RESUMEN
STUDY OBJECTIVES: Rapid eye movement sleep behavior disorder (RBD) is a condition closely associated with Parkinson disease (PD). RBD is a sleep disturbance that frequently manifests early in the development of PD, likely reflecting disruption in normal functioning of anatomical areas affected by neurodegenerative processes. Although specific neuropathological aspects shared by RBD and PD have yet to be fully documented, further characterization is critical to discovering reliable biomarkers that predict PD onset. In the current study, we tested the hypothesis of altered functional connections of the substantia nigra (SN) in patients in whom RBD was diagnosed. DESIGN: Between-groups, single time point imaging. SETTING: UTHSC-H 3 telsa MRI center. PARTICIPANTS: Ten patients with RBD, 11 patients with PD, and 10 age-matched controls. INTERVENTIONS: NA. MEASUREMENTS AND RESULTS: We measured correlations of SN time series using resting state blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) in patients with idiopathic RBD who were at risk for developing PD, patients in whom PD was diagnosed, and age-matched controls. Using voxelwise analysis of variance, different correlations (P < 0.01, whole-brain corrected) between left SN and left putamen were found in patients with RBD compared with controls and patients with PD. SN correlations with right cuneus/precuneus and superior occipital gyrus were significantly different for patients with RBD compared with both controls and patients with PD. CONCLUSIONS: The results suggest that altered nigrostriatal and nigrocortical connectivity characterizes rapid eye movement sleep behavior disorder before onset of obvious motor impairment. The functional changes are discussed in the context of degeneration in dopaminergic and cognition-related networks.
Asunto(s)
Trastorno de la Conducta del Sueño REM/patología , Sustancia Negra/patología , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Neuroimagen Funcional , Movimientos de la Cabeza , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Red Nerviosa , Vías Nerviosas/patologíaRESUMEN
BACKGROUND: Huntington disease (HD) is a genetic, neurodegenerative disorder characterized by chorea, behavioral co-morbidities, cognitive deficits, and eye movement abnormalities. We sought to evaluate whether reflexive and voluntary orienting prove useful as biomarkers of disease severity in HD. METHODS: Eleven HD subjects were evaluated with the motor subscale of the Unified Huntington Disease Rating Scale (UHDRS) and the Montreal Cognitive Assessment. Using an infrared eye tracker, we also measured latency and error rates of horizontal and vertical saccades using prosaccade and antisaccade eye movement tasks. We calculated simple and age-controlled correlations between eye movement and clinical parameters. RESULTS: Prosaccade latency correlated with total chorea score. HD patients with greater clinical severity were significantly slower in the prosaccade task. Antisaccade error rate also correlated with UHDRS motor score and total chorea score. HD patients with greater clinical severity as measured by either measure made significantly more errors in the antisaccade task. All these correlations remained significant even when age was taken into account. CONCLUSIONS: The results of the present age-controlled study show for the first time that both reflexive and voluntary eye motor control in HD patients decrease with increase in disease severity suggesting declines in both motor and cognitive function. Thus, relatively simple eye movement parameters (latency and error rate) obtained from simple tasks (prosaccade and antisaccade) may serve as quantitative biomarkers of sub-cortical and cortical disease severity in HD and could aid in predicting onset, distinguishing subtypes, or evaluating disease progression and novel therapies.
Asunto(s)
Parpadeo/fisiología , Progresión de la Enfermedad , Enfermedad de Huntington/patología , Enfermedad de Huntington/fisiopatología , Movimientos Sacádicos/fisiología , Índice de Severidad de la Enfermedad , Adulto , Anciano , Biomarcadores , Movimientos Oculares/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estimulación Luminosa/métodosRESUMEN
Schizophrenic patients are heterogeneous with respect to voluntary eye movement performance, with some showing impairment (e.g., high antisaccade error rates) and others having intact performance. To investigate how this heterogeneity may correlate with different cognitive outcomes after treatment, we used a prosaccade and antisaccade task to investigate the effects of haloperidol in schizophrenic subjects at three time points: baseline (before medication), 3-5 days post-medication, and 12-14 days post-medication. We also investigated changes on the Stroop Task and the Positive and Negative Syndrome Scale (PANSS) in these same subjects. Results were compared to matched controls. When considered as a single patient group, haloperidol had no effects across sessions on reflexive and voluntary saccadic eye movements of schizophrenic patients. In contrast, the performance of the Control group improved slightly but significantly across sessions on the voluntary eye movement task. When each subject was considered separately, interestingly, for schizophrenic patients change in voluntary eye movement performance across sessions depended on the baseline performance in a non-monotonic manner. That is, there was maximal worsening of voluntary eye movement performance at an intermediate level of baseline performance and the worsening decreased on either side of this intermediate baseline level. When patients were divided into categorical subgroups (nonimpaired and impaired), consistent with the non-monotonic relationship, haloperidol worsened voluntary eye movement performance in the nonimpaired patients and improved performance in the impaired patients. These results were only partially reflected in the Stroop Test. Both patient subgroups showed clinically significant improvement over time as measured by the PANSS. These findings suggest that haloperidol has different effects on cognitive performance in impaired and nonimpaired schizophrenic patients that are not evident in clinical ratings based on the PANSS. Given that good cognitive function is important for long-term prognosis and that there is heterogeneity in schizophrenia, these findings are critical for optimal evaluation and treatment of schizophrenic patients.
Asunto(s)
Antipsicóticos/farmacología , Trastornos del Conocimiento/tratamiento farmacológico , Cognición/fisiología , Haloperidol/farmacología , Movimientos Sacádicos/fisiología , Esquizofrenia/tratamiento farmacológico , Adulto , Antipsicóticos/uso terapéutico , Cognición/efectos de los fármacos , Femenino , Haloperidol/uso terapéutico , Humanos , Pacientes Internos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Escalas de Valoración Psiquiátrica , Movimientos Sacádicos/efectos de los fármacos , Esquizofrenia/diagnóstico , Esquizofrenia/fisiopatología , Adulto JovenRESUMEN
OBJECTIVE: The purpose of this study was to quantify volumes of specific subcortical gray matter nuclei implicated in Parkinson's disease (PD) as a preliminary step for identifying a non-invasive clinical biomarker for PD. We hypothesized that REM sleep behavior disorder (RBD) patients, at risk for developing PD, will demonstrate a pattern of neuronal degeneration reflected in reduced striatal volumes on T1-weighted MRI. METHODS: We compared measures of RBD patients confirmed by polysomnography (PSG) with groups of age/gender-matched Control subjects and early PD (EPD) patients (Hoehn & Yahr < 2). Clinical measurements included the Unified Parkinson's disease Rating Scales (UPDRS), timed gait and finger tapping tasks, the Parkinson's Disease Questionnaire (PDQ-39), and a time-synchronized video recorded single-night PSG. Volumetric measurements were derived from high-resolution T1-weighted 3 T MRI images. RESULTS: The matched Control and EPD groups were statistically similar to the RBD group in age, gender, handedness, and total brain volumes. The RBD group had smaller bilateral putamen volumes (both raw and normalized by brain tissue volume), in addition to some clinical impairment on the UPDRS and PDQ-39. CONCLUSIONS: Reduced putamen volumes may be a structural marker for RBD and reflect a pattern of neurodegeneration that predicts the development of PD.
Asunto(s)
Putamen/patología , Trastorno de la Conducta del Sueño REM/patología , Encéfalo/patología , Núcleo Caudado/patología , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Cuerpos de Lewy/patología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/etiología , Enfermedad de Parkinson/fisiopatología , Polisomnografía , Trastorno de la Conducta del Sueño REM/diagnóstico , RiesgoRESUMEN
RATIONALE: Differences in 5-hydroxytryptamine (5-HT) function have been the subject of extensive research in psychiatric studies. Many studies have manipulated L -tryptophan (Trp) levels to temporarily decrease (depletion) or increase (loading) 5-HT synthesis. While most researchers have used a 100-g formulation, there has been ongoing interest in using smaller-sized formulations. OBJECTIVES: This study examined the time course of multiple plasma indicators of brain 5-HT synthesis after a 50-g depletion and loading as a comparison to the corresponding 100-g formulations that are typically used. MATERIALS AND METHODS: Plasma was collected from 112 healthy adults at seven hourly intervals after consumption of either a 50- or 100-g depletion or loading. Self-ratings of mood and somatic symptoms were completed before and after Trp manipulations. RESULTS: The primary findings were that (1) the 50- and 100-g formulations produced the expected changes in plasma indicators after both depletion (-89% and -96%, respectively) and loading (+570% and +372%, respectively); (2) the 100-g depletion showed more robust effects at the 4, 5, and 6 h measurements than the 50-g depletion; (3) there was significant attrition after both the 100-g depletion and loading, but not after either of the 50-g formulations; and (4) both the 50- and 100-g depletions produced increases in negative self-ratings of mood and somatic symptoms, while loading significantly increased negative ratings after the 100 g only. CONCLUSIONS: There are important considerations when choosing among formulation sizes for use in Trp manipulation studies, and the complete 7-h time-course data set of the typical plasma Trp measures presented here may help researchers decide which methodology best suits their needs.
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Afecto/efectos de los fármacos , Serotonina/biosíntesis , Triptófano/deficiencia , Triptófano/farmacología , Adolescente , Adulto , Disponibilidad Biológica , Química Farmacéutica , Femenino , Hemodinámica/efectos de los fármacos , Humanos , Masculino , Triptófano/farmacocinéticaRESUMEN
BACKGROUND: The integrity of frontal systems responsible for voluntary control and their interaction with subcortical regions involved in reflexive responses were studied in patients with Parkinson's disease (PD). Previous studies have shown that patients with PD have impaired executive function, including deficits in attention, motor planning and decision making. METHODS: Executive function was measured through eye movements: reflexive (stimulus driven) prosaccades and voluntary (internally guided) antisaccades. Patients with advanced idiopathic PD, off and on their optimal levodopa therapy, were tested on a prosaccade and an antisaccade task and compared with matched controls. RESULTS: Levodopa significantly increased response time for reflexive prosaccades and reduced error rate for voluntary antisaccades. CONCLUSIONS: Consistent with our proposed model, patients with PD in the medicated state are better able to plan and execute voluntary eye movements. These findings suggest levodopa improves function of the voluntary frontostriatal system, which is deficient in PD.
Asunto(s)
Antiparkinsonianos/uso terapéutico , Levodopa/uso terapéutico , Trastornos de la Motilidad Ocular/tratamiento farmacológico , Enfermedad de Parkinson/complicaciones , Movimientos Sacádicos/efectos de los fármacos , Anciano , Antiparkinsonianos/farmacología , Femenino , Humanos , Levodopa/farmacología , Masculino , Persona de Mediana Edad , Trastornos de la Motilidad Ocular/etiología , Enfermedad de Parkinson/tratamiento farmacológico , Desempeño Psicomotor/efectos de los fármacos , Tiempo de Reacción/efectos de los fármacos , Movimientos Sacádicos/fisiologíaRESUMEN
In an attempt to distinguish and define the altered cognitive processes associated with Parkinson's disease (PD), we examine and try to dissociate the components of an effective voluntary saccade: (1) the planning and execution of a voluntary saccade; (2) the suppression of reflexive eye movements; and (3) the working memory processes required. We tested 14 PD patients (off their medications) and 11 control subjects on antisaccade (AS), delayed antisaccade (DAS), and remembered antisaccade (RAS) paradigms. The three tasks required identical responses, each task only differing in a single manipulation for direct comparison--a delay period was added in the DAS, and the target was removed during the delay period of the RAS--allowing us to study the specific cognitive processes involved in the execution of a voluntary saccade. Voluntary saccade response times were longer in the PD group compared to controls on all three tasks, suggesting difficulties in voluntary saccade execution. Furthermore, PD patients showed difficulty suppressing reflexive saccades (increased number of errors in the AS task and increased number of disinhibitions in the DAS task). Finally, our study did not show significant differences in either response time or error rate between the RAS and the DAS tasks for either control subjects or PD patients. In sum, we report evidence for voluntary saccade execution deficits together with problems inhibiting reflexive saccades in Parkinson's disease patients. These findings were correlated with each other and disease severity, suggesting that eye movement measurement may be a useful tool for studying higher cognitive function.