Chapter One

HIPPOCAMPUS From Memory to Imagination

What is the neural basis of the ability for unbounded imagination using highlevel abstract concepts? Surprisingly, the neuroscientific journey to find an answer to this question begins with the study of memory. Remembering past experiences is one thing, and imagining future events is another. Therefore, one would presume that the neural machinery for imagination differs from that for memory. In fact, that's what neuroscientists used to think until 2007, when scientists found an overlap in the brain regions in charge of memory and imagination. In particular, the hippocampus, which is well known for playing a critical role in encoding new memories, was found to be involved in imagination as well. In this chapter, we examine landmark discoveries on the hippocampus beginning from its role in memory (1950s) to its role in imagination (2000s).

HENRY MOLAISON: AN UNFORGETTABLE AMNESIAC

Henry Molaison, known by his initials, H.M., to the public until his death, was born in February 1926 in Manchester, Connecticut. He suffered from such severe epilepsy that he could not lead a normal life by the age of twentyseven. In September 1953, William Scoville, a neurosurgeon, removed parts of Molaison's brain to alleviate his symptoms. The surgery was effective in controlling the seizures. However, an unexpected side effect of the surgery deprived him of a vital brain function-remembering new experiences.

Surprisingly, other functions, such as sensation, movement, language, intelligence, short-term memories, and even old memories, were barely compromised. It appeared that only the ability to remember new experiences was profoundly impaired.

Molaison's case indicates that a separate neural system is in charge of encoding new memories. Before this case, many scientists thought that memory was a function of the entire brain rather than a specific brain structure. Consider the well-known work of Karl Lashley. After training rats to run in a maze, Lashley made various cuts on their brains to impair their memories. However, his experiment failed to find the specific brain region that, when cut, impaired the rat's memory as assessed by their behavior of running to the goal box. Instead, he found that the degree of memory impairment correlated with the degree of knife cuts. He proposed then, based on these observations, that the whole brain has the capacity to store memory. /uniF6DC

In contrast to this proposal, the Molaison case clearly demonstrates that a separate brain region specifically oversees encoding new memories without being involved in many other brain functions. Additionally, Molaison's older memories' remaining intact indicates that separate neural systems are in charge of encoding new memories and storing long-lasting memories. During his surgery, his medial temporal lobe, including the hippocampus, was removed bilaterally (see fig. 1.1). The results of this case indicate that while the medial temporal lobe is in charge of encoding new memories, it is not the final memory storage site. These astonishing discoveries had deep impacts on our understanding of memory and the brain. Molaison lost his memory but left an unforgettable legacy in neuroscience.

MEMORY CONSOLIDATION

Another unexpected finding from Molaison's case was his development of temporally graded retrograde amnesia. He lost not only the ability to form new memories (referred to as anterograde amnesia ) but also the ability to recollect some of the memories for events he experienced before the surgery (referred to as retrograde amnesia ). His retrograde amnesia was temporally graded; his recent memories were more likely to be lost while distant memories were spared. In fact, he could not remember most of the events he experienced a year or two before the surgery. This indicates that the medial temporal lobe is necessary not only to encode new memories but

FIGURE 1.1. Drawings of Henry Molaison's brain. The medial temporal lobe was removed bilaterally, but the right hemisphere is left intact here to show removed structures. Figure reproduced with permission from Suzanne Corkin et al., 'H. M.'s Medial Temporal Lobe Lesion: Findings from Magnetic Resonance Imaging,' Journal of Neuroscience 17, no. 10 (May 1997): 3965 (copyright Society for Neuroscience).

also to recollect memories of recently experienced events. According to the systems consolidation theory , which is currently the most popular theory on brainwide organization of memory, new memory is rapidly stored in the hippocampus and then goes through a 'consolidation' process so that it is eventually stored elsewhere in the brain, such as the neocortex. /uniF63A

Graded retrograde amnesia and memory consolidation indicate that the way humans encode and store experiences as memories is different from that of a digital computer. Why then do we store memory in this way? Why not simply send memories to the final storage site? Probably because it is advantageous, albeit cumbersome, to have two separate memory storage

sites. On the one hand, it would be useful to remember details of experienced events to make better choices in everyday life. On the other hand, we may run out of storage space if we store most of our experiences as permanent memories. One way to resolve this conundrum would be having two memory storage sites: one for the temporary storage of details of experiences and another for the permanent storage of the gist of experiences.

Suppose you commute to work by car. You need to remember exactly where you parked your car in the morning to get back to it in the evening. However, it wouldn't be useful to remember your exact daily parking locations for the rest of your life. Instead, remembering that you drove to work and probably parked your car in the company's parking lot would be less wasteful as a longlasting memory. The hippocampus may temporarily store detailed memories of recent experiences (this type of memory is called episodic memory ) whereas the neocortex may gradually extract general facts from ensembles of experiences and store them as permanent memories ( semantic memory ). /uniF63B

Systems consolidation is not the only existing theory on the organization of memory. According to the multiple trace theory , the hippocampus stores remote memories even after consolidation; /uniF63C the hippocampus is not necessary to recollect memories of general facts (semantic memories) but is necessary to recollect memories of specific experienced events (episodic memories) even after consolidation. /uniF63D As such, there are multiple theories on how memories are organized in the brain, indicating that we do not yet perfectly understand why and how initially acquired memories are consolidated over time to become permanent memories. In fact, memory consolidation is directly related to the central issue of this book, imagination. I think that memory consolidation is a process of actively selecting and reinforcing valuable options for the future by recombining past experiences using imagination rather than passively storing incidental events. I also think that this is a fundamental basis for the human capacity for innovation. I will discuss this matter in more detail in chapter 6.

Another important finding from Henry Molaison's case is that there are multiple forms of memory. Molaison could not remember new facts and events but could learn to perform new tasks by practice. This indicates that remembering new facts and events ( declarative or explicit memory ) is mediated by the medial temporal lobe, whereas learning new skills such as riding a bicycle ( procedural or implicit memory ) is mediated by other brain structures. Despite a large body of studies on multiple forms of memory, this book does not further explore these memory forms as they do not directly relate to the main issue at hand.

HIPPOCAMPUS AND IMAGINATION

The Molaison case, first published in 1957, changed the course of memory research. Fifty years later, in 2007, new findings were published that once /uniF63E again changed the course of memory research. In one study, Demis Hassabis and colleagues demonstrated that hippocampal amnesiacs have trouble not only in memory encoding but also in vivid imagination. /uniF63F They asked hippocampal amnesic patients and a normal control group to imagine plausible events under hypothetical situations. Some sample verbal cues for imagination are 'Imagine you are lying on a white sandy beach in a beautiful tropical bay' and 'Imagine that you are standing in the main hall of a museum containing many exhibits.'

The results of this experiment were surprising. Hippocampal amnesic patients had trouble constructing new imagined experiences. The control subjects, of course, came up with diverse imaginary scenarios with little difficulty. Try this exercise yourself. You can probably easily imagine a plausible sequence of events without much effort. However, hippocampal amnesic patients have trouble vividly imagining plausible episodes. In other words, damage to the brain structure known to play a critical role in memory can also impair the ability for vivid imagination.

Two other studies published in 2007 yielded the same conclusion using a different approach. /uniF640 They used functional magnetic resonance imaging (f MRI), a widely used brain imaging technique, to examine which brain areas are activated during imagination in neurotypical people. The hippocampus was activated when the subjects were recollecting autobiographical memories, which is expected; the hippocampus is crucial for remembering recent experiences. Surprisingly, the hippocampus was also activated when the subjects were envisioning the future. In other words, the hippocampus was active not only during remembering past episodes but also during imagining future events.

DEFAULT MODE NETWORK

To better understand hippocampal activation during imagination in a broader context, consider that certain brain areas are particularly active when we are relaxed and not paying much attention to the external world. These areas are collectively called the default mode network . Scientists have traditionally focused on how the brain processes information in response to external sensory stimuli, but little attention has been paid to brain activity during its

idle state. Surprisingly, scientists have found that certain brain regions are more active during rest than while performing attention-demanding tasks. /uniF641

The discovery of the default mode network was, in fact, accidental. Brain imaging techniques began to be widely used to investigate brain functions in the 1980s, and early studies commonly employed passive conditions, such as rest, as a control for task-performance conditions. As experimental data accumulated, scientists realized that there are certain brain areas that are more active during passive conditions. The name Marcus Raichle and colleagues collectively gave these brain regions was because they represent baseline-state (default) brain activity. /uniF6DC/uniF639

What were the subjects doing during the passive conditions? They reported that they were recollecting autobiographical memories (e.g., thinking about the previous night's dinner) or envisioning the future (i.e., daydreaming) during rest. Subsequent studies have found that the default mode network is active in association with diverse mental activities such as thinking about someone else's thoughts (called theory of mind ), making moral decisions (e.g., the trolley dilemma shown in figure 1.2), and performing creative thinking tasks (e.g., the divergent thinking task in which subjects are asked to produce multiple alternative options in response to such an open-ended question: 'In what ways can a brick be used?'). /uniF6DC/uniF6DC These results suggest that the default mode network is activated in association with internal mentation. The brain appears to be equipped with a task-associated network, which is active when we are engaged in an activity that requires us to pay attention to the external world, while the default mode network is active when we are engaged in internal mentation.

FIGURE 1.2. Trolley dilemma. A runaway trolley is hurtling toward five workers who are unaware of the trolley coming. You can save their lives by pulling a lever to divert the trolley to a sidetrack. However, there is a lone worker in the sidetrack who is also unaware of the trolley coming. What would you do? Would you kill one person to save five? Figure reproduced with permission from McGeddon, 'File:Trolley Problem.svg,' Wikimedia Commons, updated March 6, 2018, https:/ /commons.wikimedia.org/wiki/File:Trolley_Problem .svg (CC BY-SA 4.0).

As outlined in the rest of this book, innovative ideas often emerge in resting states and even during sleep. The brain may seem to be idle when we take a rest. On the contrary, the default mode network is active while we rest, and innovative ideas may appear while our minds wander freely. We will examine this issue closely in chapter 13. For now, germane to the rest of these discussions is noting that the hippocampus is a main component of the default mode network.

In summary, hippocampal damages impair one's ability to imagine, and the hippocampus, as an important part of the default mode network, is activated in association with internal mentation including envisioning the future. These findings are not without caveats, however. Patients with hippocampal damages usually have damage in other brain areas as well. Also, brain imaging studies rely on the indirect measure of brain blood flow instead of neural activity. Nevertheless, the implication of these findings is clear; the hippocampus is involved not only in memory but also in imagination. We reached a new turning point in memory research fifty years after the publication of the Henry Molaison case. For this reason, the journal Science named the discovery of the hippocampus's involvement in imagination as one of ten breakthroughs in 2007. /uniF6DC/uniF63A