The Neuropsychiatry Lab – Dr. Renana Eitan >>

The Neuropsychiatry Lab

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Our Vision

Our research aim is to develop new therapeutic approaches in order to alleviate refractory symptoms of neuropscyhiatric disorders such as OCD, Schizophrenia and Parkinson. We record subcortical (Local Field Potential) and cortical brain activity (EEG) to study the neurophysiological mechanisms of brain psychopathology on an individual level and to monitor the disease's dynamics. We stimulate subcortical targets with advanced DBS (Deep Brain Stimulation), specifically the Subthalamic Nucleus in OCD patients and negative symptoms of Schizophrenia. We apply functional neuropsychology and computational psychiatry in order to develop closed-loop adaptive DBS treatment. We are also co-leading a groundbreaking study for evaluating the efficacy and safety of FUS (Focused Ultrasound) in OCD patients. Our laboratory is located within the outpatient clinics of the psychiatry division. We work in close proximity with the functional neurosurgery unit and the neurology division.

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Contact Us

Primary Investigators
רננה תמונה

Dr. Renana Eitan, Lab PI

Chair, Psychiatry Division, Tel Aviv Sourasky Medical Center; Brigham and Women's Hospital, Harvard Medical School.
Phone: +972-3-6947204
Email: renanae@tlvmc.gov.il

תמונה קרן

Dr. Keren Avirame, Lab Director

Phone: +972-3-6947454
Email: kerenav@tlvmc.gov.il

Address

Rehabilitation building

Ground floor, Psychiatric Outpatient Clinics 13 Henrietta Szold Street, Tel Aviv ‎

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Research

Subthalamic Deep Brain Stimulation (DBS) Treatment for Negative Symptoms of Schizophrenia

 Schizophrenia is a prevalent and devastating disorder mostly recognized for its psychotic (“positive”) symptoms. However, schizophrenia also consists of negative symptoms such as blunted affect, poverty of speech, amotivation, anticipatory anhedonia and asociality. These negative symptoms severely interfere with the functional status of patients and are more related to prognosis and to high rate of suicidality. During the past decades, new therapies for negative symptoms involving the glutamatergic system and non-invasive brain stimulation failed to show significant therapeutic effects. There is an urgent need for an effective intervention that would enable rehabilitation of mental and cognitive functions, change the course of the disease and reduce stigmatism. Deep brain stimulation (DBS) treatment opens a new opportunity for severe mental illness therapy and a new window to assess the brain mechanisms underlying the pathophysiology of neuropsychiatric disorders. In this pioneering study, we intend to explore functional electrophysiology of the Subthalamic Nucleus (STN) in patients undergoing a pilot clinical DBS treatment using the Percept PC DBS System (Medtronic, LTD). We hypothesize that emotional and cognitive sub-regions of the STN have distinct electrophysiological properties in schizophrenia patients and that high-frequency adaptive stimulation of these areas can alleviate the negative symptoms of schizophrenia.

Cortical and Subcortical Interactions in Neuropsychiatric Disorders

The effects of DBS on the nervous system occur on multiple levels, from the protein and cellular levels through the network level, to behavior. Although many studies on DBS focus on target location and immediate effects, there is evidence that DBS may promote neural plasticity and even neurogenesis and neuroprotection. Moreover, long-standing changes in network activity not only extend the target nucleus, but also transform the effects of stimulation over time. Exploring the mechanisms of DBS at a network level shifts the focus from searching for the optimal target or the optimal stimulation parameters, to identifying the correlates of abnormal electrophysiology with dysfunctional behavior across time. As such, it emphasizes the discovery of the underlying neural circuitry and network interactions which are specific to behavioral and cognitive deficits, their dynamics and their response to different stimulation parameters and medications. For the purpose of exploring the relationship between subcortical and cortical activity and its effects on behavior and clinical symptoms, longitudinal recordings of functional electrophysiology will be performed in DBS patients. As such, simultaneous recording of DBS (iEEG) and surface EEG (sEEG) will be performed during disease-relevant behavioral tasks, as well as during sleep and at rest.

Closing the Loop in Brain Disorders: Towards Personalized Human Deep Brain Stimulation

Adaptive Deep Brain Stimulation (aDBS) systems that adjust stimulation according to neurophysiological signals have been recently suggested to optimize DBS therapy. Our recent studies revealed that it is unlikely that a single neurophysiological biomarker can be used in all patients, rather patients have a unique set of individualized neurophysiological biomarkers. In recent years, algorithm-based representations for computer vision, and speech recognition proved superior to manually tuned features constructed by experts. We hypothesize that learned representations will outperform existing hand-tuned features constructed by clinicians. For this purpose, we will collect a large within-patient dataset from adults diagnosed with Parkinson and OCD who underwent DBS procedure. We will use a multiple-task paradigm, in which we learn many different individual problems, with different parameters, but with a shared structure. Then, we will apply unsupervised deep learning (DL) methods for learning embeddings of neurophysiological signals which can potentially outperform manually tuned features. The DL algorithm will use individual’s data to identify neurophysiological features associated with symptoms, as well as those associated with adverse side effects. We will then configure the DBS device accordingly.

ExAblate MR-guided Focused Ultrasound Bilateral Anterior Capsulotomy for Treatment of Obsessive-Compulsive Disorder

Bilateral anterior thermo-capsulotomy and gamma-knife capsulotomy are wellknown and effective treatments for treatment-refractory OCD patients. This procedure involves the generation of bilateral lesions in the anterior capsule, a region which contains a rich network of fibers that connect both the prefrontal cortex and anterior cingulate cortex with the hippocampus, amygdala, and the thalamus. In this study we use MR-guided Focused Ultrasound (MRgFUS, Insightec Ltd) as a new method for capsulotomy in patients with refractory obsessive-compulsive disorder (OCD). This technology has recently received FDA approval for Essential Tremor and tremor-dominant Parkinson’s Disease and there are ongoing studies in Korea and Canda for other indications. Treatment-resistant OCD patients will be recruited in two stages; the first stage will be a 18-month open label study (Harvard and Stanford), and the second stage will be a 12-month multi-center double blind randomized control trial. In both stages, active FUS or sham FUS will be an add-on to best medical treatment. This research brings together an international multidisciplinary teams of psychiatrists, neurosurgeons, psychologists, radiologists and neurologists.

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Our Team

Psychiatry

Functional Neurosurgery

Neurology Division

Other collaborators:

Current funding

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Highlighted Publications

Machine learning-based personalized subthalamic biomarkers predict ON-OFF levodopa states in Parkinson patients.

Sand D, Rappel P, Marmor O, Bick AS, Arkadir D, Lu BL, Bergman H, Israel Z, Eitan R.

J Neural Eng. 2021 May 17;18(4). doi: 10.1088/1741-2552/abfc1d. PMID: 33906182.

Deep Brain Stimulation Can Differentiate Subregions of the Human Subthalamic Nucleus Area by EEG Biomarkers. Front Syst Neurosci.

Sand D, Arkadir D, Abu Snineh M, Marmor O, Israel Z, Bergman H, Hassin-Baer S, Israeli-Korn S, Peremen Z, Geva AB, Eitan R.

. 2021 Oct 20;15:747681. doi: 10.3389/fnsys.2021.747681. PMID: 34744647; PMCID: PMC8565520.

A prospective international multi-center study on safety and efficacy of deep brain stimulation for resistant obsessive-compulsive disorder.

Menchón JM, Real E, Alonso P, Aparicio MA, Segalas C, Plans G, Luyten L, Brunfaut E, Matthijs L, Raymakers S, Bervoets C, Higueras A, Katati M, Guerrero J, Hurtado M, Prieto M, Stieglitz LH, Löffelholz G, Walther S, Pollo C, Zurowski B, Tronnier V, Kordon A, Gambini O, Ranieri R, Franzini A, Messina G, Radu-Djurfeldt D, Schechtmann G, Chen LL, Eitan R, Israel Z, Bergman H, Brelje T, Brionne TC, Conseil A, Gielen F, Schuepbach M, Nuttin B, Gabriëls L.

Mol Psychiatry. 2021 Apr;26(4):1234-1247. doi: 10.1038/s41380-019-0562-6. Epub 2019 Oct 29. PMID: 31664175; PMCID: PMC7985042. 

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Theta-alpha oscillations characterize emotional subregion in the human ventral subthalamic nucleus.

Rappel P, Grosberg S, Arkadir D, Linetsky E, Abu Snineh M, Bick AS, Tamir I, Valsky D, Marmor O, Abo Foul Y, Peled O, Gilad M, Daudi C, Ben-Naim S, Bergman H, Israel Z, Eitan R.

Mov Disord. 2020 Feb;35(2):337-343. doi: 10.1002/mds.27910. Epub 2019 Nov 23. PMID: 31758821.

Real-time machine learning classification of pallidal borders during deep brain stimulation surgery.

Valsky D, Blackwell KT, Tamir I, Eitan R, Bergman H, Israel Z.

J Neural Eng. 2020 Jan 6;17(1):016021. doi: 10.1088/1741-2552/ab53ac. PMID: 31675740.

Subthalamic theta activity: a novel human subcortical biomarker for obsessive compulsive disorder.

Rappel P, Marmor O, Bick AS, Arkadir D, Linetsky E, Castrioto A, Tamir I, Freedman SA, Mevorach T, Gilad M, Bergman H, Israel Z, Eitan R.

Transl Psychiatry. 2018 Jun 18;8(1):118. doi: 10.1038/s41398-018-0165-z. PMID: 29915200; PMCID: PMC6006433

One year double blind study of high vs low frequency subcallosal cingulate stimulation for depression.

Eitan R, Fontaine D, Benoît M, Giordana C, Darmon N, Israel Z, Linesky E, Arkadir D, Ben-Naim S, Iserlles M, Bergman H, Hulse N, Abdelghani M, McGuffin P, Farmer A, DeLea P, Ashkan K, Lerer B.

J Psychiatr Res. 2018 Jan;96:124-134. doi: 10.1016/j.jpsychires.2017.09.026. Epub 2017 Oct 3. PMID: 29032294.

Local vs. volume conductance activity of field potentials in the human subthalamic nucleus.

Marmor O, Valsky D, Joshua M, Bick AS, Arkadir D, Tamir I, Bergman H, Israel Z, Eitan R.

J Neurophysiol. 2017 Jun 1;117(6):2140-2151. doi: 10.1152/jn.00756.2016. Epub 2017 Feb 15. PMID: 28202569; PMCID: PMC5454468.

Asymmetric right/left encoding of emotions in the human subthalamic nucleus.

Eitan R, Shamir RR, Linetsky E, Rosenbluh O, Moshel S, Ben-Hur T, Bergman H, Israel Z.

Front Syst Neurosci. 2013 Oct 29;7:69. doi: 10.3389/fnsys.2013.00069. PMID: 24194703; PMCID: PMC3810611.

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