Neuroscientists have uncovered much about the dorsal and ventral visual object processing pathways. However, little is understood about the functional development of these pathways in human infants. Behavioral data has shown that as early as 2.5 months, infants are sensitive to spatiotemporal information for object individuation in occlusion events. This study used Near Infrared Spectroscopy to assess neural activation (as evidenced by an increase in HbO2) in four areas of the pathways: primary visual cortex (O1), posterior parietal cortex (P3), lateral occipital (T5), and inferior temporal (T3) in awake human infants aged 5.5 months while they view either a spatiotemporaldiscontinuity event or a control event. Three major predictions were made: 1) since the events contain visually distinct objects, there should be significant neural activation in O1 to both events, 2) if the dorsal route mediates the processing of spatiotemporal discontinuities, then there should also be a significant increase in P3 in response to the spatiotemporal-discontinuity event but not to the control event, and 3) activation present in T3 and T5 should not vary by condition if the ventral pathway is not responsible for the processing of spatiotemporal discontinuities. Results supported all three predictions.

A literatura recente sugere que a fadiga mental piora o desempenho de atletas durante testes contrarrelógio (TT) de ciclismo. Assim o objetivo deste estudo foi verificar se a cafeína poderia reverter ou bloquear os efeitos negativos da fadiga mental em um contrarrelógio de 20km (TT20km). Métodos: Doze ciclistas treinados, com experiência em TT há pelo menos 2 anos, e nível de performance > 3 (34.3 ± 6.2 anos; 179.3 ± 5.1 cm; 77.6 ± 6.8 kg; 13.8 ± 4.5 % de gordura corporal; 58.9 ± 6.2 ml.kg-1.min-1; 367.0 ± 32.5 WPEAK), realizaram cinco visitas ao laboratório: 1) PRELIMINAR: para seleção dos sujeitos e familiarização com os instrumentos; 2) CONTROLE: foram realizadas três contrações voluntárias isométrica máxima (CVM), cujo maior torque encontrado entre elas definirá o valor de 70% para contração voluntária isométrica submáxima (CVIS) nas sessões seguintes. Posteriormente a CVIS, foi realizado o TT20km sem manipulação cognitiva ou suplementação; 3) FADIGA MENTAL (FM): execução do teste de atenção sustentada (RVIP), CVIS e TT20km respectivamente; 4) PLACEBO: ingestão da cápsula de placebo (FM + PLA) em seguida teste de RVIP, CVIS e TT20km; 5) CAFEÍNA: ingestão de cafeína (FM + CAF), consequentemente realizaram o teste de RVIP, CVIS e o TT20km). A atividade cerebral do córtex pré-frontal e córtex motor primário foi analisada por meio de eletroencefalografia (EEG) registrada antes e depois do teste RVIP. Igualmente, EEG do córtex pré-frontal e motor primário foi registrada durante uma contração voluntária isométrica submáxima, realizada antes do TT20km. Para as análises de comparações entre pré e pós tarefa cognitiva de atenção sustentada utilizou-se um teste T-student. Para as comparações múltiplas analisou-se por modelo misto entre a condição e a distância no TT20km, quando necessário o teste de Bonferroni foi utilizado. Resultados: CAF melhorou o desempenho em ciclistas mentalmente fatigados em ~ 1.8 % para FM e ~ 1.7 % para PLA (p = 0.00) e aumentou ~ 4.4 % para FM e ~ 3.6 % do que o placebo de WMEAN em FM + CAF (p = 0,00). A ativação cortical aumentou em ~ 4.8 % nas ondas teta de EEG após teste RVIP em FM e reduziu em FM + CAF ~ 8.8 % e FM + PLA ~ 4.8%. A razão entre PSE e WMEAN foi menor em FM + CAF do que nas outras condições (p = 0.01). Os ciclistas apresentaram maior motivação nos primeiros 2 km em FM + CAF comparado a FM e FM + PLA (p = 0.02) e maior afeto nos últimos 2 km em FM e FM + CAF do que FM + PLA (p = 0.01). Uma menor ativação cortical durante a CVIS e uma maior eficiência neuromuscular foi identificada na condição FM + CAF (p = 0.03). Conclusão: A CAF bloqueou os efeitos negativos da fadiga mental no CPF, melhorou o desempenho, diminuiu a PSE durante TT20km e aumentou a eficiência neuromuscular / Recent literature suggests that mental fatigue worsens the performance of athletes during time trial (TT) cycling tests. Thus, the aim of this study was to verify if caffeine could reverse or block the negative effects of mental fatigue in a TT of 20km (TT20km). Methods: Twelve trained cyclists with experience in TT for at least 2 years, and performance level > 3 (34.3 ± 6.2 years, 179.3 ± 5.1 cm, 77.6 ± 6.8 kg, 13.8 ± 4.5 % body fat 58.9 ± 6.2 ml .kg-1.min-1; 367.0 ± 32.5 WPEAK), carried out five visits at laboratory: 1) PRELIMINARY: for selection of subjects and familiarization with the instruments; 2) CONTROL: three maximal isometric voluntary contractions (CVM) were performed, the highest torque found between them will define the value of 70% for voluntary isometric submaximal contraction (CVIS) in the following sessions. After the CVIS, the TT20km will be performed without cognitive manipulation or supplementation; 3) MENTAL FATIGUE (FM): execution of the sustained attention test (RVIP), CVIS and TT20km respectively; 4) PLACEBO: placebo capsule intake (FM + PLA) then RVIP, CVIS and TT20km test; 5) CAFFEINE: caffeine intake (FM + CAF), consequently performed the RVIP, CVIS and TT20km tests). Brain activity of the prefrontal cortex and primary motor cortex will be analyzed by electroencephalography (EEG) recorded before and after the RVIP test. Likewise, EEG of the prefrontal cortex and primary motor will be recorded during a submaximal isometric voluntary contraction, performed before TT20km. For the analysis of comparisons between pre and post cognitive task of sustained attention was used a T-student test. For the multiple comparisons, the mixed model was analyzed for the condition and the distance in the TT20km, and the best matrix was identified for each case, when necessary the Bonferroni test was used. Results: CAF improved performance in mentally fatigued cyclists at ~ 1.8 % for FM and ~ 1.7 % for PLA (p = 0.00) and increased ~ 4.4% for FM and ~ 3.6% than WMEAN on FM + CAF (p = 0.00). Cortical activation increased by ~ 4.8 % in the theta EEG waves after RVIP test in FM and reduced in FM + CAF ~ 8.8 % and FM + PLA ~ 4.8 %. The ratio of RPE to WMEAN was lower in FM + CAF than in other conditions (p = 0.01). The ciclists started the TT20km more motivated in first 2 km (p = 0.02) and finished with more pleasure in the last 2km in FM and FM + CAF than in FM + PLA (p = 0.01). Lower cortical activation during CVIS and greater neuromuscular efficiency was identified in the FM + CAF condition (p = 0.03). Conclusion: CAF blocked the negative effects of mental fatigue on CPF, improved performance, decreased PSE over TT20km and increased neuromuscular efficiency

A literatura recente sugere que a fadiga mental piora o desempenho de atletas durante testes contrarrelógio (TT) de ciclismo. Assim o objetivo deste estudo foi verificar se a cafeína poderia reverter ou bloquear os efeitos negativos da fadiga mental em um contrarrelógio de 20km (TT20km). Métodos: Doze ciclistas treinados, com experiência em TT há pelo menos 2 anos, e nível de performance > 3 (34.3 ± 6.2 anos; 179.3 ± 5.1 cm; 77.6 ± 6.8 kg; 13.8 ± 4.5 % de gordura corporal; 58.9 ± 6.2 ml.kg-1.min-1; 367.0 ± 32.5 WPEAK), realizaram cinco visitas ao laboratório: 1) PRELIMINAR: para seleção dos sujeitos e familiarização com os instrumentos; 2) CONTROLE: foram realizadas três contrações voluntárias isométrica máxima (CVM), cujo maior torque encontrado entre elas definirá o valor de 70% para contração voluntária isométrica submáxima (CVIS) nas sessões seguintes. Posteriormente a CVIS, foi realizado o TT20km sem manipulação cognitiva ou suplementação; 3) FADIGA MENTAL (FM): execução do teste de atenção sustentada (RVIP), CVIS e TT20km respectivamente; 4) PLACEBO: ingestão da cápsula de placebo (FM + PLA) em seguida teste de RVIP, CVIS e TT20km; 5) CAFEÍNA: ingestão de cafeína (FM + CAF), consequentemente realizaram o teste de RVIP, CVIS e o TT20km). A atividade cerebral do córtex pré-frontal e córtex motor primário foi analisada por meio de eletroencefalografia (EEG) registrada antes e depois do teste RVIP. Igualmente, EEG do córtex pré-frontal e motor primário foi registrada durante uma contração voluntária isométrica submáxima, realizada antes do TT20km. Para as análises de comparações entre pré e pós tarefa cognitiva de atenção sustentada utilizou-se um teste T-student. Para as comparações múltiplas analisou-se por modelo misto entre a condição e a distância no TT20km, quando necessário o teste de Bonferroni foi utilizado. Resultados: CAF melhorou o desempenho em ciclistas mentalmente fatigados em ~ 1.8 % para FM e ~ 1.7 % para PLA (p = 0.00) e aumentou ~ 4.4 % para FM e ~ 3.6 % do que o placebo de WMEAN em FM + CAF (p = 0,00). A ativação cortical aumentou em ~ 4.8 % nas ondas teta de EEG após teste RVIP em FM e reduziu em FM + CAF ~ 8.8 % e FM + PLA ~ 4.8%. A razão entre PSE e WMEAN foi menor em FM + CAF do que nas outras condições (p = 0.01). Os ciclistas apresentaram maior motivação nos primeiros 2 km em FM + CAF comparado a FM e FM + PLA (p = 0.02) e maior afeto nos últimos 2 km em FM e FM + CAF do que FM + PLA (p = 0.01). Uma menor ativação cortical durante a CVIS e uma maior eficiência neuromuscular foi identificada na condição FM + CAF (p = 0.03). Conclusão: A CAF bloqueou os efeitos negativos da fadiga mental no CPF, melhorou o desempenho, diminuiu a PSE durante TT20km e aumentou a eficiência neuromuscular / Recent literature suggests that mental fatigue worsens the performance of athletes during time trial (TT) cycling tests. Thus, the aim of this study was to verify if caffeine could reverse or block the negative effects of mental fatigue in a TT of 20km (TT20km). Methods: Twelve trained cyclists with experience in TT for at least 2 years, and performance level > 3 (34.3 ± 6.2 years, 179.3 ± 5.1 cm, 77.6 ± 6.8 kg, 13.8 ± 4.5 % body fat 58.9 ± 6.2 ml .kg-1.min-1; 367.0 ± 32.5 WPEAK), carried out five visits at laboratory: 1) PRELIMINARY: for selection of subjects and familiarization with the instruments; 2) CONTROL: three maximal isometric voluntary contractions (CVM) were performed, the highest torque found between them will define the value of 70% for voluntary isometric submaximal contraction (CVIS) in the following sessions. After the CVIS, the TT20km will be performed without cognitive manipulation or supplementation; 3) MENTAL FATIGUE (FM): execution of the sustained attention test (RVIP), CVIS and TT20km respectively; 4) PLACEBO: placebo capsule intake (FM + PLA) then RVIP, CVIS and TT20km test; 5) CAFFEINE: caffeine intake (FM + CAF), consequently performed the RVIP, CVIS and TT20km tests). Brain activity of the prefrontal cortex and primary motor cortex will be analyzed by electroencephalography (EEG) recorded before and after the RVIP test. Likewise, EEG of the prefrontal cortex and primary motor will be recorded during a submaximal isometric voluntary contraction, performed before TT20km. For the analysis of comparisons between pre and post cognitive task of sustained attention was used a T-student test. For the multiple comparisons, the mixed model was analyzed for the condition and the distance in the TT20km, and the best matrix was identified for each case, when necessary the Bonferroni test was used. Results: CAF improved performance in mentally fatigued cyclists at ~ 1.8 % for FM and ~ 1.7 % for PLA (p = 0.00) and increased ~ 4.4% for FM and ~ 3.6% than WMEAN on FM + CAF (p = 0.00). Cortical activation increased by ~ 4.8 % in the theta EEG waves after RVIP test in FM and reduced in FM + CAF ~ 8.8 % and FM + PLA ~ 4.8 %. The ratio of RPE to WMEAN was lower in FM + CAF than in other conditions (p = 0.01). The ciclists started the TT20km more motivated in first 2 km (p = 0.02) and finished with more pleasure in the last 2km in FM and FM + CAF than in FM + PLA (p = 0.01). Lower cortical activation during CVIS and greater neuromuscular efficiency was identified in the FM + CAF condition (p = 0.03). Conclusion: CAF blocked the negative effects of mental fatigue on CPF, improved performance, decreased PSE over TT20km and increased neuromuscular efficiency

BACKGROUND: Idiopathic normal pressure hydrocephalus (INPH) is still a syndrome generating more questions than answers. Today, research focuses mainly on two areas: understanding the pathophysiology – especially how the malfunctioning CSF system affects the brain parenchyma – and finding better methods to select patients benefiting from a shunt operation. This thesis targets the aspect of finding better selection methods by investigating the measurability of intracranial pressure via lumbar space, and determining if intraparenchymal measurement of long-term ICP-oscillations (B-waves) could be replaced by short-term measurements of CSF pulse pressure waves via lumbar space. Furthermore, I look into the interaction between the CSF system and the parenchyma itself by investigating how the cortical activity of the brain changes after long-term CSF drainage, and if there is any regress in the suggested ischemia after this intervention. Finally, I examine if the neuronal integrity in the INPH brain is impaired, and if this feature is relevant for the likeliness of improvement after CSF diversion. METHODS: The comparison of intracranial and lumbar pressure was made over a vast pressure interval using our unique CSF infusion technique, and it included ten INPH patients. Pressure was measured via lumbar space and in brain tissue, and the pressures were compared using a general linear model. Short-term lumbar pressure waves were quantified by determining the slope between CSF pulse pressure and mean pressure, defined as the relative pulse pressure coefficient (RPPC). The correlation between RPPC, B-waves and CSF outflow resistance was investigated. In a prospective study, functional MRI was used to assess brain activity before and after long-term CSF drainage of 400 ml of CSF in eleven INPH patients. The functionalities tested included finger movement, memory, and attention. The results were benchmarked against the activity in ten healthy controls to identify the brain areas improving after drainage. The ischemia (Lactate) and neuronal integrity (NAA and Choline) were measured in a similar manner in 16 patients using proton MR spectroscopy, and the improvement of the patients after CSF drainage was based on assessment of their gait. RESULTS: There was excellent agreement between ICP measured in brain tissue and via lumbar space (regression coefficient = 0.98, absolute difference < 1 mm Hg). Adjusting for the separation distance between the measuring devices slightly worsened the agreement, indicating other factors influencing the measured difference as well. RPPC measured via lumbar space significantly correlated to the presence of B-waves, but not to outflow resistance. In the prospective study, controls outperformed patients on clinical tests as well as tasks related to the experiments. Improved behaviour after CSF drainage was found for motor function only, and it was accompanied by increased activation in the supplementary motor area (SMA). No lactate was detected, either before or after CSF drainage. NAA was decreased in INPH patients compared to controls, and the NAA levels were higher in the patients improving after drainage. CONCLUSIONS: ICP can be accurately measured via lumbar space in patients with communicating CSF systems. The close relation between RPPC and B-waves indicates that B-waves are primarily related to intracranial compliance, and that measurement of RPPC via lumbar space could possibly substitute B-wave assessment as selection method for finding suitable patients for shunt surgery. Improvement in motor function after CSF drainage was associated to enhanced activity in SMA, supporting the involvement of the cortico-basal ganglia-thalamo-cortical loop in the pathophysiology of INPH. There was no evidence indicating a widespread low-graded ischemia in INPH; however, there was a neuronal dysfunction in frontal white matter as indicated by the reduced levels of NAA. In addition, the level of neuronal dysfunction was related to the likeliness of improvement after CSF removal, normal levels of NAA predisposing for recovery.

A estimulação elétrica periférica (PES), que abrange diversas técnicas com respostas fisiológicas diversas, tem apresentado em alguns casos resultados clínicos promissores para o tratamento da dor e reabilitação clínica. No entanto, as respostas encontradas são heterogêneas, principalmente porque há uma falta de compreensão em relação ao seu mecanismo de ação. Neste estudo, buscamos avaliar os efeitos da PES através da medição da ativação cortical cerebral utilizando a espectroscopia funcional por infravermelho (fNIRS). A fNIRS é um método de imagem óptica funcional que avalia mudanças hemodinâmicas nas concentrações de hemoglobina oxigenada (HbO) e desoxigenada (HbR), relacionadas à atividade cortical. Nós hipotetizamos que a PES do nervo acessório espinal (ASN) pode promover a ativação do córtex motor (MC) e do córtex pré-frontal dorsolateral (DLPFC), relacionados ao processamento da dor. Quinze voluntários saudáveis receberam estimulação elétrica ativa e sham em um ensaio clínico randomizado cruzado. A resposta hemodinâmica à estimulação elétrica unilateral direita do nervo acessório com 10 Hz foi medida pela espectroscopia funcional por um sistema de 40 canais. A variação de HbO nas áreas corticais de interesse mostrou ativação do DLPFC direito (p=0,025) e do MOTOR esquerdo (p=0,042) no grupo ativo comparado com sham. Em relação ao DLPFC esquerdo (p=0,610) e ao MOTOR direito (p=0,154), não houve diferença estatística entre os grupos. Como na modulação top-down, a estimulação bottom-up do nervo acessório parece ativar as mesmas áreas corticais, relacionadas às dimensões sensório-discriminativas e afetivo-motivacionais da dor. Esses resultados fornecem evidência adicional para desenvolver e otimizar o uso clínico da estimulação elétrica periférica. / Peripheral electrical stimulation (PES), which encompasses several techniques with heterogeneous physiological responses, has shown in some cases remarkable outcomes for pain treatment and clinical rehabilitation. However, results are still mixed, mainly because there is a lack of understanding regarding its neural mechanisms of action. In this study, we aimed to assess its effects by measuring cortical activation as indexed by functional near infrared spectroscopy (fNIRS). fNIRS is a functional optical imaging method to evaluate hemodynamic changes in oxygenated (HbO) and de-oxygenated (HbR) blood hemoglobin concentrations in cortical capillary networks that can be related to cortical activity. We hypothesized that PES of accessory spinal nerve (ASN) can promote cortical activation of motor cortex (MC) and dorsolateral prefrontal cortex (DLPFC) pain processing cortical areas. Fifteen healthy volunteers received both active and sham ASN electrical stimulation in a crossover design. The hemodynamic response to unilateral right ASN burst electrical stimulation with 10 Hz was measured by a 40- channel fNIRS system. The effect of ASN electrical stimulation over HbO concentration in cortical areas of interest was observed through the activation of right- DLPFC (p=0.025) and left-MOTOR (p=0.042) in the active group but not in sham group. Regarding left-DLPFC (p=0.610) and right-MOTOR (p=0.174) there was no statistical difference between groups. As in non-invasive brain stimulation (NIBS) topdown modulation, bottom-up electrical stimulation to the accessory spinal nerve seems to activate the same critical cortical areas on pain pathways related to sensorydiscriminative and affective-motivational pain dimensions. These results provide additional mechanistic evidence to develop and optimize the effects of peripheral neural electrical stimulation.