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KEY THEME

Early researchers believed that memory was associated with physical changes in the brain, but these changes were discovered only in the past few decades.

KEY QUESTIONS

Does the name Ivan Pavlov ring a bell? We hope so. As you should recall from Chapter 5, Pavlov was the Russian physiologist who classically conditioned dogs to salivate to the sound of a bell and other neutral stimuli. Without question, learning and memory are intimately connected. Learning an adaptive response depends on our ability to form new memories in which we associate environmental stimuli, behaviors, and consequences.

Pavlov (1927) believed that the memory involved in learning a classically conditioned response would ultimately be explained as a matter of changes in the brain. However, Pavlov only speculated about the kinds of brain changes that would produce the memories needed for classical conditioning to occur. Other researchers would take up the search for the physical changes associated with learning and memory. In this section, we look at some of the key discoveries that have been made in trying to understand the biological basis of memory.

An American physiological psychologist named Karl Lashley set out to find evidence for Pavlov’s speculations. In the 1920s, Lashley began the search for the memory trace, or engram—the brain changes that were presumed to occur in forming a long-term memory (see photo caption). Guiding Lashley’s research was his belief that memory was localized, meaning that a particular memory was stored in a specific brain area.

Lashley searched for the specific location of the memory trace that a rat forms for running a maze. Lashley (1929) suspected that the specific memory was localized at a specific site in the cerebral cortex, the outermost covering of the brain that contains the most sophisticated brain areas. Once a rat had learned to run the maze, Lashley surgically removed tiny portions of the rat’s cortex. After the rat recovered, Lashley tested the rat in the maze again. Obviously, if the rat could still run the maze, then the portion of the brain removed did not contain the memory.

Over the course of 30 years, Lashley systematically removed different sections of the cortex in trained rats. The result of Lashley’s painstaking research? No matter which part of the cortex he removed, the rats were still able to run the maze (Lashley, 1929, 1950). At the end of his professional career, Karl Lashley concluded that memories are not localized in specific locations but instead are distributed, or stored, throughout the brain.

Lashley was wrong, but not completely wrong. Some memories do seem to be localized at specific spots in the brain. Some 20 years after Lashley’s death, psychologist Richard F. Thompson and his colleagues resumed the search for the location of the memory trace that would confirm Pavlov’s speculations.

Thompson classically conditioned rabbits to perform a very simple behavior—an eye blink. By repeatedly pairing a tone with a puff of air administered to the rabbit’s eye, he classically conditioned rabbits to blink reflexively in response to the tone alone (Thompson, 1994, 2005).

Thompson discovered that after a rabbit had learned this simple behavior, there was a change in the brain activity in a small area of the rabbit’s cerebellum, a lower brain structure involved in physical movements. When this tiny area of the cerebellum was removed, the rabbit’s memory of the learned response disappeared. It no longer blinked at the sound of the tone. However, the puff of air still caused the rabbit to blink reflexively, so the reflex itself had not been destroyed.

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Thompson and his colleagues had confirmed Pavlov’s speculations. The long-term memory trace of the classically conditioned eye blink was formed and stored in a very localized region of the cerebellum.

So why had Karl Lashley failed? Unlike Thompson, Lashley was working with a relatively complex behavior. Running a maze involves the use of several senses, including vision, smell, and touch. In contrast, Thompson’s rabbits had learned a very simple reflexive behavior—a classically conditioned eye blink.

Thus, part of the reason Lashley failed to find a specific location for a rat’s memory of a maze was that the memory was not a single memory. Instead, the rat had developed a complex set of interrelated memories involving information from multiple senses. These interrelated memories were processed and stored in different brain areas. As a result, the rat’s memories were distributed and stored across multiple brain locations. Hence, no matter which small brain area Lashley removed, the rat could still run the maze. So Lashley was right in suggesting that some memories are distributed throughout the brain.

Combined, the findings of Lashley and Thompson indicate that memories have the potential to be both localized and distributed. Very simple memories may be localized in a specific area, whereas more complex memories are distributed throughout the brain. A complex memory involves clusters of information, and each part of the memory may be stored in the brain area that originally processed the information (Greenberg & Rubin, 2003).

Adding support to Lashley’s and Thompson’s findings, brain imaging technology has confirmed that many kinds of memories are distributed in the human brain. When we are performing a relatively complex memory task, multiple brain regions are activated—evidence of the distribution of memories involved in complex tasks (Frankland & Bontempi, 2005; Khan & Muly, 2011).

The Focus on Neuroscience on the next page describes a clever study that looked at how memories involving different sensory experiences are assembled when they are retrieved.

What exactly is it that is localized or distributed? The notion of a memory trace suggests that some change must occur in the workings of the brain when a new long-term memory is stored. Logically, two possible changes could occur. First, the functioning of the brain’s neurons could change. Second, the structure of the neurons could change. Given those two possibilities, the challenge for memory researchers has been to identify the specific neurons involved in a given memory, a task that is virtually impossible with the human brain because of its enormous complexity. What this task required was a creature with a limited number of neurons that is also capable of learning new memories.

Enter Aplysia, a gentle, seaweed-munching sea snail that resides off the California coast. The study of Aplysia over the past 30 years has given memory researchers important insights into the brain changes involved in memory. Why Aplysia? Because Aplysia has only about 20,000 good-sized neurons. That was a key reason why memory researcher Eric Kandel (2006, 2009) chose this unassuming creature to study the neuronal changes that occur when a new memory is formed for a simple classically conditioned response.

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If you give Aplysia a gentle squirt with a WaterPik, followed by a mild electric shock to its tail, the snail reflexively withdraws its gill flap. When the process is repeated several times, Aplysia wises up and acquires a new memory of a classically conditioned response—it withdraws its gill when squirted with the WaterPik alone. This learned gill-withdrawal reflex seems to involve a circuit of just three neurons: one that detects the water squirt, one that detects the tail shock, and one that signals the gill-withdrawal reflex (see Figure 6.10).

When Aplysia acquires this new memory through repeated training trials, significant changes occur in the three-neuron circuit (Kandel, 2001). First, the function of the neurons is altered: There is an increase in the amount of the neurotransmitters produced by the neurons. Second, the structure of the snail’s neurons changes: The number of interconnecting branches between the neurons increases, as does the number of synapses, or communication points, on each branch. These changes allow the neurons involved in the particular memory circuit to communicate more easily. Collectively, these changes are called long-term potentiation, which refers to a longlasting increase in synaptic strength (Baudry & others, 2011; Lisman & others, 2012).

The same kinds of brain changes have been observed in more sophisticated mammals. Chicks, rats, and rabbits also show structural and functional neuron changes associated with new learning experiences and memories. And, as you may recall from Psych for Your Life in Chapter 2, there is ample evidence that the same kinds of changes occur in the human brain.

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In terms of our understanding of the memory trace, what do these findings suggest? Although there are vast differences between the nervous system of a simple creature such as Aplysia and the enormously complex human brain, some tentative generalizations are possible. Forming a memory seems to produce distinct functional and structural changes in specific neurons. These changes create a memory circuit. Each time the memory is recalled, the neurons in this circuit are activated. As the structural and functional changes in the neurons strengthen the communication links in this circuit, the memory becomes established as a long-term memory (Kandel, 2006, 2009).

CLUES FROM AMNESIA

KEY THEME

Important insights into the brain structures involved in normal memory have been provided by case studies of people with amnesia caused by damaged brain tissue.

KEY QUESTIONS

Prior to the advent of today’s sophisticated brain imaging technology, researchers studied individuals who had sustained a brain injury or had part of their brain surgically removed for medical reasons. Often, such individuals experienced amnesia, or severe memory loss. By relating the type and extent of amnesia to the specific damaged brain areas, researchers uncovered clues as to how the human brain processes memories.

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RETROGRADE AMNESIA

DISRUPTING MEMORY CONSOLIDATION

One type of amnesia is retrograde amnesia. Retrograde means “backward moving.” People who have retrograde amnesia are unable to remember some or all of their past, especially episodic memories for recent events. Retrograde amnesia often results from a blow to the head. Boxers sometimes suffer such memory losses after years of fighting. Head injuries from automobile and motorcycle accidents are another common cause of retrograde amnesia. Typically, memories of the events that immediately preceded the injury are completely lost, as in the case of accident victims who cannot remember details about what led up to the accident.

Apparently, establishing a long-term memory is like creating a Jell-O mold—it needs time to “set” before it becomes solid. This process of “setting” a new memory permanently in the brain is called memory consolidation (Dudai & others, 2011). More specifically, memory consolidation is the gradual, physical process of converting new long-term memories to stable, enduring memory codes (Medina & others, 2008). If memory consolidation is disrupted before the process is complete, the vulnerable memory may be lost (Dudai, 2004).

In humans, memory consolidation can be disrupted by brain trauma, such as a sudden blow, concussion, electric shock, or encephalitis (Riccio & others, 2003). Similarly, many drugs, such as alcohol and the benzodiazepines, interfere with memory consolidation. In contrast, stimulants and the stress hormones that are released during emotional arousal tend to enhance memory consolidation (Nielson & Lorber, 2009).

ANTEROGRADE AMNESIA

DISRUPTING THE FORMATION OF EXPLICIT MEMORIES

Another form of amnesia is anterograde amnesia—the inability to form new memories. Anterograde means “forward moving.” The most famous case study of anterograde amnesia lasted over 50 years. It was of a man who for years was known only by his initials—H.M. But the need to protect H.M.’s privacy ended when Henry Molaison died at the age of 82 on December 2, 2008.

In 1953, Henry was 27 years old and had a 10-year history of severe, untreatable epileptic seizures. Henry’s doctors located the brain area where the seizures seemed to originate. With no other options available at the time, the decision was made to surgically remove portions of the medial (inner) temporal lobe on each side of Henry’s brain, including the brain structure called the hippocampus (Scoville & Milner, 1957). Portions of the left and right amygdala were also removed (Annese & others, 2014).

After the experimental surgery, the frequency and severity of Henry’s seizures were greatly reduced. However, it was quickly discovered that Henry’s ability to form new memories of events and information had been destroyed. Although the experimental surgery had treated H.M.’s seizures, it also dramatically revealed the role of the hippocampus in forming new explicit memories for episodic and semantic information.

Psychologists Brenda Milner (1970) and Suzanne Corkin (2013) studied Henry extensively over the past 50 years. If you had had the chance to meet Henry, he would have appeared normal enough. He had a good vocabulary and social skills, normal intelligence, and a delightful sense of humor. And he was well aware of his memory problem. When Suzanne Corkin (2002) once asked him, “What do you do to try to remember?” Henry quipped, “Well, that I don’t know because I don’t remember [chuckle] what I tried.”

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Despite superficially appearing normal, Henry lived in the eternal present. Had you talked with Henry for 15 minutes, then left the room for 2 or 3 minutes before coming back, he wouldn’t remember having met you before. Although some of the psychologists and doctors had treated Henry for years, even decades, Henry was meeting them for the first time on each occasion he interacted with them (Corkin, 2013; MacKay, 2014).

For the most part, Henry’s short-term memory worked just fine. In fact, he could fool you. If Henry actively repeated or rehearsed information, he could hold it in short-term memory for an hour or more (Nader & Wang, 2006). Yet just moments after he switched his attention to something else and stopped rehearsing the information, it was gone forever. However, Henry’s long-term memory was partially intact. He could retrieve long-term memories from before the time he was 16 years old, when the severe epileptic seizures began.

In general, Henry was unable to acquire new long-term memories of events (episodic information) or general knowledge (semantic information). Still, every now and then, Henry surprised his doctors and visitors with some bit of knowledge that he acquired after the surgery.

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Henry’s case suggests that the hippocampus is not involved in most short-term memory tasks, nor is it the storage site for already established long-term memories. Instead, the critical role played by the hippocampus seems to be the encoding of new memories for events and information and the transfer of those new memories from short-term to long-term memory.

Implicit and Explicit Memory in Anterograde Amnesia Henry’s case and those of other patients with anterograde amnesia have contributed greatly to our understanding of implicit versus explicit memories. To refresh your memory, implicit memories are memories without conscious awareness. In contrast, explicit memories are memories with conscious awareness.

Henry could not form new episodic or semantic memories, which reflects the explicit memory system. But he could form new procedural memories, which reflects the implicit memory system. For example, when given the same logical puzzle to solve several days in a row, Henry was able to solve it more quickly each day. This improvement showed that he implicitly “remembered” the procedure involved in solving the puzzle. But if you asked Henry if he had ever seen the puzzle before, he would answer “no” because he could not consciously (or explicitly) remember having learned how to solve the puzzle. This suggests that the hippocampus is less crucial to the formation of new implicit memories, such as procedural memories, than it is to the formation of new explicit memories.

Were Henry’s memory anomalies an exception? Not at all. Studies conducted with other people who have sustained damage to the hippocampus and related brain structures showed the same anterograde amnesia (see Bayley & Squire, 2002). Like Henry, these patients are unable to form new explicit memories, but their performances on implicit memory tasks, which do not require conscious recollection of the new information, are much closer to normal. Such findings indicate that implicit and explicit memory processes involve different brain structures and pathways.

BRAIN STRUCTURES INVOLVED IN MEMORY

Along with the hippocampus, several other brain regions involved in memory include the cerebellum, the amygdala, and the frontal cortex (see Figure 6.11). As you saw earlier, the cerebellum is involved in classically conditioning simple reflexes, such as the eye-blink reflex. The cerebellum is also involved in procedural memories and other motor skill memories.

The amygdala, which is situated very close to the hippocampus, is involved in encoding and storing the emotional qualities associated with particular memories, such as fear or anger (Hamann, 2009; McGaugh, 2004). For example, normal monkeys are afraid of snakes. But if the amygdala is damaged, a monkey loses its fear of snakes and other natural predators.

The frontal lobes are involved in retrieving and organizing information that is associated with autobiographical and episodic memories (Greenberg & Rubin, 2003). The prefrontal cortex seems to play an important role in working memory (D’Esposito & Postle, 2015; McNab & Klingberg, 2008).

The medial temporal lobes, like the frontal lobes, do not actually store the information that comprises our autobiographical memories. Rather, they are involved in encoding complex memories, by forming links among the information stored in multiple brain regions (Greenberg & Rubin, 2003; Shrager & Squire, 2009). As we described in the Focus on Neuroscience, “Assembling Memories,” on page 258, retrieving a memory activates the same brain regions that were involved in initially encoding the memory.

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ALZHEIMER’S DISEASE

GRADUALLY LOSING THE ABILITY TO REMEMBER

Understanding how the brain processes and stores memories has important implications. Dementia is a broad term that refers to the decline and impairment of memory, reasoning, language, and other cognitive functions. These cognitive disruptions occur to such an extent that they interfere with the person’s ability to carry out daily activities. Dementia is not a disease itself. Rather, it describes a group of symptoms that often accompany a disease or a condition.

The most common cause of dementia is Alzheimer’s disease (AD). It is estimated that about 5.4 million Americans suffer from AD. That number is expected to dramatically escalate as more and more “baby boomers” reach age 65. The disease usually doesn’t begin until after age 60, but the risk goes up with age. About 6 percent of men and women in the 65–74 age group have AD. Among adults age 85 and older, about half may have Alzheimer’s disease (Alzheimer’s Association, 2011).

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Although the cause or causes of Alzheimer’s disease are still unknown, it is known that the brains of AD patients develop an abundance of two abnormal structures—beta-amyloid plaques and neurofibrillary tangles (Ballard & others, 2011). The plaques are dense deposits of protein and other cell materials outside and around neurons. The plaques interfere with the ability of neurons to communicate, damaging the neurons to the point that they die. The tangles are twisted fibers that build up inside the neuron and interrupt the flow of nourishment to the neuron, ultimately causing the neuron to die. Although most older people develop some plaques and tangles in their brains, the brains of AD patients have them to a much greater extent (Petersen, 2002). The Focus on Neuroscience shown above vividly portrays the progressive loss of neurons that is the root cause of Alzheimer’s disease.

In the early stages of AD, the symptoms of memory impairment are often mild, such as forgetting the names of familiar people, forgetting the location of familiar places, or forgetting to do things. But as the disease progresses, memory loss and confusion become more pervasive. The person becomes unable to remember what month it is or the names of family members. Frustrated and disoriented by the inability to retrieve even simple information, the person can become agitated and moody. In the last stage of AD, internal brain damage has become widespread. The person no longer recognizes loved ones and is unable to communicate in any meaningful way. All sense of self and identity has vanished. At the closing stages, the person becomes completely incapacitated. Ultimately, Alzheimer’s disease is fatal (Alzheimer’s Association, 2011).

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Some 14.9 million Americans provide unpaid care for a person with Alzheimer’s disease or other dementia. These unpaid caregivers are primarily family members but also include friends and neighbors. In 2010, these caregivers provided 17 billion hours of unpaid care (Alzheimer’s Association, 2011). Not only is there a financial toll, but families and caregivers struggle with great physical and emotional stress as they try to cope with the mental and physical changes occurring in their loved one. The average number of hours of unpaid care provided for a relative or friend with Alzheimer’s increases as the person’s condition worsens.

Numerous resources, such as the Alzheimer’s Disease Education & Referral Center (www.alzheimers.org) and the Alzheimer’s Association (www.alz.org), are available to help support families and other caregivers.