Available online at www.sciencedirect.com Brain oscillations and memory Emrah Duzel1,4,5, �� Will D Penny2 and Neil Burgess1,3 Oscillatory fluctuations of local field potentials (LFPs) in the theta (4���8 Hz) and gamma (25���140 Hz) band are held to play a mechanistic role in various aspects of memory including the representation and off-line maintenance of events and sequences of events, the assessment of novelty, the induction of plasticity during encoding, as well as the consolidation and the retrieval of stored memories. Recent findings indicate that theta and gamma related mechanisms identified in rodent studies have significant parallels in the neurophysiology of human and non-human primate memory. This correspondence between species opens new perspectives for a mechanistic investigation of human memory function. Addresses 1 UCL Institute of Cognitive Neuroscience, University College London, WC1N 3AR London, United Kingdom 2 Wellcome Trust Centre for Neuroimaging, University College London, WC1N 3BG London, United Kingdom 3 UCL Institute of Neurology, University College London, WC1N 3BG London, United Kingdom 4 Institute of Cognitive Neurology and Dementia Research, Otto von Guericke University, 39120 Magdeburg, Germany 5 German Centre for Neurodegenerative Diseases ��� Magdeburg, Otto von Guericke University, 39120 Magdeburg, Germany Corresponding author: Duzel, �� Emrah (e.duzel@ucl.ac.uk) Current Opinion in Neurobiology 2010, 20:143���149 This review comes from a themed issue on Cognitive neuroscience Edited by Earl Miller and Liz Phelps Available online 22nd February 2010 0959-4388/$ ��� see front matter # 2010 Elsevier Ltd. All rights reserved. DOI 10.1016/j.conb.2010.01.004 Oscillations in the theta and gamma range can be measured at different anatomical scales, ranging from invasive recordings of small neuronal populations in animals (e.g. [1 ,2]) and humans (e.g. [3���5]) to non- invasive recordings of large cortical assemblies from the surface of the scalp using electroencephalography (EEG) and magnetoencephalography (MEG) (e.g. [6��� 14]). Both types of oscillation, and the phase relationships between them (e.g. [15���17,18 ,19,20]), appear to con- tribute to memory-relevant coding of information ranging from objects (e.g. [21 ]) to environmental locations (e.g. [1 ]). In addition, theta and gamma oscillations may help to coordinate the interactions between regions required by some mnemonic processing (e.g. [18 ,22���24]) while high frequency ���ripples��� in the hippocampus may con- tribute to consolidation (e.g. [25���28]). Furthermore, by regulating the precise timing of presynaptic and postsyn- aptic neurons, theta and gamma oscillations also modulate spike-time dependent plasticity [29], a prerequisite for both short-term and long-term memory processes. Rhythmic activity in the rodent hippocampal formation underlying spatial representation, memory and consolidation The systems neurophysiology underlying brain oscil- lations and their relationship to memory has been exten- sively studied using chronically implanted electrodes in freely moving rodents. In this research there has been a focus on the hippocampal formation, because of its central role in memory, and also a focus on spatial representation, because of the interesting spatial correlates of neural firing found in and around the hippocampus, such as the ���place cells��� (e.g. [28]). The theta rhythm and spatial representation In freely moving rodents, the hippocampal LFP is domi- nated by the theta rhythm whenever the animal is in translational motion. This motion-related theta rhythm increases in frequency with both age and running speed, falling into a range from around 5 Hz to around 11 Hz. During motion, power is also seen sporadically in the gamma frequency band, with high (60���140 Hz) and low (25���50 Hz) frequency gamma being associated with different phases of theta [18 ]. During immobility the LFP shows ���large irregular activity��� characterized by the appearance of high frequency (200 Hz) ���ripples��� or ���sharp waves��� (See [15,28] for reviews). Interestingly, there are signs that human spatial navigation in virtual environ- ments is also accompanied by the presence of theta rhythmicity in intracranial recordings (e.g. [3]) and MEG [12]. The hippocampal theta rhythm depends on a circuit including the medial septum, hippocampus and entorh- inal cortex and the projections between them. Lesions to the medial septum both abolish movement related theta and impair spatial memory while generators of theta are also present in the hippocampus and entorhinal cortex (see [15,28] for reviews). Consistent with the dominant role of theta, the firing of the majority of neurons in the hippocampal formation is modulated in the theta band. However, the firing of hippocampal place cells shows a systematic phase relationship to the LFP theta rhythm. Individual place cells fire whenever the animal enters a specific part of its environment, so that together the place cells encode the location of the animal relative to its environment. However, the firing of place cells is modu- lated at a slightly higher frequency than the LFP theta www.sciencedirect.com Current Opinion in Neurobiology 2010, 20:143���149

frequency so that their firing phase shifts from late to early phases as the animal moves through the firing field [1 ]. This ���theta phase precession��� provides a phase code for location, independent of the firing rate code which also codes for location, but can be modulated by other factors such as the objects, odors or actions occurring at the location of the firing field [2]. Thetaphase precession hasalso been observedin thefiring of ���grid cells��� in the medial entorhinal cortex [30] ��� one of the main neocortical inputs to the hippocampus. It is possible that the regular spatial firing pattern of grid cells [31] results from interference between theta band mem- brane potential oscillations [32,33], and that the increase in theta frequency with running speed relates to the temporal firing pattern of these cells [34]. Interestingly, there is evidencethatsimilarspatialrepresentationsexistinhuman entorhinal cortex, and that they contribute to spatial mem- ory performance in virtual environments [35]. Oscillatory coordination of processing in multiple regions As well as providing a phase code for location within the hippocampal formation, hippocampal theta also appears to coordinate activity in other regions during the per- formance of spatial tasks by rats. Thus, during spatial memory tasks, theta activity coherent with that in hippo- campus is seen in prefrontal cortex [23,36,37] and in ventral striatum [38]. The high and low frequency gamma in CA1 that occurs at specificphasesofthetamaycoordinateflowsofinformation within the hippocampal formation [18 ]: high frequency gamma in CA1 is synchronized with high frequency gamma in entorhinal cortex while low frequency gamma in CA1 is synchronized with low frequency gamma in CA3. Thus the inputs to CA1 from memory-related recurrent processing in CA3 may occur at one phase of theta and be characterized by low frequency gamma coherence, while sensory-related input from entorhinal cortex may occur at a different phase of theta and be characterized by high frequency gamma. This would be consistent with the idea that CA1 acts as a novelty detector by comparing mne- monic and perceptual information (e.g. [19,39]), and with the idea that encoding and retrieval occur at different phases of the theta rhythm [40]. It also supports the idea that theta and gamma oscillations in the hippocampal formation work together to support memory [20]. Inter- estingly, there is evidence from intracranial recordings in humans, that phase coherence between rhinal (i.e. entorh- inal and perirhinal) and hippocampal cortices in both gamma and theta bands is predictive of subsequent mem- ory performance [4,41], see below. Oscillatory coordination of reactivation/consolidation It has long been thought that episodic information might be rapidly stored within the recurrent connections of hippocampal region CA3 and then incorporated into neocortical stores of long-term semantic memory [42]. One specific proposed mechanism is that the information encoded during motion-related theta is transmitted to neocortex by the coherent spiking of large populations of hippocampal neurons during the sharp waves/ripples occurring during subsequent immobility and slow wave sleep, reviewed in [43]. Much subsequent research has been consistent with this hypothesis: the activation pat- terns of populations of place cells seen during awake movement through an environment appear to be reiter- ated on a faster timescale during the ripples/sharp wave complexes of slow wave sleep (e.g. [25,26]). During periods of awake immobility, it is possible to observe both forward ���preplay��� of the place cell representation of upcoming locations and backward replay of recently visited locations during ripple/sharp wave complexes (e.g. [27,44]). Recent experiments have shown that se- lective disruption of sharp wave/ripple complexes follow- ing training in a spatial memory task impairs learning in rats (e.g. [45]). In addition, there is evidence from intra- cranial recording in humans that ripple-like oscillations at 80���140 Hz occur in both hippocampal and rhinal cortices, and that the number recorded during resting (but not necessarily sleeping) after encoding lists of pictures cor- relates with subsequent memory for the pictures [46]. Brain oscillations and memory maintenance Active short-term maintenance Active short-term maintenance allows information from transient events to persist in the brain as active repres- entations. This enables goal-directed decision making and learning to utilize and manipulate information beyond its transient sensory availability. Slow oscillations in the delta (1���3 Hz) and theta as well as faster oscillations in the beta (12���25 Hz) and gamma ranges have been associated with two major contributions during maintenance coordinating distributed cortical representations [14] and representing encoded stimuli and their sequence of occurrence [21]. Theta networks of maintenance Patients with bilateral hippocampal lesions are impaired in their ability to maintain associative forms of information even over short delays of a few seconds, while performing normally for non-associative information. After a brief presentation of a scene, for example, these patients are unable tokeep in mind theconfigural/relational association of multiplefeaturesin thesceneeven for very short periods of just a few seconds (e.g. [14,47]). A recent MEG study showed that theta-synchrony between occipital and temporal brain regions accompanied maintenance of con- figural/relational (CR) information about photographs depicting natural indoor or outdoor scenes, and was absent in patients with bilateral hippocampal sclerosis [14]. Occi- pito-temporal theta-synchrony may indicate the coordina- tion of cortical representations along the visual ventral stream processing hierarchy, integrating anterior repres- 144 Cognitive neuroscience Current Opinion in Neurobiology 2010, 20:143���149 www.sciencedirect.com