Paired Electrical Pulse Trains for Controlling Connectivity in Emotion-Related Brain Circuitry

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10 Scopus citations


Neurostimulation therapies for psychiatric disorders often have limited clinical efficacy. The limited efficacy might arise from a mismatch between therapy and disease mechanisms. Mental disorders are believed to arise from communication breakdown in distributed brain circuits, and thus altering connectivity between brain regions might be an effective way to restore normal brain communication. Synchronized neural oscillations (coherence) and synaptic strength are two common measures of brain connectivity. In this work, we developed an electrical stimulation method for altering narrow-frequency-band (theta, 5-8 Hz) coherence and synaptic strength. We tested this method in a circuit between infralimbic cortex (IL) and basolateral amygdala (BLA), which is broadly implicated in fear regulation. 6 Hz pulse trains were delivered into IL and BLA with various inter-train lags. These paired trains induced long-lasting synaptic strength change and a brief coherence enhancement in the IL-BLA circuit. This enhancement was specific to the 'top-down' (IL-to-BLA) direction, and only occurred when the IL and BLA pulse trains had a relative lag of 180° (83 ms). Since the IL-BLA connection is known to be highly relevant to fear regulation, this method provides a tool to study the relationship between brain connectivity and fear behaviors. Further, it may be a new approach to study the relative roles of synaptic strength and oscillatory synchrony in brain network communication.

Original languageEnglish (US)
Article number9222028
Pages (from-to)2721-2730
Number of pages10
JournalIEEE Transactions on Neural Systems and Rehabilitation Engineering
Issue number12
StatePublished - Dec 2020

Bibliographical note

Funding Information:
Manuscript received March 30, 2020; revised August 25, 2020 and October 7, 2020; accepted October 10, 2020. Date of publication October 13, 2020; date of current version January 29, 2021. This work was supported in part by the MGH-MIT Grand Challenges program, in part by the Brain Behavior Research Foundation, in part by the Harvard Brain Initiative Bipolar Disorder Fund supported by Kent & Liz Dauten, and in part by the National Institute of Mental Health under Grant 1R21MH109722-01A, Grant 1R21MH113103-01A1, and Grant 1R01MH11938402. (Corresponding author: Meng-Chen Lo.) Meng-Chen Lo and Alik S. Widge were with the Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129 USA. They are now with the Translational NeuroEngineering Laboratory, University of Minnesota, Minneapolis, MN 55455 USA (e-mail:;

Publisher Copyright:
© 2001-2011 IEEE.


  • Deep brain stimulation
  • fear circuits
  • mental disorders
  • neuromodulation
  • oscillatory synchrony


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