El objetivo principal de este estudio fue examinar, utilizando el Análisis Independiente de Componentes (AIC) aplicado a nivel espectral y sobre la actividad cerebral evocada, si es posible definir subtipos electrofisiológicos de personas diagnosticadas de Trastorno por Déficit de Atención e Hiperactividad (TDAH). Esto puede permitirnos conocer las relaciones entre las redes neuronales que componen la citoarquitectura de la corteza cerebral y la diferente tipología clínica. Para ello usamos mapas cerebrales, en estado basal y tras estimulación visual, obtenidos mediante 20 canales de electroencefalografía (EEG). Se analizó el curso temporal y tomografía de los potenciales (LORETA), así como los resultados de la escala clínica de Amen. Encontramos seis endofenotipos electrofisiológicos distintos de TDAH, claramente correlacionados con los síntomas (fenotipos clínicos), como los no respondedores a medicación, los impulsivos, los distraídos y los que muestran disregulación emocional. Se discuten las implicaciones para la práctica clínica y educativa. / The main aim of this study was to examine, from Independent Component Analysis (ICA) applied at spectral and evoked brain activity, if it is possible to define electrophysiological subtypes of person diagnosed with Attention Deficit Hyperactivity Disorder (ADHD). This may allow us to understand the relationships between the neural networks that compose the cytoarchitecture of the cerebral cortex and the different types of clinical characteristics. For this, we used brain maps obtained by 20 channel electroencephalography (EEG) recordings at baseline, and after visual stimulation. Time course and topography of potentials (LORETA) as well as Amen Clinical Scale scores were analyzed. We found six different electrophysiological ADHD endophenotypes, which were clearly correlated with symptoms (clinical phenotypes), such us the no responder to medication, impulsive, inattentive, and with emotional dysregulation ones.

El Objetivo general de la presente Tesis Doctoral fue el de estudiar la participación de la neurotransmisión glutamatérgica y del GHB en la adicción a los opiáceos y a la cocaína. En primer lugar hemos pretendido observar la contribución de estos dos sistemas de neurotransmisión en los efectos que la morfina presenta sobre las conductas sociales. Nuestra hipótesis fue que la afectación del sistema glutamatérgico, concretamente bloqueando los receptores NMDA (utilizando Memantina y MK-801) así como la facilitación de la neurotransmisión GABAérgica, mediante la administración de GHB (ácido gammahidroxibutírico) podrían modificar los efectos que sobre las conductas sociales ejerce la morfina. Igualmente nos planteamos estudiar si tanto los síntomas físicos como los motivacionales, medidos mediante el Condicionamiento Aversivo de Lugar (CAL), observados en el síndrome de abstinencia a la morfina, podían verse modificados por las acciones anteriormente mencionadas sobre el sistema glutamatérgico o GABAérgico. También hemos observado el papel del de estos dos sistemas de neurotransmisión sobre lasacciones reforzantes de la cocaína. Hemos estudiado el papel sistema glutamatérgico y del GHB sobre los efectos reforzantes de la cocaína, la adquisición, la expresión y el restablecimiento (recaída) mediante el condicionamiento de la preferencia de lugar (CPL) inducido por esta droga. Mediante esta serie de estudios tratamos de explorar el papel de estos sistemas de neurotransmisión tanto en los efectos reforzantes, como en la recaída en el consumo de cocaína. / The main aim of the present Doctoral Thesis was to study the participation of the glutamatergic neurotransmission and GHB in the addiction to opiates and cocaine. Firstly, we observed the contribution of these two systems of neurotransmission to the effects that morphine presents on social behaviours. Our hypothesis was that the impairment of the glutamatergic system by blocking the NMDA receptors (using Memantine and MK-801) as well as the facilitation of the GABAergic neurotransmission, by GHB administration (gamma-hydroxybutyric acid) could modify the effects that morphine exerts on social behaviours. Likewise, we studied whether the physical as well as the motivational symptoms, measured by means of Conditioned Place Aversion (CPA), observed in the morphine wtihdrawal syndrome, could be modified by the previously mentioned actions on the glutamatergic or GABAergic systems. We have also studied the role of these two neurotransmission systems in the rewarding actions of cocaine. We examined the influence of the glutamatergic system and GHB on the acquisition, expression and reinstatement (relapse) of the cocaine-induced conditioned place preference (CPP). With these studies we explored the role of these neurotransmission systems in the cocaine-rewarding effects and the relapse to cocaine consumption. Our results show that memantine administration significantly increased motor activity without modifiying the antiaggressive effect of morphine. Memantine blocked the physical and motivational symptoms of the morphine withdrawal, whereas MK-801 was more effective in blocking only the motivational symptoms of this withdrawal syndrome evaluated by the CPA procedure. On the other hand, we could observe that GHB potentiates morphine-induced effects on social behaviours, counteracting the hyperactivity induced by this opiate, and ameliorating the physical as well as motivational aspects of the morphine withdrawal syndrome. In addition, we have observed that GHB has no synergic action on the rewarding effects of cocaine, evaluated by the CPP procedure, It blocked the cocaine-seeking behaviour (relapse) when it was administered during the acquisition or the expression of the conditioning or with a "priming" dose of cocaine. Also we have observed that NMDA and AMPA receptors blockaded by memantine and CNQX administration prevented the acquisition and expression of cocaine-induced CPP but did not show the ability to block the relapse induced by "priming" administration of this same drug. The present study indicates that glutamatergic neurotransmission plays an important role in the establishment of morphine dependency, as is observed by the reduction of the physical and motivational signs in the morphine withdrawal after the administration of NMDA receptor blockers. Our results also indicate a clear interaction between the opiate and GABAergic systems, since GHB (a GABA metabolite) interacts with morphine, having an additive effect on morphine-affected social behaviours but counteracting morphine-induced increases in motor activity. We have confirmed that GHB is a useful tool capable of ameliorating both the physical as well as motivational aspects of opiate witdrawal. Also we verified that the relapse in cocaine-seeking behaviour could be blocked by GHB when administered during the acquisition of the conditioning procedure, the expression, or even, jointly with a priming dose of cocaine. Finally, the glutamatergic system also plays a role in the acquisition and expression of the cocaine-induced CPP, but not so in the reinstatement of this preference by a priming dose of cocaine. Our results can help to better understand the underlying neurobiological phenomena in the drugs addictive behaviour and the possible use of memantine and GHB in the treatment of addiction, suggesting their importance as therapeutic tools in the addiction to opiates and psychoestimulants (cocaine).

El objetivo de este trabajo era comprobar la capacidad de rehabilitación cognitiva de los pacientes con enfermedad de Parkinson (EP). Para ello, se seleccionó un grupo de pacientes con EP y se les sometió a una resonancia magnética mientras llevaban a cabo la tarea Stroop. Durante 6 meses la mitad de ellos realizaron un programa de entrenamiento cognitivo basado en la tarea SUDOKU. Tras este periodo, todos los pacientes y los controles fueron evaluados de nuevo. Los resultados indicaron que el entrenamiento tiene resultados beneficiosos para los pacientes con EP. / Objectives: To check the cerebral effects of cognitive training in Parkinson's disease (PD) patients. Materials and Methods:The pilot study was carried out with 16 non-demented PD patients and 16 healthy subjects. In the Test phase and Retest phase (6 months later) eight non demented PD patients and eight healthy controls were evaluated (Hoehn & Yahr, UPDRS, MMSE, MADRS scales and clinical history). All subjects underwent fMRI examination while doing the Stroop test in the modified version of Scholes (2006) with 160 stimuli (80 congruent and 80 incongruent). Then, half of PD patients completed a cognitive rehabilitation training programme lasting 6 months (PD training patients). Training consisted of completing an easy "sudoku" every day for 6 months; after which patients and controls were evaluated again with a Stroop while undergoing the fMRI test. Results:PD patients took significantly more time to complete the task than the control subjects but the difference between the scores was not statistically significant. In PD patients without training the same areas were activated as in the control subjects (this already seen activated in the Stroop task), but also some emotional areas and basal ganglia nuclei. PD patients with training showed additional temporal areas activated in respect to the controls but not in respect to untrained PD patients. Conclusions: To complete the task PD patients probably need to activate emotional areas and extra-activation of basal ganglia, which would imply an additional interactions of thalamus activation and inhibition and an impaired inhibition of the cortex. The consequence would be the activation of unnecessary areas and slower of the cognitive activity