RESUMEN
Changes in effective connectivity during the performance of a motor task appear important for the pathogenesis of motor symptoms in Parkinson's disease (PD). One type of task that is typically difficult for individuals with PD is simultaneous or bimanual movement, and here we investigate the changes in effective connectivity as a potential mechanism. Eight PD subjects off and on l-DOPA medication and 10 age-matched healthy control subjects performed both simultaneous and unimanual motor tasks in an fMRI scanner. Changes in effective connectivity between regions of interest (ROIs) during simultaneous and unimanual task performance were determined with structural equation modeling (SEM), and changes in the temporal dynamics of task performance were determined with multivariate autoregressive modeling (MAR). PD subjects demonstrated alterations in both effective connectivity and temporal dynamics compared with control subjects during the performance of a simultaneous task. l-DOPA treatment was able to partially normalize effective connectivity and temporal patterns of activity in PD, although some connections remained altered in PD even after medication. Our results suggest that difficulty performing simultaneous movements in PD is at least in part mediated by a disruption of effective communication between widespread cortical and subcortical areas, and l-DOPA assists in normalizing this disruption. These results suggest that even when the site of neurodegeneration is relatively localized, study of how disruption in a single region affects connectivity throughout the brain can lead to important advances in the understanding of the functional deficits caused by neurodegenerative disease.
Asunto(s)
Antiparkinsonianos/farmacología , Mapeo Encefálico , Levodopa/farmacología , Movimiento/efectos de los fármacos , Dinámicas no Lineales , Enfermedad de Parkinson/fisiopatología , Anciano , Análisis de Varianza , Antiparkinsonianos/uso terapéutico , Encéfalo/irrigación sanguínea , Encéfalo/efectos de los fármacos , Encéfalo/fisiopatología , Estudios de Casos y Controles , Femenino , Lateralidad Funcional , Fuerza de la Mano , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Levodopa/uso terapéutico , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Modelos Biológicos , Oxígeno/sangre , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/patología , Desempeño Psicomotor/efectos de los fármacos , Desempeño Psicomotor/fisiologíaRESUMEN
OBJECTIVES: To determine if novel methods establishing patterns in EEG-EMG coupling can infer subcortical influences on the motor cortex, and the relationship between these subcortical rhythms and bradykinesia. BACKGROUND: Previous work has suggested that bradykinesia may be a result of inappropriate oscillatory drive to the muscles. Typically, the signal processing method of coherence is used to infer coupling between a single channel of EEG and a single channel of rectified EMG, which demonstrates 2 peaks during sustained contraction: one, approximately 10 Hz, which is pathologically increased in PD, and a approximately 30 Hz peak which is decreased in PD, and influenced by pharmacological manipulation of GABAA receptors in normal subjects. MATERIALS AND METHODS: We employed a novel multiperiodic squeezing paradigm which also required simultaneous movements. Seven PD subjects (on and off L-Dopa) and five normal subjects were recruited. Extent of bradykinesia was inferred by reduced relative performance of the higher frequencies of the squeezing paradigm and UPDRS scores. We employed Independent Component Analysis (ICA) and Empirical Mode Decomposition (EMD) to determine EEG/EMG coupling. RESULTS: Corticomuscular coupling was detected during the continually changing force levels. Different components included those over the primary motor cortex (ipsilaterally and contralaterally) and over the midline. Subjects with greater bradykinesia had a tendency towards increased approximately 10 Hz coupling and reduced approximately 30 Hz coupling that was erratically reversed with L-dopa. CONCLUSIONS: These results suggest that lower approximately 10 Hz peak may represent pathological oscillations within the basal ganglia which may be a contributing factor to bradykinesia in PD.