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Cerebellar-Stimulation Evoked Prefrontal Electrical Synchrony Is Modulated by GABA

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Abstract

Cerebellar-prefrontal connectivity has been recognized as important for behaviors ranging from motor coordination to cognition. Many of these behaviors are known to involve excitatory or inhibitory modulations from the prefrontal cortex. We used cerebellar transcranial magnetic stimulation (TMS) with simultaneous electroencephalography (EEG) to probe cerebellar-evoked electrical activity in prefrontal cortical areas and used magnetic resonance spectroscopy (MRS) measures of prefrontal GABA and glutamate levels to determine if they are correlated with those potentials. Cerebellar-evoked bilateral prefrontal synchrony in the theta to gamma frequency range showed patterns that reflect strong GABAergic inhibitory function (r = − 0.66, p = 0.002). Stimulation of prefrontal areas evoked bilateral prefrontal synchrony in the theta to low beta frequency range that reflected, conversely, glutamatergic excitatory function (r = 0.66, p = 0.002) and GABAergic inhibitory function (r = − 0.65, p = 0.002). Cerebellar-evoked prefrontal synchronization had opposite associations with cognition and motor coordination: it was positively associated with working memory performance (r = 0.57, p = 0.008) but negatively associated with coordinated motor function as measured by rapid finger tapping (r = − 0.59, p = 0.006). The results suggest a relationship between regional GABA levels and interregional effects on synchrony. Stronger cerebellar-evoked prefrontal synchrony was associated with better working memory but surprisingly worse motor coordination, which suggests competing effects for motor activity and cognition. The data supports the use of a TMS-EEG-MRS approach to study the neurochemical basis of large-scale oscillations modulated by the cerebellar-prefrontal connectivity.

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Acknowledgements

LEH has received or plans to receive research funding or consulting fee on research projects from Mitsubishi, Your Energy Systems LLC, Neuralstem, Taisho, Heptares, Pfizer, Sound Pharma, Takeda, and Regeneron. All other authors declare no conflict of interest.

Funding

Support was received from NIH grants MH085646, MH103222, MH108148, MH067533, a NARSAD award, State of Maryland contract (M00B6400091), and a generous private philanthropic donation from the Clare E. Forbes Trust.

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Authors and Affiliations

  1. Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, P.O. Box 21247, Baltimore, MD, 21228, USA

    Xiaoming Du, Laura M. Rowland, Ann Summerfelt, Krista Wisner, Andrea Wijtenburg, Joshua Chiappelli, Peter Kochunov & L. Elliot Hong

  2. Department of Electrical Engineering and Computer Science, University of Maryland Baltimore County, Baltimore, MD, 21250, USA

    Fow-Sen Choa

  3. Department of Neurology, Physical Therapy and Rehabilitation Science, Internal Medicine, Older Americans Independence Center, University of Maryland, Baltimore, MD, 21201, USA

    George F. Wittenberg

  4. Department of Veterans Affairs (VA) Maryland Health Care System, Geriatrics Research, Education and Clinical Center, and Maryland Exercise & Robotics Center of Excellence, Baltimore, MD, 21201, USA

    George F. Wittenberg

Authors
  1. Xiaoming Du
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  2. Laura M. Rowland
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  3. Ann Summerfelt
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  4. Fow-Sen Choa
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  6. Krista Wisner
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  7. Andrea Wijtenburg
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  8. Joshua Chiappelli
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  9. Peter Kochunov
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  10. L. Elliot Hong
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Corresponding author

Correspondence to Xiaoming Du.

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Du, X., Rowland, L.M., Summerfelt, A. et al. Cerebellar-Stimulation Evoked Prefrontal Electrical Synchrony Is Modulated by GABA. Cerebellum 17, 550–563 (2018). https://doi.org/10.1007/s12311-018-0945-2

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  • DOI: https://doi.org/10.1007/s12311-018-0945-2

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