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Desynchronization of pathological low-frequency brain activity by the hypnotic drug zolpidem.

Stephen D. Hall¹, Naoki Yamawaki¹, Alison E. Fisher², Ralf P. Clauss³, Gavin L. Woodhall¹ & Ian M. Stanford¹

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1. Aston University, Biomedical Sciences, School of Life and Health Sciences
2. University of Bristol, Departmant of Experimental Psychology
3. Royal Surrey County Hospital, Nuclear Medicine

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Document Type:

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Date:

Received 11 June 2008 15:35 UTC; Posted 11 June 2008

Subjects:

Neuroscience, Pharmacology

Tags:

• neuroimaging
• zolpidem
• magnetoencephalography
• stroke
• desynchronisation
• slow-wave

Abstract:

Reports of the beneficial effects of the hypnotic imidazopyridine, zolpidem, described in persistent vegetative state^{1, 2} have been replicated recently in brain-injured and cognitively impaired patients^3-7. Previous single photon emission computed tomography (SPECT) studies have suggested that sub-sedative doses of zolpidem increased regional cerebral perfusion in affected areas^{5, 8}, implying enhanced neuronal metabolic activity; which has led to speculation that zolpidem ‘reawakens’ functionally dormant cortex. However, a neuronal mechanism by which this hypnotic drug affords benefits to brain injured patients has yet to be demonstrated. Here, we report the action of sub-sedative doses of zolpidem on neuronal network oscillatory activity in human brain, measured using pharmaco-magnetoencephalography (pharmaco-MEG). Study participant JP suffered a stroke in 1996, causing major damage to the left hemisphere that impaired aspects of both motor and cognitive function. Pharmaco-MEG analyses revealed robust and persistent pathological theta (4-10Hz) and beta (15-30Hz) oscillations within the lesion penumbra and surrounding cortex. Administration of zolpidem (5mg) reduced the power of pathological theta and beta oscillations in all regions of the lesioned hemisphere. This desynchronizing effect correlated well with zolpidem uptake (occurring approximately 40 minutes after acute administration) and was coincident with marked improvements in cognitive and motor function. Control experiments revealed no effect of placebo, while a structurally unrelated hypnotic, zopiclone, administered at a comparable dose (3.5mg) elicited widespread increases in cortical oscillatory power in the beta (15-30Hz) band without functional improvement. These results suggest that in JP, specific motor and cognitive impairments are related to increased low-frequency oscillatory neuronal network activity. Zolpidem is unique amongst hypnotic drugs in its ability to desynchronize such pathological low-frequency activity, thereby restoring cognitive function.

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This document is licensed to the public under the Creative Commons Attribution 3.0 License

How to cite this document:

Hall, Stephen, Yamawaki, Naoki, Fisher, Alison, Clauss, Ralf, Woodhall, Gavin, and Stanford, Ian. Desynchronization of pathological low-frequency brain activity by the hypnotic drug zolpidem.. Available from Nature Precedings <http://hdl.handle.net/10101/npre.2008.1966.1> (2008)

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