Neural oscillations organize cortico-thalamic activity, and their role in memory, attention and sleep are a central focus of systems neuroscience. Sleep spindles are among the most prominent oscillations, and have been studied at many levels of investigation, from the biophysical level, where the low threshold calcium currents are implicated in the waxing-and-waning 11-15 Hz bursts of spikes that originate in the thalamus and recruit cortical circuits, to the systems level where the electroencephalogram (EEG) and magnetoencephalogram (MEG) measured outside the skull register largescale spatial and temporal coherence in the bursting pattern across the cortex (Destexhe and Sejnowski, 2001). Despite the wealth of physiological, anatomical and computational studies, major questions remain to be resolved: How do nearby parts of the cortex become synchronized during spindles? How are spindles propagated across the cortex? Why is there a discrepancy between the temporal patterns of spindles simultaneously observed in EEG and MEG measurements? What are the consequences of spindle activity in thalamocortical systems for cortical reorganization and memory consolidation during sleep? We propose to attack these questions with a range of experimental and modeling techniques that 1) link detailed models at the biophysical level to recordings from humans at the level of current source density analysis (CSD) recordings from depth electrodes;and 2) relate large scale reduced models of cortical circuits to EEG and MEG measurements in humans. This is the first time that all of these powerful empirical and modeling approaches have been integrated into a single, multiscale approach to understanding the origin of macroscopic field measurements outside the scalp based on the specific biophysical mechanisms occurring in neurons located in different layers of the cortex and thalamus.

Public Health Relevance

The goal of these studies is to help provide a scientific basis for treatment of sleep disorders as well as promote understanding of the relationship between microscopic neuronal circuit activity and macroscopic non-invasive EEG and MEG measures.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Research Project (R01)
Project #
Application #
Study Section
Biomedical Imaging Technology Study Section (BMIT)
Program Officer
Peng, Grace
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California San Diego
Other Domestic Higher Education
La Jolla
United States
Zip Code
Mak-McCully, Rachel A; Deiss, Stephen R; Rosen, Burke Q et al. (2014) Synchronization of isolated downstates (K-complexes) may be caused by cortically-induced disruption of thalamic spindling. PLoS Comput Biol 10:e1003855
Lemieux, Maxime; Chen, Jen-Yung; Lonjers, Peter et al. (2014) The impact of cortical deafferentation on the neocortical slow oscillation. J Neurosci 34:5689-703
Moldakarimov, Samat; Bazhenov, Maxim; Sejnowski, Terrence J (2014) Top-down inputs enhance orientation selectivity in neurons of the primary visual cortex during perceptual learning. PLoS Comput Biol 10:e1003770
Bonjean, Maxime; Baker, Tanya; Bazhenov, Maxim et al. (2012) Interactions between core and matrix thalamocortical projections in human sleep spindle synchronization. J Neurosci 32:5250-63
Irimia, Andrei; Van Horn, John Darrell; Halgren, Eric (2012) Source cancellation profiles of electroencephalography and magnetoencephalography. Neuroimage 59:2464-74
Peyrache, Adrien; Dehghani, Nima; Eskandar, Emad N et al. (2012) Spatiotemporal dynamics of neocortical excitation and inhibition during human sleep. Proc Natl Acad Sci U S A 109:1731-6
Bonjean, Maxime; Baker, Tanya; Lemieux, Maxime et al. (2011) Corticothalamic feedback controls sleep spindle duration in vivo. J Neurosci 31:9124-34
Dang-Vu, Thien Thanh; Bonjean, Maxime; Schabus, Manuel et al. (2011) Interplay between spontaneous and induced brain activity during human non-rapid eye movement sleep. Proc Natl Acad Sci U S A 108:15438-43
Wei, Haiyang; Bonjean, Maxime; Petry, Heywood M et al. (2011) Thalamic burst firing propensity: a comparison of the dorsal lateral geniculate and pulvinar nuclei in the tree shrew. J Neurosci 31:17287-99
Dehghani, Nima; Cash, Sydney S; Halgren, Eric (2011) Topographical frequency dynamics within EEG and MEG sleep spindles. Clin Neurophysiol 122:229-35

Showing the most recent 10 out of 16 publications