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Contains fulltext : 218326.pdf (Publisher’s version ) (Open Access) The striatum has long been implicated in motivation, learning, and action. Recent theories have proposed that the striatum is particularly involved in the coupling of these processes, giving rise to motivational biases in the selection and learning of actions. Here we assess the causal role of the ventral striatum in the motivational biasing of action for the first time in humans by directly stimulating the nucleus accumbens with deep brain stimulation (DBS). Treatment-refractory obsessive-compulsive disorder patients (n=8) performed a motivational Go/NoGo task with concurrent EEG recordings. The subjects needed to learn to make Go or NoGo responses in order to win reward or avoid punishment, while DBS was switched ON vs. OFF in a cross-over within-subject design. As previously observed in healthy populations, performance was strongly affected by the cue valence, such that fewer and slower Go responses were made when avoiding punishment than when playing for reward. DBS attenuated the inhibitory influence of punishment cues on reaction times and marginally on the proportion Go responses when Go responses were required. For the Go cues where these Pavlovian response tendencies conflicted with the instrumental requirements, oscillatory theta (4-8Hz) activity increased over the midfrontal cortex. These putative conflict-related midfrontal theta responses were not significantly affected by DBS. Taken together, these results suggest that nucleus accumbens stimulation attenuates the motivational biasing of action, seemingly without affecting frontal control systems. These results causally implicate the human nucleus accumbens in the coupling of motivation and behavioural activation. Dissertation J.C. Swart, Radboud University

Objetivo. El objetivo de este trabajo es proporcionar una revisión de los diversos modelos experimentales de traumatismo craneoencefálico (TCE) que se han desarrollado para la investigación del daño cerebral traumático tanto en condiciones in vivo como in vitro, así como detallar los principales conocimientos fisiopatológicos obtenidos a partir de su aplicación. Se expone de forma sintética tanto el tipo de lesión cerebral traumática que cada modelo reproduce como los detalles técnicos necesarios para su utilización por investigadores en el campo del trauma cerebral. Desarrollo. El pronóstico de los pacientes que han sufrido un TCE ha mejorado gracias a las medidas iniciales de estabilización hemodinámica y control de la vía aérea, pero no existe todavía ningún tratamiento específico y eficaz para detener o limitar las lesiones cerebrales causadas por el traumatismo, exceptuando las medidas de control de la presión arterial y la presión intracraneal. Entender la fisiopatología del TCE es el paso básico y fundamental para desarrollar posibles abordajes terapéuticos con aplicación clínica. El daño cerebral traumático en humanos es una patología heterogénea y muy compleja. Por ello, cada modelo experimental se ha desarrollado con el objetivo de reproducir un tipo concreto de las diferentes lesiones cerebrales observadas en pacientes tras un TCE. El uso de estos modelos ha permitido ampliar el conocimiento sobre la fisiopatología del daño cerebral traumático, incluyendo las alteraciones inducidas a nivel celular y molecular. Conclusión. Los modelos experimentales suponen actualmente la mejor herramienta para el estudio de los mecanismos subyacentes a las lesiones cerebrales traumáticas, pero su simplicidad y por lo tanto su incapacidad de reproducir exactamente el daño heterogéneo observado en la práctica clínica puede ser uno de los motivos que explique la discrepancia en la respuesta terapéutica entre los estudios experimentales y clínicos. Aim. To provide a summary of the different experimental models of traumatic brain injury (TBI) designed under both in vivo and in vitro conditions. A comprehensible review of the specific types of brain lesions induced, as well as the technical details to reproduce each model at the laboratory is given. Development. Outcome of patients suffering from a TBI has significantly improved with the rapid application of vital supporting measures in addition to a strict control of blood and intracranial pressure at the intensive care units. However no specific treatment for post-traumatic brain lesions has proven as efficacious in the clinical settings. A deeper knowlegde of the physiopathological events associated with TBI is necessary for the development of new specific therapies. Due to the heterogeneity of the human TBI, each experimental model has been designed to reproduce a different type of brain lesion. Experimental TBI models allow the study of the dynamic evolution of brain injuries under controlled conditions. Usefulness of experimental models is limited by their reliability and reproducibility among different researchers. Small rodents have been the preferred animals to reproduce TBI injuries, mainly due to the similar cerebral physiology shared by these animals and the human beings. Conclusion. The use of experimental models of TBI is the most appropiate tool to study the mechanisms underlying this type of injury. However their simplicity precludes an exact reproduction of the heterogeneous cerebral damage observed in clinical settings. This could be the main reason for the discrepancies observed in the therapeutic effects of treatments between experimental and clinical studies.