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1.
Mov Disord ; 35(2): 337-343, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31758821

RESUMO

BACKGROUND: Therapeutic outcomes of STN-DBS for movement and psychiatric disorders depend on electrode location within the STN. Electrophysiological and functional mapping of the STN has progressed considerably in the past years, identifying beta-band oscillatory activity in the dorsal STN as a motor biomarker. It also has been suggested that STN theta-alpha oscillations, involved in impulse control and action inhibition, have a ventral source. However, STN local field potential mapping of motor, associative, and limbic areas is often limited by poor spatial resolution. OBJECTIVES: Providing a high-resolution electrophysiological map of the motor, associative and limbic anatomical sub-areas of the subthalamic nucleus. METHODS: We have analyzed high-spatial-resolution STN microelectrode electrophysiology recordings of PD patients (n = 303) that underwent DBS surgery. The patients' STN intraoperative recordings of spiking activity (933 electrode trajectories) were combined with their imaging data (n = 83 patients, 151 trajectories). RESULTS: We found a high theta-alpha (7-10 Hz) oscillatory area, located near the STN ventromedial border in 29% of the PD patients. Theta-alpha activity in this area has higher power and lower central frequency in comparison to theta-alpha activity in more dorsal subthalamic areas. When projected on the DISTAL functional atlas, the theta-alpha oscillatory area overlaps with the STN limbic subarea. CONCLUSIONS: We suggest that theta-alpha oscillations can serve as an electrophysiological marker for the ventral subthalamic nucleus limbic subarea. Therefore, theta-alpha oscillations can guide optimal electrode placement in neuropsychiatric STN-DBS procedures and provide a reliable biomarker input for future closed-loop DBS device. © 2019 International Parkinson and Movement Disorder Society.

2.
Neurobiol Dis ; 136: 104716, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31846735

RESUMO

The subthalamic nucleus (STN), a preferred target for treating movement disorders, has a crucial role in inhibition and execution of movement. To better understand the mechanism of movement regulation in the STN of Parkinson's disease patients, we compared the same movement with different context, facilitation vs. inhibition context. We recorded subthalamic multiunit activity intra-operatively while parkinsonian patients (off medications, n = 43 patients, 173 recording sites) performed increasingly complex oddball paradigms with frequent and deviant tones: first, passive listening to tone series with no movement ('None-Go' task, n = 7, 28 recording sites); second, pressing a button after every tone ('All-Go' task, n = 7, 26 recording sites); and third, pressing a button only for frequent tones, thus adding inhibition of movement following deviant tones ('Go-NoGo' task, n = 29, 119 recording sites). The STN responded mainly to movement-involving tasks. In the limbic-associative STN, evoked response to the deviant tone (inhibitory cue) was not significantly different between the Go-NoGo and the All-Go task. However, the evoked response to the frequent tone (go cue) in the Go-NoGo task was significantly reduced. The reduction was mainly prominent in the negative component of the evoked response amplitude aligned to the press. Successful movement inhibition was correlated with higher baseline activity. We suggest that the STN in Parkinson's disease patients adapts to movement inhibition context by selectively decreasing the amplitude of neuronal activity. Thus, the STN enables movement inhibition not by increasing responses to the inhibitory cue but by reducing responses to the release cue. The negative component of the evoked response probably facilitates movement and a higher baseline activity enables successful inhibition of movement. These discharge modulations were found in the ventromedial, non-motor domain of the STN and therefore suggest a significant role of the limbic- associative STN domains in movement planning and in global movement regulation.

3.
Harefuah ; 158(7): 418-422, 2019 Jul.
Artigo em Hebraico | MEDLINE | ID: mdl-31339238

RESUMO

INTRODUCTION: Treatment-resistant obsessive-compulsive disorder (OCD) is considered a severe psychiatric disorder that causes severe functional decline. In the past, these patients were treated by selective ablation of neuronal pathways related to the pathophysiology of OCD. Deep brain stimulation is an effective and safe treatment alternative that enables reversible changes in neural circuits and reduces OCD symptoms. In this paper we present the outcome of a treatment-resistant OCD patient who underwent deep brain stimulation procedure for the first time in Israel. The patient has achieved a significant decline in OCD symptoms as well as improvement in personal and social functioning. The discussion focuses on methods to implement deep brain stimulation for OCD patients in Israel.


Assuntos
Estimulação Encefálica Profunda , Transtorno Obsessivo-Compulsivo/terapia , Humanos , Israel , Resultado do Tratamento
4.
Transl Psychiatry ; 8(1): 118, 2018 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-29915200

RESUMO

Obsessive-compulsive disorder (OCD) is a common and serious psychiatric disorder. Although subthalamic nucleus deep brain stimulation (DBS) has been studied as a treatment for OCD patients the underlying mechanism of this treatment and the optimal method of stimulation are unknown. To study the neural basis of subthalamic nucleus DBS in OCD patients we used a novel, implantable DBS system with long-term local field potential sensing capability. We focus our analysis on two patients with OCD who experienced severe treatment-resistant symptoms and were implanted with subthalamic nucleus DBS systems. We studied them for a year at rest and during provocation of OCD symptoms (46 recording sessions) and compared them to four Parkinson's disease (PD) patients implanted with subthalamic nucleus DBS systems (69 recording sessions). We show that the dorsal (motor) area of the subthalamic nucleus in OCD patients displays a beta (25-35 Hz) oscillatory activity similar to PD patients whereas the ventral (limbic-cognitive) area of the subthalamic nucleus displays distinct theta (6.5-8 Hz) oscillatory activity only in OCD patients. The subthalamic nucleus theta oscillatory activity decreases with provocation of OCD symptoms and is inversely correlated with symptoms severity over time. We conclude that beta oscillations at the dorsal subthalamic nucleus in OCD patients challenge their pathophysiologic association with movement disorders. Furthermore, theta oscillations at the ventral subthalamic nucleus in OCD patients suggest a new physiological target for OCD therapy as well as a promising input signal for future emotional-cognitive closed-loop DBS.


Assuntos
Transtorno Obsessivo-Compulsivo/fisiopatologia , Núcleo Subtalâmico/fisiologia , Ritmo Teta , Adulto , Idoso , Estimulação Encefálica Profunda , Fenômenos Eletrofisiológicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Transtorno Obsessivo-Compulsivo/terapia , Resultado do Tratamento
5.
J Neurosci ; 37(27): 6394-6407, 2017 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-28546311

RESUMO

Investigation of the functional macro-scale organization of the human cortex is fundamental in modern neuroscience. Although numerous studies have identified networks of interacting functional modules in the gray-matter, limited research was directed to the functional organization of the white-matter. Recent studies have demonstrated that the white-matter exhibits blood oxygen level-dependent signal fluctuations similar to those of the gray-matter. Here we used these signal fluctuations to investigate whether the white-matter is organized as functional networks by applying a clustering analysis on resting-state functional MRI (RSfMRI) data from white-matter voxels, in 176 subjects (of both sexes). This analysis indicated the existence of 12 symmetrical white-matter functional networks, corresponding to combinations of white-matter tracts identified by diffusion tensor imaging. Six of the networks included interhemispheric commissural bridges traversing the corpus callosum. Signals in white-matter networks correlated with signals from functional gray-matter networks, providing missing knowledge on how these distributed networks communicate across large distances. These findings were replicated in an independent subject group and were corroborated by seed-based analysis in small groups and individual subjects. The identified white-matter functional atlases and analysis codes are available at http://mind.huji.ac.il/white-matter.aspx Our results demonstrate that the white-matter manifests an intrinsic functional organization as interacting networks of functional modules, similarly to the gray-matter, which can be investigated using RSfMRI. The discovery of functional networks within the white-matter may open new avenues of research in cognitive neuroscience and clinical neuropsychiatry.SIGNIFICANCE STATEMENT In recent years, functional MRI (fMRI) has revolutionized all fields of neuroscience, enabling identifications of functional modules and networks in the human brain. However, most fMRI studies ignored a major part of the brain, the white-matter, discarding signals from it as arising from noise. Here we use resting-state fMRI data from 176 subjects to show that signals from the human white-matter contain meaningful information. We identify 12 functional networks composed of interacting long-distance white-matter tracts. Moreover, we show that these networks are highly correlated to resting-state gray-matter networks, highlighting their functional role. Our findings enable reinterpretation of many existing fMRI datasets, and suggest a new way to explore the white-matter role in cognition and its disturbances in neuropsychiatric disorders.


Assuntos
Mapeamento Encefálico/métodos , Encéfalo/fisiologia , Potenciais Evocados/fisiologia , Rede Nervosa/fisiologia , Substância Branca/fisiologia , Adulto , Feminino , Humanos , Masculino , Vias Neurais/fisiologia
6.
J Neurophysiol ; 117(6): 2140-2151, 2017 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-28202569

RESUMO

Subthalamic nucleus field potentials have attracted growing research and clinical interest over the last few decades. However, it is unclear whether subthalamic field potentials represent locally generated neuronal subthreshold activity or volume conductance of the organized neuronal activity generated in the cortex. This study aimed at understanding of the physiological origin of subthalamic field potentials and determining the most accurate method for recording them. We compared different methods of recordings in the human subthalamic nucleus: spikes (300-9,000 Hz) and field potentials (3-100 Hz) recorded by monopolar micro- and macroelectrodes, as well as by differential-bipolar macroelectrodes. The recordings were done outside and inside the subthalamic nucleus during electrophysiological navigation for deep brain stimulation procedures (150 electrode trajectories) in 41 Parkinson's disease patients. We modeled the signal and estimated the contribution of nearby/independent vs. remote/common activity in each recording configuration and area. Monopolar micro- and macroelectrode recordings detect field potentials that are considerably affected by common (probably cortical) activity. However, bipolar macroelectrode recordings inside the subthalamic nucleus can detect locally generated potentials. These results are confirmed by high correspondence between the model predictions and actual correlation of neuronal activity recorded by electrode pairs. Differential bipolar macroelectrode subthalamic field potentials can overcome volume conductance effects and reflect locally generated neuronal activity. Bipolar macroelectrode local field potential recordings might be used as a biological marker of normal and pathological brain functions for future electrophysiological studies and navigation systems as well as for closed-loop deep brain stimulation paradigms.NEW & NOTEWORTHY Our results integrate a new method for human subthalamic recordings with a development of an advanced mathematical model. We found that while monopolar microelectrode and macroelectrode recordings detect field potentials that are considerably affected by common (probably cortical) activity, bipolar macroelectrode recordings inside the subthalamic nucleus (STN) detect locally generated potentials that are significantly different than those recorded outside the STN. Differential bipolar subthalamic field potentials can be used in navigation and closed-loop deep brain stimulation paradigms.


Assuntos
Potenciais de Ação , Núcleo Subtalâmico/fisiologia , Estimulação Encefálica Profunda , Eletrodos , Feminino , Humanos , Masculino , Modelos Neurológicos , Vias Neurais/fisiologia , Vias Neurais/fisiopatologia , Doença de Parkinson/fisiopatologia , Doença de Parkinson/terapia , Periodicidade , Núcleo Subtalâmico/fisiopatologia
7.
Isr Med Assoc J ; 18(6): 341-5, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27468527

RESUMO

BACKGROUND: Neurolathyrism is a toxic nutritional disorder caused by consumption of the grass pea, Lathyrus sativus. The disease, which manifests as an acute or insidiously evolving spastic paraparesis, continues to occur throughout Africa and Asia. Research on this disease is limited, and to our knowledge no imaging studies of patients with neurolathyrism have been published. OBJECTIVES: To better localize the site of damage in neurolathyrism using advanced imaging methods. METHODS: Three male patients, immigrants from Ethiopia, were included in the study. All had a history of arrested spastic paraparesis that had evolved before their emigration from Ethiopia, and a past history of exposure to grass pea without any other cause. Functional magnetic resonance imaging (fMRI) included simple motor tasks to evaluate cortical motor areas. Anatomic scans included diffusion tensor imaging (DTI) to evaluate the corticospinal tracts. RESULTS: In all patients clear activation was found in motor regions, and the patients' activity pattern was qualitatively similar to that in control sublects. In one patient in whom clinical symptoms were asymmetric, an asymmetric activity pattern in Ml was identified. DTI analysis identified intact corticospinal tracts connecting the pons and the primary motor regions, similar to control subjects. CONCLUSIONS: Advanced neuroimaging clearly identified well-functioning motor regions and tracts in neurolathyrism patients, suggesting a spinal etiology.


Assuntos
Latirismo , Imagem por Ressonância Magnética/métodos , Córtex Motor , Tratos Piramidais , Adulto , Estudos de Casos e Controles , Humanos , Israel , Latirismo/diagnóstico , Latirismo/etiologia , Latirismo/fisiopatologia , Lathyrus/toxicidade , Masculino , Córtex Motor/patologia , Córtex Motor/fisiopatologia , Exame Neurológico/métodos , Tratos Piramidais/efeitos dos fármacos , Tratos Piramidais/patologia
8.
Hum Brain Mapp ; 37(2): 589-99, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26536845

RESUMO

Posttraumatic stress disorder (PTSD) is characterized by unwanted intrusive thoughts and hyperarousal at rest. As these core symptoms reflect disturbance in resting-state mechanisms, we investigated the functional and anatomical involvement of the default mode network (DMN) in this disorder. The relation between symptomatology and trauma characteristics was considered. Twenty PTSD patients and 20 matched trauma-exposed controls that were exposed to a similar traumatic event were recruited for this study. In each group, 10 patients were exposed to military trauma, and 10 to civilian trauma. PTSD, anxiety, and depression symptom severity were assessed. DMN maps were identified in resting-state scans using independent component analysis. Regions of interest (medial prefrontal, precuneus, and bilateral inferior parietal) were defined and average z-scores were extracted for use in the statistical analysis. The medial prefrontal and the precuneus regions were used for cingulum tractography whose integrity was measured and compared between groups. Similar functional and anatomical connectivity patterns were identified in the DMN of PTSD patients and trauma-exposed controls. In the PTSD group, functional and anatomical connectivity parameters were strongly correlated with clinical measures, and there was evidence of coupling between the anatomical and functional properties. Type of trauma and time from trauma were found to modulate connectivity patterns. To conclude, anatomical and functional connectivity patterns are related to PTSD symptoms and trauma characteristics influence connectivity beyond clinical symptoms. Hum Brain Mapp 37:589-599, 2016. © 2015 Wiley Periodicals, Inc.


Assuntos
Encéfalo/patologia , Encéfalo/fisiopatologia , Militares , Transtornos de Estresse Pós-Traumáticos/patologia , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Adulto , Idoso , Ansiedade/patologia , Ansiedade/fisiopatologia , Mapeamento Encefálico , Depressão/patologia , Depressão/fisiopatologia , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Vias Neurais/patologia , Vias Neurais/fisiopatologia , Escalas de Graduação Psiquiátrica , Descanso , Índice de Gravidade de Doença , Transtornos de Estresse Pós-Traumáticos/psicologia , Adulto Jovem
9.
J Neuroophthalmol ; 35(4): 348-52, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25996300

RESUMO

BACKGROUND: The intrinsic abilities and limits of the nervous system to repair itself after damage may be assessed using a model of optic chiasmal compression, before and after a corrective surgical procedure. METHODS: Visual fields (VFs), multifocal visual evoked potentials (mfVEP), retinal nerve fiber layer (RNFL) thickness, and diffusion tensor imaging were used to evaluate a patient before and after removal of a meningioma compressing the chiasm. Normally sighted individuals served as controls. The advantage of each modality to document visual function and predict postoperative outcome (2-year follow-up) was evaluated. RESULTS: Postsurgery visual recovery was best explained by critical mass of normally conducting fibers and not associated with average conduction amplitudes. Recovered VF was observed in quadrants in which more than 50% of fibers were identified, characterized by intact mfVEP latencies, but severely reduced amplitudes. Recovery was evident despite additional reduction of RNFL thickness and abnormal optic tract diffusivity. The critical mass of normally conducting fibers was also the best prognostic indicator for functional outcome 2 years later. CONCLUSIONS: Our results highlight the ability of the remaining normally conductive axons to predict visual recovery after decompression of the optic chiasm. The redundancy in anterior visual pathways may be explained, neuroanatomically, by overlapping receptive fields.


Assuntos
Descompressão Cirúrgica/métodos , Quiasma Óptico/cirurgia , Doenças do Nervo Óptico/cirurgia , Recuperação de Função Fisiológica/fisiologia , Resultado do Tratamento , Adolescente , Adulto , Imagem de Difusão por Ressonância Magnética , Potenciais Evocados Visuais/fisiologia , Humanos , Estudos Longitudinais , Masculino , Neoplasias Meníngeas/complicações , Meningioma/complicações , Pessoa de Meia-Idade , Fibras Nervosas/patologia , Retina/patologia , Tomografia de Coerência Óptica , Campos Visuais/fisiologia , Adulto Jovem
10.
J Neurol Sci ; 334(1-2): 130-8, 2013 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-24007872

RESUMO

The clinical evaluation of consciousness in disorder of consciousness (DOC) patients based on their exhibited behavior is difficult and remains erroneous in many cases. Recent studies demonstrated different levels of stimulus processing as well as evidence of some level of awareness in sub-groups of these patients. The aim of the current study was to examine the plausibility and challenges of implementing a clinical service for evaluation of consciousness level in DOC patients. Eleven Patients (ages 11-67) diagnosed as being in vegetative or minimal conscious states were included. Functional MRI evaluations included auditory, language, voice familiarity, imagery, and visual tests. In 9 patients auditory-related activation was found, however only in 5 of the subjects was differential activation found for language. Six patients exhibited differential response to their own name. In three patients a response to visual stimuli was identified. In one patient the auditory and linguistic systems were clearly activated in a hierarchical pattern, and moreover willful modulation of brain activity was identified in the imagery test. We discuss the importance of using a wide battery of tests, the difference between our clinical cohort and previous publications, as well as the challenges of clinically implementing this method. Translating novel imaging methods into the clinical evaluation of DOC patients is essential for better diagnosis and may encourage treatment development.


Assuntos
Transtornos da Consciência/diagnóstico , Neuroimagem Funcional/métodos , Adolescente , Adulto , Idoso , Criança , Estudos de Coortes , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos
11.
J Neurol Sci ; 312(1-2): 158-65, 2012 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-21864850

RESUMO

In the last two decades functional magnetic resonance imaging (fMRI) has dominated research in neuroscience. However, only recently has it taken the first steps in translation to the clinical field. In this paper we describe the advantages of fMRI and DTI and the possible benefits of implementing these methods in clinical practice. We review the current clinical usages of fMRI and DTI and discuss the challenges and difficulties of translating these methods to clinical use. The most common application today is in neurosurgery. fMRI and DTI are done preoperatively for brain tumor patients who are having tumors removed and for epilepsy patients who are candidates for temporal resection. Imaging results supply the neurosurgeon with essential information regarding possible functional damage and thereby aid both in planning and performing surgery. Scientific research suggests more promising potential implementations of fMRI and DTI in improving diagnosis and rehabilitation. These advanced imaging methods can be used for pre-symptomatic diagnosis, as a differentiating biomarker in the absence of anatomical measurements, and for identification of mental response in the absence of motor-sensory abilities. These methods can aid and direct rehabilitation by predicting the success of possible interventions and rehabilitation options and by supplying a measure for biofeedback. This review opens a window to the state of the art neuroimaging methods being implemented these days into the clinical practice and provides a glance to the future clinical possibilities of fMRI and DTI.


Assuntos
Encefalopatias/patologia , Encefalopatias/fisiopatologia , Mapeamento Encefálico/métodos , Encéfalo/fisiologia , Imagem de Tensor de Difusão/métodos , Imagem por Ressonância Magnética/métodos , Encéfalo/patologia , Encéfalo/fisiopatologia , Humanos
12.
J Cogn Neurosci ; 23(9): 2280-90, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20961169

RESUMO

Is language processing universal? How do the specific properties of each language influence the way it is processed? In this study, we compare the neural correlates of morphological processing in Hebrew--a Semitic language with a rich and systematic morphology, to those revealed in English--an Indo-European language with a linear morphology. Using fMRI, we show that while in the bilingual brain both languages involve a common neural circuitry in processing morphological structure, this activation is significantly modulated by the different aspects of language. Whereas in Hebrew, morphological processing is independent of semantics, in English, morphological activation is clearly modulated by semantic overlap. These findings suggest that the processes involved in reading words are not universal, and therefore impose important constraints on current models of visual word recognition.


Assuntos
Mapeamento Encefálico , Encéfalo/fisiologia , Reconhecimento Visual de Modelos/fisiologia , Semântica , Adulto , Análise de Variância , Encéfalo/irrigação sanguínea , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imagem por Ressonância Magnética/métodos , Masculino , Multilinguismo , Oxigênio/sangue , Estimulação Luminosa , Tempo de Reação/fisiologia , Leitura , Vocabulário , Adulto Jovem
13.
J Cogn Neurosci ; 22(9): 1955-69, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19803693

RESUMO

Is morphology a discrete and independent element of lexical structure or does it simply reflect a fine-tuning of the system to the statistical correlation that exists among orthographic and semantic properties of words? Hebrew provides a unique opportunity to examine morphological processing in the brain because of its rich morphological system. In an fMRI masked priming experiment, we investigated the neural networks involved in implicit morphological processing in Hebrew. In the lMFG and lIFG, activation was found to be significantly reduced when the primes were morphologically related to the targets. This effect was not influenced by the semantic transparency of the morphological prime, and was not found in the semantic or orthographic condition. Additional morphologically related decrease in activation was found in the lIPL, where activation was significantly modulated by semantic transparency. Our findings regarding implicit morphological processing suggest that morphology is an automatic and distinct aspect of visually processing words. These results also coincide with the behavioral data previously obtained demonstrating the central role of morphological processing in reading Hebrew.


Assuntos
Encéfalo/fisiologia , Linguagem , Imagem por Ressonância Magnética/métodos , Reconhecimento Visual de Modelos/fisiologia , Estimulação Luminosa/métodos , Leitura , Adolescente , Adulto , Mapeamento Encefálico/métodos , Feminino , Humanos , Masculino , Adulto Jovem
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