Machine Biointerface Lab
Johns Hopkins University
General Laboratory Focus
Cyborgs!
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Part human part machine.
Here are examples of some devices that attempt to interface to the human body:
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cochlear implants deliver sound information directly to the auditory nerve for people who are otherwise deaf
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retinal implants deliver vision information directly to the optical nerve for the blind
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spinal cord stimulators block pain at the spinal cord for those suffering from chronic pain
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deep brain implants can fix motor disorders like Parkinsons
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vestibular implants can deliver head motion information directly to the brain for balance disorders
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brain-machine interfaces detect brain activity to control robotic arm or a wheel chair for the paralyzed
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We are interested in how we can make computers work seamlessly with the nervous system. Our approach is to first understand the underlying scientific principles at the interface between the machine and the nervous system. Electronics use electrons to process information -- body uses ions. The interface between the two is typically confined near the electrodes implanted in the vicinity of neurons. How neural signals are detected through electron motion in the metal electrodes and how we can manipulate neural signals by manipulating electron motion at the electrodes is the underlying problem.
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The work conducted in our laboratory includes:
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Electrophysiology to understand neural activity in response to electrical stimulation
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Computational modeling to predict electrical modulation effects on neurons
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Electronics and microfluidics work to develop novel neural implant concepts and devices
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Because our key interest is improving the underlying interface between machines and the nervous system, we do not focus on any one neuroprosthetic application. We are interested in a variety of applications and ones that we have worked on are:
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vestibular prosthesis for balance disorders
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cochlear implants for deafness
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pain block at the peripheral nerve
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detection of cancer within a nerve
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asthma attack suppression
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deep brain stimulation for a variety of neurological disorders
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Current work in the laboratory:
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Freeform Stimulator
Our lab is currently focused on developing the Freeform Stimulator (FS) (a.k.a. "Safe Direct Current Stimulation" technology, or SDCS). Unlike the currently available commercial neural prosthetic devices, such as cochlear implants, pacemakers, or Parkinson's deep brain stimulators that can only excite neurons, FS can excite, inhibit, and even sensitize them to input. In this project, our lab is developing an implantable microfluidic device that can be used to deliver ionic direct current to the target tissue in a safe and reliable way. The FS technology is designed to convert electronic pulses delivered to electrodes embedded within an implantable device to ionic direct current (iDC) at the output of the device. This multidisciplinary project uses concepts from electrical engineering to develop the circuitry needed to operate the FS device as well as techniques from microfluidics to develop an efficient solution.
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Aplin, F. P., & Fridman, G. Y. (2019). Implantable direct current neural modulation: theory, feasibility and efficacy. Frontiers in neuroscience, 13, 379.
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Cheng, C., Nair, A. R., Thakur, R., & Fridman, G. (2018). Normally closed plunger-membrane microvalve self-actuated electrically using a shape memory alloy wire. Microfluidics and nanofluidics, 22(3), 29.
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Cheng, C., Thakur, R., Nair, A. R., Sterrett, S., & Fridman, G. (2017, October). Miniature elastomeric valve design for safe direct current stimulator. In 2017 IEEE Biomedical Circuits and Systems Conference (BioCAS) (pp. 1-4). IEEE.
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Fridman, G. (2017, July). Safe Direct Current Stimulator design for reduced power consumption and increased reliability. In 2017 39th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) (pp. 1082-1085). IEEE.
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Fridman, G. Y., & Della Santina, C. C. (2013, July). Safe direct current stimulator 2: concept and design. In 2013 35th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) (pp. 3126-3129). IEEE.
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Fridman, G. Y., & Della Santina, C. C. (2013). Safe direct current stimulation to expand capabilities of neural prostheses. IEEE Transactions on Neural Systems and Rehabilitation Engineering, 21(2), 319-328.
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Vestibular Balance Restoration
The human vestibular system works by both exciting and inhibiting neurons, and patients with vestibular disorders may benefit from SDCS technology. Like all other chronically implanted neural stimulators, existing vestibular prostheses are constrained to use biphasic charge-balanced stimuli that can only excite activity. In contrast to pulsatile excitation, DC can excite and inhibit vestibular nerve afferents. Furthermore, DC stimulation increases or decreases the extracellular potential, increasing or decreasing the probability of action potential generation, but not affecting the stochastic properties of the firing pattern, resulting in a more natural encoding of the head motion than pulsatile stimulation. Our lab is currently using ionic direct current along with pulsatile stimulation to increase the dynamic range of head velocities encoded by the vestibular prosthesis and characterize the effects of DC on neuronal behavior.
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The work currently focuses on:
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computational modeling of the neural responses to prosthetic stimulation
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in-vitro electrophysiology
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behavioral assessment of the vestibulo-ocular reflex in response to stimulation
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SDCS implant development for vestibular prosthetic application
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Aplin, F. P., Singh, D., Della Santina, C. C., & Fridman, G. Y. (2019). Combined ionic direct current and pulse frequency modulation improves the dynamic range of vestibular canal stimulation. Journal of Vestibular Research, (Preprint), 1-8.
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Aplin, F. P., Singh, D., Della Santina, C. C., & Fridman, G. Y. (2018). Ionic direct current modulation for combined inhibition/excitation of the vestibular system. IEEE Transactions on Biomedical Engineering, 66(3), 775-783.
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Cortical Network Modulation
Neural population gain is a critical parameter in brain computation, influencing processes such as attention, learning, sensory adaptation, and decision-making. Despite its importance, existing neuromodulation technologies lack the temporal (milliseconds) and spatial (<200 μm) precision needed to dynamically and locally modulate gain, creating a significant gap in our ability to study and manipulate neural circuits. We are working to addresses this gap by developing and refining ionic direct current (iDC) stimulation as a novel neuromodulation tool. Unlike existing methods such as optogenetics or drugs, iDC enables high-precision modulation of neural population gain while preserving natural activity, offering unparalleled potential for investigating and manipulating brain function.
Figures show the experimental setup and results. Top figure: We deliver low amplitude iDC to modulate cortical response to a foot shock. Delivering positive (anodic) iDC increases the response and negative (cathodic) decreases it.
Middle Figure: iDC fools the brain into thinking that the foot shock was more intense or less intense than it actually was. Recordings from an electrode implanted along the depth of the cortical column.
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Lower figure shows cortical responses along the cortical layers on the Y-axis to normal brain oscillations, being modulated by iDC.
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Adkisson PW, Steinhardt CR, Fridman GY. Galvanic vs. pulsatile effects on decision-making networks: reshaping the neural activation landscape. J Neural Eng. 2024 Apr 3;21(2). doi: 10.1088/1741-2552/ad36e2. PMID: 38518369.
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Recent lecture on this work: here
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Chronic Pain Suppression
Electrical neuromodulation is an important strategy for treating chronic pain conditions that are refractory to pharmacotherapies. However, presently available neurostimulation pain therapies use alternating current and are often associated with limited efficacy and side effects. We are developing a novel Safe Direct Current Stimulator (SDCS), which converts pulses delivered to the metal electrodes inside the implantable device to use ionic direct current (iDC) at its output. So far, how does iDC affect neuronal activity in pain pathway remain unknown. Using complementary in vivo electrophysiological recording and Pirt-GCaMP6 imaging approaches, we demonstrated for the first time that application of cathodic iDC through a salt-bridge micro-catheter to sciatic nerve induced an intensity-dependent suppression of afferent conduction in As-fibers, a decrease of neuron activation in dorsal root ganglion, a reduction of C-fiber mediated local field potential (LFP) in superficial dorsal horn and responses in deep wide-dynamic range (WDR) neurons.
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Yang, F., Anderson, M., He, S., Stephens, K., Zheng, Y., Chen, Z., ... & Fridman, G. (2018). Differential expression of voltage-gated sodium channels in afferent neurons renders selective neural block by ionic direct current. Science advances, 4(4), eaaq1438.
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Thakur, R., Jin, A., Nair, A., & Fridman, G. Y. (2019). Nerve cuff electrode pressure estimation via electrical impedance measurement. Journal of neural engineering
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Su TF, Hamilton JD, Guo Y, Potas JR, Shivdasani MN, Moalem-Taylor G, Fridman GY, Aplin FP. Peripheral direct current reduces naturally evoked nociceptive activity at the spinal cord in rodent models of pain. J Neural Eng. 2024 Apr 17;21(2). doi: 10.1088/1741-2552/ad3b6c. PMID: 38579742.
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Computational modeling
Computational modeling of neural stimulation. Biological systems are complex. Computational models allow us to focus on only the parts of the biology that are implicated in the phenomena that we are studying. We typically build models from bottom up, meaning we make them as simple as possible, but complex enough to agree with the complete set of experimental data available in the literature. We use computational models to understand and form hypotheses about how both direct current and pulsatile stimuli interact with the nervous system. Our projects range from exploring the effects of electrical fields on single neurons to network effects. This work covers the vestibular system (shown above) as well as the peripheral nerves and the central nervous system.
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Steinhardt CR, Mitchell DE, Cullen KE, Fridman GY. Pulsatile electrical stimulation creates predictable, correctable disruptions in neural firing. Nat Commun. 2024 Jul 12;15(1):5861. doi: 10.1038/s41467-024-49900-y. PMID: 38997274; PMCID: PMC11245474.
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Steinhardt CR, Fridman GY. Direct current effects on afferent and hair cell to elicit natural firing patterns. iScience. 2021 Feb 20;24(3):102205. doi: 10.1016/j.isci.2021.102205. PMID: 33748701; PMCID: PMC7967006.
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Adkisson PW, Steinhardt CR, Fridman GY. Galvanic vs. pulsatile effects on decision-making networks: reshaping the neural activation landscape. J Neural Eng. 2024 Apr 3;21(2). doi: 10.1088/1741-2552/ad36e2. PMID: 38518369.
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Foxworthy GE, Fridman GY. The Significance of Concentration-dependent Components in Computational Models of C-Fibers. Annu Int Conf IEEE Eng Med Biol Soc. 2023 Jul;2023:1-7. doi: 10.1109/EMBC40787.2023.10341121. PMID: 38083017.
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Aplin, F. P., & Fridman, G. Y. (2019). Implantable Direct Current Neural Modulation: Theory, Feasibility, and Efficacy. In Frontiers in Neuroscience (Vol. 13, p. 379). https://doi.org/10.3389/fnins.2019.00379
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Helvetica Light is an easy-to-read font, with tall and narrow letters, that works well on almost every site.
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This technology is a departure from our focus, but the idea was so cool, we had to pursue it.
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MouthLab is a "tricorder" device that we invented here in Fridman Lab. The device currently obtains all vital signs within 30s: Pulse rate, breathing rate, temperature, blood pressure, blood oxygen saturation, electrocardiogram, and FEV1 (lung function) measurement. Because the device is in the mouth, it has access to saliva and to breath and we are focused now on expanding its capability to obtaining measures of dehydration and biomarkers that could be indicative of a wide range of internal disorders ranging from stress to kidney failure and even lung cancer.
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This technology is being commercialized by a company called Aidar Health.
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Fridman, G. Y., Tang, H., Feller-Kopman, D., & Hong, Y. (2015). MouthLab: a tricorder concept optimized for rapid medical assessment. Annals of biomedical engineering, 43(9), 2175-2184.
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