EVALUATING THE INTEGRITY OF CORTICO-SUBCORTICAL FUNCTIONAL NETWORKS BY DEEP BRAIN STIMULATION OF THE ACCUMBENS NUCLEUS AND THE SUBTALAMIC NUCLEUS (Q3152924): Difference between revisions
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EVALUATING THE INTEGRITY OF CORTICO-SUBCORTICAL FUNCTIONAL NETWORKS BY DEEP BRAIN STIMULATION OF THE ACCUMBENS NUCLEUS AND THE SUBTALAMIC NUCLEUS | |||
Revision as of 02:37, 9 October 2021
Project Q3152924 in Spain
| Language | Label | Description | Also known as |
|---|---|---|---|
| English | EVALUATING THE INTEGRITY OF CORTICO-SUBCORTICAL FUNCTIONAL NETWORKS BY DEEP BRAIN STIMULATION OF THE ACCUMBENS NUCLEUS AND THE SUBTALAMIC NUCLEUS |
Project Q3152924 in Spain |
Statements
62,920.0 Euro
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78,650.0 Euro
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80.0 percent
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1 January 2018
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31 December 2020
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UNIVERSIDAD DE CADIZ
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11012
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EL NUCLEO ACCUMBENS (NAC) Y EL NUCLEO SUBTALAMICO (STN) CONSTITUYEN DOS ESTRUCTURAS FUNDAMENTALES DE LOS GANGLIOS BASALES CON EXTENSAS CONEXIONES A LA CORTEZA CEREBRAL, AL TALAMO Y AL TRONCO ENCEFALICO, EJERCIENDO EL CONTROL SOBRE UNA GRAN VARIEDAD DE CONDUCTAS, COMO LOS MOVIMIENTOS MOTORES VOLUNTARIOS, EL APRENDIZAJE PROCEDIMENTAL, O EL FUNCIONAMIENTO COGNITIVO. AMBOS NUCLEOS COMPONEN TAMBIEN UN ELEMENTO CENTRAL DE LOS CIRCUITOS EMOCIONALES Y MOTIVACIONALES, POR LO QUE DICHAS ESTRUCTURAS SUELEN SER EL FOCO DE NUEVOS TRATAMIENTOS PARA DIVERSOS TRASTORNOS NEUROLOGICOS Y PSIQUIATRICOS, COMO LA ENFERMEDAD DE PARKINSON (PD) O EL TRASTORNO OBSESIVO-COMPULSIVO (OCD), DOS DE LOS TRASTORNOS CEREBRALES CRONICOS MAS INCAPACITANTES, Y QUE SUS FORMAS MAS SEVERAS Y FARMACO-RESISTENTES, PUEDEN AFECTAR SERIAMENTE A SU FUNCIONAMIENTO COGNITIVO Y SOCIAL. LA EVIDENCIA EMPIRICA HA DEMOSTRADO QUE TANTO EL STN COMO EL NAC PODRIAN SER UNA DIANA TERAPEUTICA EFECTIVA EN EL TRATAMIENTO DEL PD Y DEL OCD, RESPECTIVAMENTE, MEDIANTE LA ESTIMULACION ELECTRICA CEREBRAL PROFUNDA (DBS) A TRAVES DE ELECTRODOS PERMANENTEMENTE IMPLANTADOS, UNA PROMETEDORA ALTERNATIVA A LA CIRUGIA ABLATIVA EN ESTOS TRASTORNOS. SIN EMBARGO, AUNQUE DIFERENTES ESTUDIOS CLINICOS Y DE NEUROIMAGEN HAN DEMOSTRADO LA IMPLICACION ACTIVA DEL STN Y DEL NAC EN CONDUCTAS RELACIONADAS CON LA TOMA DE DECISIONES, EL APRENDIZAJE, O EL CONTROL EMOCIONAL E INHIBITORIO, EL PRECISO PAPEL FUNCIONAL DE ESTAS DOS AREAS EN LA FISIOPATOLOGIA DEL PD Y OCD, SIGUE DEBATIENDOSE. ADEMAS, LOS ESTUDIOS COMBINANDO NEUROIMAGEN Y DBS SON MUY ESCASOS, DESCONOCIENDOSE EN GRAN PARTE LOS MECANISMOS POR LOS QUE LA DBS CONSIGUE MEJORAR LOS SINTOMAS NEURO-PSIQUIATRICOS EN ESTOS PACIENTES. POR ELLO, SON NECESARIOS NUEVAS INVESTIGACIONES QUE PERMITAN CARACTERIZAR LOS MECANISMOS NEURALES SUBYACENTES POR LOS QUE TANTO LA DBS-NAC O LA DBS-STN LOGRAN MODULAR LA ACTIVIDAD CEREBRAL, FAVORECIENDO EL "RE-ENSAMBLAJE" ENTRE LAS CONEXIONES CEREBRALES DISFUNCIONALES. EN ESTE PROYECTO, GRACIAS A LA POSIBILIDAD DE PODER TRABAJAR EN PACIENTES CON ELECTRODOS EXTERNALIZADOS UBICADOS EN EL STN Y EL NAC, REGISTRAREMOS LA ACTIVIDAD NEURAL DESDE DICHAS ESTRUCTURAS UTILIZANDO PARA ELLO EL MISMO ELECTRODO DBS, Y SIN NINGUN RIESGO ADICIONAL PARA EL PACIENTE. ESTE ENFOQUE NOS PERMITIRA UN REGISTRO DUAL DESDE ESTRUCTURAS PROFUNDAS ESPECIFICAS CON ELECTRODOS INTRACRANEALES (LFP) Y DESDE REGIONES CORTICALES MEDIANTE ELECTROENCEFALOGRAFIA (EEG), PERMITIENDO, POR TANTO, EL REGISTRO SIMULTANEO TANTO DE LFP-EEG COMO DE EEG DURANTE DBS. EL OBJETIVO PRINCIPAL DE NUESTRA PROPUESTA TRATA DE CLARIFICAR LA INTEGRIDAD DE LAS ACTIVACIONES NEURALES Y DE LA CONECTIVIDAD FUNCIONAL EN LAS DISTINTAS REDES CEREBRALES A GRAN ESCALA EN PACIENTES CON PD Y OCD, DURANTE LA REALIZACION DE TAREAS COGNITIVAS Y EMOCIONALES Y EN ESTADOS DE REPOSO, Y SU RELACION CON LA SINTOMATOLOGIA CLINICA. AL ESTUDIAR LA DBS-STN Y LA DBS-NAC RESPECTIVAMENTE EN EL PD Y EL OCD DURANTE PERIODOS DE ESTIMULACION 'ON/OFF', PRETENDEMOS EVALUAR LAS INTERACCIONES CRITICAS A NIVEL CORTICO-SUBCORTICAL ENTRE LA CORTEZA FRONTAL Y LOS GANGLIOS BASALES. NUESTRO ENFOQUE PUEDE DAR LUGAR A UNA EVALUACION CEREBRAL Y FUNCIONAL MAS DETALLADA DESDE DIFERENTES PERSPECTIVAS, Y CONSTITUYE UNA OPORTUNIDAD UNICA PARA INVESTIGAR TANTO LA DINAMICA OSCILATORIA NEURAL ESPONTANEA E INDUCIDA EN DIFERENTES REDES CEREBRALES COMO SU RELACION CON LA PATOGENESIS, EL MANTENIMIENTO Y LA REDUCCION DE LA SINTOMATOLOGIA CRONICA. (Spanish)
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THE HUMAN NUCLEUS ACCUMBENS (NAC) AND SUBTHALAMIC NUCLEUS (STN) CONSTITUTE TWO MAJOR STRUCTURES OF THE BASAL GANGLIA WITH EXTENSIVE CONNECTIONS TO THE CEREBRAL CORTEX, THALAMUS AND BRAINSTEM, EXERTING A CONTROL OVER DIVERSE BEHAVIOURS SUCH AS VOLUNTARY MOTOR MOVEMENTS, PROCEDURAL LEARNING, EYE MOVEMENTS, AND COGNITION. THEY ARE ALSO A CENTRAL COMPONENT OF THE MOTIVATION AND EMOTIONAL CIRCUITS, WHICH MAKES THESE STRUCTURES PROMISING TARGETS FOR THE TREATMENT OF MANY NEUROLOGICAL AND PSYCHIATRIC DISORDERS, SUCH AS PARKINSON'S DISEASE (PD) AND OBSESSIVE-COMPULSIVE DISORDER (OCD), TWO OF THE MOST PROMINENT CHRONIC AND HIGHLY DISABLING BRAIN-RELATED DISORDERS WHICH IN THE MOST SEVERE AND DRUG-RESISTANT FORMS, CAN SEVERELY IMPAIR SOCIAL AND COGNITIVE FUNCTIONING. AS A CONSEQUENCE OF DIFFERENT EMPIRICAL OBSERVATIONS, STN AND NAC HAVE RECENTLY BECOME A TARGET IN PD AND OCD RESPECTIVELY FOR DEEP BRAIN ELECTRICAL STIMULATION (DBS), AN EFFECTIVE AND PROMISING ALTERNATIVE TO ABLATIVE SURGERY FOR NEUROLOGICAL AND PSYCHIATRIC CONDITIONS THAT CONSISTS OF THE APPLICATION OF LOW-INTENSITY ELECTRIC IMPULSES TO STRATEGIC SITES IN THE BRAIN THROUGH PERMANENTLY IMPLANTED ELECTRODES. HOWEVER, ALTHOUGH CLINICAL AND NEUROIMAGING STUDIES HAVE PROVIDED EVIDENCE THAT THE HUMAN STN AND NAC BECOME ACTIVE DURING REWARD LEARNING, EMOTIONAL, INHIBITORY CONTROL, OR DECISION-MAKING BEHAVIOURS, THE PRECISE FUNCTIONAL ROLE OF THESE AREA IN HUMANS, AND INDEED IN THE PATHOPHYSIOLOGY OF PD AND OCD, REMAINS DEBATED OR UNKNOWN. MOREOVER, STUDIES COMBINING NEUROIMAGING AND DBS ARE SPARSE AND MANY QUESTIONS REMAIN TO BE ANSWERED ABOUT THE MECHANISMS BY WHICH DBS CAN IMPROVE NEUROLOGICAL AND PSYCHIATRIC SYMPTOMS IN SOME PATIENTS BUT NOT IN OTHERS. FURTHERMORE, MUCH WORK REMAINS TO BE DONE TO CHARACTERISE THE UNDERLYING NEURAL MECHANISM BY WHICH NAC-DBS AND STN-DBS MODULATE BRAIN ACTIVITY FAVOURING THE ¿RE-ASSEMBLY" OF ABNORMAL CONNECTIONS BETWEEN BRAIN REGIONS. IN THIS PROPOSAL, WE WILL TAKE ADVANTAGE OF WORKING WITH PD AND OCD PATIENTS WITH EXTERNALIZED ELECTRODES LOCATED IN THE STN AND NAC RESPECTIVELY TO RECORD NEURAL ACTIVITY FROM DEEP-BRAIN STRUCTURES USING THE SAME DBS ELECTRODE, WITHOUT ANY ADDITIONAL RISK TO THE PATIENT. THIS APPROACH ENABLES A DUAL RECORDING OF SELECTED DEEP STRUCTURES WITH THE INTRACRANIAL ELECTRODES (LFP) AND SUPERFICIAL STRUCTURES WITH ELECTROENCEPHALOGRAPHY (EEG), ENABLING THEREFORE BOTH THE SIMULTANEOUS LFP-EEG RECORDING AND THE STUDY OF CHANGES OF THE SURFACE EEG ACTIVITY DURING DBS. HERE, THE MAIN OBJECTIVE OF THIS PROJECT AIMS TO CLARIFY THE INTEGRITY ON THE ACTIVITY OF LARGE-SCALE BRAIN NETWORKS AND FUNCTIONAL CONNECTIVITY IN PD AND OCD PATIENTS DURING RESTING STATE AND SUBSEQUENT COGNITIVE AND EMOTIONAL TASK PERFORMANCE, AND ITS RELATIONSHIP WITH PD/OCD SYMPTOM DIMENSIONS. BY STUDYING STN-DBS IN PD AND NAC-DBS IN OCD DURING DBS 'ON/OFF' PERIODS, WE WILL ASSESS THE CRITICAL INTERACTIONS OF ¿FRONTAL-BASAL GANGLIA¿ (CORTICAL-SUBCORTICAL) NETWORKS IN THESE TWO DISABLING BRAIN CONDITIONS. OUR APPROACH MAY RESULT IN A MORE DETAILED FUNCTIONAL BRAIN EVALUATION FROM DIFFERENT PERSPECTIVES, WHICH HOLDS POTENTIAL TO OPEN A UNIQUE WINDOW TO INVESTIGATE (SPONTANEOUS AND STIMULUS-INDUCED) NEURONAL ¿OSCILLATORY¿ DYNAMICS IN DIFFERENT BRAIN NETWORKS AS WELL AS ITS RELATIONSHIP TO THE PATHOGENESIS, MAINTENANCE, AND REDUCTION OF CHRONIC SYMPTOMS. (English)
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Cádiz
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Identifiers
PSI2017-85951-R
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