NEUROPSYCHOLOGY OF MEMORY

The neural networks of the brain are capable of responding to experience by the activation of
particular patterns of distributed activation. Donald Hebb described a basic principle of memory
that has been repeatedly supported by research: “Neurons which fire together, wire together.”
Neurons that are activated in a particular pattern at one time will tend to fire together in a
similar pattern in the future—this is the essence of memory.

The brain has various forms of circuits responsible for different systems of memory (Implicit
and explicit memory). The form of memory most commonly thought of as “memory” is termed
explicit or declarative memory. This form involves the conscious sensation of something being
recalled at the time of retrieval and allows for the awareness of the autobiographical or factual
knowledge to be shared, often verbally, with others and the self. This explicit memory system
requires the involvement of focal attention and the activation of the hippocampus within the
medial temporal lobe memory circuits for encoding and retrieval. Items focally attended are
placed in working memory, processed further, and then placed in long-term memory. After a
period of weeks to months, items are thought to undergo a process called cortical consolidation
that places them in permanent memory where their retrieval no longer requires the
hippocampus. Cortical consolidation helps to explain the phenomenon of retrograde amnesia
following a physical trauma to the head. The finding that cortical consolidation may require
rapid eye movement (REM) sleep also raises important questions regarding the relationships
among posttraumatic stress disorder, disturbances in REM sleep, and unresolved traumatic
memory.

Before explicit autobiographical memory processing becomes available after the first years of
life (during which time the hippocampus and orbitofrontal cortex are maturing), a form of
memory called implicit or nondeclarative memory is already in place and remains active
throughout the lifespan. Implicit memory involves a wide range of systems including behavioral,
emotional, and perceptual memory. When these circuits are activated in retrieval, they do not
have the sensation of something being recalled. For example, when riding a bicycle a person
may not recall having learned to ride and may not even feel that anything is being recalled.
Similarly, a person with a fear of dogs may be unable to explicitly recall (consciously) any event
that may explain such an emotional response. The existence of intact implicit recollection in the
absence of explicit memory is found in various conditions including surgical anesthesia,
hypnotic amnesia, the adverse effects of some benzodiazepines, neurological conditions such as
Korsakoff's syndrome and bilateral hippocampal strokes, divided attention, and childhood
amnesia. Such a dissociation in usually associated mental processes may also occur in response
to trauma and in individual with dissociative disorders. Thus, patients with post-traumatic stress
disorder may have an inability to recall a traumatic event and yet may avoid contextual stimuli

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similar to the initial trauma, evidence startle response and anxiety, and have intrusive
perceptual images each reflecting impaired explicit memory and intact elements of behavioral,
emotional, and perceptual implicit memory. Supported by initial imaging studies, this
explanation needs further validation through research into memory processes in the disorder.

1. Current understanding of the biology of memory has significant implications for several
fundamental issues in psychiatry. One example is the phenomenon of infantile amnesia, the
apparent absence of conscious memory for experiences from approximately the first 3 years of
life. Traditional views of infantile amnesia have emphasized repression (psychoanalytic theory)
and retrieval failure (developmental psychology). A common assumption has been that adults
retain memories of early events but cannot bring them into consciousness. However, another
possibility is that the capacity for classical conditioning and skill learning (i.e., nondeclarative
memory) emerges early in infancy, whereas declarative memory does not become available
until about the third year; limbic and diencephalic structures essential for declarative memory
may not be fully developed until that time. According to this view, infantile amnesia results not
from the adult's failure to retrieve early memories but from the child's failure to store them in
the first place. This is an intriguing suggestion, but recent evidence has not supported it. First,
recall-like memory abilities have been demonstrated in young infants. In addition, it now
appears that one of the most commonly employed tests of infant recognition memory, the
visual-paired comparison task, depends on declarative memory.

2.What probably limits the development of declarative memory is not the slow maturation of
the limbic-diencephalic structures essential for declarative memory, but rather the gradual
development and maturation of the neocortex. As the neocortex develops, memories
supported and stored there become more complex. Strategies emerge for organizing incoming
information, language develops, and declarative memories become more richly encoded and
interconnected, and more persistent. The existence of multiple forms of memory and the
gradual maturation of neocortex suggest an alternative to traditional views of infantile amnesia.
It is not necessary to suppose that fully formed childhood memories persist but cannot be
retrieved. An alternative view is that the capacity to store a viable declarative memory develops
only gradually.

3.The existence of multiple memory systems also has implications for issues in psychoanalytic
theory, including the construct of the unconscious. In considering the effects of past
experience, it matters what view one takes of the nature of memory. By the traditional view,
memory is a unitary faculty, and representations in memory vary mainly in strength and
accessibility. According to this view, material that is unconscious is below some threshold of
accessibility and could potentially be made available to consciousness. An alternative view
begins with the distinction between memory that by its nature can be brought to mind (i.e.,

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declarative memory) and other kinds of memory that are by their nature nonconscious in the
sense that the knowledge is expressed through performance without affording any conscious
memory content. In this view, early experience might affect later behavior, but the experience
can persist to affect behavior without necessarily including a record of the event itself. Behavior
can change as experience accumulates in altered dispositions, preferences, conditioned
responses, habits, and skills, but these changes do not afford any actual awareness that
behavior is being influenced by past experience. Nor is there any necessity that any particular
past experience has been recorded. In this sense, the unconscious does not become conscious.
Behavioral change can occur when new habits are acquired that supersede old ones or when
sufficient awareness of a habit is gained such that it can to some extent be isolated or when the
stimuli that elicit it can be processed differently. However, one does not become aware of its
content in the same sense that one knows the content of a declarative memory, and one does
not become aware of the early experiences that gave rise to the habit.

4. A better understanding of the biology of memory has also shed light on the imperfect nature
of memory retrieval. It is quite possible to remember events that never happened. One way to
conceptualize this problem is to consider the phenomenon of source amnesia, which occurs
when an individual remembers some information without being able to remember how, where,
or when the information was learned. If an individual imagines a certain event, at some later
time it is possible to forget the moment when the scene was imagined while still recalling
details as if they really happened. In this way, memory distortions can be caused by
misattributions of source. Inferences and other thoughts invoked when recalling an experience
can also be incorporated into memory such that a subsequent retrieval mistakenly includes the
intervening information. Thus, the reconstructive nature of recollection poses problems for
interpreting apparently “recovered” memories of traumatic events and emphasizes the
importance of corroboration. As documented by experiments in adults and in children, illusory
memories can be created, and children appear to be particularly susceptible to these effects.
Several lines of evidence suggest that processing in the frontal lobes is essential for accurate
source memory. For example, failures of source memory in the elderly appear to be associated
with frontal lobe dysfunction. Patients with frontal lobe damage are highly susceptible to
source errors, and they also tend to confabulate, sometimes producing bizarre responses that
are inaccurate as well as implausible. Convergent results from PET studies in normal subjects
imply that frontal regions, especially in the right hemisphere, play a key role in mediating
accurate retrieval.

5. Finally, the biological understanding of declarative memory developed here is important in

relation to the topic of consciousness. Declarative memory entails both a lasting influence of
prior experience and an awareness of that remembering. The varieties of nondeclarative
memory, such as priming, commonly occur without this awareness of remembering. To the

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extent that this contrast between memory with awareness versus memory without awareness
can be understood at the neural level, a neuroscientific foundation can be developed to explain
why certain types of neural processing lead to the subjective experience of remembering.
Particular combinations of neocortical processing networks working in concert with the medial
temporal lobe appear to come into play during the experience of remembering, whereas
altered activity in a localized neocortical area can lead to the phenomenon of priming without
explicit remembering. In this way, it may be possible to move from probing the neural
substrates of declarative memory to addressing the question of why neural processing
engenders consciousness at all, a problem that is central to the study of the neural basis of the
mind.

CORTICAL ORGANIZATION OF MEMORY

The question of where memories are stored in the brain has long been a major research issue.
In the 1920s Karl Lashley carried out a series of experiments that were directed at this
problem.Lashley recorded the number of trials that rats needed to relearn a preoperatively
learned maze problem after removal of different amounts of cerebral cortex. The deficit was
proportional to the amount of cortex removed and, further, it seemed to be qualitatively
similar, regardless of what region of cortex was removed. Lashley concluded that memory for
the maze habit was not localized in any one part of the brain, but instead was distributed
equally over the entire cortex. Subsequent work has led to a revision of this idea. Maze learning
in rats depends on many forms of information, including visual, tactual, spatial, and olfactory
information. These various forms of information are processed and stored in different areas.
Thus, the correlation between retention score and lesion size that Lashley observed reflects the
progressive encroachment on specialized cortical areas serving the many components of
cognition important to maze learning.

Many parts of the nervous system participate in storing representations of an event in memory.
During an event, visual information is stored in inferotemporal cortex so that the same visual
material can later be recognized as familiar. Concurrently, other components of the event—
including spatial, temporal, tactile, olfactory, emotional, and other sorts of information—are
processed and stored separately. Memory storage in the cerebral cortex thus depends on a
fractionation of experience as follows. First, any particular event or learning task is composed of
a number of components. Second, each component engages a particular processing site or set
of sites. Third, each processing site stores information as an outcome of the processing that is
done. Thus, memory is both distributed and localized in the nervous system. It is distributed in
the sense that, as Lashley concluded, there is no unitary cortical center dedicated solely to the
storage of memories. Yet, memory is localized in the sense that different aspects or dimensions

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of events are stored at specific cortical sites—the same regions specialized to analyze and
process those particular aspects or dimensions of information.

BIOLOGY OF LEARNING
Learning leads to neurochemical changes in the central nervous system. Research with simple
organisms has revealed that the learning of avoidance behavior alters the chemical structure of
cells in the nervous system; when the avoidance is unlearned, the chemical changes are
reversed. Thus, the foundation for understanding the neurochemistry of learning has been laid,
and a reciprocal interaction is evident between biological processes in the central nervous
system and behavior changes resulting from environmental influences. Research conducted by
Eric Kandel and his colleagues at Columbia University with Aplysia californica has been
particularly well covered in the psychiatric literature. The aplysia, a sea mollusk, is a useful
animal to study because of the simplicity of its nervous system, which contains about 20,000
neurons, many of which are large and readily identifiable. The specific behavior studied is a
defensive reflex involving withdrawal of the snail's siphon when the animal is tactually
stimulated. When the mollusk is touched repeatedly, it learns not to withdraw its siphon and
gill, a process known as habituation. If the mollusk then receives a strong stimulus, such as an
electric shock, it becomes sensitized, such that even a previously subthreshold tactile
stimulation causes the animal to withdraw its gill and siphon. Furthermore, the snail can be
classically conditioned so that it withdraws its siphon and gill to a conditioned stimulus.
Habituation, sensitization, and classical conditioning of the reflex in the snail can be considered
forms of learning and memory. In learning, a short-term stimulus has to be translated into long-
lasting changes that involve a series of biochemical changes that are functionally interlinked
and operate in overlapping time ranges.

Many but not all of the neuronal anatomical and chemical bases for the learning processes have
been worked out in this animal model. Sensory neurons receiving tactile information form
excitatory synapses with the gill and siphon motor neurons that cause the withdrawal activity.
Habituation, sensitization, and classical conditioning all involve neurochemical changes in the
sensory neuron, resulting in alterations in the amount of excitatory neurotransmitter released.
The neurochemical basis of habituation is that, after repeated stimulation of the sensory
neuron (e.g., repeated tactile stimulation), less calcium than usual enters the presynaptic nerve

terminal, resulting in less neurotransmitter being released and, thus, less activity by the motor
neurons. Sensitization requires the presence of additional neurons, called facilitator

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interneurons, that synapse onto the sensory neurons. The sensitizing stimulus, such as an
electric shock, causes the facilitator interneuron to release serotonin that binds to serotonin
receptors on the sensory neuron. Activation of the serotonin receptors activates adenylate
cyclase, producing cyclic adenosine monophosphate (cAMP), thereby activating a cAMP-
dependent protein kinase, which is believed to phosphorylate an S-type potassium channel.
Phosphorylation of the potassium channel results in increased calcium influx during the action
potential and increased neurotransmitter release. Although classical conditioning also results in
an increased amount of neurotransmitter released by the sensory neuron, the neurochemical
basis is less well understood at this time but may involve additional protein kinases.

Because psychotherapy is best viewed as a learning process, and learning produces changes in
neuronal architecture, the behavior changes associated with therapy should produce
anatomical changes in the central nervous system. As Eric Kandel notes, such changes should
be detectable by imaging methods. In an interesting study of patients with obsessive-
compulsive disorder, positron emission tomography was used to investigate changes in cerebral
metabolic rates for glucose before and after treatment. The effects of two treatments were
compared: fluoxetine hydrochloride, and behavior therapy consisting of exposure and response
prevention. Although the study involved nine patients per group, glucose metabolic rates in the
right head of the caudate nucleus changed when the obsessive-compulsive disorder was
successfully treated with either fluoxetine or behavior therapy; these changes did not occur in
patients who did not respond to treatment, which suggests that the changes in brain
metabolism consequent upon learning-based changes in behavior may be similar to those
induced by pharmacotherapy. These results underline the reciprocal interaction between
learning and the central nervous system.