Shirvalkar Lab

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Welcome!
The Shirvalkar Lab (Pain Neuromodulation Lab) is led by Prasad Shirvalkar MD, PhD, a neurologist and pain physician-scientist who treats the full range of chronic pain syndromes.

Among the amazing things that the brain does, it is responsible for generating and representing the most fundamental human percept: Pain. We focus on studying basic brain mechanisms of acute and chronic pain in humans using neuropsychology, behavior, imaging (DTI, fMRI), neurophysiology (invasive recordings and EEG), computational neuroscience, signal processing and machine learning.  Our short term goal is to understand of how pain circuits live in the brain and how these circuits go awry to produce chronic pain states. The long term goal is to use this new knowledge to develop new technology for spine and brain stimulation to treat patients, and improve quality of life.

Our lab is physically located across three campuses: Parnassus, Mount Zion and Mission Bay. We collaborate with critical partners in anesthesiology, neurology and neurological surgery to tackle these urgent problems. We are always looking for enthusiastic and accomplished people to join us. Welcome!

Study News

Tailoring Deep Brain Stimulation to Treat Chronic Pain

By Jen A. Miller on February 03, 2020

One in four U.S. adults suffer from chronic pain, many from chronic pain that is resistant to treatment. People with conditions like post-stroke pain, phantom limb pain, nerve pain and pain from spinal injuries are often left with in agony but little hope for relief.

That could change as deep brain stimulation (DBS) goes from a way to treat motor diseases to a possible treatment for chronic pain – treatment that can be customized to the patient’s brain makeup and their own brain’s feedback.

“Never before have patients with chronic pain had the opportunity to walk around and deliver neural data in real time,” said Prasad Shirvalkar, MD, PhD, assistant professor of Anesthesiology at UC San Francisco. “We’re at the front edge of trying to open up new indications for DBS.”

DBS already is used to treat movement disorders, like Parkinson’s disease, dystonia and essential tremors. Patients have electrodes implanted deep into the parts of their brain that control movement, and receive electrical current via a stimulator put into their chest.

The problem with current DBS treatment is that the electrical current is constant. It doesn’t take in feedback or adjust based on what’s really happening in the brain. Patients can suffer side effects like trouble speaking and change in personality – even seizure or stroke. Their brains can also become acclimated to the treatment so that it doesn’t work anymore.

Shirvalkar – along with Edward Chang, MD, and Philip Starr, MD, PhD, professors of Neurological Surgery and members of the USCF Weill Institute for Neurosciences – have received a $7.56 million, five-year grant from the National Institutes of Health (NIH) to improve DBS as a treatment for chronic pain. It’s one of 10 grants worth more than $40 million that UCSF researchers have been awarded as part of the NIH Helping to End Addiction Long-Term (HEAL) Initiative.

Instead of providing a continuous current, this grant is helping researchers make the electric charge more customized by first identifying new targets for stimulation, and creating systems that can take feedback from the brain and adjust the device accordingly.

“When we find those new targets, the next goal is identifying brain biomarkers of chronic pain for each patient,” Shirvalkar said. That means recording direct from patients’ brains while they experience natural pain fluctuations. “By combining their neural signals with their pain reports, we’re trying to build a model of how their brain represents pain.”

Shirvalkar likens current DBS to what they hope for to a space heater versus a thermostat. A space heater “provides constant heat. You might get too hot and then have to turn it off,” he said. “A thermostat is feedback controlled heating. We are trying to build a model to serve as a thermostat to control electronic stimulation to provide pain relief.”

The grant started in October 2019, and Shirvalkar said they are still enrolling patients. The grant includes funding for travel, so patients do not need to live in California. Those interested in being part of the trial can contact the Pain Management Center at [email protected].

UCSF Receives 10 NIH Grants to Study Pain and Opioid Addiction

By Nina Bai on October 10, 2019

The National Institutes of Health (NIH) has awarded 10 grants this year to UC San Francisco researchers as part of the NIH Helping to End Addiction Long-term (HEAL) Initiative.

The awards to UCSF total more than $40 million and will fund projects ranging from better technologies for MRI imaging of back pain, to the use of deep-brain stimulation for treating chronic pain, to a new interdisciplinary research center for low back pain.

In 2016, an estimated 50 million U.S. adults suffered from chronic pain – generally defined as pain that lasts more than three months – and low back pain, headaches, arthritis, neuropathy and other forms cost about $635 billion annually. In 2018, an estimated 10.3 million Americans age 12 and older misused opioids, including heroin.

Several of the grants to UCSF focus on low back pain, a common yet hard-to-treat condition. According to the Global Burden of Disease 2010 Study, low back pain ranked highest in terms of years lived with disability, yet no consistently effective and durable pharmacologic intervention exists for chronic low back pain, though opioids are a common treatment.

The largest of the new grants, $29.4 million, will go to creating the Core Center for Patient-centric Mechanistic Phenotyping in Chronic Low Back Pain (REACH) at UCSF, an interdisciplinary consortium of basic and clinical scientists working to define different types of chronic low back pain and pain mechanisms that may lead to effective, personalized treatments for patients. REACH will be led by Jeffrey C. Lotz, PhD, professor and vice chair of research in Orthopaedic Surgery.

Other UCSF projects that received HEAL funding:

  • Aaron Fields, PhD, associate professor of Orthopaedic Surgery, and Roland Krug, PhD, associate professor of Radiology and Biomedical Imaging, are leading a $3.6 million award ($1.1 million for phase I) for their team to develop new MRI methods for measuring endplate pathologies (endplates separate discs and vertebrae in the spine) to better select patients for non-addictive and minimally invasive treatments.
  • Sharmila Majumdar, PhD, the Margaret Hart Surbeck Distinguished Professor of Advanced Imaging, received $4.39 million ($513,742 for phase I) for her team to improve imaging of low back pain, including developing deep-learning-based technologies for faster image reconstruction, tissue segmentation and spinal degeneration detection.
  • Prasad Shirvalkar, MD, PhD, assistant professor of Anesthesiology, received $7.56 million to improve deep brain stimulation for chronic pain, which has shown early promise. Shirvalkar’s team aims to develop long-term implants for intracranial stimulation from multiple brain sites that automatically adjust to personalized brain signals of pain. He is collaborating with Edward Chang, MD, and Philip Starr, MD, professors of Neurological Surgery and members of the UCSF Weill Institute for Neurosciences, on this project.
  • Michael McManus, PhD, professor in the UCSF Diabetes Center, and Lily Jan, PhD, professor of Physiology, were awarded $500,000 to better understand the function of ion channels, which are critical to the nervous system. They aim to generate data and reagents for poorly characterized ion channels, to illuminate the underlying interacting genetic components, and ultimately to identify ion channel phenotypes relevant to human disease.
  • James Sorensen, PhD, professor of Psychiatry, was awarded five grants totaling $2.62 million to study the efficacy of early interventions to prevent the progression from risky opioid use to opioid use disorder. His team will test a subthreshold opioid use disorder prevention (STOP) intervention program in the primary care setting, which consists of a practice-embedded nurse care manager who provides patient education and monitoring, advice delivered by the primary care physician, and phone counseling.  

The NIH launched the HEAL Initiative in April 2018 to speed scientific solutions to stem the national opioid public health crisis. It aims to prevent addiction through enhanced pain management and to improve treatment for opioid misuse disorder and addiction. This year, the HEAL Initiative has awarded $945 million to approximately 375 projects nationwide.

“It’s clear that a multi-pronged scientific approach is needed to reduce the risks of opioids, accelerate development of effective non-opioid therapies for pain and provide more flexible and effective options for treating addition to opioids,” NIH Director Francis S. Collins, MD, PhD, said in a press release about the awards. “This unprecedented investment in the NIH Heal Initiative demonstrates the commitment to reversing this devastating crisis.”

People

Principal Investigator

 Prasad Shirvalkar MD, PhD

 Assistant Professor Department of Anesthesiology (Pain Management)

 UCSF Profile 

 Shirvalkar Lab at UCSF

Research Team

 Kristin Sellers PhD

 Associate Professional Researcher in the Chang Lab

 UCSF Profile

 

 Ashlyn Schmitgen

 Clinical Research Coordinator

 

 

 Jordan Prosky

 Clinical Research Coordinator

 

 

 Bella Joseph

 Clinical Research Coordinator

 

 

 Chad Sitgraves

 Clinical Research Coordinator

 

 

 Ana Shaughnessy

 Clinical Research Coordinator

 

 

Collaborators

 Edward Chang MD

 UCSF Neurosurgeon

 UCSF Profile

 

 Philip Starr MD, PhD

 UCSF Neurosurgeon

 UCSF Profile

 

 Lawrence Poree MD, PhD, MPH

 Professor, Anesthesia. Pain Medicine Specialist

 UCSF Profile

 

 Doris Wang MD, PhD

 UCSF Neurosurgeon

 UCSF Profile

 

 Maryam Shanechi PhD

 Associate Professor and Viterbi Early Career Chair in Electrical and Computer Engineering at USC

 USC Profile

 

 Coralie de Hemptinne MS, PhD

 Assistant Professor in the Normal Fixel Institute for Neurological Diseases at University of Florida

 UF Profile

Publications

Analysis-rcs-data: Open-Source Toolbox for the Ingestion, Time-Alignment, and Visualization of Sense and Stimulation Data From the Medtronic Summit RC+S System.

Frontiers in human neuroscience

Kristin K. Sellers, Ro’ee Gilron, Juan Anso, Kenneth H. Louie, Prasad R. Shirvalkar, Edward F. Chang, Simon J. Little, Philip A. Starr

Emerging Therapies for the Treatment of Complex Regional Pain Syndrome.

Po-Yi Paul Su, Shikha Sharma, Prasad Shirvalkar, Lawrence Poree

Musical Hallucinations in Chronic Pain: The Anterior Cingulate Cortex Regulates Internally Generated Percepts.

Frontiers in neurology

Schmitgen A, Saal J, Sankaran N, Desai M, Joseph I, Starr P, Chang EF, Shirvalkar P

Proceedings of the Eighth Annual Deep Brain Stimulation Think Tank: Advances in Optogenetics, Ethical Issues Affecting DBS Research, Neuromodulatory Approaches for Depression, Adaptive Neurostimulation, and Emerging DBS Technologies.

Frontiers in human neuroscience

Vedam-Mai V, Deisseroth K, Giordano J, Lazaro-Munoz G, Chiong W, Suthana N, Langevin JP, Gill J, Goodman W, Provenza NR, Halpern CH, Shivacharan RS, Cunningham TN, Sheth SA, Pouratian N, Scangos KW, Mayberg HS, Horn A, Johnson KA, Butson CR, Gilron R, de Hemptinne C, Wilt R, Yaroshinsky M, Little S, Starr P, Worrell G, Shirvalkar P, Chang E, Volkmann J, Muthuraman M, Groppa S, Kühn AA, Li L, Johnson M, Otto KJ, Raike R, Goetz S, Wu C, Silburn P, Cheeran B, Pathak YJ, Malekmohammadi M, Gunduz A, Wong JK, Cernera S, Wagle Shukla A, Ramirez-Zamora A, Deeb W, Patterson A, Foote KD, Okun MS

The American Society of Pain and Neuroscience (ASPN) Practical Guidelines to Study Design and Scientific Manuscript Preparation in Neuromodulation.

Journal of pain research

A Tale of Two Cords: Diastematomyelia.

Pain Medicine

Westin Tom, Thoha Pham, Prasad Shirvalkar

A Deep Brain Stimulation Trial Period for Treating Chronic Pain.

Journal of clinical medicine

Shirvalkar P, Sellers KK, Schmitgen A, Prosky J, Joseph I, Starr PA, Chang EF

A Comprehensive Practice Guideline for Magnetic Resonance Imaging Compatibility in Implanted Neuromodulation Devices.

Neuromodulation : journal of the International Neuromodulation Society

Sayed D, Chakravarthy K, Amirdelfan K, Kalia H, Meacham K, Shirvalkar P, Falowski S, Petersen E, Hagedorn JM, Pope J, Leever J, Deer T

Transcranial Magnetic Stimulation for Pain, Headache, and Comorbid Depression: INS-NANS Expert Consensus Panel Review and Recommendation.

Neuromodulation : journal of the International Neuromodulation Society

Leung A, Shirvalkar P, Chen R, Kuluva J, Vaninetti M, Bermudes R, Poree L, Wassermann EM, Kopell B, Levy R

Large expert-curated database for benchmarking document similarity detection in biomedical literature search.

Database

eter Brown, Aik-Choon Tan, Mohamed A El-Esawi, Thomas Liehr, Oliver Blanck, Douglas P Gladue, Gabriel M F Almeida, Tomislav Cernava, Carlos O Sorzano, Andy W K Yeung, Michael S Engel, Arun Richard Chandrasekaran, Thilo Muth, Martin S Staege, Swapna V Daulatabad, Darius Widera, Junpeng Zhang, Adrian Meule, Ken Honjo, Olivier Pourret, Cong-Cong Yin, Zhongheng Zhang, Marco Cascella, Willy A Flegel, Carl S Goodyear, Mark J van Raaij, Zuzanna Bukowy-Bieryllo, Luca G Campana, Nicholas A Kurniawan, David Lalaouna, Felix J Hüttner, Brooke A Ammerman, Felix Ehret, Paul A Cobine, Ene-Choo Tan, Hyemin Han, Wenfeng Xia, Christopher McCrum, Ruud P M Dings, Francesco Marinello, Henrik Nilsson, Brett Nixon, Konstantinos Voskarides, Long Yang, Vincent D Costa, Johan Bengtsson-Palme, William Bradshaw, Dominik G Grimm, Nitin Kumar, Elvis Martis, Daniel Prieto, Sandeep C Sabnis, Said E D R Amer, Alan W C Liew, Paul Perco, Farid Rahimi, Giuseppe Riva, Chongxing Zhang, Hari P Devkota, Koichi Ogami, Zarrin Basharat, Walter Fierz, Robert Siebers, Kok-Hian Tan, Karen A Boehme, Peter Brenneisen, James A L Brown, Brian P Dalrymple, David J Harvey, Grace Ng, Sebastiaan Werten, Mark Bleackley, Zhanwu Dai, Raman Dhariwal, Yael Gelfer, Marcus D Hartmann, Pawel Miotla, Radu Tamaian, Pragashnie Govender, Oliver J Gurney-Champion, Joonas H Kauppila, Xiaolei Zhang, Natalia Echeverría, Santhilal Subhash, Hannes Sallmon, Marco Tofani, Taeok Bae, Oliver Bosch, Páraic O Cuív, Antoine Danchin, Barthelemy Diouf, Tuomas Eerola, Evangelos Evangelou, Fabian V Filipp, Hannes Klump, Lukasz Kurgan, Simon S Smith, Olivier Terrier, Neil Tuttle, David B Ascher, Sarath C Janga, Leon N Schulte, Daniel Becker, Christopher Browngardt, Stephen J Bush, Guillaume Gaullier, Kazuki Ide, Clement Meseko, Gijsbert D A Werner, Jan Zaucha, Abd A Al-Farha, Noah F Greenwald, Segun I Popoola, Shaifur Rahman, Jialin Xu, Sunny Y Yang, Noboru Hiroi, Ozgul M Alper, Chris I Baker, Michael Bitzer, George Chacko, Birgit Debrabant, Ray Dixon, Evelyne Forano, Matthew Gilliham, Sarah Kelly, Karl-Heinz Klempnauer, Brett A Lidbury, Michael Z Lin, Iseult Lynch, Wujun Ma, Edward W Maibach, Diane E Mather, Kutty S Nandakumar, Robert S Ohgami, Piero Parchi, Patrizio Tressoldi, Yu Xue, Charles Armitage, Pierre Barraud, Stella Chatzitheochari, Luis P Coelho, Jiajie Diao, Andrew C Doxey, Angélique Gobet, Pingzhao Hu, Stefan Kaiser, Kate M Mitchell, Mohamed F Salama, Ivan G Shabalin, Haijun Song, Dejan Stevanovic, Ali Yadollahpour, Erliang Zeng, Katharina Zinke, C G Alimba, Tariku J Beyene, Zehong Cao, Sherwin S Chan, Michael Gatchell, Andreas Kleppe, Marcin Piotrowski, Gonzalo Torga, Adugna A Woldesemayat, Mehmet I Cosacak, Scott Haston, Stephanie A Ross, Richard Williams, Alvin Wong, Matthew K Abramowitz, Andem Effiong, Senhong Lee, Muhammad Bilal Abid, Cyrus Agarabi, Cedric Alaux, Dirk R Albrecht, Gerald J Atkins, Charles R Beck, A M J J Bonvin, Emer Bourke, Thomas Brand, Ralf J Braun, James A Bull, Pedro Cardoso, Dee Carter, Robin M Delahay, Bernard Ducommun, Pascal H G Duijf, Trevor Epp, Eeva-Liisa Eskelinen, Mazyar Fallah, Debora B Farber, Jose Fernandez-Triana, Frank Feyerabend, Tullio Florio, Michael Friebe, Saori Furuta, Mads Gabrielsen, Jens Gruber, Malgorzata Grybos, Qian Han, Michael Heinrich, Heikki Helanterä, Michael Huber, Albert Jeltsch, Fan Jiang, Claire Josse, Giuseppe Jurman, Haruyuki Kamiya, Kim de Keersmaecker, Erik Kristiansson, Frank-Erik de Leeuw, Jiuyong Li, Shide Liang, Jose A Lopez-Escamez, Francisco J Lopez-Ruiz, Kevin J Marchbank, Rolf Marschalek, Carmen S Martín, Adriana E Miele, Xavier Montagutelli, Esteban Morcillo, Rosario Nicoletti, Monika Niehof, Ronan O’Toole, Toshihiko Ohtomo, Henrik Oster, Jose-Alberto Palma, Russell Paterson, Mark Peifer, Maribel Portilla, M C Portillo, Antonia L Pritchard, Stefan Pusch, Gajendra P S Raghava, Nicola J Roberts, Kehinde Ross, Birgitt Schuele, ...

Closed-Loop Deep Brain Stimulation for Refractory Chronic Pain.

Frontiers in computational neuroscience

Shirvalkar P, Veuthey TL, Dawes HE, Chang EF

Chapter 47 The Development of Algorithms for Pain Care Including Neuromodulation Therapies Introducing the SAFE Principles.

Neuromodulation

Prasad Shirvalkar, Lawrence R. Poree, Elliot S. Krames

List of Contributors of Volume 2.

Neuromodulation

Al-Kaisy Adnan, Andreas Alexopoulos, Kenneth M. Alo, Ron L. Alterman, Arun Amar, Pablo Andrade, Sailesh Arulkumar, Ahmed J. Awad, Gordon Baltuch, Giancarlo Barolat, Ernest J. Barthélemy, Neil U. Barua, Maria E. Bennett, Nicole Bentley, Yarema B. Bezchlibnyk, Kelly R. Bijanki, William Bingaman, Joseph W. Boggs, Paul Boon, Brigitte A. Brouwer, Lucas W. Campos, Anthony Caparso, Annamaria Capozzo, John Chae, Jin Woo Chang, Jennifer Cheng, David Copenhaver, Timothy R. Deer, Milind Deogaonkar, Deepali Dhar, Keeley Dohmeier, Darin D. Dougherty, Dominique M. Durand, Kelly Foote, Jeffrey Gilligan, Steven S. Gill, Jorge Gonzalez-Martinez, Benjamin D. Greenberg, Robert E. Gross, Michael H. Pourfar, Clement Hamani, Salim M. Hayek, Paul E. Holtzheimer, Brian M. Ilfeld, Haiyan Jin, Bert Joosten, Na Young Jung, Chong H. Kim, Young Goo Kim, Martin Klehr, Paul Koch, Sina Kohl, Brian H. Kopell, Daniel Kramer, Elliot S. Krames, Balu Krishnan, Vibhor Krishna, Jens Kuhn, Jason Kyung-soo Hong, Kapural Leonardo, Michael S. Leong, Dianyou Li, Andreas A. Linninger, Nir Lipsman, Charles Liu, Andres M. Lozano, Michael Mackow, Mark N. Malinowski, Helen S. Mayberg, Paolo Mazzone, Ankit I. Mehta, Vivek Mehta, Reversa Mills-Joseph, Dileep Nair, Richard B. North, Michael Okun, Nikunj K. Patel, Parag G. Patil, Jason E. Pope, Lawrence R. Poree, Joshua P. Prager, Robrecht Raedt, Jonathan J. Rasouli, Serge Rasskazoff, Richard Rauck, Kevin Reeves, Ali R. Rezai, Jonathan Russin, Abraham Sabersky, Michael Saulino, Eugenio Scarnati, Stefan Schu, Mayur Sharma, Jane Shipley, Prasad Shirvalkar, Konstantin V. Slavin, Michael Stanton-Hicks, Scellig Stone, William A. Stuart, Bomin Sun, Kevin Tangen, Stewart J. Tepper, Maarten van Kleef, Tim Vancamp, Paul Verrills, Fabio Viselli, Veerle Visser-Vandewalle, Flora Vitale, Kristl Vonck, Tao Wang, Xuelian Wang, Richard L. Weiner, Alik S. Widge, Amorn Wongsarnpigoon, Alon Y. Mogilner, Kurt A. Yaeger, Tony L. Yaksh, Dali Yin, Kristina Zeljic, Chencheng Zhang, Shikun Zhan

Improving lower limb strength in incomplete spinal cord injury with non-invasive spinal associative stimulation.

Brain Stimulation

M. Cortes, G. Thickbroom, J. Valls-Sole, P. Shirvalkar, A. Pascual-Leone, D. Edwards

American neuroborreliosis presenting as cranial polyneuritis and radiculoneuritis.

Neurology(R) neuroimmunology & neuroinflammation

Wang E, Shirvalkar PR, Maciel CB, Merkler AE, Safdieh J, Gupta A

Memory-guided learning: CA1 and CA3 neuronal ensembles differentially encode the commonalities and differences between situations.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Bahar AS, Shirvalkar PR, Shapiro ML

Memory modulates journey-dependent coding in the rat hippocampus.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Ferbinteanu J, Shirvalkar P, Shapiro ML

Design and construction of a cost effective headstage for simultaneous neural stimulation and recording in the water maze.

Journal of visualized experiments : JoVE

Shirvalkar PR, Shapiro ML

Infrageniculate Interventions in Female Patients: Improved Patency Rates but Higher Rates of Postoperative Complications.

Journal of Vascular Surgery

Tejas R. Shah, Angeliki Vouyouka, Daniel K. Han, Sharif Ellozy, Robert Lookstein, Prasad Shirvalkar, Michael Marin, Peter L. Faries

Bidirectional changes to hippocampal theta-gamma comodulation predict memory for recent spatial episodes.

Proceedings of the National Academy of Sciences of the United States of America

Shirvalkar PR, Rapp PR, Shapiro ML

The multiple origins and laminar topography of the hippocampal theta rhythm.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Shirvalkar P, Bahar AS

Hippocampal neural assemblies and conscious remembering.

Journal of neurophysiology

Shirvalkar PR

Cognitive enhancement with central thalamic electrical stimulation.

Proceedings of the National Academy of Sciences of the United States of America

Shirvalkar P, Seth M, Schiff ND, Herrera DG

Regulation of neurogenesis in the aging vertebrate brain: role of oxidative stress and neuropsychiatric factors.

Clinical Neuroscience Research

Evelyn Kim, Prasad Shirvalkar, Daniel G. Herrera