Search

Traumatic brain injury (TBI) is a leading cause of cognitive disability in adults, often characterized by marked deficits in episodic memory and executive function. Prior studies have found that direct electrical stimulation of the temporal cortex yielded improved memory in epilepsy patients, but it is not clear if these results generalize to patients with a specific history of TBI. Here we asked whether applying closed-loop, direct electrical stimulation to lateral temporal cortex could reliably improve memory in a TBI cohort. Among a larger group of patients undergoing neurosurgical evaluation for refractory epilepsy, we recruited a subset of patients with a history of moderate-to-severe TBI. By analyzing neural data from indwelling electrodes as patients studied and recalled lists of words, we trained personalized machine-learning classifiers to predict momentary fluctuations in mnemonic function in each patient. We subsequently used these classifiers to trigger high-frequency stimulation of the lateral temporal cortex (LTC) at moments when memory was predicted to fail. This strategy yielded a 19% boost in recall performance on stimulated as compared with non-stimulated lists (P = 0.012). These results provide a proof-of-concept for using closed-loop stimulation of the brain in treatment of TBI-related memory impairment., Competing Interests: Declaration of competing interest B.C.J. receives research funding from NeuroPace, Inc. and Harvard Pilgrim, Inc. not relating to this research. R.E.G. serves as a consultant to Medtronic, which was previously a subcontractor on this project, and receives compensation for these services. The terms of this arrangement have been reviewed and approved by Emory University in accordance with its conflict of interest policies. M.J.K. holds a greater than 5% equity interest in Nia Therapeutics Inc., a company intended to develop and commercialize brain stimulation therapies for memory restoration. R.E.G. holds a less than 5% equity interest in Nia Therapeutics, Inc. P.A.W. is employed by Blackrock Microsystems Europe GmbH. E.A.S. has served as a compensated technical consultant to Nia Therapeutics Inc., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Brain stimulation has emerged as a powerful tool in human neuroscience, becoming integral to next-generation psychiatric and neurologic therapeutics. Theta-burst stimulation (TBS), in which electrical pulses are delivered in rhythmic bouts of 3-8 Hz, seeks to recapitulate neural activity seen endogenously during cognitive tasks. A growing literature suggests that TBS can be used to alter or enhance cognitive processes, but little is known about how these stimulation events influence underlying neural activity., Objective: Our study sought to investigate the effect of direct electrical TBS on mesoscale neural activity in humans by asking (1) whether TBS evokes persistent theta oscillations in cortical areas, (2) whether these oscillations occur at the stimulated frequency, and (3) whether stimulation events propagate in a manner consistent with underlying functional and structural brain architecture., Methods: We recruited 20 neurosurgical epilepsy patients with indwelling electrodes and delivered direct cortical TBS at varying locations and frequencies. Simultaneous iEEG was recorded from non-stimulated electrodes and analyzed to understand how TBS influences mesoscale neural activity., Results: We found that TBS rapidly evoked theta rhythms in widespread brain regions, preferentially at the stimulation frequency, and that these oscillations persisted for hundreds of milliseconds post stimulation offset. Furthermore, the functional connectivity between recording and stimulation sites predicted the strength of theta response, suggesting that underlying brain architecture guides the flow of stimulation through the brain., Conclusions: By demonstrating that cortical TBS induces frequency-specific oscillatory responses, our results suggest this technology can be used to directly and predictably influence the activity of cognitively-relevant brain networks., Competing Interests: Declaration of competing interest M.J.K. and D. S. R. have co-founded a company, Nia Therapeutics (“Nia”), intended to develop and commercialize brain stimulation therapies for memory restoration. E.A.S has served as a compensated technical consultant for Nia. P.A.W is employed by Blackrock Microsystems Europe GmbH., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Researchers have used direct electrical brain stimulation to treat a range of neurological and psychiatric disorders. However, for brain stimulation to be maximally effective, clinicians and researchers should optimize stimulation parameters according to desired outcomes., Objective: The goal of our large-scale study was to comprehensively evaluate the effects of stimulation at different parameters and locations on neuronal activity across the human brain., Methods: To examine how different kinds of stimulation affect human brain activity, we compared the changes in neuronal activity that resulted from stimulation at a range of frequencies, amplitudes, and locations with direct human brain recordings. We recorded human brain activity directly with electrodes that were implanted in widespread regions across 106 neurosurgical epilepsy patients while systematically stimulating across a range of parameters and locations., Results: Overall, stimulation most often had an inhibitory effect on neuronal activity, consistent with earlier work. When stimulation excited neuronal activity, it most often occurred from high-frequency stimulation. These effects were modulated by the location of the stimulating electrode, with stimulation sites near white matter more likely to cause excitation and sites near gray matter more likely to inhibit neuronal activity., Conclusion: By characterizing how different stimulation parameters produced specific neuronal activity patterns on a large scale, our results provide an electrophysiological framework that clinicians and researchers may consider when designing stimulation protocols to cause precisely targeted changes in human brain activity., Competing Interests: Declaration of competing interest M.K. and D.R. have started a company, Nia Therapeutics, Inc., intended to develop and commercialize brain stimulation therapies for memory restoration. Each of them holds >5% equity interest in Nia. R.E.G. serves as a consultant to Medtronic, which was a subcontractor on the RAM project. The terms of this arrangement have been reviewed and approved by Emory University in accordance with its conflict of interest policies. B.J. receives research funding from NeuroPace and Medtronic not relating to this research. G.W. has rights to receive future royalties from the licensing of brain stimulation technology. Mayo Clinic has a financial interest related to brain stimulation technology, and is co-owner of Cadence Neuroscience Inc, the development of which has been assisted by G.W. The remaining authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)