RESUMO
The functional significance of electrical rhythms in the mammalian brain remains uncertain. In the motor cortex, the 12-20 Hz beta rhythm is known to transiently decrease in amplitude during movement, and to be altered in many motor diseases. Here we show that the activity of neuronal populations is phase-coupled with the beta rhythm on rapid timescales, and describe how the strength of this relation changes with movement. To investigate the relationship of the beta rhythm to neuronal dynamics, we measured local cortical activity using arrays of subdural electrocorticographic (ECoG) electrodes in human patients performing simple movement tasks. In addition to rhythmic brain processes, ECoG potentials also reveal a spectrally broadband motif that reflects the aggregate neural population activity beneath each electrode. During movement, the amplitude of this broadband motif follows the dynamics of individual fingers, with somatotopically specific responses for different fingers at different sites on the pre-central gyrus. The 12-20 Hz beta rhythm, in contrast, is widespread as well as spatially coherent within sulcal boundaries and decreases in amplitude across the pre- and post-central gyri in a diffuse manner that is not finger-specific. We find that the amplitude of this broadband motif is entrained on the phase of the beta rhythm, as well as rhythms at other frequencies, in peri-central cortex during fixation. During finger movement, the beta phase-entrainment is diminished or eliminated. We suggest that the beta rhythm may be more than a resting rhythm, and that this entrainment may reflect a suppressive mechanism for actively gating motor function.
Assuntos
Relógios Biológicos , Eletroencefalografia/métodos , Potencial Evocado Motor , Dedos/fisiopatologia , Córtex Motor/fisiopatologia , Movimento , Rede Nervosa/fisiopatologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
PURPOSE: Exclusive right hemisphere language lateralization is rarely observed in the Wada angiography results of epilepsy surgery patients. Cortical stimulation mapping (CSM) is infrequently performed in such patients, as most undergo nondominant left hemisphere resections, which are presumed not to pose any risk to language. Early language reorganization is typically assumed in such individuals, taking left hemisphere epileptiform activity as confirmation of change resulting from a pathologic process. We present data from CSM and Wada studies demonstrating that right hemisphere language occurs in the absence of left hemisphere pathology, suggesting it can exist as a normal, but rare variant, in some individuals. Furthermore, these data confirm the Wada test findings of atypical dominance. METHODS: Cortical stimulation mapping data were examined for all right hemisphere surgical patients with right hemisphere speech at our center between 1974 and 2006. Of 1,209 interpretable Wada procedures, 89 patients (7.4%) had exclusive right hemisphere speech, and 21 (1.7%) of these patients underwent surgery involving the right hemisphere. Language site location was determined by examining intraoperative photographs, and site distribution was statistically compared to published findings from left hemisphere language dominant patients. KEY FINDINGS: Language cortex was identified in the right hemisphere during CSM for all patients with available data. All sites could be classified in superior or middle temporal gyri, inferior parietal lobe, or inferior frontal gyrus, all of which were common zones where language was identified in the left hemisphere dominant comparison sample. SIGNIFICANCE: Results suggest that the Wada procedure is a valid measure for identifying right hemisphere language processing without any false lateralization found in the patients mapped with CSM (i.e., a positive Wada is 100% sensitive for finding right hemisphere language sites), and that the distribution of language sites is consistent across right hemisphere and left hemisphere language dominant patients, supporting the theory that right hemisphere language can occur as a normal variant of language lateralization.
Assuntos
Amobarbital , Mapeamento Encefálico , Córtex Cerebral/fisiopatologia , Dominância Cerebral/fisiologia , Epilepsia/patologia , Idioma , Adolescente , Adulto , Angiografia Cerebral , Epilepsia/cirurgia , Feminino , Humanos , Período Intraoperatório , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECT: Posttraumatic epilepsy (PTE) is a common cause of medically intractable epilepsy. While much of PTE is extratemporal, little is known about factors associated with good outcomes in extratemporal resections in medically intractable PTE. The authors investigated and characterized the long-term outcome and patient factors associated with outcome in this population. METHODS: A single-institution retrospective query of all epilepsy surgeries at Regional Epilepsy Center at the University of Washington was performed for a 17-year time span with search terms indicative of trauma or brain injury. The query was limited to adult patients who underwent an extratemporal resection (with or without temporal lobectomy), in whom no other cause of epilepsy could be identified, and for whom minimum 1-year follow-up data were available. Surgical outcomes (in terms of seizure reduction) and clinical data were analyzed and compared. RESULTS: Twenty-one patients met inclusion and exclusion criteria. In long-term follow-up 6 patients (28%) were seizure-free and an additional 6 (28%) had a good outcome of 2 or fewer seizures per year. Another 5 patients (24%) experienced a reduction in seizures, while only 4 (19%) did not attain significant benefit. The presence of focal encephalomalacia on imaging was associated with good or excellent outcomes in 83%. In 8 patients with the combination of encephalomalacia and invasive intracranial EEG, 5 (62.5%) were found to be seizure free. Normal MRI examinations preoperatively were associated with worse outcomes, particularly when combined with multifocal or poorly localized EEG findings. Two patients suffered complications but none were life threatening or disabling. CONCLUSIONS: Many patients with extratemporal PTE can achieve good to excellent seizure control with epilepsy surgery. The risks of complications are acceptably low. Patients with focal encephalomalacia on MRI generally do well. Excellent outcomes can be achieved when extratemporal resection is guided by intracranial EEG electrodes defining the extent of resection.
Assuntos
Epilepsia/etiologia , Epilepsia/cirurgia , Lobo Temporal/cirurgia , Resultado do Tratamento , Adolescente , Adulto , Lesões Encefálicas/complicações , Eletroencefalografia , Feminino , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada de Emissão de Fóton Único , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
OBJECT: Where no society-based or manufacturer guidance on radiation limits to neuromodulation devices is available, this research provides the groundwork for neurosurgeons and radiation oncologists who rely on the computerized treatment plan clinically for cancer patients. The focus of the article is to characterize radiation parameters of attenuation and scatter when an incident therapeutic x-ray beam is directed upon them. At the time of this writing, manufacturers of Neuromodulation products do not recommend direct exposure of the device in the beam nor provide guidance for the maximum dose for these devices. METHODS: Ten neuromodulation models were chosen to represent the finite class of devices marketed by Medtronic before 2011. CT simulations permitted computer treatment modeling for dose distribution analysis as used routinely in radiation oncology for patients. Phantom case results were directly compared to actual clinical patient cases. Radiation detection measurements were then correlated to computational results. Where the x-ray beam passes through the device and is attenuated, dose reduction was identified with Varian Eclipse computer modeling for these posterior locations. RESULTS: Although the computer algorithm did not identify physical processes of side-scatter and back-scatter, these phenomena were proven by radiation measurement to occur. In general, the computer results underestimated the level of change seen by measurement. CONCLUSIONS: For these implantable neurostimulators, the spread in dose changes were found to be -6.2% to -12.5% by attenuation, +1.7% to +3.8% by side-scatter, and +1.1% to +3.1% by back-scatter at 6 MV. At 18 MV, these findings were observed to be -1.4% to -7.0% by attenuation, +1.8% to 5.7% by side-scatter, and 0.8% to 2.7% by back-scatter. No pattern for the behavior of these phenomena was deduced to be a direct consequence of device size.
Assuntos
Neuroestimuladores Implantáveis , Modelos Teóricos , Dosagem Radioterapêutica/normas , Planejamento da Radioterapia Assistida por Computador/normas , Simulação por Computador , Humanos , Imagens de Fantasmas , Planejamento da Radioterapia Assistida por Computador/métodos , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Recognition of human behavioral activities using local field potential (LFP) signals recorded from the Subthalamic Nuclei (STN) has applications in developing the next generation of deep brain stimulation (DBS) systems. DBS therapy is often used for patients with Parkinson's disease (PD) when medication cannot effectively tackle patients' motor symptoms. A DBS system capable of adaptively adjusting its parameters based on patients' activities may optimize therapy while reducing the stimulation side effects and improving the battery life. METHOD: STN-LFP reveals motor and language behavior, making it a reliable source for behavior classification. This paper presents LFP-Net, an automated machine learning framework based on deep convolutional neural networks (CNN) for classification of human behavior using the time-frequency representation of STN-LFPs within the beta frequency range. CNNs learn different features based on the beta power patterns associated with different behaviors. The features extracted by the CNNs are passed through fully connected layers and then to the softmax layer for classification. RESULTS: Our experiments on ten PD patients performing three behavioral tasks including "button press", "target reaching", and "speech" show that the proposed approach obtains an average classification accuracy of â¼88 %. Comparison with existing methods: The proposed method outperforms other state-of-the-art classification methods based on STN-LFP signals. Compared to well-known deep neural networks such as AlexNet, our approach gives a higher accuracy using significantly fewer parameters. CONCLUSIONS: CNNs show a high performance in decoding the brain neural response, which is crucial in designing the automatic brain-computer interfaces and closed-loop systems.
Assuntos
Estimulação Encefálica Profunda , Aprendizado Profundo , Doença de Parkinson , Núcleo Subtalâmico , Humanos , Doença de Parkinson/terapia , FalaRESUMO
BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus is an established therapeutic option for managing motor symptoms of Parkinson's disease. We conducted a double-blind, sham-controlled, randomised controlled trial to assess subthalamic nucleus DBS, with a novel multiple independent contact current-controlled (MICC) device, in patients with Parkinson's disease. METHODS: This trial took place at 23 implanting centres in the USA. Key inclusion criteria were age between 22 and 75 years, a diagnosis of idiopathic Parkinson's disease with over 5 years of motor symptoms, and stable use of anti-parkinsonian medications for 28 days before consent. Patients who passed screening criteria were implanted with the DBS device bilaterally in the subthalamic nucleus. Patients were randomly assigned in a 3:1 ratio to receive either active therapeutic stimulation settings (active group) or subtherapeutic stimulation settings (control group) for the 3-month blinded period. Randomisation took place with a computer-generated data capture system using a pre-generated randomisation table, stratified by site with random permuted blocks. During the 3-month blinded period, both patients and the assessors were masked to the treatment group while the unmasked programmer was responsible for programming and optimisation of device settings. The primary outcome was the difference in mean change from baseline visit to 3 months post-randomisation between the active and control groups in the mean number of waking hours per day with good symptom control and no troublesome dyskinesias, with no increase in anti-parkinsonian medications. Upon completion of the blinded phase, all patients received active treatment in the open-label period for up to 5 years. Primary and secondary outcomes were analysed by intention to treat. All patients who provided informed consent were included in the safety analysis. The open-label phase is ongoing with no new enrolment, and current findings are based on the prespecified interim analysis of the first 160 randomly assigned patients. The study is registered with ClinicalTrials.gov, NCT01839396. FINDINGS: Between May 17, 2013, and Nov 30, 2017, 313 patients were enrolled across 23 sites. Of these 313 patients, 196 (63%) received the DBS implant and 191 (61%) were randomly assigned. Of the 160 patients included in the interim analysis, 121 (76%) were randomly assigned to the active group and 39 (24%) to the control group. The difference in mean change from the baseline visit (post-implant) to 3 months post-randomisation in increased ON time without troublesome dyskinesias between the active and control groups was 3·03 h (SD 4·52, 95% CI 1·3-4·7; p<0·0001). 26 serious adverse events in 20 (13%) patients occurred during the 3-month blinded period. Of these, 18 events were reported in the active group and 8 in the control group. One death was reported among the 196 patients before randomisation, which was unrelated to the procedure, device, or stimulation. INTERPRETATION: This double-blind, sham-controlled, randomised controlled trial provides class I evidence of the safety and clinical efficacy of subthalamic nucleus DBS with a novel MICC device for the treatment of motor symptoms of Parkinson's disease. Future trials are needed to investigate potential benefits of producing a more defined current field using MICC technology, and its effect on clinical outcomes. FUNDING: Boston Scientific.
Assuntos
Estimulação Encefálica Profunda/métodos , Doença de Parkinson/terapia , Núcleo Subtalâmico/metabolismo , Adulto , Idoso , Método Duplo-Cego , Discinesias/terapia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Deep brain stimulation (DBS) has become a routine therapy for Parkinson's disease. Standard CT imaging, often used to evaluate DBS electrodes in patients with limited benefit or significant side effects, has limitations including inability to distinguish different metallic components of the DBS lead. CT imaging with an extended Hounsfield unit (EHU) scale allows advanced image processing techniques to detect individual electrodes. EHU-CT may be co-registered to MRI volumes to provide accurate anatomical visualization of DBS lead contacts.
Assuntos
Estimulação Encefálica Profunda/instrumentação , Eletrodos Implantados , Tomografia Computadorizada por Raios X/métodos , Estimulação Encefálica Profunda/métodos , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodosRESUMO
Deep brain stimulation (DBS) provides significant therapeutic benefit for movement disorders, such as Parkinson's disease (PD). Current DBS devices lack real-time feedback (thus are open loop) and stimulation parameters are adjusted during scheduled visits with a clinician. A closed-loop DBS system may reduce power consumption and side effects by adjusting stimulation parameters based on patient's behavior. Subthalamic nucleus (STN) local field potential (LFP) is a great candidate signal for the neural feedback, because it can be recorded from the stimulation lead and does not require additional sensors. In this paper, we introduce a behavior detection method capable of asynchronously detecting the finger movements of PD patients. Our study indicates that there is a motor-modulated inter-hemispheric connectivity between LFP signals recorded bilaterally from the STN. We utilize a non-linear regression method to measure this inter-hemispheric connectivity for detecting finger movement. Our experimental results, using the recordings from 11 patients with PD, demonstrate that this approach is applicable for behavior detection in the majority of subjects (average area under curve of 70±12%).
Assuntos
Encéfalo/fisiologia , Estimulação Encefálica Profunda/métodos , Movimento , Núcleo Subtalâmico/fisiopatologia , Idoso , Algoritmos , Potenciais Evocados , Retroalimentação , Feminino , Dedos/fisiologia , Lateralidade Funcional , Humanos , Masculino , Pessoa de Meia-Idade , Vias Neurais , Dinâmica não Linear , Doença de Parkinson/reabilitação , Curva ROC , Núcleo Subtalâmico/anatomia & histologiaRESUMO
This paper presents the results of our recent work on studying the effects of deep brain stimulation (DBS) and medication on the dynamics of brain local field potential (LFP) signals used for behavior analysis of patients with Parkinson's disease (PD). DBS is a technique used to alleviate the severe symptoms of PD when pharmacotherapy is not very effective. Behavior recognition from the LFP signals recorded from the subthalamic nucleus (STN) has application in developing closed-loop DBS systems, where the stimulation pulse is adaptively generated according to subjects' performing behavior. Most of the existing studies on behavior recognition that use STN-LFPs are based on the DBS being "off". This paper discovers how the performance and accuracy of automated behavior recognition from the LFP signals are affected under different paradigms of stimulation on/off. We first study the notion of beta power suppression in LFP signals under different scenarios (stimulation on/off and medication on/off). Afterward, we explore the accuracy of support vector machines in predicting human actions ("button press" and "reach") using the spectrogram of STN-LFP signals. Our experiments on the recorded LFP signals of three subjects confirm that the beta power is suppressed significantly when the patients take medication (p-value < 0.002) or stimulation (p-value < 0.0003). The results also show that we can classify different behaviors with a reasonable accuracy of 85% even when the high-amplitude stimulation is applied.
Assuntos
Estimulação Encefálica Profunda , Doença de Parkinson , Núcleo Subtalâmico , Humanos , Máquina de Vetores de SuporteRESUMO
BACKGROUND: Classification of human behavior from brain signals has potential application in developing closed-loop deep brain stimulation (DBS) systems. This paper presents a human behavior classification using local field potential (LFP) signals recorded from subthalamic nuclei (STN). METHOD: A hierarchical classification structure is developed to perform the behavior classification from LFP signals through a multi-level framework (coarse to fine). At each level, the time-frequency representations of all six signals from the DBS leads are combined through an MKL-based SVM classifier to classify five tasks (speech, finger movement, mouth movement, arm movement, and random segments). To lower the computational cost, we alternatively use the inter-hemispheric synchronization of the LFPs to make three pairs out of six bipolar signals. Three classifiers are separately trained at each level of the hierarchical approach, which lead to three labels. A fusion function is then developed to combine these three labels and determine the label of the corresponding trial. RESULTS: Using all six LFPs with the proposed hierarchical approach improves the classification performance. Moreover, the synchronization-based method reduces the computational burden considerably while the classification performance remains relatively unchanged. COMPARISON WITH EXISTING METHODS: Our experiments on two different datasets recorded from nine subjects undergoing DBS surgery show that the proposed approaches remarkably outperform other methods for behavior classification based on LFP signals. CONCLUSION: The LFP signals acquired from STNs contain useful information for recognizing human behavior. This can be a precursor for designing the next generation of closed-loop DBS systems.
Assuntos
Atividade Motora/fisiologia , Fala/fisiologia , Núcleo Subtalâmico/fisiologia , Máquina de Vetores de Suporte , Análise de Ondaletas , Idoso , Sincronização Cortical , Estimulação Encefálica Profunda/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Boca/fisiologia , Análise Multinível , Doença de Parkinson/fisiopatologia , Núcleo Subtalâmico/fisiopatologia , Extremidade Superior/fisiologiaRESUMO
OBJECTIVE: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has become standard care for the surgical treatment of Parkinson's disease (PD). Reliable interpretation of microelectrode recording (MER) data, used to guide DBS implantation surgery, requires expert electrophysiological evaluation. Recent efforts have endeavored to use electrophysiological signals for automatic detection of relevant brain structures and optimal implant target location.The authors conducted an observational case-control study to evaluate a software package implemented on an electrophysiological recording system to provide online objective estimates for entry into and exit from the STN. In addition, they evaluated the accuracy of the software in selecting electrode track and depth for DBS implantation into STN, which relied on detecting changes in spectrum activity. METHODS: Data were retrospectively collected from 105 MER-guided STN-DBS surgeries (4 experienced neurosurgeons; 3 sites), in which estimates for entry into and exit from the STN, DBS track selection, and implant depth were compared post hoc between those determined by the software and those determined by the implanting neurosurgeon/neurophysiologist during surgery. RESULTS: This multicenter study revealed submillimetric agreement between surgeon/neurophysiologist and software for entry into and exit out of the STN as well as optimal DBS implant depth. CONCLUSIONS: The results of this study demonstrate that the software can reliably and accurately estimate entry into and exit from the STN and select the track corresponding to ultimate DBS implantation.
Assuntos
Estimulação Encefálica Profunda/métodos , Doença de Parkinson Pós-Encefalítica/tratamento farmacológico , Doença de Parkinson Pós-Encefalítica/terapia , Antiparkinsonianos/uso terapêutico , Encéfalo/patologia , Terapia Combinada , Humanos , Levodopa/uso terapêutico , Imageamento por Ressonância Magnética , Masculino , Transtornos Mentais/etiologia , Transtornos Mentais/terapia , Pessoa de Meia-Idade , Oftalmoplegia/etiologia , Doença de Parkinson Pós-Encefalítica/psicologia , Núcleo SubtalâmicoRESUMO
Medically refractory epilepsy accounts for more than 30% of the epilepsy population. Scalp EEG electrodes have limited ability to localize seizure onset from deep structures and implantation of subdural electrodes with long term monitoring provides additional information. Apart from clinical application, this patient population provides a unique opportunity for acquiring electrocorticography data in research paradigms. We present a method for rapid localization of electrodes using lateral and anterior-posterior X-rays. Skull landmarks and proportions are used for co-registration with the standardized Talairach coordinate system. This MATLAB-based "Location on Cortex" (LOC) package facilitates rapid visualization of clinical and experimental data in a user-friendly manner.
Assuntos
Mapeamento Encefálico , Córtex Cerebral/fisiopatologia , Eletroencefalografia/métodos , Epilepsia/fisiopatologia , Córtex Cerebral/anatomia & histologia , Eletrodos , HumanosRESUMO
Deep Brain Stimulation (DBS) has gained increasing attention as an effective method to mitigate Parkinson's disease (PD) disorders. Existing DBS systems are open-loop such that the system parameters are not adjusted automatically based on patient's behavior. Classification of human behavior is an important step in the design of the next generation of DBS systems that are closed-loop. This paper presents a classification approach to recognize such behavioral tasks using the subthalamic nucleus (STN) Local Field Potential (LFP) signals. In our approach, we use the time-frequency representation (spectrogram) of the raw LFP signals recorded from left and right STNs as the feature vectors. Then these features are combined together via Support Vector Machines (SVM) with Multiple Kernel Learning (MKL) formulation. The MKL-based classification method is utilized to classify different tasks: button press, mouth movement, speech, and arm movement. Our experiments show that the lp-norm MKL significantly outperforms single kernel SVM-based classifiers in classifying behavioral tasks of five subjects even using signals acquired with a low sampling rate of 10 Hz. This leads to a lower computational cost.
Assuntos
Algoritmos , Estimulação Encefálica Profunda/métodos , Monitorização Fisiológica/métodos , Núcleo Subtalâmico/fisiologia , Braço/fisiopatologia , Feminino , Humanos , Masculino , Movimento/fisiologia , Doença de Parkinson/terapia , Fala/fisiologia , Máquina de Vetores de SuporteRESUMO
Deep Brain Stimulation (DBS) provides significant therapeutic benefit for movement disorders such as Parkinson's disease. Current DBS devices lack real-time feedback (thus are open loop) and stimulation parameters are adjusted during scheduled visits with a clinician. A closed-loop DBS system may reduce power consumption and DBS side effects. In such systems, DBS parameters are adjusted based on patient's behavior, which means that behavior detection is a major step in designing such systems. Various physiological signals can be used to recognize the behaviors. Subthalamic Nucleus (STN) Local Field Potential (LFP) is a great candidate signal for the neural feedback, because it can be recorded from the stimulation lead and does not require additional sensors. A practical behavior detection method should be able to detect behaviors asynchronously meaning that it should not use any prior knowledge of behavior onsets. In this paper, we introduce a behavior detection method that is able to asynchronously detect the finger movements of Parkinson patients. As a result of this study, we learned that there is a motor-modulated inter-hemispheric connectivity between LFP signals recorded bilaterally from STN. We used non-linear regression method to measure this connectivity and use it to detect the finger movements. Performance of this method is evaluated using Receiver Operating Characteristic (ROC).
Assuntos
Núcleo Subtalâmico , Estimulação Encefálica Profunda , Dedos , Humanos , Movimento , Doença de ParkinsonRESUMO
OBJECT: Transplantation of fetal dopaminergic tissue is being investigated in animal models and clinical trials for its potential as a treatment for advanced Parkinson disease. At the same time, the availability of fetal tissue is limited, making its storage time prior to transplantation a key practical issue. Although it results in a smaller percentage of surviving cells. a longer storage time enables fetal tissue obtained over several days to be pooled for transplantation in a recipient. Glial cell line-derived neurotrophic factor (GDNF) has been shown to improve survival of human dopaminergic tissue that has been stored prior to transplantation. The objective of this study was to evaluate the effects on fetal dopaminergic tissue of GDNF-supplemented hibernation for extended periods of 6 to 15 days. METHODS: The ventral mesencephalon (VM) was harvested in a total of 27 14-day-old rat fetuses, and three VMs were cultured immediately (fresh control group). The remaining 24 VMs were divided sagittally along the midline to yield 48 equal pieces of hemimesencephalon. Twenty-four pieces were stored with GDNF-supplemented hibernation medium for 6, 9, 12, or 15 days, and the 24 "partner" hemimesencephalon pieces were stored in control hibernation medium for the same periods of time. Tissue was cultured for 48 hours and processed for tyrosine hydroxylase (TH) immunoreactivity and double-stained with cresyl violet. Cell counts for all cultures and the percentage of TH-immunoreactive cells were obtained. The percentage of TH-immunoreactive cells for the fresh control group was 6.3 +/- 0.5%. The percentage of TH-immunoreactive cells in cultures derived from tissue stored in GDNF-supplemented medium was significantly increased at 6 and 9 days posthibernation compared with the fresh control group and the "partner" groups stored in hibernation medium only. No significant increase in the percentage of TH-immunoreactive cells was observed in the 12- and 15-day groups. CONCLUSIONS: In this study the authors have demonstrated that fetal dopaminergic tissue can be safely stored for up to 9 days in GDNF-supplemented hibernation medium. Furthermore, the percentage of TH-immunoreactive cells is significantly increased after 6 and 9 days of storage in this medium, improving the yield of TH-immunoreactive cells prior to transplantation. These observations have practical clinical implications for collecting fetal dopaminergic cells and improving their survival after transplantation.
Assuntos
Transplante de Tecido Encefálico , Sobrevivência Celular/efeitos dos fármacos , Transplante de Tecido Fetal , Fatores de Crescimento Neural/farmacologia , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson/cirurgia , Preservação de Tecido/métodos , Área Tegmentar Ventral/transplante , Animais , Linhagem Celular , Meios de Cultura , Dopamina/metabolismo , Fator Neurotrófico Derivado de Linhagem de Célula Glial , Humanos , Técnicas Imunoenzimáticas , Ratos , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
OBJECT: Investigation of fetal dopaminergic tissue transplantation is being conducted in animal models and clinical trials as a potential treatment for advanced Parkinson disease (PD). Because the availability of fetal tissue is limited, however, the duration of its storage prior to transplantation is a key practical issue. Longer storage times may enable fetal tissue obtained over several days to be pooled together for transplantation in a recipient. Glial cell line-derived neurotrophic factor (GDNF) has been shown to improve survival of stored human dopaminergic tissue prior to transplantation. The objective of this study was to evaluate GDNF-supplemented hibernation of fetal dopaminergic tissue for extended periods of 6 to 15 days. METHODS: A total of 27 rat ventral mesencephalons (VMs) were obtained in gestation Day 14 rat fetuses, and three were cultured immediately (fresh-culture control group). The remaining 24 VMs were divided sagittally along the midline to form 48 equal pieces of hemimesencephalons. Twenty-four pieces were stored with GDNF-supplemented hibernation medium for 6, 9, 12, or 15 days, and the 24 "partner" hemimesencephalons were stored in control hibernation medium for the same periods of time. Tissue was cultured for 48 hours and processed for tyrosine hydroxylase (TH) immunoreactivity and cresyl violet. Cell counts for all cultures and percentage of TH-immunoreactive cells were obtained. The percentage of TH-positive cells for the fresh control group was 6.3 +/- 0.5%; that measured in cultures derived from tissue hibernated in GDNF-supplemented medium was significantly increased at 6 and 9 days posthibernation compared with the fresh-culture control group and the partner groups stored in hibernation medium only. No significant increase in percentage of TH-immunoreactive cells was observed in the 12- and 15-day hibernation groups. CONCLUSIONS: In summary the authors found that fetal dopaminergic tissue can safely be stored up to 9 days in GDNF-supplemented hibernation medium. Furthermore the percentage of TH-immunoreactive cells is significantly increased after 6 and 9 days of storage in this medium, improving the yield of TH-positive cells prior to transplantation. These observations may have important clinical implications for collecting fetal dopaminergic cells and improving their survival after transplantation.
Assuntos
Fator Neurotrófico Derivado de Linhagem de Célula Glial/farmacologia , Mesencéfalo/citologia , Mesencéfalo/transplante , Neurônios/citologia , Neurônios/transplante , Doença de Parkinson , Preservação de Tecido/métodos , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Humanos , Mesencéfalo/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Doença de Parkinson/patologia , Doença de Parkinson/cirurgia , Ratos , Refrigeração/métodos , Fatores de TempoRESUMO
Cortical networks and quantitative measures of connectivity are integral to the study of brain function. Despite lack of direct connections between left and right subthalamic nuclei (STN), there are apparent physiological connections. During clinical examination of patients with Parkinson's disease (PD), this connectivity is exploited to enhance signs of PD, yet our understanding of this connectivity is limited. We hypothesized that movement leads to synchronization of neural oscillations in bilateral STN, and we implemented phase coherence, a measure of phase-locking between cortical sites in a narrow frequency band, to demonstrate this synchronization. We analyzed task specific phase synchronization and causality between left and right STN local field potentials (LFPs) recorded from both hemispheres simultaneously during a cued movement task in four subjects with PD who underwent Deep Brain Stimulation (DBS) surgery. We used a data driven approach to determine inter-hemispheric channel pairs and frequencies with a task specific increase in phase locking.We found significant phase locking between hemispheres in alpha frequency (8-12 Hz) in all subjects concurrent with movement of either hand. In all subjects, phase synchronization increased over baseline upon or prior to hand movement onset and lasted until the motion ceased. Left and right hand movement showed similar patterns. Granger causality (GC) at the phase-locking frequencies between synchronized electrodes revealed a unidirectional causality from right to left STN regardless of which side was moved.Phase synchronization across hemispheres between basal ganglia supports existence of a bilateral network having lateralized regions of specialization for motor processing. Our results suggest this bilateral network is activated by a unilateral motor program. Understanding phase synchronization in natural brain functions is critical to development of future DBS systems that augment goal directed behavioral function.
RESUMO
Deep Brain Stimulation (DBS) has been a successful technique for alleviating Parkinson's disease (PD) symptoms especially for whom drug therapy is no longer efficient. Existing DBS therapy is open-loop, providing a time invariant stimulation pulse train that is not customized to the patient's current behavioral task. By customizing this pulse train to the patient's current task the side effects may be suppressed. This paper introduces a method for single trial recognition of the patient's current task using the local field potential (LFP) signals. This method utilizes wavelet coefficients as features and support vector machine (SVM) as the classifier for recognition of a selection of behaviors: speech, motor, and random. The proposed method is 82.4% accurate for the binary classification and 73.2% for classifying three tasks. These algorithms will be applied in a closed loop feedback control system to optimize DBS parameters to the patient's real time behavioral goals.