REVIEW ARTICLE

Understanding Memory Dysfunction

Andrew E. Budson, MD

associated with conscious awareness (explicit) and can be consciously

Background: Although traditionally memory has been viewed as a simple
recalled (declarative), whereas others are typically unconscious (non-
concept, converging and complementary evidence from patient studies and
declarative) and are instead expressed by a change in behavior (implic-
more recent neuroimaging research suggest that memory is a collection of
it).6 Memory can also be categorized in other ways, such as the nature
mental abilities that use different neuroanatomical systems within the brain.
of the material to be remembered, verbal7 versus visual.8
Neurologic injury may cause damage to one or more of these memory
systems.
Review Summary: In this review a number of different memory systems are
Episodic Memory
discussed, including their function, neuroanatomy, and the different disor-
ders that disrupt them. Episodic memory, the most clinically relevant
memory system, depends upon the hippocampus and other medial temporal
lobe structures, the limbic system, and the frontal lobes. Several other kinds Episodic memory refers to the explicit and
of memory are contrasted with episodic memory, including semantic mem-
ory, simple classic conditioning, procedural memory, priming, and working declarative memory system used to remember a
memory.
particular episode of your life.
Conclusion: Improved understanding of these different types of memory
will aid the clinician in the diagnosis and treatment of the memory disorders
of their patients. As more specific therapeutic strategies are developed for the
treatment of diseases which cause memory dysfunction, this knowledge will
become increasingly important.
Episodic memory refers to the explicit and declarative mem-
ory system used to remember a particular episode of your life, such
Key Words: memory, Alzheimer disease, frontal lobes, false memory, as sharing a meal with a friend. This memory system is dependent
memory distortions upon the medial temporal lobes (including the hippocampus), as
(The Neurologist 2009;15: 71–79) episodic memory has been largely defined by what patients with
medial temporal lobe lesions cannot remember relative to healthy
individuals. Other critical structures in the episodic memory system
(some of which are associated with a circuit described by Papez in
N eurologists are increasingly referred patients with complaints
of impaired memory. Memory dysfunction can be caused by a
diverse group of neurologic disorders, including neurodegenerative
19379) include the basal forebrain with the medial septum and
diagonal band of Broca, the retrosplenial cortex, the presubiculum,
the fornix, mammillary bodies, the mammillothalamic tract, and the
diseases, strokes, tumors, head trauma, hypoxia, cardiac surgery, anterior nucleus of the thalamus (Fig. 1).2 A lesion in any one of
malnutrition, attention deficit hyperactivity disorder, depression, these structures may cause the impairment that is characteristic of
anxiety, and medication effects.1,2 Memory function can also be dysfunction of the episodic memory system.
altered by normal aging.3 Although once thought to be a simple Memory loss due to dysfunction of the episodic memory
concept, we now consider memory to be a collection of mental system generally follows a pattern known as Ribot’s law, which
abilities that use different systems and components within the brain. states that events just prior to an ictus are most vulnerable to decay,
Memory research that began with neuropsychological studies of whereas remote memories are more resistant. Thus, dysfunction
patients with focal brain lesions and now includes newer methods of the episodic memory system typically causes greatest disrup-
such as positron emission tomography, functional MRI, and event- tion in the ability to learn new information (anterograde amnesia)
related potentials has provided the rationale for a more refined and and moderate disruption in the ability to recall recently learned
improved classification system.4 In this article, a number of different information (retrograde amnesia), whereas the ability to recall
forms of memory will be reviewed, including the important ana- remotely learned information is generally intact (Fig. 2).10
tomic structures for each, and the major neurologic disorders that
disrupt them (Tables 1 and 2). A greater understanding of these
memory systems will aid neurologists in their diagnosis and treatment
of the memory disorders of their patients. This improved understanding
will become increasingly important as new therapeutic interventions for The core of the episodic memory system is the
memory disorders are developed.
A memory system is a way for the brain to process informa-
medial temporal lobe and hippocampus.
tion that will be available for use at a later time.5 Some systems are

From the *Center for Translational Cognitive Neuroscience, Geriatric Research The core of the episodic memory system is the medial temporal
Education Clinical Center, Bedford VA Hospital, Bedford, MA; *Boston
University Alzheimer’s Disease Center, Department of Neurology, Boston lobe and hippocampus. It is worth examining these structures more
University School of Medicine, Boston, MA. closely. The medial temporal lobes may seem simple but they are
Reprints: Andrew E. Budson, MD, Bldg 62, Rm B30, Bedford VA Hospital, 200 actually neuroanatomically complex structures with multiple regions
Spring Road, Bedford MA 01730. E-mail: [email protected]. and subregions. In Figure 3 you can see the medial temporal lobe
Copyright © 2009 by Lippincott Williams & Wilkins
ISSN: 1074-7931/09/1502-0071 structures, including the parahippocampal gyrus, presubiculum, subic-
DOI: 10.1097/NRL.0b013e318188040d ulum, and hippocampus proper, including its subregions.

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Budson The Neurologist • Volume 15, Number 2, March 2009

TABLE 1. Selected Memory Systems

Memory System Examples Awareness Length of Storage Major Anatomical Structures
Episodic memory Remembering a short story, Explicit declarative Minutes to years Medial temporal lobe, anterior
what you had for dinner thalamic nucleus, mamillary
last night, and what you body, fornix, prefrontal
did on your last birthday cortex
Semantic memory Knowing who was the first Explicit declarative Minutes to years Inferior lateral temporal lobes
President of the US, the
color of a lion, and how a
fork and comb are
different
Autonomic simple classical Pavlov’s dog; a fear response Implicit nondeclarative Minutes to years Amygdala and basolateral
conditioning limbic system
Motoric simple classical Eye-blink conditioning Implicit nondeclarative Minutes to months Cerebellum
conditioning
Procedural memory Driving a standard Implicit nondeclarative Minutes to years Basal ganglia, cerebellum,
transmission car, and supplementary motor area
learning the sequence of
numbers on a touch-tone
phone without trying
Perceptual priming Word-stem completion: Implicit nondeclarative Minutes to days Cortical sensory association
octopus3oct____ areas (eg, extrastriate visual
cortex for visual perceptual
priming)
Conceptual priming Word-stem completion: Implicit nondeclarative Minutes to days Inferior prefrontal cortex
sea creatures3oct____
Working memory Phonological: keeping a Explicit declarative Seconds to minutes; Phonological: prefrontal cortex,
phone number “in your information actively Broca’s area, Wernicke’s area
head” before dialing rehearsed or Spatial: prefrontal cortex,
Spatial: mentally following manipulated visual association areas
a route, or rotating an
object in your mind

TABLE 2. Selective Memory System Disruptions in Common Clinical Disorders

Episodic Semantic Simple Classical Procedural Working
Disease Memory Memory Conditioning Memory Priming Memory
Alzheimer disease ⫹⫹⫹ ⫹⫹ ⫹ ⫺ ⫺perceptual ⫹conceptual ⫹⫹
Frontotemporal dementia ⫹⫹ ⫹⫹ ? ⫺ ? ⫹⫹⫹
Semantic dementia ⫹ ⫹⫹⫹ ? ? ? ⫺
Lewy body dementia ⫹⫹ ? ? ? ? ⫹⫹
Stroke and vascular dementia ⫹ ⫹ ⫾ ⫹ ⫾ ⫹⫹
Parkinson disease ⫹ ⫹ ⫺ ⫹⫹⫹ ⫺ ⫹⫹
Huntington disease ⫹ ⫹ ⫺ ⫹⫹⫹ ⫺ ⫹⫹⫹
Progressive supranuclear palsy ⫹ ⫹ ? ⫹⫹ ? ⫹⫹⫹
Korsakoff syndrome ⫹⫹⫹ ⫺ ⫹ ⫺ ⫾ ⫾
Multiple sclerosis ⫹ ⫾ ⫾ ? ⫺ ⫹⫹
Transient global amnesia ⫹⫹⫹ ⫾ ? ⫺ ⫺ ⫺
Hypoxic-ischemic injury ⫹⫹ ⫺ ⫺ ⫺ ⫾ ⫾
Head trauma ⫹ ⫹ ⫾ ⫾ ? ⫹⫹
Tumors ⫾ ⫾ ⫾ ⫾ ⫾ ⫾
Depression ⫹ ⫾ ? ⫹⫹ ? ⫾
Anxiety ⫹ ⫺ ⫾ ⫺ ⫾ ⫾
Obsessive compulsive disorder ⫹ ⫺ ⫾ ⫹⫹ ⫾ ⫹⫹
Attention deficit hyperactivity ⫺ ⫺ ⫺ ? ⫾ ⫹
disorder
⫹⫹⫹ indicates early and severe impairment; ⫹⫹, moderate impairment; ⫹, mild impairment; ⫾, occasional impairment or impairment in some studies, but not others; ⫺, no
significant impairment; ?, unknown.

Although we do not completely understand how the medial riences an episode of their life, such as having breakfast that
temporal lobes store and retrieve memories, our current understand- morning. The cortically distributed patterns of neural activity rep-
ing from cognitive neuroscience is as follows. An individual expe- resenting the sights, sounds, smells, tastes, emotions, and thoughts

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The Neurologist • Volume 15, Number 2, March 2009 Understanding Memory Dysfunction

FIGURE 1. Episodic memory. The me-

dial temporal lobes, including the hip-
pocampus and parahippocampus, form
the core of the episodic memory sys-
tem. Other brain regions are also nec-
essary for episodic memory to function
correctly. In addition to being involved
in episodic memory, the amygdala is
also important for the autonomic con-
ditioning. (Adapted with permission
from Budson and Price, New England
Journal of Medicine, 2005).

FIGURE 2. Ribot’s law.

during that episode are transferred first to the parahippocampal

region and then to the hippocampus proper (Fig. 4). After being
transferred to the entorhinal cortex, the information is processed in
the dentate gyrus, and then transferred to the CA3 region where it is
further processed (Fig. 5). It is in this CA3 region where the critically
important hippocampal index is assigned, allowing the memory to be stored
in a unique way so that it can later be recalled.
Typically memories are retrieved when a cue from the environ-
ment matches a part of the stored memory. Continuing our breakfast
example, years later the individual might now bite into a little cake that FIGURE 3. Detailed anatomy of the medial temporal lobe.
tastes remarkably like the one that he had previously at breakfast. This PHG, indicates parahippocampal gyrus; Pr, presubiculum; v,
sensory cue is transferred from the cortex to the parahippocampal ventricle; S, subiculum. CA1, CA2, and CA3 are subregions
region and to the hippocampus (Fig. 4). After the cue is transferred from of the hippocampus, and ML, GL, and PL are different re-
the entorhinal cortex it now goes directly to the CA3 region where the gions of the dentate gyrus of the hippocampus. (Adapted
original hippocampal index is retrieved (Fig. 6). When found, the with permission from Martin JH. Neuroanatomy: Text and
hippocampal index may be used to retrieve much of the original pattern Atlas. New York, NY.: Elsevier, 1989, p. 391; permission
of the neural activity representing the original episode stored in mem- granted by Elsevier).
ory. This retrieved pattern of activity may then be transferred to the
CA1 region, the subiculum, the entorhinal cortex, and then back to the
cortex—recreating all sights, sounds, smells, tastes, emotions, and The hippocampus remains critical for memory retrieval until
thoughts of the original memory episode (Fig. 4). a process known as consolidation occurs. Much research still needs
to be done to better understand consolidation, but one thought is
that once a memory is consolidated the distributed pattern of
cortical neural activity is directly linked together, such that when
a cue is encountered, the memory may be retrieved directly from
The hippocampus remains critical for cortical-cortical connections, without the need for the hippocam-
pus. And, although there are many details that need to be learned,
memory retrieval until a process known as there is much data suggesting that sleep is critical for consolida-
consolidation occurs. tion to occur.11,12
In looking at the cognitive neuroscience model just presented
of how memories are stored and retrieved, it is the CA3 region of the

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Budson The Neurologist • Volume 15, Number 2, March 2009

FIGURE 6. Schematic representation of retrieval in the

medial temporal lobe.

half-way down the aisle on the left (Fig. 7a). On the second day, the car
is parked in the Blue area, on the 2nd floor, and it was not such as good
day. Nonetheless, this distinct pattern of neural activity allows a unique
hippocampal index to form that enables one to remember that the car
was parked in the Blue area, on the 2nd floor, and half-way down the
aisle on the right (Fig. 7b). On the third day, the car is also parked in the
Blue area, on the 2nd floor, and it again was not such a good day (Fig.
7c). Although one might wish that a hippocampal index will form to
FIGURE 4. Areas of the cerebral cortex, including sensory
enable one to remember that the car was parked in the Blue area, on the
areas, are connected bidirectionally to the parahippocampal
2nd floor, and all the way down the aisle on the left—there is a problem.
region, which is in turn bidirectionally connected to the hip-
When there are completely overlapping patterns of neural activity, a
pocampus. (Adapted with permission from Eichenbaum,
separate hippocampal index cannot form. Instead, there is a single
1997; permission granted by Science Magazine).
hippocampal index that forms for both days 2 and 3 (Fig. 7d). This
hippocampal index is strengthened for the common aspects of the 2
memories: parking in the Blue area, on the 2nd floor. But, this index
will also contain divergent aspects of the memory: half-way down the
aisle on the right and all the way down the aisle on the left. Thus, on day
3, it will be easy to remember that the car is parked in the Blue area on
the 2nd floor, but it will be difficult to remember if it is parked half-way
down the aisle on the right or all the way down the aisle on the left.

Over the last 10 years, it has become increasingly

clear that in addition to the medial temporal lobes
and Papez’s circuit, the frontal lobes are also
FIGURE 5. Schematic representation of encoding in the me-
dial temporal lobe. important for episodic memory.

hippocampus that seems most critical—it is this region in which the

hippocampal index is formed, and in which pattern matching of cues
and memories occurs. Although we do not exactly know how the Over the last 10 years, it has become increasingly clear that in
CA3 region is involved in these activities, a number of models using addition to the medial temporal lobes and Papez’s circuit, the frontal
neural networks have been proposed. A simplified example of such lobes are also important for episodic memory.13,14 Whereas the medial
a model is as follows. In this example, we will show how an temporal lobes are critical for the retention of information, the frontal
individual can find their car when they park in a parking garage over lobes are important for the acquisition, registration, or encoding of
3 successive days—and also why it is sometimes difficult for an information7; retrieval of information without contextual and other
individual to find their car. In this mythical parking garage, there are cues15; recollection of the source of information16; and assessment of
2 areas, Red and Blue, and 2 levels, 1st and 2nd. Two affective the temporal sequence and recency of events.17 Also, notable is that the
states, happy and sad, are also shown to represent not only emotions left medial temporal and left frontal lobes are most active when a person
but other contextual details that may differ between one day and the is learning words,7 and that the right medial temporal and right frontal
next. On the first day, the car is parked in the Red area, on the 1st lobes are most active when learning visual scenes.8
floor, and it was a good day. From this distributed pattern of neural One important reason why the frontal lobes are highly in-
activity a hippocampal index can be formed that helps one remem- volved in episodic memory is that they enable the individual to focus
ber that the car was parked in the Red area, on the 1st floor, and their attention on the information to be remembered and to engage

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The Neurologist • Volume 15, Number 2, March 2009 Understanding Memory Dysfunction

FIGURE 7. A neural network model.

See text for details.

the medial temporal lobes. Dysfunction of the frontal lobes may memory dysfunction attributable to Alzheimer disease versus depression.
cause a variety of memory problems, including distortions of epi- Patients with Alzheimer disease have a dysfunctional “recent memory file
sodic memory and false memories, such as when information be- cabinet,” whereas patients with depression have a dysfunctional “file clerk.”
comes associated with the wrong context18 or incorrect specific The time course of the patient’s episodic memory deficit is often
details.19 Extreme memory distortions are often synonymous with extremely helpful in distinguishing different disorders. Disorders of
confabulations, which occur when “memories” are created to be episodic memory may be transient, such as those due to concussion,
consistent with current information,18 such as “remembering” that seizure, or transient global amnesia. Static disorders, including trau-
someone broke into the house and rearranged household items. matic brain injury, hypoxic or ischemic injury, single strokes, surgical
A clinically useful analogy can be used to help conceptualize the lesions, and encephalitis, are typically maximal at onset, improve, and
dysfunction in episodic memory that occurs due to damage to the medial then become stable. (Note that in static disorders the onset may last
temporal lobes (and Papez’s circuit) versus damage to the frontal several days, and the period of improvement may last 2 years or more.)
lobes.20,21 The frontal lobes are analogous to the “file clerk” of the Degenerative diseases, such as Alzheimer disease,22 dementia with
episodic memory system, the medial temporal lobes to the “recent Lewy bodies, and frontotemporal dementia, begin insidiously and
memory file cabinet,” and other cortical regions to the “remote memory progress gradually. Disorders that affect multiple brain regions, such as
file cabinet” (Table 3). Thus, if the frontal lobes are impaired, it is multiple sclerosis and vascular dementia, generally progress in a step-
difficult— but not impossible—to get information in and out of storage. wise manner. Some disorders of memory can have a more complicated
For example, getting information into storage may require stronger and variable time course, including memory dysfunction attributable to
encoding, and getting information out of storage may require stronger tumors, hypoglycemia, medications, and Korsakoff syndrome.
cues from the environment. Additionally, when the frontal lobes are When a disorder of episodic memory is suspected due to inabil-
impaired the information stored in memory may be distorted due to
ity to remember recent information and experiences accurately, further
“improper filing” that leads to an inaccurate source, context, or se-
evaluation is warranted. A detailed history of the memory dysfunction
quence. If, on the other hand, the medial temporal lobes are impaired,
should be taken, with particular emphasis on the time course of the
it may be impossible for recent information to be stored. This will often
memory disorder. Speaking with a caregiver or other informant is
lead the patient to ask for the same information again and again—perhaps
20 times in an hour. Older information that has been consolidated over usually critical, since the patient with memory dysfunction will invari-
months to years is likely stored in other cortical regions and will therefore ably not remember important aspects of the history. A history of other
be available for retrieval even when the medial temporal lobes or Papez’s cognitive deficits (such as deficits in attention, language, visuospatial,
circuit are damaged. To illustrate this analogy we can compare the episodic and executive function) should be obtained. Medical and neurologic
examinations should be performed, searching for signs of systemic
illness, focal neurologic injury, and neurodegenerative disorders.
TABLE 3. A Filing Analogy of Episodic Memory Brief cognitive testing may be performed by asking the patient to
remember several words or a short story, or by using tools such as
Brain Structure Analogy Mini-Mental State Examination,23 the Blessed Dementia Scale,24 the
Frontal lobes File clerk Three Words-Three Shapes memory test,2 the word list memory test of
Medial temporal lobes Recent memory files the Consortium to Establish a Registry for Alzheimer disease,25 the
Other cortical regions Remote memory files Drilled Word Span Test,2 and the Seven-Minute Screen.26 To help
distinguish episodic memory dysfunction attributable to impairment

© 2009 Lippincott Williams & Wilkins 75

Budson The Neurologist • Volume 15, Number 2, March 2009

of the frontal lobes versus impairment of the medial temporal lobes, Almost any disorder that can disrupt the anterior and infero-
difficulties in the encoding and retrieval of information should be lateral temporal lobes may cause impairment of semantic memory,
contrasted with a primary failure of storage. When information including traumatic brain injury, stroke, surgical lesions, encepha-
cannot be remembered even when multiple rehearsals have maxi- litis, and tumors (Table 2). Patients with semantic dementia (the
mized encoding, and retrieval demands have been minimized with temporal variant of frontotemporal dementia) exhibit deficits in all
the use of a multiple-choice recognition test, a primary failure of functions of semantic memory, such as naming, single-word com-
storage is present. In complex cases, a formal neuropsychological prehension, and impaired general knowledge (such as the color of
evaluation should be obtained. common items). Other aspects of cognition, however, are relatively
The history, examination, and cognitive testing will suggest a preserved, including components of speech, perceptual and nonver-
differential diagnosis, which in turn will determine which laboratory bal problem-solving skills, and episodic memory.40
and imaging studies are indicated. Treatment depends upon the specific Although naming difficulties (particularly with proper nouns)
disorder identified. Cholinesterase inhibitors have been approved by the are common in healthy older adults, naming difficulties may also be
Food and Drug Administration (FDA) to treat Alzheimer disease27 and a sign of a disorder of semantic memory. When a disorder of
Parkinson disease dementia28; these medications have also been used to semantic memory is suspected, the evaluation should include the
treat vascular dementia29 and dementia with Lewy bodies.30 Meman- same components as the evaluation for episodic memory disorders.
tine has been approved to treat Alzheimer disease, with or without One of the first aspects of the history and cognitive examination that
concomitant treatment with cholinesterase inhibitors.31 should be ascertained is whether the problem is solely one of
difficulty in recalling people’s names and other proper nouns (com-
mon in healthy older adults) or to a true loss of semantic informa-
Semantic Memory tion. Patients with mild dysfunction of semantic memory may show
only reduced generation of words in a semantic category (for
example, the number of grocery items that can be generated in 1
minute), whereas patients with a more severe impairment of seman-
Semantic memory refers to our store of conceptual tic memory usually show a 2-way naming deficit: they are unable to
name an item when it is described, and they are also unable to
and factual knowledge that is not related to any describe an item when it is named. General knowledge is also
impoverished in these more severely affected patients. Treatment
specific memory. will depend upon the specific disorder identified.

Simple Classic Conditioning

Semantic memory refers to our store of conceptual and factual Simple classic conditioning involves the pairing of 2 stimu-
knowledge that is not related to any specific memory, such as the color li—an unconditioned stimulus and a conditioned stimulus. When
of broccoli or what a fork is used for. Like episodic memory, semantic paired together repeatedly, the response can then be elicited by the
memory, is an explicit and declarative memory. Evidence that semantic conditioned stimulus alone (Table 1). Think of the famous case of
memory and episodic memory are separate memory systems has come Pavlov’s dog: the meat (the unconditioned stimulus) is paired with
from both neuroimaging studies4 and the fact that previously acquired the bell (the conditioned stimulus). After a number of pairings, the
semantic memory is spared in patients who have severe impairment of the response—salivation—is elicited by the bell (the conditioned stim-
episodic memory system, such as with disruption of Papez’s circuit or ulus) alone.41 This form of memory is nondeclarative and implicit
surgical removal of the medial temporal lobes.32 because conscious awareness (although often present) is not neces-
In its broadest sense, semantic memory includes all our knowl- sary for the learning to take place. Two types of conditioning are that
edge of the world not related to any specific episodic memory. It could of an autonomic conditioned response (such as a fear response), and
therefore be argued that semantic memory resides in multiple cortical a motoric conditioned response (such as an eyeblink). The amyg-
areas throughout the brain. For example, there is evidence that visual dala, related structures, and connections in the basolateral limbic
images are stored in nearby visual association areas.33 A more restrictive system (including the dorsomedial thalamic nuclei, subcallosal area,
view of semantic memory justified in light of the naming and categorization and the stria terminalis) are important for autonomic conditioning
tasks by which it is usually tested, however, localizes semantic memory to (Fig. 1).42 In motoric conditioning, the cerebellum appears to play
the anterior and inferolateral temporal lobes (Fig. 8).34,35 the most important role (Fig. 8).43,44
The most common clinical disorder disrupting semantic memory Although disruption of this form of memory rarely comes to
is Alzheimer disease. This disruption may be due to pathology in the clinical attention, patients have been described with selective im-
anterior and inferolateral temporal lobes36 or to pathology in the frontal pairment of simple classic conditioning. In one study, 3 patients are
cortex,37 leading to poor activation and retrieval of semantic informa- reported. The first, who had selective bilateral amygdala damage,
tion.38 Supporting the idea that 2 separate memory systems are im- had no difficulty with episodic memory (remembering a new list of
paired in Alzheimer disease, episodic and semantic memory decline items) but could not acquire a classic conditioning autonomic
independently of each other in this disorder.39 response. The second patient, who had selective bilateral hippocam-
pal damage, showed episodic memory dysfunction (being unable to
remember the list of items) but did acquire the classic conditioning.
The third, who had bilateral damage to both amygdala and hip-
pocampi, showed impairment in episodic memory and also did not
Almost any disorder that can disrupt the anterior acquire the classic conditioning.45 Other patients who have disruption
in the amygdala, thalamus, or cerebellum may also show impairments of
and inferolateral temporal lobes may cause one or more types of simple classic conditioning, including those with
impairment of semantic memory. Alzheimer disease (impaired autonomic conditioning due primarily to
pathology in amygdala46) and those with damage to the cerebellum or its
connections (impaired motor conditioning47).

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The Neurologist • Volume 15, Number 2, March 2009 Understanding Memory Dysfunction

FIGURE 8. Semantic, procedural, and

working memory. The anterior and in-
ferolateral temporal lobes are important
in the naming and categorization tasks
by which semantic memory is typically
assessed. However, in the broadest sense,
semantic memory may reside in multiple
and diverse cortical areas that are related
to various types of knowledge. The basal
ganglia, cerebellum, and supplementary
motor area are critical for procedural
memory. The prefrontal cortex is active
in virtually all working memory tasks;
other cortical and subcortical brain re-
gions will also be active, depending on
the type and complexity of the working
memory task. In addition to being in-
volved in procedural memory, the cere-
bellum is also important for the motoric
conditioning. (Adapted with permission
from Budson and Price, New England
Journal of Medicine, 2005).

Procedural Memory memory tests.47,50 Other causes of damage to the basal ganglia or
cerebellum including tumors, strokes, and hemorrhages may also
disrupt procedural memory. Patients with major depression also
show impairment in procedural memory tasks, perhaps because
depression involves dysfunction of the basal ganglia.51
Procedural memory refers to the ability to Disruption of procedural memory should be suspected when
learn cognitive and behavioral skills and patients show evidence of either substantial difficulties in learning
new skills (compared with their baseline) or the loss of previously
algorithms that operate at an automatic, learned skills. For example, patients may lose the ability to perform
automatic, skilled movements, such as writing, swinging a tennis
unconscious level. racket, or playing a musical instrument. Although these patients may
be able to relearn the fundamentals of these skills, explicit thinking
becomes required for their performance. As a result, patients with
damage to the procedural memory system lose the automatic effort-
Procedural memory refers to the ability to learn cognitive and lessness of simple motor tasks that healthy individuals take for
behavioral skills and algorithms that operate at an automatic, un- granted. The evaluation of disorders of procedural memory is similar
conscious level. Procedural memory is nondeclarative and implicit. to that of disorders of episodic memory; treatment depends upon the
Examples include learning to ride a bike or play the piano (Table 1). specific disease process. Lastly, it is worth noting that patients
Because procedural memory is spared in patients who have severe whose episodic memory has been devastated by a static disorder,
deficits of the episodic memory system (such as those who have such as encephalitis, have had successful rehabilitation by using
undergone surgical removal of the medial temporal lobes), it is clear procedural memory (and other nondeclarative forms of memory) to
that the procedural memory system is separate and distinct from the learn new skills.52
episodic memory system.32,47
Functional imaging research has shown that a number of Priming
brain regions involved in procedural memory become active as a
Priming occurs when a prior encounter with a particular item
new task is learned, including the supplementary motor area, basal changes the response to the current item (Table 1). Because this
ganglia, and cerebellum (Fig. 8).48 Convergent evidence comes from phenomenon occurs even if the individual does not consciously
studies of patients with damage to the basal ganglia or cerebellum remember encountering the prior item, priming is another example
who show impairment in learning procedural skills.49 Because the of an implicit and nondeclarative form of memory. Priming is often
basal ganglia and cerebellum are relatively spared in early Alzhei- divided into perceptual priming, which is modality specific (eg,
mer disease, despite their episodic memory deficit these patients auditory, visual) and does not benefit from elaborate encoding when
show normal acquisition and maintenance of their procedural mem- materials are being learned, versus conceptual priming, which is not
ory skills. modality specific and shows enhancement with increased encoding.
Parkinson disease is the most common disorder disrupting Perceptual priming depends upon a perceptual representation
procedural memory. Patients in the early stages of Huntington system, involved in processing information regarding the form and
chorea and olivopontocerebellar degeneration also show impaired structure of items but not their meanings.53 Converging evidence
procedural memory while performing nearly normally on episodic suggests that posterior cortical regions involved in processing of

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Budson The Neurologist • Volume 15, Number 2, March 2009

sensory information are important for perceptual priming. A patient der, obsessive compulsive disorder, depression, and schizophrenia,
with bilateral occipital lobe lesions demonstrated normal episodic can also impair working memory.64 – 66
memory and conceptual priming while failing to show perceptual Disorders of working memory may present in several differ-
priming.54 Neuroimaging studies of visual perceptual priming using ent ways. Often the patient will exhibit an inability to concentrate or
PET and fMRI show changes in activation of visual peristriate pay attention. Impairment in performing a new task with multistep
cortex.55 By contrast, neuroimaging studies of conceptual priming instructions is frequently seen. Interestingly, a disorder of working
typically show changes in left prefrontal regions.55 Most studies have memory may also present as a problem with episodic memory,
shown that patients with early degenerative diseases that do not affect because information must first be “kept in mind” by working
the sensory association cortices, such as Alzheimer, Parkinson, and memory in order for episodic memory to encode it.13 Such cases will
Huntington diseases, demonstrate normal perceptual priming.56 For therefore show a primary impairment in encoding.
conceptual priming, however, many studies have found these groups to The evaluation of disorders of working memory is similar to
be impaired.47 that of disorders of episodic memory. Treatment depends upon the
underlying cause. Stimulants, approved by the FDA for the treat-
Working Memory ment of attention deficit hyperactivity disorder,67,68 will often be
helpful in disorders of working memory.

CONCLUSION
Working memory refers to the ability to temporarily Although traditionally, memory has been viewed as a simple
concept, converging and complementary evidence from patient stud-
maintain and manipulate information that one ies and more recent neuroimaging research suggest that memory is
needs to keep in mind. composed of separate and distinct systems. Improved understanding
of these different types of memory will aid the clinician in the
diagnosis and treatment of the memory disorders of their patients.
As more specific therapeutic strategies are developed for the treat-
ment of diseases that cause memory dysfunction, this knowledge
Bringing together the traditional fields of attention, concen- will become increasingly important.
tration, and short-term memory, working memory refers to the
ability to temporarily maintain and manipulate information that one
needs to keep in mind. Requiring active and conscious participation, ACKNOWLEDGMENTS
working memory is an explicit and declarative memory system. This work was supported by National Institute on Aging grant
Working memory has traditionally been divided into 3 components: P30 AG13846. This material is also the result of work supported
one that processes phonologic information (eg, keeping a phone with resources and the use of facilities at the Edith Nourse Rogers
number “in your head”), one that processes spatial information (eg, Memorial Veterans Hospital in Bedford, MA.
mentally following a route), and an executive system that allocates
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