Partial Recall
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“Atlas of Human Anatomy and Surgery”, Jean Baptiste Marc Bourgery. Illustration by Nicolas Henri Jacob, 1830
Science

Partial Recall

A Neuroscientist Explains Memory
Aleksandra Pezda
Reading
time 10 minutes

What makes our brains remember, can they be trained to recall more? Professor Małgorzata Kossut on memory, plasticity, and the science of mind-reading.

Aleksandra Pezda: What is memory?

Professor Małgorzata Kossut: Memory is the ability to store and retrieve information. All information received by the human brain leaves a physical trace in the form of new neuronal circuits, strongly connected sets of cells—we call them engrams. In this way it is remembered. Some of these traces are stored, forming long-term memories that can be recollected when necessary. The concept of the engram was described by the German scientist Richard Wolfgang Semon at the beginning of the twentieth century. Even then, he argued that there is a relationship between physiological states of the body and memory, and there must be some kind of physical memory trace.

The relationship between memory and the brain was not at all obvious, if we look at the history of science. Although Plato had already claimed that memories “imprint traces on the human organism” as late as the nineteenth-century, phrenologists—who divided protuberances on the skull into areas responsible for specific mental functions—were unable to isolate the area responsible for memory. It took us almost an entire century to figure out what engrams are and to confirm Semon’s theory.

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Is there no single area in the brain responsible for memory?

Back in the 1930s, researchers were convinced they had to look for this one specific center in the brain. They would damage specific sections of the brains in experimental animals to find out through elimination. The techniques they used were poor, equally poor were the results. For example, the otherwise outstanding psychologist Karl Lashley, who conducted his research mainly before the Second World War, assumed that memory is located in the cerebral cortex. He trained a rat to search for food, after which he removed particular areas of its cerebral cortex to see when the rat’s memory would be impaired. But nothing interfered with the task, the rat was still able to find food where anticipated, that is, where it was taught to find it. Lashley performed a number of other experiments with equally disappointing results. In 1950, he published a paper titled “In search of the engram,” in which he wrote, “this series of experiments has yielded a good bit of information about what and where the memory trace is not… I sometimes feel, in reviewing the evidence on the localization of the memory trace, that the necessary conclusion is that learning just is not possible.”

What mistake were the researchers making?

They weren’t looking for the right thing, although they could not possibly know it. Two years after Lashley gave up, Canadian neurosurgeon Wilder Penfield made a breakthrough discovery on the road to tracking down engrams. Penfield studied the brains of patients with epilepsy. He irritated the cerebral cortex—and these were open brain surgeries— with small electrical impulses. His goal was to locate the epileptic focus. By chance, however, he discovered that among certain patients the stimulation of the cerebral cortex’s frontal lobe elicited vivid memories of very distant events. Repeated irritation in the same place would have the same effect. These memories were extraordinarily detailed, with patients recalling details of events they could no longer remember before the operation. This discovery shook the scientific world. First of all, Penfield overcame Lashley’s defeatism with his research. Besides that, it turns out that our brains store distant images, hidden on a daily basis, that can be artificially restored.

Did Penfield help to establish which parts of the brain store and process memories?

No, but he led us out of chaos. In the 1950s, there was another incident that again pushed the understanding of memory-related processes forward a bit. First, there was the famous American patient H.M., “the star of neurology” whose name was not declassified until 2009, a year after his death. Well, a young American named Henry Molaison suffered from severe headaches and epilepsy, probably caused by a bicycle accident in childhood. Nothing helped, Molaison was unable to work or function normally. In 1953, at the age of twenty-seven, he underwent drastic surgery to remove the epileptic focus. It was a risky experiment. Doctors removed both sides of the hippocampus and five centimeters of both medial temporal lobes of his brain. The surgery was successful, but only partially. The epilepsy and headaches ceased, but Molaison paid a high price for this comfort. He lost his ability to remember. He remembered his life before the operation, retaining his intelligence, language skills, and acquired knowledge; he could still play the guitar. However, he remembered what happened for only a few minutes. He could carry a conversation, but he could not remember that he’d just eaten lunch. He reintroduced himself to the hospital staff every day. He could draw a plan of both his childhood home and the hospital where he had surgery, but he would get lost on his way to the hospital bathroom. He read the same newspaper over and over again, and drank every coffee for “the first time in my life.” Molaison survived like this until the age of eighty-two. To the end, he thought he was twenty-seven; the ability to remember current events never returned to him. Still, he eagerly cooperated with researchers and finally donated his brain to science. After his death, it was sliced into 2,034 pieces, which are now available to those seeking the truth about human memory. What we learned is that the hippocampus is the most important—though not the only—part of the brain responsible for storing and processing memories.

Clive Wearing, the famous British tenor and former conductor of the BBC Orchestra, also has his coffee every day “for the first time in his life,” is he like Molaison?

Clive Wearing suffers from both retrograde and anterograde amnesia. This means that he has no ability to remember new events, but he has also lost all of his memories. A herpes virus destroyed his brain, specifically the hippocampus, in the mid-1980s. Wearing was already an older man at the peak of his career. Since then, he has lived through the constant horror of the present. He meets his wife every day anew, but interestingly still loves her very much. He is still able to conduct but after the fact declares that he didn’t do it all and that he doesn’t know how. Therapists proposed he keep a journal to help him relate better to reality but the notes all looked like this: “8:31, I am completely awake. 9:06, now I am completely, fully awake. 9:34, I am awake to the highest degree…” etc.

Both of these examples show how complicated, or rather how life freezes when one loses the ability to remember. The loss of memory leads to depersonalization, it takes away their “me.” It turns out that you can lose a kidney, a leg, half a liver, you can have someone else’s heart implanted, but we can still remain ourselves. When we lose memory and our life story, we lose our identity. Memory is an incredibly important function of the brain.

What is the capacity of the human brain?

Practically limitless, according to recent estimates, its capacity is around 2.5 terabytes. There is really nothing to worry about, everything will fit in your head. You only need to pack it sensibly, because the brain can sometimes get clogged. The famous mnemonist Solomon Shereshevsky, after many years of exploiting his phenomenal memory,  suffered from a glut of memories accumulated since childhood. He remembered too much, he had trouble forgetting unnecessary information. It happened that he failed to recognize a loved one on the phone because he remembered too well their voice from the past, which differed from its sound in the present. There are many methods to improve memory, which are supposed to be effective. As MRI studies have been conducted on how the brain behaves after such training: you could see that neurons reorganize and form new connections. Still, do these methods make sense for the average person? They’d have to train continuously for the effects to be spectacular.

Let’s go back to the engram, how is memory stored in the brain?

We currently believe that a set of neurons responsible for a given memory are formed in the brain. Under the influence of a given stimulus, e.g. an experience lived, a book read, a person met, a smell, touch or music, neurons that were strongly activated while experiencing such an event form the associated neuronal circuit. Thanks to modern brain imaging and biotechnology methods, we can simply watch this happen. This has been made possible by the development of methods such as fMRI [functional magnetic resonance imaging] and PET [positron emission tomography], along with the discovery made by American chemists Shimomura, Chalfi, and Tsien, for which they were awarded the Nobel Prize in 2008: a jellyfish protein with fluorescent properties. The luminescent protein has since become a standard research tool in neurobiology, and is used to label and track cells. This allows you to closely examine the processes that occur inside them. By linking—with the help of biotechnological tricks—the expression of this protein to the activation of a certain gene when neurons create a memory circuit, it is possible to see the glowing engram cells. Moreover, we know for sure that this is an actual engram, because these neurons can be artificially stimulated or suppressed, causing mice to behave as if they remembered or forgot something.

We can thus observe the responses of neuronal networks to memory-related stimuli in the vicinity of the prefrontal cortex, as well as the hippocampus, the amygdala, the temporal lobes, and even in the cerebellum. We know that two lobes are crucial: the frontal lobe when it comes to short-term memory and information processing; the medial temporal lobe, including the hippocampus, when memorizing, and the rest of the temporal lobe when we talk about long-term memory, organization, and storing information.

How do neural networks work?

Discovered in the 1970s, the phenomenon of long-term synaptic potentiation says that when you stimulate a neuron intensively, it increases the response of the next neuron connected to it. Something changes in the synapse—the link between neurons—and we already know what it is. The result is certain and repeatable, which is not that common in biology and medicine. Well, it is about so-called synaptic plasticity. It was discovered that the neuron has a reserve of neurotransmitter receptors, which can be activated when the signal is amplified. If the effect of a stimulus—a powerful experience, important information—is a long-term synaptic gain, these spare receptors insert themselves into the membrane of the synapse, causing the cell to react more strongly to incoming signals. When stimulated more intensely, one neuron can activate others in a chain reaction that quickly changes their morphology. That means the stimulated synapses become larger and even new ones are formed. If synaptic contact intensifies, causing synapses to grow bigger and stronger, neural paths are forged…

So our brain is literally swelling?

You could say that. This reminds me of a very interesting study being conducted by one of the labs in California under the supervision of Professor Jack Gallant. Well, scientists with the help of functional magnetic resonance imaging, fMRI, of people subjected to the same experience: they listen to the same text of a radio program several times. The researchers analyze brain activity maps, that is, which regions of the brain respond to what category of words or even individual lexemes, and imagine what was discovered.

That all people’s brains react similarly?

The same categories and the same words activate the exact same parts of the brain in different people. Researchers carried out another experiment in which the subjects did not listen but read the same material. Again, their maps came out almost identical! This means that regardless whether we hear  “puppy” or read “puppy,” the same memory traces are activated in our brains.

Does this mean we will be able to read people’s minds?

Theoretically, we already can. Very simple thoughts, but artificial intelligence learns quickly.  But to carry out mind reading on a large scale? I doubt it. It would be too difficult and too expensive.


Małgorzata Kossut:

Małgorzata Kossut is professor of natural sciences at the Nencki Institute of Experimental Biology of the Polish Academy of Sciences. She specializes in the plasticity of the neural system and the neuronal mechanisms of learning and memory.

Parts of this interview have been edited and condensed for clarity and brevity

This translation was re-edited for context and accuracy on May 19, 2022

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