NERD Lab
Neural Engineering and Rehabilitation Design
The focus of our lab is on developing novel neural interfaces as well as investigating the plasticity mechanism of the brain. Our goal is to reveal underlying mechanisms of brain plasticity that lead to functional recovery from brain damage, which can provide us with vital insight to develop stimulation-based therapies for a broad range of neurological disorders such as stroke. We use a combination of electrophysiological recordings in behaving animals, real-time detection and manipulation of physiological patterns, and perturbation of neural activity in specific circuits during behavior, to determine causal links between physiological phenomena and therapeutic outcomes. In particular, the unique tool we use is optogenetics since it enables us to manipulate neural activity with high spatial and temporal resolution via virally transfected neurons containing light-sensitive ion channels. In addition to its potential for greater spatial resolution and cell-type specificity, this technique offers the significant advantage of artifact-free electrophysiological recording during stimulation. This novel use of optogenetics offers new opportunities to create sophisticated closed-loop stimulation and recording paradigms, and helps us to understand the role of the basic physiological and therapeutic phenomena.
Our research projects
Targeted brain reorganization using optogenetic stimulation in non-human primates
The goal of this project is to reveal underlying mechanisms of brain plasticity that lead to functional connectivity and recovery from injury.
In this project we use activity-dependent stimulation to provide more robust neural plasticity, higher functional and temporal specificity and to restore normal patterns of functional connectivity between brain regions post-injury. Furthermore the use of optogenetics enables us to manipulate neural activity with high spatial and temporal resolution via virally transfected neurons containing light-sensitive ion channels.
This project provides critical insight into the fundamentals of functional connectivity and its role in brain plasticity following injury, demonstrates the power of targeted, activity-dependent cortical stimulation to drive rehabilitative reorganization, and may have a profound impact on future therapeutic interventions for neurological disorders.
See our papers below related to this research:
- A. Yazdan-Shahmorad*, D. Silversmith* (Equal contribution), P. N. Sabes, “Targeted cortical reorganization using optogenetics in non-human primates”, eLife, 2018 May 29. PMID: 29809133.
- J. Bloch, K. Khateeb, D. Silversmith, J. E. O’Doherty, P. N. Sabes, A. Yazdan-Shahmorad, “Cortical Stimulation Induces Network-Wide Coherence Change in Non-Human Primate Cortex“, IEEE EMBC 2019, PMID: 31947318.
- J. Bloch, A. Greaves-Tunnell, E. Shea-Brown, A. Shojaie, Z. Harchoui, A. Yazdan-Shahmorad, “Network structure mediates functional reorganization induced by optogenetic stimulation of non-human primate sensorimotor cortex”. 2022 May 20; iScience, DOI: 10.1016/j.isci.2022.104285.
And watch the video of our recent work:
Multi-modal large-scale neural interfaces
In order to study the complex relationships between neuronal populations and between neural activity and the vascular system across multiple brain areas over long periods of time, we are designing multi-modal large-scale optogenetic interfaces. Our interfaces will allow for electrical stimulation and recording of neural activity concurrent with optogenetic neuromodulation. With these interfaces we will be able to activate and suppress different regions of the brain to study neural plasticity and develop therapeutic approaches for neurological diseases, such as stroke. We are also designing our interfaces to be compatible with optical imaging approaches, such as optical coherence tomography angiography which is used to study microvasculature. Large-scale imaging of microvasculature over long-term stimulation-based experiments promises to provide critical insight into the relationships between the brain’s microvasculature and neural activity and plasticity. The data collected with these interfaces will provide large-scale, long-term, and multi-modal perspectives for both basic and applied neuroscience.
See our papers below related to this research:
- A. Yazdan-Shahmorad, C. Diaz-Botia, T. Hanson, P. Ledochowitsch, M. M. Maharbiz, P. Sabes, “A large interface for optogentic stimulation and recording in non-human primates”, Neuron; 2016 Feb 10. PMID: 26875625.
- P. Ledochowitsch*, A. Yazdan-Shahmorad* (Equal contribution), K. E. Bouchard, C. Diaz-Botia, T. L. Hanson, J.W. He, B. Seyboldt, E. Olivero, E. A. K. Phillips, T. J. Blanche, C. E. Schreiner, A. Hasenstaub, E. F. Chang, P. N. Sabes, M. M. Maharbiz, “Strategies for optical control and simultaneous electrical readout of extended cortical circuits”, Journal of Neuroscience methods (2015). Dec;256:220-31. PMID: 26296286.
- A. Yazdan-Shahmorad, C. Diaz-Botia, T. Hanson, P. Ledochowitsch, M. M. Maharabiz, P. N. Sabes, “Demonstration of a setup for chronic optogenetic stimulation and recording across cortical areas in non-human primates” SPIE BIOS, 2015, Feb 7-12, San Francisco, California, USA, DOI: 10.1117/12.2080405.
- A. Yazdan-Shahmorad, D. Silversmith, Philip N. Sabes, “Novel techniques for large-scale manipulations of cortical networks in non-human primates” 40th IEEE EMBS Annual International Conference, July 17-21, 2018, USA.
- A. Yazdan-Shahmorad*, N. Tian*, V. Kharazia* (Equal contribution), A. Kells, J. He, J. Bringas, K. H. Rosenbluth, K. Bankiewickz, P. Sabes, “Widespread cortical expression of ChR2 in Macaque via MR-guided, convection enhanced delivery (CED) of AAV vector to the thalamus”, Journal of Neuroscience methods, Volume 293, January 1, 2018. PMID: 29042259.
- K. Khateeb, D. J. Griggs, P. N. Sabes, A. Yazdan-Shahmorad, “Convection Enhanced Delivery of an Optogenetic Adeno-associated Viral Vector to the Rhesus Macaque Cortex with Online MRI Images”, Journal of Visualized Experiments, 2019 May 23;(147). DOI: 10.3791/59232. PMID:31180352.
- D. J. Griggs, K. Khateeb, S. Philips, J. W. Chan, W.K.S. Ojemann, A. Yazdan-Shahmorad, “Optimized large-scale optogenetic interface for non-human primates“, SPIE BIOS, 2019, Feb 7-12, San Francisco, California, USA.
- S. Macknik, R. Alexander, O. Caballero, K. Nielsen, N. Nishimura, C. Schaffer, H. Slovin, A. Babayoff, S. Tang, N. Ju, A. Yazdan-Shahmorad, J. M. Alonso, E. Malinskiy, and S. Martinez-Conde, “Advanced Circuit and Cellular Imaging Methods in Non-Human Primates” Jounral of Neuroscience, 2019, Oct 16, 39 (42), 8267-8274. PMID: 31619496.
- W.K.S. Ojemann, D.J. Griggs, Z. Ip, O. Caballero, S. Martinez-Conde , S. Macknik, A. Yazdan-Shahmorad, “MRI based toolbox for neurosurgical planning in non-human primates,” Journal of Visualized Experiments, July 17, 2020, DOI: 10.3791/61098, PMID: 32744531.
- D.J. Griggs, K. Khateeb, Jasmine Zhou, T. Liu, R.Wang, A. Yazdan-Shahmorad, “Multi-modal artificial dura for simultaneous large-scale optical access and large-scale electrophysiology in non-human primate cortex“, Journal of Neural Engineering, 2021 March 26; DOI: 10.1088/1741-2552/abf28d, PMID: 33770770.
- D.J. Griggs, T. Belloir, A. Yazdan-Shahmorad, “Large-scale neural interfaces for optogenetic actuators and sensors in non-human primates” Integrated Sensors for Biological and Neural Sensing 11663, 1166305, SPIE BIOS, March 6-11, 2021.
- D.J. Griggs, A. D. Garcia, W. Y. Au, W. K. S. Ojemann1, A. G. Johnson, J. T. Ting, E. A. Buffalo, A. Yazdan-Shahmorad, “Improving the efficacy and accessibility of intracranial viral vector delivery in non-human primates”. 2022 July 8; Invited paper for the special issue on Brain Drug Delivery for Pharmaceutics, DOI: 10.3390/pharmaceutics14071435, PMID: 35890331, PMCID: PMC9323200.
A lesion-based toolbox to study cortical physiology
Cortex is a highly complex structure responsible for a variety of sophisticated tasks and behaviors including facilitating long-term memory storage, sensation, movement, and vision. Neurological disorders affecting cortex have deleterious effects on these and other important behaviors. Historically, lesioning studies have been crucial for elucidating the functions of broad cortical regions. However, little is understood with respect to the underlying cortical physiology and dynamics following perturbation. Such studies would allow for the development of improved tools and strategies for treating neurological disorders. To address these challenges and accelerate the development of novel and effective therapies, we developed a highly versatile lesion-based toolbox for studying cortical physiology. With this toolbox we have the capability of inducing targeted, modular, and focal ischemic lesions that extend through all cortical layers. Additionally, our system offers a tool to validate the disruption of cortical blood flow and measure lesion sizein vivo. Moreover, our paradigm also allows for the simultaneous recording of the underlying neural activity across the network as lesions develop over time. With our toolbox, lesion volumes can be measured through histological analysis and predicted by a computational model based on modular experimental parameters. The use of these tools in combination with our large-scale neural interfaces (see above) allows us to investigate underlying cortical physiology such as vascular and neural dynamics during the formation of, in the presence of, and during the subsequent recovery from an induced lesion. In combination with behavioral findings, this toolbox can provide critical insights into fundamental cortical functions and drive the development of future rehabilitative therapies for stroke and other neurological disorders.
See our papers below related to this research:
- Z. Yao, A. Yazdan-Shahmorad, “A Quantitative Model for Estimating the Scale of Photochemically Induced Ischemic Stroke”, 40th IEEE EMBS Annual International Conference, July 17-21, 2018, USA.
- K. Khateeb, Z. Yao, V. Kharazia, E. Burunova, S. Song, R. Wang, A. Yazdan-Shahmorad, “A Practical Method for Creating Targeted Focal Ischemic Stroke in the Cortex of Nonhuman Primates”, IEEE EMBC 2019, PMID: 31946636.
- K. Khateeb, J. Bloch, J. Zhou, M. Rahimi, D. J. Griggs, M.N. Lee, V. Kharazia, R. Wang, A. Yazdan-Shahmorad, “A Versatile toolbox for studying cortical physiology in primates“. 2022 March 28; Cell Reports Methods, DOI:10.1016/j.crmeth.2022.100183, PMID: 35445205, PMCID: PMC9017216.
Studying the underlying mechanisms of post-stroke cognitive impairment
Post-stroke cognitive impairment in various domains from attention deficits to memory problems are very common in stroke victims. The goal of this project is to investigate cortical and hippocampal oscillations following cortical stroke in rats to understand the underlying neural mechanisms.
See our papers below related to this research:
- J.W. He, G. Rabiller, Y. Nishijima, Y. Akamatsu, K. Khateeb2, X. Leinekugel, A. Yazdan-Shahmorad,J. Liu, “Experimental cortical stroke induces aberrant increase of sharp wave associated ripples in the hippocampus and disrupts cortico-hippocampal communication”, Journal of Cerebral Blood Flow and Metabolism, 2019, Sep 26:271678X19877889.PMID: 31558106.
- Z. Ip, G. Rabiller, J.W. He, Z. Yao, Y. Akamatsu, Y. Nishijimi, J. Liu, A. Yazdan-Shahmorad, “Cortical stroke affects activity and stability of theta/delta states in remote hippocampal regions“, IEEE EMBC 2019, PMID: 31947036.
- Z. T Ip, G. Rabiller, J.He, S. Chavan, Y. Nishijima, Y. Akamatsu, J. Liu, Azadeh Yazdan-Shahmorad, “Local Field Potentials identify features of cortico-hippocampal communication impacted by stroke and environmental enrichment therapy”. 2021 June; Journal of Neural Engineering. DOI: 10.1088/1741-2552/ac0a54, PMID: 34111845.
- Sato, O. Schmitt, G. Rabiller, S. Omodaka, Z. Ip, T. Tominaga, A. Yazdan-Shahmorad, J. Liu, “Pathological changes of brain oscillations following ischemic stroke“, 2022 June 25; Journal of Cerebral Blood Flow and Metabolism, DOI: 10.1177/0271678X221105677, PMID: 35754347.