DOI: 10.1126/science.1128115 , 1626 (2006); 313Science et al.R. T. Canolty,Oscillations in Human NeocortexHigh Gamma Power Is Phase-Locked to Theta www.sciencemag.org (this information is current as of December 3, 2007 ):The following resources related to this article are available online at http://www.sciencemag.org/cgi/content/full/313/5793/1626version of this article at: including high-resolution figures, can be found in the onlineUpdated information and services, http://www.sciencemag.org/cgi/content/full/313/5793/1626/DC1 can be found at: Supporting Online Material http://www.sciencemag.org/cgi/content/full/313/5793/1626#otherarticles, 13 of which can be accessed for free: cites 25 articlesThis article 22 article(s) on the ISI Web of Science. cited byThis article has been http://www.sciencemag.org/cgi/content/full/313/5793/1626#otherarticles 5 articles hosted by HighWire Press; see: cited byThis article has been http://www.sciencemag.org/cgi/collection/neuroscienceNeuroscience : subject collectionsThis article appears in the following http://www.sciencemag.org/about/permissions.dtl in whole or in part can be found at: this articlepermission to reproduce of this article or about obtaining reprintsInformation about obtaining registered trademark of AAAS. is aScience2006 by the American Association for the Advancement of Science; all rights reserved. The title CopyrightAmerican Association for the Advancement of Science, 1200 New York Avenue NW, Washington, DC 20005. (print ISSN 0036-8075; online ISSN 1095-9203) is published weekly, except the last week in December, by theScience on December 3, 2007 www.sciencemag.orgDownloaded fromHigh Gamma Power Is Phase-Lockedto Theta Oscillations inHuman NeocortexR. T. Canolty,1*E. Edwards,1,2S. S. Dalal,3M. Soltani,1,2S. S. Nagarajan,3,4H. E. Kirsch,5M. S. Berger,6N. M. Barbaro,5,6R. T. Knight1,2,3,5,6We observed robust coupling between the high- and low-frequency bands of ongoing electricalactivity in the human brain. In particular, the phase of the low-frequency theta (4 to 8 hertz)rhythm modulates power in the high gamma (80 to 150 hertz) band of the electrocorticogram, withstronger modulation occurring at higher theta amplitudes. Furthermore, different behavioral tasksevoke distinct patterns of theta/high gamma coupling across the cortex. The results indicate thattransient coupling between low- and high-frequency brain rhythms coordinates activity indistributed cortical areas, providing a mechanism for effective communication during cognitiveprocessing in humans.Neuronal oscillations facilitate synapticplasticity (1), influence reaction time(2), correlate with attention (3) and per-ceptual binding (4), and are proposed to play arole in transient, long-range coordination ofdistinct brain regions (5). Direct cortical record-ings reveal that ongoing rhythms encompass awide range of spatial and temporal scales—ultraslow rhythms less than 0.05 Hz coexistwith fast transient oscillations 500 Hz or greater(1), with spatial coherence between these os-cillations extending fr om several centimetersfor the corticospinal tract (6) to the micrometerscale for subthreshold membrane oscillations inasingleneuron(7). Exactly how these transientoscillations influence each other and coordinateprocessing at both the si ngle -neuron andpopulation levels remains unknown.Evidence for cross-frequency coupling, whereone frequency band modulates the activity of adifferent frequen cy band, is more abundant inanimal than human data. For example, the thetarhythm can modulate the firing rate and spiketiming of a single neuron (8–11)aswellasthegamma power of the intracortical local fieldpotential (8, 12, 13). Task-related changes intheta power have been observed in humans(14–16), and cross-frequency coupling at fre-quencies up to 40 Hz has been detected at thescalp (17, 18). However, given the difficulty inlocalizing electrical sources from scalp record-ings alone (19), subdural electrodes that recorddirectly from the human cortex are needed toaddress this question. Furthermore, subduralelectrodes are ideal for studying activity inthe recently described human high gammaband (HG) at 80 to 150 Hz. HG activity ismodulated by sensory, motor, and cognitiveevents (20), is functionally distinct from lowgamma (30 to 80 Hz) with different physiolog-ical origins (21), and is correlated with the func-tional magne tic resonance imaging bloodoxygen level–dependent (fMRI BOLD) signal(22–24). There have been no reports of couplingbetween any low-frequency rhythm and HG insignals recorded either at the scalp or directlyfrom human sensory, motor, or association cor-tex. We therefore focus exclusively on theta/HGcoupling in this report.We analyzed multichannel subdural electro-corticogram (ECoG) data from five patientsundergoing neurosurgical treatment for epilepsy.Typically, the events of interest in behavioralparadigms are the stimulus onsets and motorresponses that evoke frequency-specific changesin the electrical activity of the brain. In contrast,the events of interest in cross-frequency couplingare features of the ongoing oscillatory activityitself. That is, cross-frequency coupling refers tostatistical dependence between distinct frequencybands of the ongoing ECoG rather than depen-dence between the ECoG and external stimulusevents. The dependence between two frequen-cies f1and f2can assume many forms, includingcoupling between the amplitude envelopes A1(t)and A2(t), the phase time series f1(t)andf2(t), oran amplitude-phase coupling between A1(t)andf2(t). We focus here on the last type of couplingand use an index of cross-frequency coupling thatdirectly combines the amplitude envelope timeseries A1(t þ t) of a high-frequency band withthe phase time series f2(t)ofalow-frequencyband into one composite, complex-valued signalz(t, t). The (normalized) temporal mean of thiscomposite signal provides a sensitive measure ofthe coupling strength and preferred phase be-tween the two frequencies (25).Animal evidence for theta phase modulationof single-unit firing and the strong connec-tion of theta to learning, attention, and memory(26, 27) suggested to us that high-frequencyoscillations in human neocortex may be modu-lated by the theta rhythm. Accordingly, weanalyzed the ECoG across a range of behavior-1Helen Wills Neuroscience Institute,2Department of Psychol-ogy, University of California, Berkeley, CA 94720, USA.3Department of Bioengineering,4Department of