220 Chapter 8
for maintaining recent memories, it is no longer needed once
the memory has become consolidated into a more stable, long-
term form. An amnesiac patient known as “E.P.” with bilateral
damage to his medial temporal lobes, for example, was able to
remember well the neighborhood he left 50 years before but
had no knowledge of his current neighborhood.
Using functional magnetic resonance imaging (fMRI) of
subjects asked to remember words, scientists detected more brain
activity in the left medial temporal lobe and left frontal lobe for
words that were remembered compared to words that were sub-
sequently forgotten. The increased fMRI activity in these brain
regions seems to indicate the encoding of the memories. Indeed,
lesions of the left medial temporal lobe impairs verbal memory,
while lesions of the right medial temporal lobe impairs nonver-
bal memories, such as the ability to remember faces.
Surgical removal of the right and left medial temporal lobes
was performed in one patient, designated “H.M.,” in an effort
to treat his epilepsy. After the surgery he was unable to consoli-
date any short-term memory. He could repeat a phone number
and carry out a normal conversation; he could not remember
the phone number if momentarily distracted, however, and if
the person to whom he was talking left the room and came back
a few minutes later, H.M. would have no recollection of hav-
ing seen that person or of having had a conversation with that
person before. Although his memory of events that occurred
before the operation was intact, all subsequent events in his life
seemed as if they were happening for the first time.
H.M.’s deficit was in declarative memory. His nondeclara-
tive memory —perceptual and motor skills, such as how to drive
a car—were still intact. The effects of the bilateral removal of
H.M.’s medial temporal lobes highlight the importance of these
structures—including the hippocampus, amygdala ( fig. 8.15 ),
and surrounding structures (including the entorhinal, perirhi-
nal, and parahippocampal cortexes not shown in the figure)—in
declarative memories. Surgical removal of the left medial tem-
poral lobe impairs the consolidation of short-term verbal mem-
ories into long-term memory, and removal of the right medial
temporal lobe impairs the consolidation of nonverbal memories.
On the basis of additional clinical experience, it appears
that the hippocampus is a critical component of the memory
system. Magnetic resonance imaging (MRI) reveals that the
hippocampus is often shrunken in living amnesic patients.
However, the degree of memory impairment is increased when
other structures, as well as the hippocampus, are damaged. The
hippocampus and associated structures of the medial temporal
lobe are thus needed for the acquisition of new information
about facts and events, and for the consolidation of short-term
into long-term memory, which is stored in the cerebral cortex.
Sleep, particularly slow-wave (non-REM) sleep, but perhaps
also REM sleep, is needed for optimum memory consolidation
by the hippocampus. Emotional arousal, acting via the struc-
tures of the limbic system, can enhance or inhibit long-term
memory storage. For example, stress has been shown to pro-
duce deficits in hippocampus-dependent learning and memory.
Recent studies indicate that individual neurons of the
medial temporal lobe, including the hippocampus, respondfrontal cortex and the hypothalamus can deliver shocks
that function as a reward. In rats, this reward is more
powerful than food or sex in motivating behavior. Simi-
lar studies have been done in humans, who report feelings
of relaxation and relief from tension, but not of ecstasy.
Electrodes placed in slightly different positions apparently
stimulate a punishment system in experimental animals,
who stop their behavior when stimulated in these regions.Memory
Brain Regions in Memory
Clinical studies of amnesia (loss of memory) suggest that sev-
eral different brain regions are involved in memory storage and
retrieval. Amnesia can result from damage to the temporal lobe
of the cerebral cortex, the hippocampus, the head of the caudate
nucleus (in Huntington’s disease), or the dorsomedial thalamus
(in alcoholics suffering from Korsakoff’s syndrome with thia-
mine deficiency). A number of researchers now believe that
there are several different systems of information storage in the
brain. One system relates to the simple learning of stimulus-
response that even invertebrates can do to some degree. This,
together with skill learning and different kinds of conditioning
and habits, is retained in people with amnesia.
There are different categories of memory, as revealed by
patients with particular types of brain damage and by numerous
scientific investigations. Scientists distinguish between short-
term memory and long-term memory. Long-term memory,
but not short-term memory, depends on the synthesis of new
RNA and protein, so that drugs that disrupt genetic transcrip-
tion or translation interfere with long-term (but not short-term)
memory. People with head trauma, and patients who undergo
electroconvulsive shock (ECS) therapy, may lose their memory
of recent events but retain their older memories. The conversion
of a short-term memory into a more stable long-term memory is
called memory consolidation. Memory consolidation requires
the activation of genes, the production of new proteins, and the
formation of new synapses. There is now evidence (in rodents)
that memory consolidation in the hippocampus also requires
glycogenolysis and lactate production in astrocytes at about the
time of training.
Long-term memory is classified as nondeclarative (or
implicit ) memory and declarative (or explicit ) memory. Non-
declarative memory refers to memory of simple skills and condi-
tioning (such as remembering how to tie shoelaces). Declarative
memory is memory that can be verbalized; it is subdivided
into semantic (fact) and episodic (event) memory. A semantic
memory would be remembering the names of the bones; an epi-
sodic memory would be remembering the experience of taking a
practical exam on the skeletal system.
People with amnesia have impaired declarative memory.
Scientists have discovered that the consolidation of short-
term into long-term declarative memory is a function of the
medial temporal lobe, particularly of the hippocampus and
amygdala ( fig. 8.15 ). Although the hippocampus is important