Brain Rhythms in the Human Medial Temporal Lobe

Ever since the discovery of the electroencephalogram (EEG), brain oscillations have been a major focus of neuroscientific research. The perpetual interactions among multiple network oscillators enable the brain to perform global computations on multiple spatial and temporal scales. A prominent example of interacting oscillations is the phenomenon of phase precession of place cells in the rodent hippocampus (O'Keefe and Recce, 1993). When the rat traverses a particular region in its environment, these cells fire periodic bursts at a slightly faster rhythm than the ongoing theta oscillation in the hippocampus. The firing thus occurs at increasingly early phase angles of the local field oscillations, and the spatial position of the animal can be decoded from these phase angles.

In this issue, Mormann et al. (2008) investigate oscillatory activity in the human hippocampus and in its main input structure, the entorhinal cortex. Using a unique data set of intracranial EEG signals directly recorded from the healthy medial temporal lobes of epilepsy patients with strictly unilateral seizure onset, the authors perform an elegant data analysis and provide evidence for the existence of independent theta generators in the human hippocampus and entorhinal cortex.

Of these two independent theta rhythms, the entorhinal rhythm is seen as being mediated by sensory and other cortical inputs, whereas the hippocampal rhythm is assumed to reflect theta activity autonomously generated within the hippocampus itself, mediated by inputs from the medial septum. Furthermore, the authors consider the hypothesis that the two independent rhythms represent the two oscillators of slightly different frequencies postulated by the interference model of theta phase precession (O'Keefe and Recce, 1993). Recent advances in recording technology that allow simultaneous recording of local field potentials and single-neuron activity in humans make this hypothesis an exciting and, more importantly, a testable one.

Previous studies on intracranial EEG recordings have shown that successful memorization of presented words is associated with an increase in entorhinal-hippocampal theta coherence (Fell et al., 2003). Mormann et al. now conjecture that the independent theta rhythms found in the entorhinal cortex and hippocampus may need to be actively synchronized to facilitate the synaptic plasticity involved in memory encoding. This hypothesis is backed by findings that the theta phase at which an action potential arrives in the rodent hippocampus determines the direction of plasticity, i.e. whether it results in long-term potentiation or depression. Synchronization of theta activity between the hippocampus and entorhinal cortex could thus create a slowly modulated facilitating state that provides a temporal basis for encoding or retrieval of separate items. A potential mechanism to generate the synchronization was discovered by Mormann et al. (2005). In a continuous word recognition paradigm, the authors found that the presentation of a visual stimulus causes a simultaneous phase reset of ongoing oscillatory activity in the hippocampus and entorhinal cortex.

Furthermore, the existence of independent theta rhythms plays an important role for a number of mechanisms related to gamma oscillations (Fries et al., 2007), as gamma activity has been found to be coupled to the phase of ongoing theta oscillations (Canolty et al., 2006; Demiralp et al., 2007; Mormann et al., 2005).