance gradient that was constrained with several experimental measurements. This neuron was driven by dendritic excitatory synapses and perisomatic inhibitory synapses, both theta-modulated with a phase difference of +60º between their arrivals timings. We increased the excitatory synaptic conductance with distance from the soma to account for the fact that irrespective of the location of the synapse in the dendrites, the unitary excitatory post-synaptic potential remains the same at the soma. Employing these model configurations, we generated 25 different synaptic distributions on the same neuronal morphology to account for the input variability and for each of these models, we recorded transmembrane currents from all the compartments, for 8–10 cycles of the theta-modulated inputs. To model LFPs using the forward modelling scheme of line source approximation, we designed a cylindrical neuropil of 40 µm height and 100 µm radius and inserted a virtual linear electrode with 7 contact points distributed on the probe at the canter of the neuropil such that we could compute the LFP at all the strata of the CA1 region. Accounting for the volume of the neuropil and the density of neurons in this region, we took 440 instances of the morphology, rotated them at uniformly distributed angles, and distributed the somata of these model neurons within the neuropil. Each of these 440 neurons received transmembrane currents from one of the 25 models picked uniformly. With a passive model, where we did not introduce HCN channels, we expectedly observed the formation of a source-sink structure that expressed as a progressive phase shift spanning different strata, owing to the perisomatic inhibitory currents coupled with the dendritic excitatory currents. On introducing a somatodendritic gradient of HCN conductance with identical input conditions, we observed a phase lead in the LFPs across all the layers, with the magnitude of the lead increasing with distance from the soma in a manner that was correlated with the increase in HCN conductance. Next, we computed spike phases, for each of the 25 neuron models, with reference to the stratum pyramidale (SP) LFP for model configurations with and without HCN channels. We found that the spikes showed a phase lag in the presence of a gradient of HCN channels when compared to the spike phases measured from the passive neuron models. Finally, we computed the coherence of spikes across all the 25 passive or 25 active (with HCN channels) neuron models and found that the presence of HCN channels greatly enhanced spike phase coherence across neurons. Together, these results demonstrate that the presence of HCN channels introduces a lead in the theta-frequency LFP phase, a lag in the associated spike phase, and a significant enhancement of spike phase coherence. Exploring the robustness of these findings to the model configuration, we first found these conclusions to be robust to increases in neuropil size (400-µm diameter neuropil with 1797 neurons, and 1-mm diameter neuropil with 11297 neurons). Next, we introduced heterogeneities in the population of neurons (in terms of morphology as well as passive and active properties) that formed the neuropil, and found our conclusions to be invariant to such degeneracy in the underlying neuronal population. It has been observed that under certain pathological conditions like epilepsy, an entire population of CA1 neurons can undergo intrinsic plasticity, such as global (i.e., across the entire neuronal topograph) downregulation of HCN channels. To assess the impact of such up/downregulation on LFPs, we respectively increased/decreased HCN channel conductance globally in our model neurons, and found the magnitude of the lead in the LFP phase to progressively increase with HCN-channel conductance. Similarly, the magnitude of the spike-phase lag and the spike phase coherence also progressively increased as functions of HCN-channel conductance. Although such population-level global intrinsic plasticity is observed under pathological conditions, a more physiological scenario would be when a single neuron, in the process of encoding new inputs (such as encoding spatial or episodic memories), undergoes intrinsic plasticity. To assess this, we increased or decreased HCN-channel conductance specifically in a single neuron placed closest to the electrode, while leaving the HCN expression in other neurons of the neuropil at the baseline level. Expectedly, we did not find significant changes in LFP amplitude or phase, but we did find a significant lag in the spike phase preference of the neuron that underwent an upregulation of HCN conductance. Another physiological scenario is when the rat experiences a reward or exhibits anxiety-like behaviour, which can lead to changes in hormonal or neuromodulator concentrations. These changes, functioning through the activation of G-protein coupled receptors and the consequent elevation of cytosolic cyclic adenosine monophosphate (cAMP) concentrations, could shift the half-maximal activation voltage ( V1/2 ) of HCN channels to a more depolarized potential. Would such a shift in V1/2 impact LFPs and spike phases in a manner similar to that observed with increasing the conductance of HCN channels? Assessing this within our modeling framework, we found that shifting the V1/2 by +5 mV resulted in an increased lead in the LFP phase, an increased lag in the spike phase and an enhanced spike phase coherence compared to the case with a hyperpolarized V1/2 . What are the biophysical mechanisms that underlie these robust changes observed in LFPs and spike phases observed as a consequence of these several ways of increasing the current through HCN channels? We reasoned that our observations could be explained by one of the two distinct changes conferred on CA1 pyramidal neuron physiology by the presence of HCN channels. First, in the presence of HCN channels, the voltage response of CA1 pyramidal neurons shows a phase lead with reference to a sinusoidal current input (inductive phase lead) in the theta frequency range. Second, HCN channels regulate the excitability of these cells by decreasing the input resistance and impedance amplitude. To delineate the differential role of the inductive changes vs. changes in excitability, we replaced HCN channels by a faster variant (HCNFast) such that neuronal excitability remained the same while abolishing the inductive phase lead in the theta band. On doing so, we found that the lead in the LFP phase and the lag in the spike phase brought about by HCN channels was partially reversed when HCN conductance values were low. However the reversal was not substantial when HCN conductance values were high, suggesting that the inductive phase component dominates at lower HCN channel conductances, whereas the excitability component plays a critical role at higher HCN conductances. Akin to intrinsic plasticity mentioned above, under certain pathological conditions, an entire population of neurons can undergo scaling of their excitatory or inhibitory synapses. In assessing the implications for such synaptic plasticity, we first found that our conclusions on the roles of HCN channels in introducing a lead in the LFP phase, a lag in the spike phase and an enhancement of spike phase coherence were invariant to the specific values of synaptic conductances, or the phase difference between excitatory and inhibitory theta-modulated inputs. While these observations further established the robustness of the changes brought about by HCN channels to LFPs and associated spikes, we next asked whether synaptic plasticity, mediated by changes in subthreshold synaptic conductances, could itself bring about changes in the LFP and spike phase. Expectedly, we found that scaling up of excitatory synapses introduced a mild lag in the LFP phase and a lead in the spike phase, whereas scaling up of inhibitory synapses introduced a lead in the LFP phase and a lag in the spike phase. Finally, we observed a critical role of the arrival phase of inhibition with reference to excitation in altering both, the stratum pyramidale LFP and associated spike phases, with the magnitude of change in both the LFP and the spike phase roughly following the magnitude of the shift in the excitatory-inhibitory phase difference. However, in contrast to changes observed with HCN-channel plasticity, there was no significant change in spike phase coherence with any of the three forms of synaptic changes explored. Together, our results identify definite roles for HCN channels and synaptic receptors in phase-coding schemas and in the formation and dynamic reconfiguration of neuronal cell assemblies and present a clear case for the incorporation of subthreshold-activated ion channels, their gradients, and their plasticity into the computation of LFPs. Given the rich expression of several subthreshold ion channels — including HCN, A-type potassium and T-type calcium — in neuronal dendrites, future work could focus on the impact of subthreshold channels on LFPs recorded in different brain regions under different behavioral states. This thesis is organized into seven chapters. Chapter 1 provides the motivations for the study, introduces the aim of the study and poses the specific questions asked in our endeavor to understand the role of subthreshold conductances in regulating LFPs and spike phases. Chapter 2 discusses the physiological foundations and relevant literature that places the questions posed in the first chapter in the context of the aim of the thesis, with an emphasis on the literature on HCN channels. In chapter 3, we introduce the computational and theoretical foundations required to model neurons and to compute LFPs. In chapter 4, we look at the consequences of the presence of a non-uniform density of somatodendritic HCN channels on LFPs and spike phase and test the robustness of the effects observed. In chapter 5, we present our assessment of the impact of intrinsic plasticity/modulation of HCN channels on LFPs and spike phases, also exploring the biophysical mechanisms underlying such an impact. In chapter 6, we test if the observed effects still hold under synaptic plasticity, and assess the regulation of LFPs and spike phases by synaptic changes. In chapter 7, we summarize and conclude the results presented in the preceding chapters and provide some potential directions for future studies.

Introdução: Crianças com transtorno fonológico (TF) apresentam dificuldade na percepção de fala, em processar estímulos acústicos quando apresentados de forma rápida e em sequência. A percepção dos sons complexos da fala, dependem da integridade no processo de codificação analisado pelo Sistema Nervoso Auditivo. Por meio do Potencial Evocado Auditivo de Tronco Encefálico com estímulo complexo (PEATEc) é possível investigar a representação neural dos sons em níveis corticais e obter informações diretas sobre como a estrutura do som da sílaba falada é codificada no sistema auditivo. Porém, acredita-se que esse potencial sofre interferências tanto de processos bottom-up quanto top-down, o que não se sabe é quanto e como cada um desses processos modifica as respostas do PEATEc. Uma das formas de investigar a real influência dos aspectos top-down e bottom-up nos resultados do PEATEc é estimulando separadamente esses dois processos por meio do treinamento auditivo e da terapia fonoaudiológica. Objetivo: Verificar o impacto da estimulação sensorial (processamento bottom-up) e cognitiva (processamento top-down), separadamente, nos diferentes domínios da resposta eletrofisiológica do PEATEc. Método: Participaram deste estudo 11 crianças diagnosticadas com TF, com idades entre 7 e 10:11, submetidas a avaliação comportamental e eletrofisiológica e então dividas nos grupos Bottom-up (B-U) (N=6) e Top-down T-D (N=5). A estimulação bottom-up foi voltada ao treinamento das habilidades sensoriais, através de softwares de computador. A estimulação top-down foi realizada por meio de tarefas para estimular as habilidades cognitiva por meio do Programa de Estimulação Fonoaudiológica (PEF). Ambas as estimulações foram aplicadas uma vez por semana, num período de aproximadamente 45 minutos por 12 semanas. Resultados: O grupo B-U apresentou melhoras em relação aos domínios onset e harmônicos e no valor da pontuação do escore após ser submetido à estimulação bottom-up. Por sua vez, após serem submetidos à estimulação top-down, o grupo T-D apresentou melhoras em relação aos domínios onset, espectro-temporal, fronteiras do envelope e harmônicos e para os valores da pontuação do escore. Conclusão: Diante dos resultados obtidos neste estudo, foi possível observar que a estimulação sensorial (processamento bottom-up) e a estimulação cognitiva (processamento top-down) mostraram impactar de forma diferente a resposta eletrofisiológica do PEATEc / Introduction: Children with speech sound disorder present difficulties in speech perception specially regarding the processing of acoustic stimuli when they occur rapidly and sequentially. The perception of complex sounds of speech depends on the integrity of the codification process analyzed by the auditory system. Through the Auditory Brainstem Response to complex sounds (cABR) it is possible to investigate the neural representation of sounds in cortical levels to obtain direct information about how the sound structure of the stressed syllable is codified in the auditory system. However, it is believed that bottom-up and top-down processes interfere in the cABR, though the level of intensity and the way through which they can change the response of the cABR is still unkown. One of the methods for investigating the actual influences of the bottom-up and top-down processes in cABR responses is by stimulating separately those two processes by means of auditory training and speech therapy. Objective: Verify the impact of both sensory stimulation (bottom-up processing) and cognitive stimulation (top-down processing) separately, in the different domains of the cABR electrophysiological response. Method: The participants of the study were 11 children of 7 to 10:11 year-old diagnosed with speech sound disorder, who underwent behavioral and electrophysiological assessment and were divided in the following groups: Bottom-up (B-U) (N=6) and Top-down (T-D) (N-5). The bottom-up stimulation focused on sensorial skills by using computer softwares. Top-down stimulation was prosecuted by using tasks to stimulate cognitive skills through the Speech Stimulation Program. Both stimuli were applied once a week for 45 minutes, in a period of 12 weeks. Results: The B-U group showed improvement in relation to onset and harmonic domains, and in relation to the score punctuation values after being subjected to bottom-up stimulation. On the other hand, the T-D group, after being subjected to top-down stimulation, showed improvement in relation to the onset, time domain spectrum, envelope boundaries and harmonics, and to the score punctuation values. Conclusions: According to the results of this study, it was possible to conclude that sensorial stimulation (bottom-up processing) and cognitive stimulation (top-down processing) showed different impacts on the cABR electrophysiological response

Title: Effect of robot-assisted therapy on upper limb function in activities of daily living in patients after acquired brain injury Aims: The main aim of the thesis was to evaluate and compare the effectiveness of two therapeutic approaches using robot-assisted glove Gloreha Sinfonia to perform Activity of daily living in patients after acquired brain injury. Methods: The study is an empirical quantitative research, a monocentric randomized controlled, simply blinded study. The study compares two groups, group A (n = 20) used a robot-assisted Gloreha glove with a bimanual approach, group B (n = 20) had therapy with a robot-assisted Gloreha glove with an unimanual approach. All patients were evaluated for eligibility and underwent initial testing (T1). Patients in both groups had therapy (unimanual / bimanual) for three weeks (15x), retest (T2) was performed after completion of the intervention, and a follow-up evaluation was performed after 1 month (T3). Patients were always evaluated by the Upper Extremity Motor Activity Log (UE MAL), Motor Assessment Scale (MAS), Action Research Arm Test (ARAT), Box and Block test (BBT) and Motricity Index (MI). Results: According to the results of the MAS test in group A, there was a statistically significant improvement in upper limb function in category 8 at...

No / Phosphorylation or SUMOylation of the kainate receptor (KAR) subunit GluK2 have both individually been shown to regulate KAR surface expression. However, it is unknown whether phosphorylation and SUMOylation of GluK2 are important for activity-dependent KAR synaptic plasticity. We found that protein kinase C-mediated phosphorylation of GluK2 at serine 868 promotes GluK2 SUMOylation at lysine 886 and that both of these events are necessary for the internalization of GluK2-containing KARs that occurs during long-term depression of KAR-mediated synaptic transmission at rat hippocampal mossy fiber synapses. Conversely, phosphorylation of GluK2 at serine 868 in the absence of SUMOylation led to an increase in KAR surface expression by facilitating receptor recycling between endosomal compartments and the plasma membrane. Our results suggest a role for the dynamic control of synaptic SUMOylation in the regulation of KAR synaptic transmission and plasticity.