医学博士Albert Fenoy实验室
The Deep Brain Stimulation (DBS) surgery program led byDr. Albert Fenoyfocuses on delivering optimal treatment to patients suffering from movement disorders such as Parkinson’s disease, tremor, and dystonia, as well as refining treatments for patients with refractory psychiatric disease states, such as treatment resistant depression. In the majority of these surgeries, we record from the subcortical structures of the awake patient in an effort to better understand the disease process, refine the targeting, and together with new brain imaging techniques provide exemplar outcomes. Thus, the operating room is our chief laboratory space, to both learn from each patient and optimize treatment strategies.
在手术室外，使用成像来说明通过深脑刺激治疗的各种病理生理的网络的结构和功能连通性可以改善我们对疾病过程的理解，并可能导致更具战略性的治疗范式。
Simultaneously with learning intraoperatively from human research subjects, animal models of disease enable us to understand the biochemical mediators of such pathological cortical states and how the intervention of deep brain stimulation improves aberrant subcortical firing to improve symptomatology.
Albert J. Fenoy, MD,is Associate Professor and Director of Deep Brain Stimulation at the University of Texas Health Science Center at Houston. He completed his residency in neurosurgery at the University of Iowa and completed a fellowship in functional neurosurgery at the Centre Hospitalier Universitaire de Grenoble, France.
CURRENT PROJECTS:
Elucidating the temporality of structural and functional connectivity changes in essential tremor after successful deep brain stimulation of the dentato-rubro-thalalmic tract
Supported by: NIH Grant Number 1R01NS113893
Principal Investigator: Albert J. Fenoy, MD
Project Period: 09/15/2020 – 08/31/2025
Total Cost support: $2.1 M
The symptoms of Essential Tremor (ET), the most common movement disorder in adults, are seriously disabling and are only marginally improved by medication alone. Tremor control has improved greatly with the use of deep brain stimulation (DBS) to the ventrointermediate nucleus (Vim) of the thalamus, a node along a circuit of abnormal rhythmic output in ET that travels from the cerebellar dentate nucleus to the contralateral red nucleus and cortex via the dentato-rubro-thalamic tract (DRTt).
Recent advances in diffusion imaging have led to the development of tractography techniques where thestructural connectivity纤维的交易cts such as the DRTt can be illustrated and then, as we have shown,directly targetedduring DBS surgery for excellent clinical effect. Despite such novel targeting methodology and initial tremor improvement, however, the development of side effects such as progressive gait ataxia and waning efficacy after years of chronic stimulation points to the fact that the pathology of essential tremor is poorly understood.
Suchincomplete knowledge of the network effects of chronic stimulation in ETis a major barrier that needs to be overcome through understanding the dysfunction and modulation of theconnectivity随着时间的流逝，小脑 - 丘脑 - 皮层（CTC）网络的网络。
Resting state functional MRI (rsfMRI) has emerged as a powerful tool to explore the功能连接between different brain regions and has improved the idea of ET as a基于网络的疾病不限于电动机电路, including parietal visuomotor processing cortices; however, comparisons pre- and post- DBS have not been performed.
The use of positron emission tomography (PET) has correlated ataxic side effect with cerebellar metabolic changes after chronic DBS; however, associated changes seen with rsfMRI are unknown. Ourlong-term goalis to understand how stimulation of the DRTt causes network-level effects over time. Our中央假设is thatstructural and functional connectivity of the DRTt correlates with clinical response to DBS以时间依赖的方式。In pursuit of this hypothesis, we will recruit new ET patients已经经历了DBS和additionallyperform imaging analysis to elucidate the effects of stimulation并定义DRTtconnectivity.First, we will seek to define the structural connectivity of the DRTt by using tractography methods and compare over time diffusivity changes correlated with clinical response and/or ataxic side effect. Second, we seek to detect functional network changes due to DBS by using rsfMRI obtained serially in ON/OFF states, where we will track the evolution of altered connectivity changes over time. Third, we seek to confirm the cortical mediators of tremor identified by tractography and rsfMRI through the use of intraoperative electrocorticography during DBS. This使用新颖的靶向技术和跨DBS状态的串行成像的创新组合will advance our understanding of the larger network response to DBS, which is essential to develop more specific stimulation of fibers to improve response and avoid side effects in ET.
Deep Brain Stimulation for Treatment Resistant Depression: Clinical Trial
Performed in conjunction with the UT Center of Excellence on Mood Disorders, led by chairmanJair C. Soares, MD, PhD, this is an FDA-approved clinical trial for patients suffering from treatment resistant depression. This study is aimed to determine feasibility, safety and efficacy of DBS applied to the supero-lateral branch of the medial forebrain bundle (slMFB). UT is the only site in the US to perform such surgery at this target, and the second in the world.
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Deep Brain Stimulation for Treatment Resistant Depression: Animal models
Performed in collaboration with the UT Translational Psychiatry Program at the Behavioral and Biomedical Sciences Building (BBSB), led byJoao Quevedo, MD, PhD., this project aims to evaluate the mechanisms by which MFB DBS improves depression. In the rodent, once a depression model is created using chronic unpredictable stress, MFB DBS is applied to observe behavioral improvement. Afterward, histological analysis is performed on subcortical/cortical structures investigating the involvement or modulation of the dopamine-reward pathway, which is hypothesized to be a key factor in how MFB DBS can incur a reversal of anhedonia.
SeeTranslational Psychiatry Program和rodent behavior core facility where animal experimentation occurs.
深脑刺激中的扩散张量脑成像
Many of the disease states treated by DBS involve placement of an electrode into to an anatomical area of the brain that has historically been seen to be part of a neuronal circuit subserving some function, such as the motor system. These anatomical nodes within this network are visible on standard imaging, but the circuits connecting them are not. Use of diffusion tensor imaging to identify tracts linking subcortical/cortical structures has elucidated novel and more refined targeting protocols for certain disease states, such as tremor. Evolution of imaging acquisitioning, stereotactic analysis and targeting schemes is underway to optimize outcomes.
TEAM MEMBERS:
克里斯·康纳（Chris Conner），医学博士，博士，PGY6神经外科
动物协议团队：
Manoj Dandekar, PhD, post-doc fellow
Vija Giriharan, PhD, post-doc fellow
Agata Migut BS, Medical Student
Jenny Shin BS, Medical Student
接触：
Fenoy Laboratory
Department of Neurosurgery
The University of Texas Medical School-Houston
Phone: 281-500-7788
电子邮件：Albert.J.Fenoy@uth.tmc.edu
SELECTED PUBLICATIONS:
Fenoy AJ, Schulz P, Selvaraj S, Burrows C, Spiker D, Cao B, Zunta-Soares G, Gajwani P, Quevedo J, Soares J. Deep brain stimulation of the medial forebrain bundle: Distinctive responses in resistant depression. J Affect Disord. 203:143- 151, 2016
Fenoy AJ, McHenry MA, Schiess MC. Speech changes induced by deep brain stimulation of the subthalamic nucleus in Parkinson disease: involvement of the dentato-rubro-thalamic tract. J Neurosurg. 2016 Sep 9:1-11.
Fenoy AJ, Schiess MC. Deep Brain Stimulation of the Dentato-Rubro-Thalamic tract: Outcomes of Direct Targeting for Tremor. Neuromodulation. 2017. DOI: 10.1111/ner.12585.
Dandekar MP, Luse D, Hoffmann C, Cotton P, Peery T, Ruiz C, Hussey C, Giridharan VV, Soares JC, Quevedo J, Fenoy AJ. Increased dopamine receptor expression and anti-depressant response following deep brain stimulation of the medial forebrain bundle. J Affect Disord. 2017 Apr 5;217:80-88. DOI: 10.1016/j.jad.2017.03.074.
Fenoy AJ，Schulz P，Selvaraj S，Burrows C，Zunta-Soares G，Durkin K，Zanotti-Fregonara P，Quevedo J，Soares J. SoaresJ。一项关于对治疗抗药性抑郁症的内侧前脑束的深脑刺激的纵向研究。翻译精神病学。2018年6月4日;8（1）：111。doi：10.1038/s41398-018-0160-4。
Fenoy AJ, Schiess MC. Comparison of Tractography-Assisted to Atlas-Based Targeting for Deep Brain Stimulation in Essential Tremor. Mov Disord. 2018; 33(12):1895-1901. DOI: 10.1002/mds.27463.
Dandekar MP, Saxena A, Scaini G, Shin JH, Migut A, Giridharan VV, Zhou Y, Barichello T, Soares JC, Quevedo J, Fenoy AJ. Medial Forebrain Bundle Deep Brain Stimulation Reverses Anhedonic-Like Behavior in a Chronic Model of Depression: Importance of BDNF and Inflammatory Cytokines. Molecular Neurobiology. 2019; 56(6): 4364-4380.