Studying Amnesia Helps Researchers Understand Memory

BRAIN WONDERS, RESEARCH DECEMBER 2020/JANUARY 2021 BY SUSAN FITZGERALD Studying Amnesia Helps Researchers Understand Memory Examining cases of amnesia—the inability to retrieve or make memories—allows researchers to plumb the mysteries of memory.

Illustration by Sergio Membrillas

Cole Kazdin was a writer and performer in New York City in her twenties when she was playing a cheerleader in a TV pilot. Partway through filming, the director ordered a stunt the cast was unprepared for. It involved her being tossed into the air and caught by other actors. The stunt went horribly wrong, and Kazdin crashed to the floor. When she regained consciousness, she was in an ambulance racing to a New Jersey hospital, dressed in a cheerleading outfit. She had no memory of what had happened. Worse, she couldn't remember basic details of her life.

At the hospital, she was told she had sustained a concussion that caused amnesia, wiping out both her long-term and short-term memory. She could not recall much of her pre-injury life nor what she had done only a few moments before.

After Kazdin returned home, she kept telling a visiting friend that she needed to call her father, something she had just done three times in a row. She watched Dirty Rotten Scoundrels repeatedly, laughing each time as if she hadn't just seen the movie and couldn't remember that it had been one of her favorites. When a boyfriend she had broken up with before her accident visited, she didn't recognize him or any of the photographs from their life together. The only way she could be convinced that she had shared Thanksgiving dinner with her mother and sister earlier in the day was seeing the dirty dishes in the sink.

Kazdin plastered sticky notes throughout her home to keep track of daily activities like when to take her medication and to remind her of who she had been—a vegetarian, a cat owner, a writer. In the months after her accident, Kazdin struggled to reclaim her pre-amnesia identity and rediscover what had given her satisfaction and joy.

The kind of memory loss known as amnesia ﬁts into two broad categories— retrograde and anterograde. In retrograde amnesia, the brain is unable to retrieve already stored memories. In anterograde amnesia, the brain does not store new memories. (Kazdin had both.) Both types can result from an acute injury, such as a concussion; an infection, like meningitis; a stroke; a seizure; a brain tumor; or a chronic disorder, such as Alzheimer's disease. Anterograde amnesia is a common early sign of dementia or Alzheimer's, when loved ones repeatedly ask the same question. Some people experience transient global amnesia, which resolves quickly in the aftermath of an injury or illness. It's rare that amnesia wipes out a person's entire identity.

Imperfect Filing System "Memory is a complex and multifaceted phenomenon," says Roy Hamilton, MD, FAAN, behavioral neurologist and cognitive neuroscientist at the University of Pennsylvania in Philadelphia. He says anterograde amnesia affects almost everyone in small ways. "People don't store every bit of information that comes their way," he says. For instance, many people drive to work every day but don't recall much of it. "Some degree of forgetting is [also] part of the aging process," he says. "Memory is not perfect, and its abilities change over a life span."

Neuroscientists are using new approaches to study how the brain forms and recollects memories. "They are mapping speciﬁc patterns that emerge when people call to mind particular experiences," says Dr. Hamilton. "These approaches can help us understand how the representation of speciﬁc memories evolves over time, and how related memories may organize themselves within the brain."

Human memory is like a computer, says Barry Gordon, MD, PhD, FAAN, professor of neurology and cognitive science at Johns Hopkins Medicine in Baltimore. "Unless you save a ﬁle you're working on, it's lost," he says. "You have a working memory, but it has to be saved in a permanent form. If it's not, it's forgotten."

The hippocampus, a structure deep in the brain's lower (temporal) lobes, is one of the key places regulating how memories are saved. "Other parts of the brain, including other parts of the temporal lobes, the thalamus, and parts of the frontal lobes, also seem to be important in determining the storage and retrieval of memories," says Dr. Gordon. Anterograde amnesia is the most dramatic consequence of damage to the hippocampus and other structures, he says. Retrograde amnesia often accompanies anterograde amnesia.

Applying Technology Researchers like John Hart Jr., MD, distinguished chair in neuroscience at the University of Texas at Dallas, use functional MRIs and electroencephalograms to understand the circuits and structures involved in various types of memory. Dr. Hart is particularly interested in the storage and retrieval of semantic memory, which includes general knowledge accumulated over a person's lifetime, such as colors, letters, and names.

Another type of memory, called procedural, refers to the ability to perform ingrained tasks, such as tying shoes or playing the piano, without having to consciously tap into stored memories. It explains why someone may remember how to ride a bike but not remember that he or she just went for a bike ride.

Whether people have retrograde or anterograde amnesia depends on how their brains were affected by injury or illness. "Damage to white matter after a brain injury may affect connections needed to make new memories, so people may not be able to recall the name of someone they've just met or the items they need to pick up at the store, but they can still recall memories about their fourth-grade classmates," says Dr. Hart.

He and his research team are using electromodulation—in which low-level electrical stimulation is delivered through electrodes placed on the scalp— to determine if it can improve memory retrieval in patients with traumatic brain injury. In one study, a group of patients who received electrical stimulation had signiﬁcant improvement in verbal retrieval, and the improvement persisted for at least eight weeks, Dr. Hart says.

The key to addressing amnesia is identifying and treating the underlying cause. So, for example, if seizures are causing memory dysfunction, treatment would entail antiseizure medication, says Hugo Botha, MD, assistant professor of neurology at Mayo Clinic in Rochester, MN. If the cause is an acute injury, such as a stroke or a blow to the head, memory often comes back gradually as the brain heals. Adaptive strategies like making lists or leaving things in the same place every day can help people function better. But memory loss can take a psychological and emotional toll as people also may lose their sense of self. "We all construct narratives of who we were, who we are, and how we imagine ourselves in the future," says Dr. Botha. "When you lose your memory and the ability to make new memories, it's hard to know your place in the world."

Full Recovery For Cole Kazdin, now a journalist in Los Angeles, her memory gradually returned as the concussion healed. "It was not a case of suddenly waking up and everything was back," she says. "It came back in bits and pieces, in a very nonlinear way," over a six-month period.

One time early on, she was lying in bed and overheard people in the kitchen talking about her. It occurred to her, I used to have this great life and I was a vibrant, regular person.

A clear moment in her recovery came when she glanced at a book in her apartment and had a ﬂeeting memory that she had written a review of it. A thought came to her: Oh, I'm a writer. "That was a big thing for me to remember," she says.

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Almost 20 years later, Kazdin has no lingering symptoms and is grateful for a valuable lesson she learned—that it's important to live in the moment. She also came away with coping skills that have stuck.

"I am very self-conscious about forgetting things," she says. "I write a lot of things down, like 'Get gas in the car.' There's a little piece of me that doesn't trust my memory."