VII.

Biological Basis of Memory

One of the most exciting topics of scientific investigation lies in cognitive neuroscience: How do physical processes in the brain give rise to our psychological experiences? In particular, a great deal of research is trying to uncover the biological basis of learning and memory. How does the brain code experience so that it can be later remembered? Where do memory processes occur in the brain?

In the early and mid-1900s, psychologists engaged in the “search for the engram.” They used the term engram to refer to the physical change in the nervous system that occurs as a result of experience. (Today most psychologists use the term memory trace to describe the same thing.) The researchers hoped to find some particular location in the brain where memories were stored. This early work, conducted mostly with animals, failed to find a specific locus of memory in the brain. For example, American psychologist Karl Lashley trained rats to solve a maze, then surgically removed various parts of the rats’ brains. No matter what part of the brain he removed, the rats always retained at least some ability to solve the maze. From such research, psychologists concluded that memory is distributed across the brain, not localized in one place.

A.

Brain Structures Involved in Memory

Modern research confirms the hypothesis that memories are not localized in one place in the brain, but rather involve interacting circuits operating across the brain. Many of the neural regions used in perceiving and attending to information seem also to be involved in the encoding and subsequent retrieval of information. Thus, although different brain regions perform different memory-related processes, the memories themselves do not appear to reside in any particular place.

The hippocampus is thought to be one of the most important brain structures involved in memory. The case of the patient H.M. (only his initials were used to preserve his anonymity), one of the most famous case studies in neuropsychology, strikingly demonstrates the importance of the hippocampus. In 1953, as a 27-year-old man, H.M. underwent brain surgery to control severe epileptic seizures. The surgeons removed his medial temporal lobes, which included most of the hippocampus, the amygdala, and surrounding structures. Although the operation successfully controlled H.M.’s seizures, it had an altogether unexpected and devastating side effect: H.M. was unable to form new long-term memories in a way that he could later retrieve them. That is, he could not remember anything that happened to him after the surgery. His memory of events prior to the surgery was mostly intact, and his reasoning and thinking skills remained strong. But he could not remember meeting new people or new experiences for more than a few minutes. Researchers concluded that the hippocampus and its surrounding structures in the medial temporal lobe play a critical role in the encoding of episodic memories, especially in binding elements of memories together to locate the memories in particular times and places.

Further evidence for the importance of the hippocampus and other regions of the brain in human memory has been provided by advanced brain imaging techniques, such as positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). Brain imaging methods allow researchers to see the activity of the living human brain on a computer screen as a person engages in different types of cognitive tasks, such as reading, solving math problems, or memorizing a list of words. These scanning methods take advantage of the fact that when a brain region becomes active, the rate at which neurons (brain cells) fire increases within this region. Increased neuronal firing in a region causes an increase in blood flow to that region, which the scanners can measure. Therefore, if a person is encoding new information into memory and the hippocampus is active during encoding, we would expect to see increased blood flow to the hippocampus. This is exactly the pattern observed in most studies.

Neuroimaging techniques have revealed other brain regions involved in memory. The frontal lobes play an important role in encoding and retrieving memories. For example, certain areas of the left frontal lobe seem especially active during encoding of memories, whereas those in the right frontal lobe are more active during retrieval. An area in the right anterior prefrontal cortex becomes active when a person is trying to retrieve a previously experienced episode. Some evidence indicates that this region may be even more active when the retrieval attempt is successful—that is, when the person not only attempts to remember but is able to remember some previous occurrence.

For more information on brain imaging methods, See also Brain: Brain Imaging.

B.

Biochemistry of Memory

The study of the biochemistry of memory is another exciting scientific enterprise, but one that can only be touched upon here. Scientists estimate that an adult human brain contains about 100 billion neurons. Each of these is connected to hundreds or thousands of other neurons, forming trillions of neural connections. Neurons communicate by chemical messengers called neurotransmitters. An electrical signal travels along the neuron, triggering the release of neurotransmitters at the synapse, the small gap between neurons. The neurotransmitters travel across the synapse and act on the next neuron by binding with protein molecules called receptors. Most scientists believe that memories are somehow stored among the brain’s trillions of synapses, rather than in the neurons themselves.

Scientists who study the biochemistry of learning and memory often focus on the marine snail Aplysia because its simple nervous system allows them to study the effects of various stimuli on specific synapses. A change in the snail’s behavior due to learning can be correlated with a change at the level of the synapse. One exciting scientific frontier is discovering the changes in neurotransmitters that occur at the level of the synapse.

Other researchers have implicated glucose (a sugar) and insulin (a hormone secreted by the pancreas) as important to learning and memory. Humans and other animals given these substances show an improved capacity to learn and remember. Typically, when animals or humans ingest glucose, the pancreas responds by increasing insulin production, so it is difficult to determine which substance contributes to improved performance. Some studies in humans that have systematically varied the amount of glucose and insulin in the blood have shown that insulin may be the more important of the two substances for learning.

Scientists also have examined the influence of genes on learning and memory. In one study, scientists bred strains of mice with extra copies of a gene that helps build a protein called N-methyl-D-aspartate, or NMDA. This protein acts as a receptor for certain neurotransmitters. The genetically altered mice outperformed normal mice on a variety of tests of learning and memory. In addition, other studies have found that chemically blocking NMDA receptors impairs learning in laboratory rats. Future discoveries from genetic and biochemical studies may lead to treatments for memory deficits from Alzheimer’s disease and other conditions that affect memory.