Corticothalamic phase synchrony and cross-frequency coupling predict human memory formation

  • Sweeney-Reed C
  • Zaehle T
  • Voges J
  • et al.
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The anterior thalamic nucleus (ATN) is thought to play an important role in a brain network involving the hippocampus and neocortex, which enables human memories to be formed. However, its small size and location deep within the brain have impeded direct investigation in humans with non-invasive techniques. Here we provide direct evidence for a functional role for the ATN in memory formation from rare simultaneous human intrathalamic and scalp electroencephalogram (EEG) recordings from eight volunteering patients receiving intrathalamic electrodes implanted for the treatment of epilepsy, demonstrating real-time communication between neocortex and ATN during successful memory encoding. Neocortical-ATN theta oscillatory phase synchrony of local field potentials and neocortical-theta-to-ATN-gamma cross-frequency coupling during presentation of complex photographic scenes predicted later memory for the scenes, demonstrating a key role for the ATN in human memory encoding.Memories, both the mundane and the significant, play an integral role in our daily lives. Scientists have long sought to establish exactly how our memories are formed; how does an experience, with its sights, sounds and feelings, become a mental representation stored within our brain?One way to investigate this question is to look at the activity of different parts of the brain. Brain imaging techniques have helped researchers identify two key brain regions that are involved in the process of memory formation: the neocortex and the hippocampus. The neocortex forms the outer layer of the brain, and performs complex tasks such as decision-making and language comprehension. The hippocampus, which sits deeper within the brain, deals primarily with memory and navigation. Research has shown that memory formation depends on communication between the neocortex and the hippocampus. However, scientists suspected that additional structures located beneath the neocortex—among them, the anterior thalamic nuclei (ATN)—are also crucial for forming memories. This has been difficult to confirm as the small size of the ATN, and their location deep within the brain, make their activity almost impossible to monitor using standard brain imaging techniques.One way reliable data can be recorded from the ATN is by inserting electrodes into the brain. Brain surgery of course cannot be carried out on healthy human participants, but occasionally an opportunity arises to study the brain activity of patients who have electrodes inserted for therapeutic purposes. For example, in cases where a patient's epilepsy does not respond to conventional treatments, electrodes may be implanted to electrically stimulate the ATN in an attempt to improve their symptoms.Sweeney-Reed et al. asked eight volunteers to perform a memory task, and monitored the activity of each volunteer's ATN via electrodes that had already been implanted in their brain to treat epilepsy. Simultaneously, electrodes attached to the scalps of the volunteers recorded the activity of the neocortex. When a memory was successfully stored in the brain, the activity of the two regions became synchronized. This suggests that successful memory formation depends upon communication between the ATN and the neocortex.While the involvement of the ATN in human memory formation has long been a topic of speculation, Sweeney-Reed et al. now provide direct biological evidence for its crucial role in the process. Consequently, future research into memory formation should focus upon the ATN in addition to the more familiar structures of the neocortex and the hippocampus.




Sweeney-Reed, C. M., Zaehle, T., Voges, J., Schmitt, F. C., Buentjen, L., Kopitzki, K., … Richardson-Klavehn, A. (2014). Corticothalamic phase synchrony and cross-frequency coupling predict human memory formation. ELife, 3.

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