Thinking Outside the Box About Memory

Since Brenda Milner’s pioneering studies of the amnesic patient H.M. in the 1950s, we’ve known that a brain structure called the hippocampus is critical for memory formation. Yet modern brain scanning techniques point to other brain regions as being essential for memory, and also show that the hippocampus supports a wide range of other cognitive functions, so exactly how our memories of life events are represented in the brain, and how they are encoded into, and retrieved from, long-term storage remain key unanswered questions.

Eleanor Maguire, a professor of cognitive neuroscience at University College London, presented a fresh perspective on these questions in the EBBS-Behavioural Brain Research Prize Lecture at the 11^th FENS Forum of Neuroscience in Berlin last month. “Autobiographical memories are crucial because they underpin our sense of self and provide continuity in our lives,” said Maguire. “I want to do a bit of thinking outside the box about how they are implemented in the brain.”

Not forgotten

Henry Molaison, the patient known as H.M., suffered from severe drug-resistant epilepsy, likely the result of a childhood cycling accident, which became increasingly debilitating as he grew older. In 1953, aged 27, he underwent radical surgery to remove the hippocampus from both sides of his brain. This region had been identified as the source of the abnormal electrical activity causing H.M.’s seizures; as such, the operation cured his epilepsy, but it had a dramatic effect – it left him apparently unable to form any new memories.

Milner began investigating H.M.’s memory function shortly after his surgery, and published a series of influential studies which confirmed that the hippocampus is critical for the formation of certain types of memory, but not others, and in doing so, established the field of human neuropsychology. (See: “One Man’s Continuing Contribution to the Science of Memory”)

Today, memory is one of the most intensively studied subjects in neuroscience and psychology, and while modern research confirms many of Milner’s initial findings, it reveals further complexity to the brain’s memory systems. We now know, for example, that the hippocampus is also a major component of the brain’s global positioning system, which makes vital contributions to mapping and navigating our surroundings. (See: “The Journey to the Cognitive Map and Mapping Spatial Navigation Abilities”)

Maguire’s work has already started to change the way we think about memory. It’s widely accepted, for example, that recalling life events involves reconstructing fragments of the memory rather than retrieving it as one complete piece of information. This process is susceptible to errors and biases, and has major implications for the criminal justice system, which relies heavily on eyewitness testimonies and identification of suspects. (See: “Reforming Forensics”)

In 2007, Maguire and her colleagues published evidence that people with hippocampal damage cannot imagine new experiences, leading some researchers to suggest that memory may have evolved not to recall the past, but to simulate future events by pasting together unrelated fragments of similar past experiences. More recently, results from the Maguire lab’s high-resolution brain scanning studies suggest that different portions of the hippocampus are used for memory, spatial navigation, and future-thinking, and contain circuits that separately process objects, associations, and scenes. These circuits are distinct from one another and receive inputs from different parts of the cerebral cortex, but they likely overlap, and may be engaged in different combinations, depending on the nature of the memory being recalled.

A related line of work shows that the hippocampus does not act alone in storing and retrieving autobiographical memories, and that this function is instead supported by a whole network of structures distributed widely throughout the brain. One other region in particular, the ventromedial prefrontal cortex (vmPFC) is also crucial for proper functioning of autobiographical memory, and Maguire’s group has also been trying to understand the relative contributions of each structure to memory function: “One of the key questions I’m trying to address in my research is, how do the hippocampus and vmPFC interact to produce seamless re-experiencing of a past event?”

Encoding, not retrieving

Until relatively recently, it was widely believed that the hippocampus would be critical not only for memory encoding, but also for memory retrieval. Subsequent research revealed, however, that retrieval becomes less dependent on the hippocampus and more so on the prefrontal cortex, with time, a finding that is consistent with the observed impermanence of synaptic connections in the hippocampus. Together, these findings suggest that memories are encoded and initially stored in the hippocampus before being transferred to the frontal cortex for long-term consolidation.

To examine this in more detail, Maguire and her colleagues scanned participants’ brains while they recalled recent and remote autobiographical memories, and found that, while traces of remote memories are more readily detectable in the frontal lobes, information about both kinds of memory was also present in the hippocampus, regardless of how remote the memory was. Last month, they published a study showing that people with vmPFC damage have difficulty reconstructing scenes from memory, supporting the idea that the vmPFC and hippocampus play complementary, critical roles.

Together, this work has led Maguire to re-examine the role of the hippocampus, and to a new perspective on the brain systems supporting autobiographical memories. “I argue that the hippocampus stores nothing in the longer term,” she said. “Autobiographical memory is orchestrated by the vmPFC, and the hippocampus plays a subordinate, but critical role.”

Maguire is collaborating on the development of a portable brain scanning system, and combining this with immersive virtual reality. “We can have people walking through virtual worlds while things happen to them,” she says. “That will allow us to capture the inception of autobiographical memory and see what that looks like in the brain, and then track the neural signatures of these memories as they evolve over time, in a much more realistic way.”