Bio

Bio


Rajat S. Shivacharan, Ph.D. is a Postdoctoral Research Fellow in the Department of Neurosurgery sponsored by Dr. Casey H. Halpern (Assistant Professor of Neurosurgery). He received his B.S. in Bioengineering from the University of Maryland in 2013. He went on to earn his Ph.D. in Biomedical Engineering at Case Western Reserve University in May 2019 in the laboratory of Dr. Dominique M. Durand (Director of Neural Engineering Center), studying the role of endogenous electric fields, or ephaptic coupling, in the recruitment of self-propagating, non-synaptic hippocampal waves under pathophysiological conditions. Now, he investigates the role of neuromodulation for neuropsychiatric indications, specifically mechanistic neurophysiology and closed-loop (or responsive) deep brain stimulation (DBS), to improve current neuromodulation therapies for mental disorders with loss of control. Outside of the lab, Rajat likes to cook (or attempt to cook) different types of cuisine, play video games, and enjoys exploring the beautiful Bay Area through biking, hiking, and camping/offroading with his Jeep.

Honors & Awards


  • Doctoral Excellence Award in Biomedical Engineering, Case Western Reserve University School of Medicine (2019)
  • 1st Place, Senior Capstone – System for Monitoring Endotracheal Tubes with RFID Technology (SMERT), University of Maryland (2013)

Professional Education


  • Ph.D., Case Western Reserve University, Biomedical Engineering (2019)
  • B.S., University of Maryland, Bioengineering (2013)

Stanford Advisors


Publications

All Publications


  • Anticipatory human subthalamic area beta-band power responses to dissociable tastes correlate with weight gain. Neurobiology of disease Kakusa, B., Huang, Y., Barbosa, D. A., Feng, A., Gattas, S., Shivacharan, R., Lee, E. B., Kuijper, F. M., Saluja, S., Parker, J. J., Miller, K. J., Keller, C., Bohon, C., Halpern, C. H. 2021: 105348

    Abstract

    The availability of enticing sweet, fatty tastes is prevalent in the modern diet and contribute to overeating and obesity. In animal models, the subthalamic area plays a role in mediating appetitive and consummatory feeding behaviors, however, its role in human feeding is unknown. We used intraoperative, subthalamic field potential recordings while participants (n = 5) engaged in a task designed to provoke responses of taste anticipation and receipt. Decreased subthalamic beta-band (15-30 Hz) power responses were observed for both sweet-fat and neutral tastes. Anticipatory responses to taste-neutral cues started with an immediate decrease in beta-band power from baseline followed by an early beta-band rebound above baseline. On the contrary, anticipatory responses to sweet-fat were characterized by a greater and sustained decrease in beta-band power. These activity patterns were topographically specific to the subthalamic nucleus and substantia nigra. Further, a neural network trained on this beta-band power signal accurately predicted (AUC ≥ 74%) single trials corresponding to either taste. Finally, the magnitude of the beta-band rebound for a neutral taste was associated with increased body mass index after starting deep brain stimulation therapy. We provide preliminary evidence of discriminatory taste encoding within the subthalamic area associated with control mechanisms that mediate appetitive and consummatory behaviors.

    View details for DOI 10.1016/j.nbd.2021.105348

    View details for PubMedID 33781923

  • 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, J., Gill, J., Goodman, W., Provenza, N. R., Halpern, C. H., Shivacharan, R. S., Cunningham, T. N., Sheth, S. A., Pouratian, N., Scangos, K. W., Mayberg, H. S., Horn, A., Johnson, K. A., Butson, C. R., 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., Kuhn, A. A., Li, L., Johnson, M., Otto, K. J., Raike, R., Goetz, S., Wu, C., Silburn, P., Cheeran, B., Pathak, Y. J., Malekmohammadi, M., Gunduz, A., Wong, J. K., Cernera, S., Wagle Shukla, A., Ramirez-Zamora, A., Deeb, W., Patterson, A., Foote, K. D., Okun, M. S. 2021; 15: 644593

    Abstract

    We estimate that 208,000 deep brain stimulation (DBS) devices have been implanted to address neurological and neuropsychiatric disorders worldwide. DBS Think Tank presenters pooled data and determined that DBS expanded in its scope and has been applied to multiple brain disorders in an effort to modulate neural circuitry. The DBS Think Tank was founded in 2012 providing a space where clinicians, engineers, researchers from industry and academia discuss current and emerging DBS technologies and logistical and ethical issues facing the field. The emphasis is on cutting edge research and collaboration aimed to advance the DBS field. The Eighth Annual DBS Think Tank was held virtually on September 1 and 2, 2020 (Zoom Video Communications) due to restrictions related to the COVID-19 pandemic. The meeting focused on advances in: (1) optogenetics as a tool for comprehending neurobiology of diseases and on optogenetically-inspired DBS, (2) cutting edge of emerging DBS technologies, (3) ethical issues affecting DBS research and access to care, (4) neuromodulatory approaches for depression, (5) advancing novel hardware, software and imaging methodologies, (6) use of neurophysiological signals in adaptive neurostimulation, and (7) use of more advanced technologies to improve DBS clinical outcomes. There were 178 attendees who participated in a DBS Think Tank survey, which revealed the expansion of DBS into several indications such as obesity, post-traumatic stress disorder, addiction and Alzheimer's disease. This proceedings summarizes the advances discussed at the Eighth Annual DBS Think Tank.

    View details for DOI 10.3389/fnhum.2021.644593

    View details for PubMedID 33953663

  • The insulo-opercular cortex encodes food-specific content under controlled and naturalistic conditions. Nature communications Huang, Y., Kakusa, B. W., Feng, A., Gattas, S., Shivacharan, R. S., Lee, E. B., Parker, J. J., Kuijper, F. M., Barbosa, D. A., Keller, C. J., Bohon, C., Mikhail, A., Halpern, C. H. 2021; 12 (1): 3609

    Abstract

    The insulo-opercular network functions critically not onlyin encoding taste, but also inguiding behavior based on anticipated food availability. However, there remains no direct measurement of insulo-opercular activity when humans anticipate taste. Here, we collect direct, intracranial recordings during a food task that elicits anticipatory and consummatory taste responses, and during ad libitum consumption of meals. While cue-specific high-frequency broadband (70-170Hz) activity predominant in the left posterior insula is selective for taste-neutral cues, sparse cue-specific regions in the anterior insulaare selective for palatable cues. Latency analysis reveals this insular activity is preceded by non-discriminatory activity in the frontal operculum. During ad libitum meal consumption, time-locked high-frequency broadband activity at the time of food intake discriminates food types and is associated with cue-specific activity during the task. These findings reveal spatiotemporally-specificactivity in the human insulo-opercular cortex that underlies anticipatory evaluation of food across both controlled and naturalistic settings.

    View details for DOI 10.1038/s41467-021-23885-4

    View details for PubMedID 34127675

  • Neural recruitment by ephaptic coupling in epilepsy. Epilepsia Shivacharan, R. S., Chiang, C. C., Wei, X. n., Subramanian, M. n., Couturier, N. H., Pakalapati, N. n., Durand, D. M. 2021

    Abstract

    One of the challenges in treating patients with drug-resistant epilepsy is that the mechanisms of seizures are unknown. Most current interventions are based on the assumption that epileptic activity recruits neurons and progresses by synaptic transmission. However, several experimental studies have shown that neural activity in rodent hippocampi can propagate independently of synaptic transmission. Recent studies suggest these waves are self-propagating by electric field (ephaptic) coupling. In this study, we tested the hypothesis that neural recruitment during seizures can occur by electric field coupling.4-Aminopyridine was used in both in vivo and in vitro preparation to trigger seizures or epileptiform activity. A transection was made in the in vivo hippocampus and in vitro hippocampal and cortical slices to study whether the induced seizure activity can recruit neurons across the gap. A computational model was built to test whether ephaptic coupling alone can account for neural recruitment across the transection. The model prediction was further validated by in vitro experiments.Experimental results show that electric fields generated by seizure-like activity in the hippocampus both in vitro and in vivo can recruit neurons locally and through a transection of the tissue. The computational model suggests that the neural recruitment across the transection is mediated by electric field coupling. With in vitro experiments, we show that a dielectric material can block the recruitment of epileptiform activity across a transection, and that the electric fields measured within the gap are similar to those predicted by model simulations. Furthermore, this nonsynaptic neural recruitment is also observed in cortical slices, suggesting that this effect is robust in brain tissue.These results indicate that ephaptic coupling, a nonsynaptic mechanism, can underlie neural recruitment by a small electric field generated by seizure activity and could explain the low success rate of surgical transections in epilepsy patients.

    View details for DOI 10.1111/epi.16903

    View details for PubMedID 33979453

  • Self-propagating, non-synaptic epileptiform activity recruits neurons by endogenous electric fields EXPERIMENTAL NEUROLOGY Shivacharan, R. S., Chiang, C., Zhang, M., Gonzalez-Reyes, L. E., Durand, D. M. 2019; 317: 119–28

    Abstract

    It is well documented that synapses play a significant role in the transmission of information between neurons. However, in the absence of synaptic transmission, neural activity has been observed to continue to propagate. Previous studies have shown that propagation of epileptiform activity takes place in the absence of synaptic transmission and gap junctions and is outside the range of ionic diffusion and axonal conduction. Computer simulations indicate that electric field coupling could be responsible for the propagation of neural activity under pathological conditions such as epilepsy. Electric fields can modulate neuronal membrane voltage, but there is no experimental evidence suggesting that electric field coupling can mediate self-regenerating propagation of neural activity. Here we examine the role of electric field coupling by eliminating all forms of neural communications except electric field coupling with a cut through the neural tissue. We show that 4-AP induced activity generates an electric field capable of recruiting neurons on the distal side of the cut. Experiments also show that applied electric fields with amplitudes similar to endogenous values can induce propagating waves. Finally, we show that canceling the electrical field at a given point can block spontaneous propagation. The results from these in vitro electrophysiology experiments suggest that electric field coupling is a critical mechanism for non-synaptic neural propagation and therefore could contribute to the propagation of epileptic activity in the brain.

    View details for DOI 10.1016/j.expneurol.2019.02.005

    View details for Web of Science ID 000470803400011

    View details for PubMedID 30776338

  • Slow periodic activity in the longitudinal hippocampal slice can self-propagate non-synaptically by a mechanism consistent with ephaptic coupling JOURNAL OF PHYSIOLOGY-LONDON Chiang, C., Shivacharan, R. S., Wei, X., Gonzalez-Reyes, L. E., Durand, D. M. 2019; 597 (1): 249–69

    Abstract

    Slow periodic activity can propagate with speeds around 0.1 m s-1 and be modulated by weak electric fields. Slow periodic activity in the longitudinal hippocampal slice can propagate without chemical synaptic transmission or gap junctions, but can generate electric fields which in turn activate neighbouring cells. Applying local extracellular electric fields with amplitude in the range of endogenous fields is sufficient to modulate or block the propagation of this activity both in the in silico and in the in vitro models. Results support the hypothesis that endogenous electric fields, previously thought to be too small to trigger neural activity, play a significant role in the self-propagation of slow periodic activity in the hippocampus. Experiments indicate that a neural network can give rise to sustained self-propagating waves by ephaptic coupling, suggesting a novel propagation mechanism for neural activity under normal physiological conditions.Slow oscillations are a standard feature observed in the cortex and the hippocampus during slow wave sleep. Slow oscillations are characterized by low-frequency periodic activity (<1 Hz) and are thought to be related to memory consolidation. These waves are assumed to be a reflection of the underlying neural activity, but it is not known if they can, by themselves, be self-sustained and propagate. Previous studies have shown that slow periodic activity can be reproduced in the in vitro preparation to mimic in vivo slow oscillations. Slow periodic activity can propagate with speeds around 0.1 m s-1 and be modulated by weak electric fields. In the present study, we show that slow periodic activity in the longitudinal hippocampal slice is a self-regenerating wave which can propagate with and without chemical or electrical synaptic transmission at the same speeds. We also show that applying local extracellular electric fields can modulate or even block the propagation of this wave in both in silico and in vitro models. Our results support the notion that ephaptic coupling plays a significant role in the propagation of the slow hippocampal periodic activity. Moreover, these results indicate that a neural network can give rise to sustained self-propagating waves by ephaptic coupling, suggesting a novel propagation mechanism for neural activity under normal physiological conditions.

    View details for DOI 10.1113/JP276904

    View details for Web of Science ID 000454605100022

    View details for PubMedID 30295923

    View details for PubMedCentralID PMC6312416

  • Slow moving neural source in the epileptic hippocampus can mimic progression of human seizures SCIENTIFIC REPORTS Chiang, C., Wei, X., Ananthakrishnan, A., Shivacharan, R. S., Gonzalez-Reyes, L. E., Zhang, M., Durand, D. M. 2018; 8: 1564

    Abstract

    Fast and slow neural waves have been observed to propagate in the human brain during seizures. Yet the nature of these waves is difficult to study in a surgical setting. Here, we report an observation of two different traveling waves propagating in the in-vitro epileptic hippocampus at speeds similar to those in the human brain. A fast traveling spike and a slow moving wave were recorded simultaneously with a genetically encoded voltage sensitive fluorescent protein (VSFP Butterfly 1.2) and a high speed camera. The results of this study indicate that the fast traveling spike is NMDA-sensitive but the slow moving wave is not. Image analysis and model simulation demonstrate that the slow moving wave is moving slowly, generating the fast traveling spike and is, therefore, a moving source of the epileptiform activity. This slow moving wave is associated with a propagating neural calcium wave detected with calcium dye (OGB-1) but is independent of NMDA receptors, not related to ATP release, and much faster than those previously recorded potassium waves. Computer modeling suggests that the slow moving wave can propagate by the ephaptic effect like epileptiform activity. These findings provide an alternative explanation for slow propagation seizure wavefronts associated with fast propagating spikes.

    View details for DOI 10.1038/s41598-018-19925-7

    View details for Web of Science ID 000423154000094

    View details for PubMedID 29367722

    View details for PubMedCentralID PMC5784157

  • Propagating Neural Source Revealed by Doppler Shift of Population Spiking Frequency JOURNAL OF NEUROSCIENCE Zhang, M., Shivacharan, R. S., Chiang, C., Gonzalez-Reyes, L. E., Durand, D. M. 2016; 36 (12): 3495–3505

    Abstract

    Electrical activity in the brain during normal and abnormal function is associated with propagating waves of various speeds and directions. It is unclear how both fast and slow traveling waves with sometime opposite directions can coexist in the same neural tissue. By recording population spikes simultaneously throughout the unfolded rodent hippocampus with a penetrating microelectrode array, we have shown that fast and slow waves are causally related, so a slowly moving neural source generates fast-propagating waves at ∼0.12 m/s. The source of the fast population spikes is limited in space and moving at ∼0.016 m/s based on both direct and Doppler measurements among 36 different spiking trains among eight different hippocampi. The fact that the source is itself moving can account for the surprising direction reversal of the wave. Therefore, these results indicate that a small neural focus can move and that this phenomenon could explain the apparent wave reflection at tissue edges or multiple foci observed at different locations in neural tissue.The use of novel techniques with an unfolded hippocampus and penetrating microelectrode array to record and analyze neural activity has revealed the existence of a source of neural signals that propagates throughout the hippocampus. The source itself is electrically silent, but its location can be inferred by building isochrone maps of population spikes that the source generates. The movement of the source can also be tracked by observing the Doppler frequency shift of these spikes. These results have general implications for how neural signals are generated and propagated in the hippocampus; moreover, they have important implications for the understanding of seizure generation and foci localization.

    View details for DOI 10.1523/JNEUROSCI.3525-15.2016

    View details for Web of Science ID 000372747100011

    View details for PubMedID 27013678

    View details for PubMedCentralID PMC4804007

  • Can Neural Activity Propagate by Endogenous Electrical Field? JOURNAL OF NEUROSCIENCE Qiu, C., Shivacharan, R. S., Zhang, M., Durand, D. M. 2015; 35 (48): 15800–15811

    Abstract

    It is widely accepted that synaptic transmissions and gap junctions are the major governing mechanisms for signal traveling in the neural system. Yet, a group of neural waves, either physiological or pathological, share the same speed of ∼0.1 m/s without synaptic transmission or gap junctions, and this speed is not consistent with axonal conduction or ionic diffusion. The only explanation left is an electrical field effect. We tested the hypothesis that endogenous electric fields are sufficient to explain the propagation with in silico and in vitro experiments. Simulation results show that field effects alone can indeed mediate propagation across layers of neurons with speeds of 0.12 ± 0.09 m/s with pathological kinetics, and 0.11 ± 0.03 m/s with physiologic kinetics, both generating weak field amplitudes of ∼2-6 mV/mm. Further, the model predicted that propagation speed values are inversely proportional to the cell-to-cell distances, but do not significantly change with extracellular resistivity, membrane capacitance, or membrane resistance. In vitro recordings in mice hippocampi produced similar speeds (0.10 ± 0.03 m/s) and field amplitudes (2.5-5 mV/mm), and by applying a blocking field, the propagation speed was greatly reduced. Finally, osmolarity experiments confirmed the model's prediction that cell-to-cell distance inversely affects propagation speed. Together, these results show that despite their weak amplitude, electric fields can be solely responsible for spike propagation at ∼0.1 m/s. This phenomenon could be important to explain the slow propagation of epileptic activity and other normal propagations at similar speeds.

    View details for DOI 10.1523/JNEUROSCI.1045-15.2015

    View details for Web of Science ID 000366055500004

    View details for PubMedID 26631463

    View details for PubMedCentralID PMC4666910

  • Propagation of Epileptiform Activity Can Be Independent of Synaptic Transmission, Gap Junctions, or Diffusion and Is Consistent with Electrical Field Transmission JOURNAL OF NEUROSCIENCE Zhang, M., Ladas, T. P., Qiu, C., Shivacharan, R. S., Gonzalez-Reyes, L. E., Durand, D. M. 2014; 34 (4): 1409–19

    Abstract

    The propagation of activity in neural tissue is generally associated with synaptic transmission, but epileptiform activity in the hippocampus can propagate with or without synaptic transmission at a speed of ∼0.1 m/s. This suggests an underlying common nonsynaptic mechanism for propagation. To study this mechanism, we developed a novel unfolded hippocampus preparation, from CD1 mice of either sex, which preserves the transverse and longitudinal connections and recorded activity with a penetrating microelectrode array. Experiments using synaptic transmission and gap junction blockers indicated that longitudinal propagation is independent of chemical or electrical synaptic transmission. Propagation speeds of 0.1 m/s are not compatible with ionic diffusion or pure axonal conduction. The only other means of communication between neurons is through electric fields. Computer simulations revealed that activity can indeed propagate from cell to cell solely through field effects. These results point to an unexpected propagation mechanism for neural activity in the hippocampus involving endogenous field effect transmission.

    View details for DOI 10.1523/JNEUROSCI.3877-13.2014

    View details for Web of Science ID 000330360700031

    View details for PubMedID 24453330

    View details for PubMedCentralID PMC3898297

Latest information on COVID-19