Epilepsy and Behavior 18 (2010) 3–12

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Epilepsy and Behavior

j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / ye b e h

Review

The contribution of neuropsychology to diagnostic assessment in epilepsy

Marilyn Jones-Gotman a,⁎, Mary Lou Smith b, Gail L. Risse c, Michael Westerveld d, Sara J. Swanson e,
Anna Rita Giovagnoli f, Tatia Lee g, Maria Joana Mader-Joaquim h, Ada Piazzini i
a
Montreal Neurological Institute, McGill University, Montreal, QC, Canada
b
Department of Psychology, University of Toronto, Hospital for Sick Children, Toronto, ON, Canada
c
Minnesota Epilepsy Group, St. Paul, MN and Dept. of Neurology, University of Minnesota Medical School, Minneapolis, MN, USA
d
Medical Psychology Associates, Orlando, FL, USA; Psychology, University of Central Florida, Orlando, FL, USA; Neurosurgery, Yale University School of Medicine, New Haven CT, USA
e
Department of Neurology, Medical College of Wisconsin, Milwaukee, WI, USA
f
Laboratory of Neuropsychology, Department of Clinical Neuroscience, Carlo Besta Neurological Institute, Milan, Italy
g
Laboratory of Neuropsychology, The University of Hong Kong, Hong Kong, China
h
Epilepsy Surgery Program and Psychology Services, Clinical Hospital, Federal University of Paraná, Curitiba, Brazil
i
Regional Epilepsy Center, S. Paolo Hospital, University of Milan, Milan, Italy

a r t i c l e i n f o a b s t r a c t

Article history: Neuropsychology plays a vital role in the treatment of epilepsy, providing information on the effects of
Received 21 December 2009 seizures on higher cortical functions through the measurement of behavioral abilities and disabilities. This is
Received in revised form 18 February 2010 accomplished through the design, administration and interpretation of neuropsychological tests, including
Accepted 20 February 2010
those used in functional neuroimaging or cortical mapping and in intracarotid anesthetic procedures. The
Available online 14 May 2010
objective of this paper is to define and summarize in some detail the role and methods of neuropsychologists
in specialized epilepsy centers. Included are information and recommendations regarding basic ingredients
Keywords:
Neuropsychology
of a thorough neuropsychological assessment in the epilepsy setting, as well as suggestions for an
Cognition abbreviated alternative exam when needed, with emphasis on functions associated with specific brain
Language regions. The paper is intended for novice and experienced neuropsychologists to enable them to develop or
Memory evaluate their current practices, and also for other clinicians, who seek a better understanding of the
Tests methodology underlying the neuropsychological input to their work.
Assessment © 2010 Elsevier Inc. All rights reserved.
Functional neuroimaging
Intracarotid anaesthetic procedure

1. Introduction and overview
Over the past half century, neuropsychology has played an
increasingly vital role in the diagnostic assessment of epilepsy.
Advances in our understanding of brain-behavior relationships have
mirrored the rapidly expanding technologies of diagnostic neuro-
physiology, and structural and functional neuroimaging, resulting in a
more accurate understanding of the effects of seizures on higher
cortical functions. In addition to the design, administration and
interpretation of a neuropsychological test battery, neuropsycholo-
gists have a primary role in the design and interpretation of
intracarotid anesthetic procedures and functional neuroimaging or
cortical mapping paradigms as alternative methods of assessing the
integrity of brain structures and networks. The integration of
neuropsychologists in comprehensive epilepsy programs has also
led to their involvement in assessing the cognitive side effects of
antiepileptic drugs and in the psychosocial aspects unique to this
⁎ Corresponding author. Montreal Neurological Institute, 3801 University Street,
Montreal, Quebec, Canada H3A 2B4. Tel.: +1 514 398 8907; fax: +1 514 398 8540.
E-mail address: marilyn.jonesgotman@mcgill.ca (M. Jones-Gotman).
population of patients. The objective of this paper is to define and
summarize in some detail the role and methods of the neuropsychol-
ogist in a specialized epilepsy center. It is intended for novice and
experienced neuropsychologists to enable them to develop or
evaluate their current practices; it is also intended for other clinicians,
who seek a better understanding of the methodology underlying the
neuropsychological input to their work. The authors, an international
group of individuals working in the neuropsychology of epilepsy,
presented several workshops together on this field while members of
an International League Against Epilepsy subcommission. That earlier
collaboration led to the current production of this paper aimed at
providing basic information that can be applied in various settings and
geographical locations.
Neuropsychological data have long been shown to correlate with
focal areas of brain dysfunction in patients with epilepsy [1–12] and to
predict cognitive outcome following epilepsy surgery, particularly when
combined with other variables such as structural brain pathology, age
of seizure onset, language lateralization or unilateral memory perfor-
mance during intracarotid anesthetic procedures [13–21]. The specific
contribution of neuropsychology is unique in that cognitive assessment
describes and quantifies behavioral abilities and disabilities, whereas

1525-5050/$ – see front matter © 2010 Elsevier Inc. All rights reserved.
doi:10.1016/j.yebeh.2010.02.019
4 M. Jones-Gotman et al. / Epilepsy and Behavior 18 (2010) 3–12
other diagnostic methods, such as EEG or brain imaging, assess ana-
tomical or neurophysiological abnormality. By localizing behavioral
dysfunction, neuropsychological findings can reinforce or question data
from other sources about the site of seizure focus. Disagreement
with results from other diagnostics leads to further investigation; for
example, an unsuspected atypical representation of language can be
discovered owing to discrepant behavioral and anatomical findings.
Thus, neuropsychological assessment makes its own valuable contri-
bution to diagnosis in epilepsy, and the integration of those findings
with the data from multiple sources provides the most comprehensive
picture for a given patient.
In the paragraphs that follow, it is our intention to provide a
framework rather than a recipe for maximizing the contribution of
neuropsychology. We present information and recommendations on
what we believe to be basic ingredients for a thorough neuropsycho-
logical assessment in the epilepsy setting. Our emphasis will be on
functions associated with particular brain regions, with reference to
some specific tests. Excellent descriptions and norms of tests that are
commonly used in the field can be found in the books by Lezak,
Howieson and Loring [22] and Strauss, Sherman and Spreen [23].
2. The neuropsychological assessment
2.1. Indications
Neuropsychological assessment is indicated in all patients being
considered for epilepsy surgery, to assist in localizing areas of dys-
function and in counselling patients and their families regarding
postoperative cognitive outcome. This should be followed up with a
postoperative assessment no earlier than three to six months
following surgery because some deficits prior to this time may be
transient. Follow-up evaluations at one- to two-year intervals can be
performed as indicated to track recovery or evolution of cognitive
abilities.
The evaluation is also appropriate when patients present with
cognitive complaints, such as poor memory or impaired concentra-
tion. In many cases their concerns are driven by practical problems
such as educational and occupational limitations. The neuropsycho-
logical evaluation can help define the details of the problem and can also
provide a baseline for later evaluations as indicated. A third group of
seizure patients who should always be referred are those suspected of
experiencing cognitive side effects of their antiepileptic medications. In
these instances, brief screening procedures (see below) are more useful
than a comprehensive test battery because they can be repeated easily
to assess change in function associated with a change in medications. In
the broadest sense, epilepsy patients should be referred for neuropsy-
chological assessment whenever the patient or the treating neurologist
would benefit from a more detailed cognitive profile, particularly as it
relates to the patient's seizure type and frequency.
2.2. Content of test battery
A basic neuropsychological assessment should sample many
different cognitive functions, thus testing the status of different
brain regions and networks. Such an assessment, if thorough, requires
six to eight hours of direct contact between patient and examiner, as
can be appreciated from the discussion (below) of tests to be included.
The information obtained provides a broad picture of a patient's
cognitive strengths and weaknesses as well as highly specific aspects
of brain function. The scores generated by such an evaluation allow
objective conclusions to be drawn, comparing an individual's scores to
norms and to those of other patients with known lesions, and they
provide a solid baseline to which later assessments can be compared if
patients are re-evaluated. The formal tests should be complemented
by careful behavioral observations of the patient's attitude, effort and
strategies, thus providing a context for interpretation of test scores.
2.2.1. IQ testing
Neuropsychological examinations almost invariably include basic
intelligence quotient (IQ) testing. There is considerable evidence
indicating that seizure disorders are associated with an increased
cognitive risk [e.g., 24]. Although superior IQs have been reported in
individuals with epilepsy, the distribution of IQ scores tends to be
skewed toward lower values [25]. We measure intelligence in
individuals with epilepsy because IQ scores are good predictors of
educational, vocational and economic outcome, and because –owing
to standardization on large samples– they are highly reliable. In
addition, the high correlation between verbal IQ and school
performance allows us to use educational achievement to estimate
premorbid IQ and to detect cognitive decline in patients. In contrast,
nonverbal intelligence is largely independent of education and thus
may provide additional balance in interpreting the neuropsycholog-
ical profile. As IQ scores are moderately correlated with scores on
other cognitive tasks, comparison of general level of ability as
reflected in IQ to performance on specialized tasks contributes to
detection of specific deficits.
Although a variety of techniques are used to assess intelligence, the
most common measures used in epilepsy centers are the Wechsler
Scales. These tests provide only a basic overall measure of cognitive
level; they do not provide localizing or lateralizing information. There-
fore, as administration of IQ tests is very time-consuming (2 hours, on
average, in patients with epilepsy), we recommend administering a
short form. A number of short forms are available, and factors such as
language considerations and the particular information to be derived
other than an IQ estimate will guide one's choice. The time thus saved
can be devoted to tasks that are sensitive to specific side and/or site of
dysfunction and to those that address other issues of interest. An ex-
ception to this recommendation is with assessment of children because
schools often require a full IQ test for provision of special services.
2.2.2. Attention
Attention is a complex cognitive construct that includes the ability to
respond to basic sensory stimulation, selectively attend to relevant
stimuli while suppressing responses to irrelevant stimuli, maintain
focus on the environment and respond to changing demands. Attention
is subserved by a complex network involving frontal, parietal and
subcortical regions. Disruption of attention is common among patients
with epilepsy due to a variety of factors including seizures, side effects of
medications and underlying neuropathology. Problems with attention,
along with memory deficits, are among the most commonly cited
cognitive symptoms for epilepsy patients of all ages.
Attention is a building block for other cognitive functions. There-
fore, its disruption can interfere with cognitive performance in other
domains, especially memory. Thus it is crucial to identify problems
with attention to understand better its impact on the interpretation
of results from these other measures, as they reflect independent
localizable deficits. For example, a patient may have severe memory
problems due to inability to attend to the stimuli adequately for en-
coding and storage. Without proper assessment of attention, the
memory impairment may create the misleading impression of signif-
icant temporal lobe dysfunction.
Measurement of attention can be accomplished at several levels,
and is driven by both neuroanatomical and theoretical models [26,27].
Although clinical observations can play a valuable role in assessing
attention, there are also direct methods and psychometric tests available
for this purpose. Symptoms of inattention to sensory / environmental
stimuli can be assessed through double simultaneous stimulation to
look for unilateral suppression. Hemispatial inattention for visual
stimuli is typically assessed through visual search tasks [e.g., 28].
Selective attention, sustained attention, and vigilance are most often
assessed using visual or auditory continuous performance tasks. More
complex aspects of attention, such as shifting focus, are addressed later
in the section on executive functions.
 M. Jones-Gotman et al. / Epilepsy and Behavior 18 (2010) 3–12
2.2.3. Nonverbal cognitive functions
Nonverbal cognition encompasses a wide range of functions
believed to be largely independent of linguistic processing, many of
which are mediated by the nondominant hemisphere. Nonverbal
cognition has traditionally been evaluated almost exclusively with
tasks of visual perception and visual spatial ability; assessment of
auditory perception may also be important in certain cases. Perception
and spatial reasoning in any sensory modality represent higher level
cognitive processes that can only occur successfully if primary sensory
input and other supportive functions, such as sustained attention, are
intact. Thus, when designing a battery of tests it is important to
consider this functional hierarchy and, when necessary, to screen for
more basic deficits such as visual disturbance, visual inattention or
hemispatial neglect, which might preclude valid assessment of higher
level abilities.
2.2.3.1. Visual perception. Tasks include visual cancellation and visual
scanning [28], and drawing of simple symmetric objects such as a clock
face, a daisy or a Greek cross. More complex asymmetric drawing tasks
such as the copy condition of the Rey-Osterrieth Complex Figure [29,30]
may also be helpful, especially if the deficit is subtle.
Assuming that primary visual processing skills are adequate,
assessment of visual perception should include measures of visual
recognition, as well as visual organization/ integration. Visual
recognition involves the discrimination and interpretation of complex
visual stimuli. Facial recognition is a relatively pure measure of this
ability if no memory component is involved, as in the Benton Facial
Recognition test [31]. The test involves matching pictures of human
faces presented in identical views, and in a more difficult condition,
matching front view with three-quarter view photographs. Visual
recognition can also be assessed by tasks involving interpretation of a
pictorial scene in which the subject must identify what is missing or
anomalous in a picture. Tests of visual organization/integration might
involve the ability to identify a figure from its disassembled or dis-
organized parts as in the Hooper Visual Organization test [32] or to
perform visual closure based on degraded or fragmented drawings [33].
2.2.3.2. Spatial ability and constructional skills. The cognitive proces-
sing of spatial relationships can be evaluated both with measures that
require only mental manipulation of stimuli and with procedures
requiring the actual construction of drawings or objects. Mental tests
of spatial ability overlap to some extent with measures of visual
perception, but typically require a spatial manipulation or judgment.
An excellent example of this type of task is the Judgment of Line
Orientation [31], which requires matching the visual angle of a line to
a sample.
Constructional tasks of spatial ability involve a manual motor
component. These vary from measures of graphomotor speed as in
Digit Symbol Coding, to copying or drawing tasks, to tests involving
two and three dimensional construction.
These measures of visual perceptual and spatial ability are believed
to assess the integrity of left or right parietal lobe or the nondominant
temporal lobe. However, specific sensitivity of individual tests to focal
cortical dysfunction has been difficult to demonstrate in many cases,
particularly in populations of patients with focal seizure onset in the
absence of a structural lesion. Nonetheless, inclusion of a variety of
these measures in a comprehensive test battery can often result in the
identification of trends in performance across tasks that are ultimately
consistent with the area of epileptogenesis.
2.2.3.3. Auditory perception. Tests of nonverbal auditory perception
may be helpful in patients with compromise of auditory association
cortex in the nondominant hemisphere. Meaningful interpretation of
these higher level auditory functions is possible only in the presence
of appropriate auditory acuity.
5
2.2.4. Language
Language tasks measure the integrity of the dominant hemisphere
and, when compared to performance on visual spatial tasks, can be
used to detect lateralized dysfunction. A typical language assessment
for epilepsy includes measures of naming, comprehension, generative
fluency, single word reading, sentence repetition and reading [34].
When resection from the dominant temporal lobe is being
considered, visual object naming and auditory or responsive naming
[35,36] are the most important language tests because these patients
are at risk for postoperative dysnomia [37]. In patients undergoing
dominant posterior temporal or extratemporal resections, some
additional specialized language tests may be added. Administration
of a comprehensive aphasia examination is rarely necessary for
patients with epilepsy, who typically are not aphasic prior to or
following surgery.
Dichotic listening tasks may be used as an index of hemispheric
dominance for language [38] when it is not feasible to conduct an
intracarotid anesthetic procedure, fMRI, or other cortical mapping
procedure.
2.2.5. Executive functions
The term “executive functions” includes the cognitive processes of
initiation, planning, regulation of behavior, overcoming of habitual
responses, attention, working memory, mental flexibility, planning
and reasoning that are necessary for the execution of goal directed
activity. These abilities are stressed most clearly when the individual
encounters novel situations that call for new forms of behavior based
on deliberation and choice.
Examination of executive functions in epilepsy is useful for
detecting focal deficits associated with frontal lobe epilepsy where
attention deficits, impulsivity, impaired motor coordination, and
difficulty changing behavioral strategies are common. In contrast to
patients with temporal lobe seizures, patients with frontal lobe
epilepsy may show deficits in planning and behavioral adaptation in
the context of intact memory [39]. Assessment of basic frontal lobe
functions is necessary in any comprehensive neuropsychological
evaluation for epilepsy, but a more extensive assessment is recom-
mended for patients with frontal lobe seizures or those being
considered for frontal topectomy.
2.2.5.1. Attention. Patients with frontal lobe disturbances are sensitive
to distracting sensory information and have problems inhibiting,
shifting and sustaining attentional focus. Inhibition may depend
critically upon prefrontal and anterior cingulate cortex [40,41], and
can be examined using Stroop tests [42; see 23]. Difficulties with
sustained attention and inhibition can also be detected using
continuous performance tests [e.g., 43] and Go-No Go tasks. The
Trail Making Test [44] taps the ability to switch attention and may be
most sensitive to dorsolateral frontal damage [45].
2.2.5.2. Fluency. Fluency tasks may be verbal (e.g., phonemic tasks
requiring patients to produce words beginning with a specific letter,
or semantic tasks requiring them to name items by category such as
animals or foods) or nonverbal. The Design Fluency test evaluates
nonverbal fluency in the nondominant hemisphere [46]. Patients are
asked to invent abstract designs without drawing objects or any
nameable forms. Comparing performance on verbal with nonverbal
fluency tasks helps detect lateralized frontal lobe dysfunction in
patients with focal seizure disorders.
2.2.5.3. Memory. Performance of patients with frontal lobe dysfunction
on learning and memory tasks may be compromised by impairments
in working memory. Working memory tasks involve holding in mind
and manipulating information, as in backward span or supraspan tests
[e.g., 47]. In addition, frontal lobe patients may have difficulty
recollecting the source of information, such as the context or order
6 M. Jones-Gotman et al. / Epilepsy and Behavior 18 (2010) 3–12
of events. This may be tested by exposing patients to two different sets
of stimuli (e.g., lists of words) and later asking them to differentiate
between the two.
2.2.5.4. Planning. Planning requires the ability to look ahead, conceive
of alternatives, weigh choices (think strategically), follow rules,
inhibit impulses, and sustain attention. Planning can be assessed
with simple measures, such as the Porteus mazes [48], or with more
difficult ones such as tower tasks (London, Hanoi, and Toronto; e.g.,
[49]). Also, a patient's approach to copying a complex figure (e.g., the
Rey Complex Figure) may provide insight into planning ability.
2.2.5.5. Concept formation. The most widely-used test of concept
formation is the Wisconsin Card Sorting Test (WCST; [50]), which
requires that the patient derive a principle, maintain it for a period of
time and then switch to another one with minimal feedback from the
examiner. Thus the WCST relies on working memory, the ability to
make inferences and deductions, to switch an ongoing action or adapt
to circumstances, and the ability to benefit from feedback. Although
this test is used to assess frontal lobe damage [51], some patients with
temporal lobe epilepsy also have difficulty performing the task [52],
likely due to metabolic disruption of frontostriatal pathways in these
patients [53]. In addition, the WCST is useful for examining the
processes used to solve complex problems. Conceptual reasoning can
also be assessed with WAIS subtests such as Matrix Reasoning and
Similarities or with a measure of complex problem solving and
hypothesis testing such as the Booklet Category Test [54].
2.2.5.6. Social behavior and personality. Lesions of the orbital surface of
the frontal lobes may cause affective and personality changes [55]
including poor social judgment, disinhibition or social inappropriate-
ness, a tendency to place immediate gratification over long-term con-
sequences of behavior, or excessive behavioral rigidity. A number of
scales have been developed to assess behavior change due to pathology
in the frontal systems [56]; examples are the BRIEF [57] and the Frontal
Systems Behavior Scale [58]. In addition, the clinical interview and
observations assist in assessing these aspects of behavior.
2.2.6. Somatosensory and motor functions
Somatosensory and motor testing is conducted to assess the
functions of the primary somatosensory cortex (postcentral gyrus)
and the primary motor cortex (precentral gyrus), and to provide
lateralizing and localizing information for patients being evaluated as
surgical candidates. For some nonsurgical patients, the results provide
information about hand function that may impact on the patient's
daily living skills or vocational options.
Testing of somatosensory and motor function is typically conducted
on the hands. There are a number of quantitative tests of somatosensory
function available [22,23,59], including but not limited to the following:
1) two-point discrimination, the ability to detect separation of two
stimuli presented simultaneously; 2) point localization; the ability to
judge whether two successive stimuli were at the same or different
locations; 3) position sense in the distal joints; 4) stereognosis, or
recognition of stimuli by touch; 5) double-simultaneous stimulation,
a measure of tactile attention; 6) graphesthesia, tactile identification
of symbols traced on the skin. Two-point discrimination provides the
greatest sensitivity and specificity [59]. In administering somatosensory
tests, the patient's attentional state should be monitored; interpretation
of these data should take into account sex differences in sensory dis-
crimination [23].
Assessment of motor function involves two aspects of hand function:
preference (handedness) and proficiency (strength, speed and dexter-
ity). Handedness is often associated with the hand used for writing, but
that activity is not always concordant with hand choice for other
unimanual tasks; therefore, it is best to use a questionnaire [e.g., 60] that
assesses a variety of manual activities. The three most commonly used
indices of hand proficiency are grip strength (using a hand dynamom-
eter), speed (finger tapping), and dexterity (measured with pegboard
tasks). The preferred hand is not necessarily the most proficient, and
large discrepancies between the hands are not unusual in normal
subjects. Despite the possibility of these discrepancies, highly deviant
performance across several motor tasks is rare in normal subjects [23].
Therefore, conclusions about laterality of cerebral dysfunction are best
based on results derived from several motor tasks.
2.2.7. Memory
2.2.7.1. Components of memory and anatomic correlates. The profound
memory impairments known to result from bilateral lesions in the
medial temporal lobe are rare. In contrast, the more restricted,
material-specific memory deficits of patients with unilateral temporal
lobe dysfunction occur commonly. Therefore, a thorough memory
assessment should address each hemisphere with tasks appropriate
to its specialization– verbal learning and memory tasks to evaluate
the dominant temporal lobe, and visuospatial or visuoperceptual
learning and memory tasks to evaluate the nondominant temporal
lobe. Verbal tasks use names, word lists, stories or number sequences
as stimuli, while nonverbal tasks use faces, places, music or abstract
designs. It is best to use tasks that are as purely verbal, or purely
nonverbal, as possible to maximize differences between the hemi-
spheres and to increase the probability that the tasks challenge
primarily one temporal lobe [61].
2.2.7.2. Memory batteries. Many neuropsychologists working in
epilepsy programs use memory tests from published batteries
because these are convenient and are usually standardized on large
samples. The most common is the Wechsler Memory Scale (WMS); the
most recent evidence with respect to its efficacy in epilepsy has been
for the WMS-III, published in 1997 [62]. Subtests are divided into
verbal and visual modalities in that version of the WMS, but normative
data specific to focal lesion populations were not reported and only a
few studies over the past decade have examined the sensitivity of
WMS-III subtests to left or right temporal lobe pathology. In a meta-
analysis of memory studies specific to epilepsy, WMS subtests did not
differentiate left from right temporal lobe groups [63]. However, one
recent study has reported material specific differences in performance
of WMS-III subtests by temporal lobectomy patients, with relative
impairment on verbal memory measures associated with left temporal
lobectomy and relative impairment of visual memory in cases of right
temporal lobectomy [64].
One reason for the limited predictive value of the WMS is that the
stimuli used in most subtests contain both verbal and nonverbal
elements rather than reflecting primarily the functions of one hemi-
sphere or the other. Another difficulty with standardized test batteries
in general is that although the subtests attempt to tap different aspects
of memory, the verbal and nonverbal tasks are dissimilar and thus
cannot provide a direct comparison of the hemispheres. It remains to
be seen whether the WMS-IV, published in 2009, will demonstrate
improved sensitivity to material-specific memory functions.
2.2.7.3. Key factors in selecting and designing effective memory
measures. An important factor in assessing memory functions in the
two hemispheres is using tasks that are as similar as possible in
structure and procedure, differing only in being either highly verbal or
highly nonverbal. This allows one to compare the efficacy of one
temporal lobe to the other, even within individual patients. A growing
number of tasks paired in this way are now being used by
neuropsychologists working in epilepsy programs, and some exam-
ples will be given below.
Another important variable is whether a task involves a single
exposure to the material to be learned followed by a retention test, or
whether it is a learning task involving several learning trials and a
 M. Jones-Gotman et al. / Epilepsy and Behavior 18 (2010) 3–12
later retention test. We recommend against single-exposure tasks.
They yield results that can vary considerably owing to effects of
attention, comprehension, and individual strategies, which are likely
to play a bigger role on an only trial (or on a first trial), and these
effects can confound memory findings. Learning tasks provide the
opportunity to improve with additional exposure to the material,
increasing the difference between people with a true learning deficit
and those who do poorly after a single exposure for other reasons.
Using tasks with several learning trials permits observation of how a
patient would remember material after a single exposure, because the
first trial provides that information.
2.2.7.4. Matched verbal vs. nonverbal learning and memory tests.
Several matched memory tasks have been developed in recent years,
many of which arise from the addition of a nonverbal analog to a
previously-existing verbal test. Thus, there are now nonverbal analogs
to the Rey Auditory Verbal Learning Test (RAVLT; [22,65]; nonverbal:
[66]), and the Buschke Selective Reminding Test (SRT; [67];
nonverbal: [68]). In contrast, in one instance a verbal task was
added to an existing nonverbal one [69]. These tests vary in how
closely matched the verbal and nonverbal versions are to each other,
and although encouraging results in presurgical epilepsy patients
have been published [70], many of these tests await further empirical
confirmation.
The Warrington Recognition Memory test (WRM) is a matched
pair of tasks using words and faces. It has been reported to be sensitive
to the effects of temporal lobe lesions in patients with neoplasms and
infarctions [71], but its clinical utility in distinguishing left from right
presurgical epilepsy patients is very limited [e.g., 72]. The WRM uses a
single-exposure paradigm, and its poor diagnostic efficiency in focal
epilepsy may result from that, and/or from the fact that memory is
tested immediately after presentation of the stimuli. To best evaluate
medial temporal lobe functions, memory tests should incorporate a
delayed recall or recognition trial.
2.2.7.5. Other verbal and nonverbal learning and memory tests. A
number of single tasks have been reported to be sensitive to memory
deficits in unoperated epilepsy patients. In the verbal domain these
include the RAVLT, the California Verbal Learning Test (CVLT; [73]),
and the SRT. All of these use lists of single words that are presented for
learning over several trials, with retention tested again after a delay
interval. Although we recommend using these tests with their
nonverbal analogs, published reports indicate good results also
when used alone, especially on delayed retention scores.
To sample memory in a way that is closer to the demands of
everyday life, it is valuable to include a test using meaningful prose, as in
a short story. Several such tests are available, including in the WMS. Our
recommendation is to choose a test of story learning rather than a test
requiring recall of a story that has been presented only once [74,75].
There are many reports in the literature stating that “nonverbal”
memory measures had little success in detecting right temporal lobe
damage, but until relatively recently those tests were essentially all
single-trial tasks. The Rey-Osterrieth Complex Figure test [29,30] is
used by most neuropsychologists in epilepsy programs, but this
supposedly nonverbal test does not reliably differentiate left from
right temporal lobe dysfunction [76]. It is an example of a task with a
single exposure and dually-encodable material, and its usefulness as a
memory test for individual cases is very limited. The copy phase of this
task is useful, however, for assessment of parietal lobe dysfunction.
Using visuoperceptual tasks involving learning over several trials,
deficits in patients with nondominant temporal lobe dysfunction have
been documented for learning such things as lists of abstract designs
[77], arrays of dots [78] or arrangements of matchsticks [79]. Memory
for faces is believed to be a relatively pure nonverbal task, although
this is not true of the Faces subtest of the WMS-III, which does not
control for several potentially verbal factors including gender, race,
7
and age. This subtest was not included in the recent WMS-IV revision.
The ideal face memory task would incorporate a learning rather than a
single exposure paradigm [80], and would expose the faces one at a
time as opposed to showing them in an array as is the case in many
face memory tasks.
Although experimental work has shown the importance of the
right medial temporal lobe structures in spatial memory, these
findings have not yet been translated into standardized tests for
clinical use. Some experimental tasks show more promise than others.
An analog of the radial arm maze revealed selective impairments in
spatial memory in both operated and unoperated patients with right
temporal lobe epilepsy compared with left temporal lobe groups and
controls [81]. However, on a test of memory for the spatial locations of
objects in a scene, differences in accuracy between unoperated
temporal lobe epilepsy patients and controls were not found [82].
Further work on the development of clinically useful spatial memory
tests is needed.
2.2.7.6. Semantic memory. Semantic memory, that component of
memory reflecting knowledge of the world acquired from education,
experience and repeated exposure to stimuli, can be impaired in
people with temporal lobe epilepsy. Given its explicit verbalized
nature, semantic memory overlaps with the construct of language.
Semantic memory impairment may be observable in verbal deficits
involving naming and single-word comprehension, as well as in visual
knowledge and association deficits, while phonological, syntactic, and
perceptual abilities are preserved. In temporal lobe epilepsy, deficits
in naming, semantic organization, classification, encoding and judg-
ment have been described frequently, relating to lateral or medial
temporal lobe damage and reflecting loss of knowledge and/or im-
paired access to the semantic store [83]. A number of tests have been
reported to provide a valid assessment of semantic memory in
patients with epilepsy [83] including, for example, measures of object
naming and association of verbal and visual stimuli.
2.2.7.7. Summary. Although some studies have reported that tradi-
tional memory tests such as the Rey Complex Figure test or certain
subtests from the Wechsler Memory Scales can be sensitive to
laterality of temporal lobe focus, others show that those tasks are not
sensitive, particularly in presurgical evaluation. Nonverbal memory
deficits have been especially difficult to demonstrate with traditional
tasks, but newer tests have been shown to be sensitive to non-
dominant temporal lobe dysfunction in unoperated patients. We
recommend the use of learning tasks over those with a single-
exposure paradigm and the use of “matched” verbal and nonverbal
tasks, as these provide the best lateralizing and localizing data. For
more detailed information about specific memory tests, see Djordjevic
and Jones-Gotman [74] and Jones-Gotman and Djordjevic [84].
2.2.8. Abbreviated test battery
Although we believe that an ideal evaluation should assess brain
function as thoroughly as our current tools allow, in some settings time
and resources do not allow such comprehensive testing. If time is
limited, we recommend sacrificing some portion of the IQ testing, even
beyond the previously recommended short forms. A minimum estimate
of overall ability could be based on a vocabulary measure together with
one constructional task such as the Block Design subtest or another
measure of nonverbal intelligence. The inclusion of a short naming test
would enhance the assessment of verbal skills, adding little time to the
overall assessment. An abbreviated memory evaluation should include
matched (verbal and nonverbal) experimental learning measures
similar to those described above, even if extensive normative data are
unavailable. It is important that the tasks chosen include a learning
component, avoiding the pitfalls associated with one-exposure memory
paradigms. Executive function testing should focus on material-specific
measures with appropriate counterparts such as verbal and nonverbal
8 M. Jones-Gotman et al. / Epilepsy and Behavior 18 (2010) 3–12
fluency, and should include a task requiring creative problem solving.
Psychomotor and sensory testing and measures of higher order visual
perceptual and language processing can be considered optional, but
should be selected when specific circumstances dictate the need. As noted
below, severely shortened test batteries may be appropriate to screen for
side effects of antiepileptic medications or other highly selective
assessments (e.g. return to baseline following a cluster of seizures), but
those procedures should not be substituted for a multifaceted diagnostic
evaluation. Thus, when time or resources are limited and an abbreviated
battery is needed, we recommend using one verbal and one “nonverbal”
subtest as a rough IQ measure, a naming task, one verbal and one
visuoperceptual learning and retention task, a verbal and nonverbal
fluency test, and a creative problem-solving task. This shortened
evaluation can be administered in approximately two hours and would
allow a retention interval of about two hours for the memory tests.
3. Intracarotid anesthetic procedures (IAP)
The intracarotid amobarbital procedure was introduced by Wada
and Rasmussen in the 1950s to determine hemispheric language
dominance prior to epilepsy surgery, and was expanded a few years
later to include evaluation of memory functions [85–87]. This technique
involves the injection of a short-acting anesthetic directly into the
internal carotid artery, resulting in unilateral inactivation of a single
hemisphere while the opposite hemisphere is tested. Despite the
invasive nature of the procedure, it was long considered the “gold
standard” for obtaining this critical information in preoperative patients.
More recently, drugs other than amobarbital have also been used
in the IAP. These include propofol [88], the shorter acting methohex-
ital [89], and most recently etomidate [90–92]. The methohexital test
protocol differs from the basic original, as the very short drug effect
necessitates injecting additional drug during the procedure. The
etomidate procedure introduced the modification of continuous
infusion of the drug after the initial bolus injection, thereby extending
the period of hemianesthesia to ensure completion of the memory
protocol during maximum drug effect.
Noninvasive neuroimaging techniques such as PET, functional MRI,
and Magnetic Source Imaging are used increasingly to lateralize and
localize language cortex. To date, the clinical validity of these methods
for assessing risk to memory functions after surgery has not been
demonstrated. Therefore, we recommend the continued use of the IAP
in the presurgical diagnostic evaluation of surgical candidates, with
careful consideration of the guidelines listed below.
3.1. General recommendations
When an IAP is performed, we strongly recommend that both
hemispheres be tested. The possibility of bilateral representation of
language can be determined only by testing both hemispheres, and
different information about memory function is obtained from each
hemisphere. Furthermore, comparing memory results obtained from
the two hemispheres helps determine the side of seizure onset [93,94].
The dose should be held constant over the two injections.
If there is an option of testing the two hemispheres on separate
days, this is desirable, as it has been shown that there is a lingering
drug effect from the first injection that affects the second [95]. When
testing on different days is not possible there should be a minimum of
30 minutes between injections. The hemisphere of the proposed
surgery should be injected first in these cases, as the first injection is
believed to yield more accurate data.
3.2. Patient selection
Determination of cerebral dominance for language is needed in
people who are non-right handers or have a family history of left
handedness, who have suffered early trauma to the left hemisphere,
or who have neuropsychological findings suggesting atypical lateral-
ization. Patients whose seizure focus is clearly lateralized according to
all clinical tests (EEG, neuroimaging and neuropsychological), or in
whom there is no reason to suspect atypical organization of language,
do not need to undergo an IAP. In many centers functional
neuroimaging studies are being performed for language lateralization.
When the results of these studies are unambiguous, an IAP for
language is unnecessary. With respect to memory, an IAP is necessary
in patients who are candidates for resection from a temporal lobe if
they are suspected of having bitemporal dysfunction, based on
neuropsychological, EEG or neuroimaging findings, and may be
desirable to help predict the risk to material specific (especially
verbal) memory decline postoperatively.
3.3. Recommendations for language assessment
There is no standardized protocol available for determining
language dominance. Centers have typically developed their own
procedures, which are, however, based on broad consensus, and are
frequently quite similar.
1) Protocols should sample multiple language modalities including
automatic or rote speech, naming, reading, repetition and auditory
comprehension. Stimulus items used in naming can double as
memory items and should consist of real objects or realistic
colored pictures to maximize correct perception of the items.
2) Testing for language should be conducted during the period of
maximum drug effect, with relatively greater weight given to
responses occurring prior to the onset of motor recovery if the
protocol involves a single injection of anesthesia.
3) The diagnosis of left hemisphere language dominance should be based
on evidence of appropriate language responses following the right
injection combined with the presence of a global aphasia following
the left injection, and paraphasic errors during the recovery period.
4) The diagnosis of reversed language dominance or bilateral
language representation should be based on production of correct
language responses following the left injection as well as language
errors following the right injection [96].
3.4. Recommendations for memory assessment
In general, results of memory testing in the IAP have been less
reliable and more difficult to interpret than language data. While
some concern has arisen over the incomplete irrigation of the hip-
pocampus with internal carotid injection, it has been demonstrated
that the hippocampus appears to be disabled or disconnected [97].
The duration of drug effect is a critical factor in obtaining reliable
memory data because language testing may take place first, resulting
in memory items being shown during recovery from the drug. This
problem can be avoided using the etomidate version of IAP, in which
following the initial bolus injection the level of anesthesia is
maintained until all memory items have been presented [91,92].
1) Memory stimulus items should consist primarily of real objects
that can be encoded as verbal or visual information to maximize
their “memorability.” Some protocols have successfully included
modality-specific memory stimuli such as words or abstract
designs, but these should not be substituted for “general memory”
items. A minimum of eight memory items is recommended for
presentation during the drug condition.
2) Memory should be tested in a recognition paradigm presented
after full recovery from the drug effect.
3) Interpretation of memory results must take into account the
“memory dominance” effect in which injection into the nondom-
inant hemisphere elicits less memory deficit than injection into the
dominant hemisphere. This trend is exaggerated when the seizure
focus is on the nondominant side.
 M. Jones-Gotman et al. / Epilepsy and Behavior 18 (2010) 3–12
4) Memory performance should be at least 60% accurate to indicate
adequate memory in a given hemisphere.
3.5. The IAP with pediatric patients
Because of the invasive nature and high level of cooperation
needed for this test, not all children who are candidates for epilepsy
surgery may be able to successfully complete the procedure,
particularly the memory assessment; factors such as age and IQ may
help identify children in whom the IAP may be more difficult [98,99].
IAP memory testing in children, as in adults, has been used to predict
seizure and memory outcome [100,101]. The IAP can be successfully
used in children as young as 6 years if they are cooperative. Many
centers now routinely use fMRI for language localization in pediatric
patients [102], resulting in less use of the IAP in children.
Pre-IAP preparation is an important factor in maximizing a
successful and valid procedure. Preparation includes pre-testing the
child to determine the appropriate developmental level for language
assessment. In addition, a pre-IAP visit to the angiography suite to orient
the child to the testing environment is recommended to reduce the
child's anxiety and introduce key personnel. This is particularly
important when the angiography procedure is performed under general
anesthesia and the patient may awaken confused and disoriented.
4. Functional neuroimaging/cortical mapping
In contrast to traditional neurocognitive assessment, which can be
used to detect focal, lateralized or diffuse brain dysfunction based on
profiles of test scores, fMRI is used to localize cerebral function
through task-correlated blood flow changes. Unlike the IAP, where
language and memory are lateralized to a hemisphere using an
inactivation procedure (hemianesthesia), fMRI employs an activation
procedure to not only lateralize but also localize cognitive function
prior to epilepsy surgery. Applications of fMRI in epilepsy include
determining hemispheric representation of language and memory
functions, studying functional reorganization and predicting cognitive
outcome after temporal lobe resection.
fMRI mapping techniques are widely available for language, but
fMRI for clinical evaluation of memory in individual patients requires
further task development and validation. Examination of fMRI
activation in specific regions of interest and with carefully designed,
well-controlled testing protocols offers a powerful method for
functional localization and for predicting language and memory
outcome [103]. At present, however, it is not clear whether activation
maps from language protocols can be used to guide the resection
boundaries as it has not been demonstrated that resection of activated
voxels is correlated with language decline.
While considerable progress has been made in the design and
interpretation of fMRI studies of language and memory, it is not the time
to abandon IAP [104]. IAP has the methodological advantage of being an
inactivation procedure and the practical advantages of not being limited
by claustrophobia. On the other hand, limitations of the IAP include the
relatively short time period of drug activation in which testing can be
done, and its invasive aspects. While fMRI provides detailed information
about functional localization, it is unclear to what extent activated
voxels represent networks critical for the performance of a cognitive
activity or represent tertiary associated or non-task specific functions.
Finally, fMRI task protocols differ and not all have the same validity,
particularly where careful attention has not been paid to control or
contrast tasks. For example, fMRI language activation based on passive
listening, silent repeating or categorizing, reading or naming contrasted
with rest or visual fixation is not concordant with language dominance
from IAP (see [105] for a review).
Application of Magnetoencephalography/Magnetic Source Imag-
ing in mapping cortical functions is rapidly gaining credibility as an
alternative noninvasive method of localizing language cortex in
9
epilepsy surgery candidates [106–108]. Magnetic Source Imaging
has the advantage of measuring neuronal activity in real time,
providing excellent temporal resolution in relation to stimulus
onset, while the spatial resolution of the signal is also considered
equal to or better than fMRI [109]. The development of paradigms to
activate the medial temporal structures is also underway [110].
5. Pediatric issues
Assessment of children requires a different conceptual approach.
With children, one has to consider the effects of dysfunction within a
developing nervous system, ongoing maturational changes, behav-
ioral and structural plasticity, and the impact of environmental and
social factors on development [111]. Moreover, the long-term impact
of surgical treatment is likely to be very different in a child compared
with adult patients, and prediction of risk of cognitive morbidity vs.
benefit is more complex. Developmental factors such as these
indicate that the brain-behavior relationships derived from the
study of adults do not apply to children and necessitate a sub-
stantially different approach to the assessment and interpretation of
results in children.
There is a large and well-established literature on the lateralizing
and localizing signs seen in adults with focal epilepsy, but these may
or may not be present in children with epilepsy for a variety of
reasons. The underlying pathological substrate is frequently different
in children compared with adults. For example, Porter and colleagues
found that 64% of pediatric patients with refractory temporal lobe
epilepsy who underwent temporal lobe resection had cortical
dysplasia [112]. The majority of intractable seizures in children are
due to disorders of cortical development, which results in more
widespread anatomical and functional disturbance [113].
Another difference is the degree to which cognitive skills are
dissociable in early childhood. In addition to the theoretical
complexity of dealing with the developing nervous system and the
small body of published findings on preoperative assessments with
pediatric candidates for epilepsy surgery, the neuropsychologist is
faced with other challenges in working in pediatric programs. A wide
range of assessment skills and experience are necessary to assess
children from infancy to adolescence, with a wide range of etiologies
that may result in patterns of atypical development or generally
normal development with only specific deficits [114]. The type of
assessment and the choice of procedures will depend on the age and
developmental level of the child.
Based on these factors, the recommended approach to assessment
of children should encompass the following basic principles:
5.1. Theoretically based developmental assessment
Assessment should employ techniques that are sensitive to
developmental differences in ability that are theoretically grounded
and based on sound developmental principles in emergence of the
skill being tested. For example, language assessment should take into
account the expected developmental emergence of symbolic repre-
sentation, grammatical structure, and word knowledge for the child's
chronological age. Differences in pragmatic use of language, compre-
hension and language-based academic achievement are also impor-
tant. Simple language tasks that encompass word finding and verbal
fluency will be insufficient to provide information about functional
integrity of language substrate in the dominant hemisphere for
purposes of seizure localization or prediction of language outcome in
the event of surgical intervention.
5.2. Use of tests with strong normative and psychometric backgrounds
The use of clinical signs will always be an important component
of comprehensive neuropsychological testing, however normal
10 M. Jones-Gotman et al. / Epilepsy and Behavior 18 (2010) 3–12
development encompasses a wide range of ages at which develop-
mental milestones can be met and still be considered “normal”.
Normative references are helpful in establishing not only when
emergence of a skill is delayed, but how frequently such a delay occurs
in the non-referred population. This is a critical element in
determining the clinical significance of patterns of test performance
in children.
Establish baseline level of function as early as possible following
diagnosis. It is understood that by the time a seizure disorder is
diagnosed, cognitive symptoms may already be present [115].
However, changes in cognitive function are critical for determining
disease progression, distinguishing iatrogenic effects from disease-
related variables, and identifying postoperative changes in patients
who undergo surgery.
5.3. Re-assessment
Developmental change may result in the emergence of different
patterns of competencies and deficits over time. Developmental
change may also be impacted by fluctuations in seizure status or
alterations in medications to produce changes in the child's cognitive
or behavioral competencies. These different patterns may interact
with increasing educational demands as the child progresses through
the school system, and re-assessment will be helpful in providing
recommendations to enhance educational progress.
5.4. Comprehensive multidisciplinary assessment
This principle is shared with adult neuropsychological assess-
ments in that cognitive domains, psychosocial function, and emo-
tional development are all inter-related. However, the pediatric
patient may be more affected and have fewer internal resources and
coping mechanisms compared to adults. Identifying patients at risk
for learning problems, emotional disturbance, and poor psychosocial
development at an early stage will facilitate treatment and long-term
favorable outcomes.
6. Cognitive effects of antiepileptic drugs
An exhaustive report of antiepileptic drugs (AEDs) and their
potential cognitive side effects is beyond the scope of this report.
However, it can be said that the effects of AEDs on cognitive function
are linked to their efficacy controlling seizures. Adverse side effects
are the greatest factor in non-compliance, and cognitive complaints
are a common reason for discontinuing medication [116].
Assessing the potential side effects of AEDs can be challenging, as it
may be difficult to disentangle such effects from those of the seizures
and the underlying neural abnormality. If possible, test-retest on and
off the AED can be helpful, as long as alternate test forms are available.
As testing twice poses a burden on the examiner and the patient,
an alternative approach when feasible is to wean the patient off the
AED before performing that patient's neuropsychological assessment,
carrying out the testing several days after the last dose. Alternatively,
when AED toxicity is suspected, administration of a brief screening
battery may identify individuals in whom a full neuropsychological
battery should be deferred. Screening measures should include tests
of working memory, and psychomotor and mental processing speed –
tasks generally not subject to significant practice effects.
Special individual factors (such as age, presence of intellectual
disabilities or use of other prescription medications) should be con-
sidered when educational, quality of life and communication issues
must be balanced with other clinical factors [117,118]. Finally, the
subjective experience of cognitive decline cannot be discounted in the
clinical setting. Indeed the perception of decline can be as important
as formal neuropsychological test results in a patient's/physician's
decision to continue or discontinue a given treatment [119].
7. Quality of life
Quality of life (QOL) has been defined by the World Health
Organization (1995) as a subjective, multidimensional and dynamic
entity that encompasses physical, cognitive, psychological, social, and
spiritual aspects, resulting from an interaction between expectations
and actual experiences. Satisfactory QOL is an important goal of
epilepsy treatment, representing, together with seizure control, an
outcome of pharmacological trials and surgery, and a goal of cognitive
rehabilitation and psychosocial interventions.
The International League against Epilepsy's Commission on Outcome
Measurement in Epilepsy suggested that a standard QOL battery should
include both epilepsy-specific and generic scales [120]. Epilepsy-related
factors account for only about 5% of the variance in QOL, much of the
remaining being attributable to psychological and social factors such as
mood, cognitive impairment, self-image, subjective perception of
epilepsy severity and disability, attitudes towards epilepsy and chronic
medication, and fear of stigma [121–123]. A comprehensive assessment
of quality of life should include consideration of these factors. Specific
QOL instruments have been reviewed by Cramer [120].
8. Cross-cultural issues
Cultural diversity presents a challenge to professionals who wish to
apply the methods discussed in the preceding sections to their local
populations. Accurate measurement of neuropsychological function is
culture-dependent [124]. Not only is there concern about whether the
functional domains are assessed accurately by the procedures described,
but whether cognitive functions operate in the same manner across
ethnic/cultural backgrounds (i.e., the concept of “functional equiva-
lence”; [125]). Potential sources of bias include test content, the
standardization sample, language and socioeconomic factors.
8.1. Content
Development of standardized tests tends to rely on the experiences of
the dominant culture for which the test is primarily intended to be used.
An example of this is the commonly used Wechsler Scales for assessment
of general intelligence. Cultural references abound in both the verbal and
nonverbal tasks of this battery. The Wechsler scales have been adapted for
several different languages, with revisions to content also based on
culture. However changes to the content may introduce a different source
of interpretive ambiguity, specifically whether the constructs being
measured have been altered by the content changes.
8.2. Standardization
During standardization, publishers make every effort to represent
ethnic diversity to the degree that a group is represented in the
population. However, this may not be adequate, in that groups with
small representation in the population may not be represented
adequately in the normative sample, rendering the norm-referenced
standard scores marginal for these under-represented groups.
Furthermore, even groups that are represented often comprise a
relatively small part of the complete standardization sample, watering
down the validity across populations. Minority groups that are
included may also represent a select subsample of the larger group.
8.3. Language
Effective communication between the clinician and the patient is
critical. Even subtle differences in dialect can create barriers to clarity
of interpretation of individual responses, resulting in lower scores due
to language differences rather than differences in verbal cognitive
abilities. In addition, the difficulty level for items on language tasks is
not necessarily the same across different languages and cultures.
 M. Jones-Gotman et al. / Epilepsy and Behavior 18 (2010) 3–12
8.4. Socioeconomic
There are often educational differences (both level and quality)
associated with socioeconomic differences, even within a particular
geographic region. Attention to socioeconomic factors that may affect
performance on cognitive tasks is important for valid inferences
regarding performance on tests as a measure of brain function.
Differences within as well as across geographic regions can be
profound, and can interact with cultural and ethnic differences.
8.5. Recommendations
While it may not be possible to create the literally thousands of
versions of tests needed to address all of these concerns, attention to
these issues and their influence on assessment of nonverbal as well as
verbal abilities is important to further develop our understanding of
the effects of epilepsy on cognitive function. We strongly encourage
development of culturally relevant norms to facilitate reliable and
valid inferences that may be drawn about brain-behavior relation-
ships from the results of neuropsychological examination.
9. Conclusion
Neuropsychology occupies a unique position among diagnostic
methods in epilepsy because it is the sole technique for understanding
the functional impact of epilepsy and its treatment. Cognitive and
behavioral strengths and weaknesses identified by neuropsychological
assessments contribute to a number of important decisions in medical
management, such as the identification of candidates for surgery,
potential risk, benefits and efficacy of treatments, and rehabilitation.
Neuropsychology is an important part of any comprehensive care
program for persons with epilepsy.
References
[1] Kimura D. Right temporal-lobe damage: perception of unfamiliar stimuli after
damage. Arch Neurol 1963;8:264–71.
[2] Milner B. Brain mechanisms suggested by studies of temporal lobes. In: Millikan
CH, Darley FL, editors. Brain mechanisms underlying speech and language. New
York: Grune & Stratton; 1967. p. 122–45.
[3] Jones MK. Imagery as a mnemonic aid after left temporal lobectomy: contrast between
material-specific and generalized memory disorders. Neuropsychologia 1974;12:21–30.
[4] Milner B. Advances in neurology. In: Purpura DP, Penry JK, Walter RD, editors.
Psychological aspects of focal epilepsy and its neurosurgical management. New York:
Raven Press; 1975. p. 299–301.
[5] Jones-Gotman M, Milner B. Right temporal-lobe contribution to image-mediated verbal
learning. Neuropsychologia 1978;16(1):61–71.
[6] Sass KJ, Spencer DD, Kim JH, Westerveld M, Novelly RA, Lencz T. Verbal memory
impairment correlates with hippocampal pyramidal cell density. Neurology 1990;40:
1694–7.
[7] Lencz T, McCarthy G, Bronen RA, et al. Quantitative magnetic resonance imaging in
temporal lobe epilepsy: relationship to neuropathology and neuropsychological
function. Ann Neurol 1992;31:629–37.
[8] Hermann BP, Wyler AR, Somes G, Berry III AD, Dohan Jr FC. Pathological status of the
mesial temporal lobe predicts memory outcome from left anterior temporal lobectomy.
Neurosurgery 1992;31:652–6.
[9] Saling MM, Berkovic SF, O'Shea MF, Dalnins RM, Darby DG, Bladin PF. Lateralization of
verbal memory and unilateral hippocampal sclerosis; evidence of task-specific effects. J
Clin Exp Neuropsychol 1993;15:608–18.
[10] Baxendale SA, Van Paesschen W, Thompson PJ, et al. The relationship between
quantitative MRI and neuropsychological functioning in temporal lobe epilepsy.
Epilepsia 1998;39:158–66.
[11] Baxendale SA, Sisodiya SM, Thompson PJ, et al. Disproportion in the distribution of gray
and white matter: neuropsychological correlates. Neurology 1999;52:248–52.
[12] Wendel JD, Trenerry MR, Xu YC, et al. The relationship between quantitative T2
relaxometry and memory in nonlesional temporal lobe epilepsy. Epilepsia 2001;42:
863–8.
[13] Loring DW, Lee GP, Meador KJ, et al. The intracarotid amobarbital preocedure as a
predictor of memory failure following unilateral temporal lobectomy. Neurology
1990;40:605–10.
[14] Wyllie E, Naugle R, Awad I, et al. Intracarotid amobarbital procedure: I. prediction
of decreased modality-specific memory scores after temporal lobectomy. Epilepsia
1991;32:857–64.
[15] Chelune GJ, Naugle RI, Luders H, Awad IA. Prediction of cognitive change as a function of
preoperative ability status among temporal lobectomy patients seen at 6-month follow
up. Neurology 1991;41:399–404.
11
[16] Hermann BP, Seidenberg M, Haltiner A, Wyler AR. Relationship of age at onset,
chronological age, and adequacy of preoperative performance to verbal memory change
after anterior temporal lobectomy. Epilepsia 1995;36:137–45.
[17] Kneebone AC, Chelune GJ, Dinner DS, Naugle RI, Awad IA. Intracarotid amobarbital
procedure as a predictor of material-specific memory change after anterior temporal
lobectomy. Epilepsia 1995;36:857–65.
[18] Sawrie SM, Chelune GJ, Naugle RI, Lüders H. Empirical methods for assessing
meaningful neuropsychological change following epilepsy surgery. J Int Neuropsychol
Soc 1996;2:556–64.
[19] Martin RC, Sawrie SM, Roth DL, et al. Individual memory change after anterior
temporal lobectomy: a base rate analysis using regression-based outcome
methodology. Epilepsia 1998;39(10):1075–82.
[20] Chiaravalloti ND, Glosser G. Material-specific memory changes after anterior temporal
lobectomy as predicted by the intracarotid amobarbital test. Epilepsia 2001;42:902–11.
[21] Baxendale S, Thompson P. Defining meaningful postoperative change in epilepsy
surgery patients: measuring the unmeasurable? Epilepsy Behav 2005;6:2007–11.
[22] Lezak M, Howieson D, Loring D. Neuropsychological assessment. 4th ed. New York:
Oxford University Press; 2004.
[23] Strauss E, Sherman E, Spreen O. A compendium of neuropsychological tests: admin-
istration, norms and commentary. 3rd ed. New York: Oxford University Press; 2006.
[24] Aldenkamp AP, Alpherts WC, Dekker MJ, Overweg J. Neuropsychological aspects of
learning disabilities in epilepsy. Epilepsia 1990;31(Suppl 4):S9–S20.
[25] Holmes GL. The long-term effects of seizures on the developing brain: clinical and
laboratory issues. Brain Dev 1991;13:393–409.
[26] Mirsky AF, Anthony BJ, Duncan CC, Ahearn MB, Kellam SG. Analysis of the elements of
attention: a neuropsychological approach. Neuropsychol Rev 1991;2:109–45.
[27] Posner MI, Peterson SE. The attention systems of the human brain. Ann Rev Neurosci
1990;13:25–42.
[28] Mesulam M. Principles of behavioral and cognitive neurology. New York: Oxford
University, New York; 2000.
[29] Osterrieth P. Le test de copie d'une figure complexe. Arch Psychologie 1944;30:
206–356.
[30] Rey A. L'examen psychologique dans les cas d'encéphalopathie traumatique. Arch
Psychologie 1942;28:286–340.
[31] Benton AL, Hamsher KD, Varney NR, Spreen O. Contributions to neuropsychological
assessment. New York: Oxford University Press; 1983.
[32] Hooper HE. Hooper Visual Organization Test (VOT). Los Angeles: Western Psychological
Services; 1983.
[33] James M, Warrington EK. Visual Object and Space Perception Battery. Bury St. Edmunds,
Suffolk: Thames Valley Test Co; 1991.
[34] Jones-Gotman M, Smith ML, Zatorre RJ. Neuropsychological testing for localizing and
lateralizing the epileptogenic region. In: Engel Jr J, editor. Surgical treatment of the
epilepsies. 2nd ed. New York: Raven Press; 1993. p. 245–61.
[35] Bell BD, Seidenberg M, Hermann BP, Douville K. Visual and auditory naming in patients
with left or bilateral temporal lobe epilepsy. Epilepsy Res 2003;55:29–37.
[36] Hamberger MJ, Seidel WT, McKhann 2nd GM, Perrine K, Goodman RR. Brain stimulation
reveals critical auditory naming cortex. Brain 2005;128:2742–9.
[37] Hermann BP, Perrine K, Chelune GJ, et al. Visual confrontation naming following left
anterior temporal lobectomy: a comparison of surgical approaches. Neuropsychology
1999;13:3–9.
[38] Zatorre RJ. Perceptual asymmetry on the dichotic fused words test and cerebral speech
lateralization determined by the carotid sodium amytal test. Neuropsychologia
1989;27:1207–19.
[39] Culhane-Shelburne K, Chapieski L, Hiscock M, Glaze D. Executive functions in children
with frontal and temporal lobe epilepsy. J Int Neuropsychol Soc 2002;8:623–32.
[40] Kerns JG, Cohen JD, MacDonald AW, Cho RY, Stenger VA, Carter CS. Anterior cingulate
conflict monitoring and adjustments in control. Science 2004;303:1023–6.
[41] Stuss DT, Floden D, Alexander MP, Levine B, Katz D. Stroop performance in focal lesion
patients: dissociation of processes and frontal lobe lesion location. Neuropsychologia
2001;39:771–86.
[42] Stroop JR. Studies of interference in serial verbal reactions. J Exp Psychol 1935;18:
643–62.
[43] Connors CK. Conners' Continuous Performance Test-II. Toronto: Multi Health Systems;
2001.
[44] Army Individual Test Battery. Manual of directions and scoring. Washington, DC: War
Department, Adjutant General's Office; 1944.
[45] Stuss DT, Bisschop SM, Alexander MP, Levine B, Katz D, Izukawa D. The Trail Making
Test: A study in focal lesion patients. Psychol Assess 2001;13:230–9.
[46] Jones-Gotman M. Localization of lesions by psychological testing. Epilepsia 1991;32
(Suppl 5):41–52.
[47] Wagner DD, Sziklas V, Garver KE, Jones-Gotman M. Material-specific lateralization of
working memory in the medial temporal lobe. Neuropsychologia 2009;47:112–22.
[48] Porteus SD. Porteus Maze Test. Fifty years' application. New York: The Psychological
Corporation; 1965.
[49] Goel V, Grafman J. Are the frontal lobes implicated in “planning” functions? Interpreting
data from the Tower of Hanoi. Neuropsychologia 1995;35:623–42.
[50] Grant DA, Berg EA. A behavioral analysis of degreee of impairment and ease of shifting
to new responses in a Weigle-type card sorting problem. J Exp Psychol 1948;39:404–11.
[51] Milner B. Effects of different brain lesions on card sorting. The role of the frontal lobes.
Arch Neurol 1963;9:90–100.
[52] Hermann BP, Wyler AR, Richey ET. Wisconsin card sorting test performance in patients
with complex partial seizures of temporal-lobe origin. J Clin Exp Neuropsychol 1988;10:
467–76.
[53] Martin RC, Sawrie SM, Gilliam FG, et al. Wisconsin card sorting performance in patients
with temporal lobe epilepsy: Clinical and neuroanatomical correlates. Epilepsia
2000;41:1626–32.
12 M. Jones-Gotman et al. / Epilepsy and Behavior 18 (2010) 3–12
[54] DeFilippis NA, McCampbell E. Manual for the Booklet Category Test. Odessa, FL:
Psychological Assessment Resources; 1991.
[55] Damasio AR, Anderson SW. (2003) The frontal lobes. In: Heilman KM, Valenstein E,
editors. Clinical neuropsychology. New York: Oxford University Press; 2003. p. 404–46.
[56] Malloy P, Grace J. A review of rating scales for measuring behavior change due to frontal
systems damage. Cog Behav Neurol 2005;18:18–27.
[57] Gioia GA, Isquith PK, Guy SC, Kenworthy L. Behavior Rating Inventory of Executive
Function. Lutz, FL: Psychological Assessment Resources; 2000.
[58] Grace J, Malloy PF. Frontal Systems Behavior Scale (FrSBe): Professional manual. Lutz,
FL: Psychological Assessment Resources; 2001.
[59] Corkin S, Milner B, Rasmussen T. Somatosensory thresholds. Arch Neurol 1970;23:
41–58.
[60] Annett M. A classification of hand preference by association analysis. Br J Psychol
1970;61:303–21.
[61] Jones-Gotman M. Neuropsychological techniques in the identification of epileptic foci.
Epilepsy Res 1992:87–94 Suppl. 5.
[62] Wechsler D. WMS-III. Administration and Scoring Manual. The Psychological
Corporation. San Antonio: Harcourt Brace Jovanovich; 1997.
[63] Lee TMC, Yip JTH, Jones-Gotman M. Memory deficits after resection from left or right
anterior temporal lobe in humans: A meta-analytic review. Epilepsia 2002;43:
283–91.
[64] Doss RC, Chelune GJ, Naugle RI. WMS-III performance in epilepsy patients following
temporal lobectomy. J Int Neuropsychol Soc 2004;10:173–9.
[65] Rey A. L'examen clinique en psychologie. Paris: Presses Universitaire de France, Paris;
1964.
[66] Majdan A, Sziklas V, Jones-Gotman M. Performance of healthy subjects and patients
with resection from the anterior temporal lobe on matched tests of verbal and
visuoperceptual learning. J Clin Exp Neuropsychol 1996;18:416–30.
[67] Buschke H, Fuld PA. Evaluating storage, retention, and retrieval in disordered memory
and learning. Neurol 1974;24:1019–25.
[68] Fletcher JM. Memory for verbal and nonverbal stimuli in learning disability subgroups:
Analysis by selective reminding. J Exp Child Psychol 1985;40:244–59.
[69] Jones-Gotman M, Zatorre RJ, Olivier A, et al. Learning and retention of words and
designs following excision from medial or lateral temporal-lobe structures. Neuropsy-
chologia 1997;35:963–73.
[70] Jones-Gotman M. Psychological evaluation for epilepsy surgery. In: Shorvon S., Dreifuss
F.D., Fish D., Thomas D., editors. The treatment of epilepsy. Oxford: Blackwell Science
Ltd.; 1996. p. 621-30.
[71] Warrington EK. Recognition memory test. Berkshire: NFER-Nelson; 1994.
[72] Hermann BP, Connell B, Barr WB, Wyler A. The utility of the Warrington Recognition
Memory Test for temporal lobe epilepsy: Pre- and postoperative results. J Epilepsy
1995;8:139–45.
[73] Delis DC, Kramer J, Ober BA, Kaplan E. The California Verbal Learning Test. New York:
Life Science Associates; 1993.
[74] Djordjevic J, Jones-Gotman M. Psychological testing in presurgical evaluation of
epilepsy. In: Shorvon S, Perucca E, Fish D, Dodson E, editors. The treatment of epilepsy.
2nd ed. Oxford: Blackwell Science Ltd.; 2004. p. 699–715.
[75] Frisk V, Milner B. The role of the left hippocampal region in the acquisition and retention
of story content. Neuropsychologia 1990;28:349–59.
[76] Barr WB, Chelune GJ, Hermann BP, et al. The use of figural reproduction tests and
measures of nonverbal memory in epilepsy surgery candidates. J Int Neuropsychol Soc
1997;3:435–43.
[77] Jones-Gotman M. Right hippocampal excision impairs learning and recall of a list of
abstract designs. Neuropsychologia 1986;24:659–70.
[78] Risse GL, Doss RC, Hempel AM. Penovich, PE The performance of temporal lobe epilepsy
(TLE) patients on verbal and nonverbal selective reminding procedures: pre and
postoperative comparisons. Epilepsia 2006;47(Suppl 4):102.
[79] Helmstaedter C, Pohl C, Hufnagel A, Elger CE. Visual learning deficits in nonresected
patients with right temporal lobe epilepsy. Cortex 1991;27:547–55.
[80] Dade LA, Jones-Gotman M. Face learning and memory: the twins test. Neuropsychology
2001;15:525–34.
[81] Abrahams S, Pickering A, Polkey CE, Morris RG. Spatial memory deficits in patients with
unilateral damage to the right hippocampal formation. Neuro-psychologia 1997;35:
11–24.
[82] Baxendale SA, Thompson PJ, Van Paesschen W. A test of spatial memory and its clinical
utility in the pre-surgical investigation of temporal lobe epilepsy patients. Neuropsy-
chologia 1998;36:591–602.
[83] Giovagnoli AR, Erbetta A, Villani F, Avanzini G. Semantic memory in partial epilepsy:
verbal and non-verbal deficits and neuroanatomical relationships. Neuropsychologia
2005;43:1482–92.
[84] Jones-Gotman M, Djordjevic J. Neuropsychological testing in presurgical evaluation. In:
Shorvon S, Perucca E, Engel J, editors. The treatment of epilepsy. 3rd ed. Oxford:
Blackwell Science Ltd; 2009. p. 851–63.
[85] Branch C, Milner B, Rasmussen T. Intracarotid sodium Amytal for the lateralization of
cerebral speech dominance: Observations in 123 patients. J Neurosurg 1964;21:
399–405.
[86] Milner B, Branch C, Rasmussen T. Study of short-term memory after intracarotid
injection of sodium Amytal. Trans Am Neurol Assoc 1962;87:224–6.
[87] Wada J, Rasmussen T. Intracarotid injection of sodium Amytal for the lateralization of
cerebral speech dominance: Experimental and clinical observations. J Neurosurg
1960;17:226–82.
[88] Takayama M, Miyamoto S, Ikeda A, et al. Intracarotid propofol test for speech and
memory dominance in man. Neurol 2004;63:510–5.
[89] Buchtel HA, Passaro EA, Selwa LM, Deveikis J, Gomez-Hassan D. Sodium methohexital
(Brevital) as an anesthetic in the Wada test. Epilepsia 2002;43:1056–61.
[90] Andelman F, Kipervasser S, Maimon S, Neufeld M, Kramer U, Fried I. Are WADA test
results a function of the drug used? Epilepsia 2008;49(Suppl 7):155.
[91] Jones-Gotman M, Sziklas V, Djordjevic J, et al. Etomidate speech and memory test
(eSAM): A new drug and improved intracarotid procedure. Neurol 2005;65:1723–9.
[92] Jones-Gotman M, Sziklas V, Djordjevic J. Intracarotid amobarbital procedure and
etomidate speech and memory test. Can J Neurol Sci 2009;36(Suppl 2):S51–4.
[93] Loring DW, Murr AM, Meador KJ, et al. Wada memory testing and hippocampal volume
measurements in the evaluation for temporal lobectomy. Neurol 1993;43:1789–93.
[94] Perrine K, Westerveld M, Sass KJ, et al. Wada memory disparities predict seizure
laterality and postoperative seizure control. Epilepsia 1995;36:851–6.
[95] Bengner T, Haettig H, Merschhemke M, Dehnicke C, Meencke HJ. Memory assessment
during the intracarotid amobarbital procedure: Influence of injection order. Neurol
2003;61:1582–7.
[96] Risse GL, Gates JR, Fangman MD. A reconsideration of bilateral language repre-
sentation based on the intracarotid amobarbital procedure. Brain Cogn 1997;33:
118–32.
[97] Gotman J, Bouwer MS, Jones-Gotman M. Intracranial EEG study of brain structures
affected by internal carotid injection of sodium amobarbital. Neurol 1992;42:2136–43.
[98] Westerveld M, Zawacki T, Sass KJ, Spencer SS, Novelly RA, Spencer DD. Intracarotid
amytal procedure evaluation of hemispheric speech and memory function in children
and adolescents. J Epilepsy 1994;7:295–302.
[99] Hamer HM, Wyllie E, Stanford L, Mascha E, Kotagal P, Wolgamuth B. Risk factors for
unsuccessful testing during the intracarotid amobarbital procedure in preadolescent
children. Epilepsia 2000;41:554–63.
[100] Lee GP, Park YD, Westerveld M, Hempel L, Blackburn LB, Loring DW. Wada memory
performance predicts seizure outcome after epilepsy surgery in children. Epilepsia
2003;44:936–43.
[101] Lee GP, Westerveld M, Blackburn LB, Park YD, Loring DW. Prediction of verbal memory
decline after epilepsy surgery in children: Effectiveness of Wada memory asymmetries.
Epilepsia 2005;46:97–103.
[102] Sachs BC, Gaillard WD. Organization of language networks in children: functional
magnetic resonance imaging studies. Curr Neurol Neurosci Rep 2003;3:157–62.
[103] Binder JR, Sabsevitz DS, Swanson SJ, Hammeke TA, Raghavan M, Mueller WM. Use of
preoperative functional MRI to predict verbal memory decline after temporal lobe
epilepsy surgery. Epilepsia 2008;49:1377–94.
[104] Binder JR. fMRI could, in principle, replace the Wada Test. In: Miller JW, Silbergeld DL,
editors. Controversies in epilepsy surgery. New York: Marcel Dekker, Inc; 2006.
p. 342–3.
[105] Binder JR, Achten E, Constable RT, et al. Functional MRI in epilepsy. Epilepsia 2002;43
(Suppl 1):S51–63.
[106] Papanicolaou AC, Simos PG, Breier JI, et al. Magnetoencephalographic mapping of the
language-specific cortex. J Neurosurg 1999;90:85–93.
[107] Papanicolaou AC, Simos PG, Castillo EM, et al. Magnetoencephalography: a noninvasive
alternative to the Wada procedure. J Neurosurg 2004;70:867–76.
[108] Doss RC, Zhang W, Risse GL, Dickens DL. Lateralizing language with magnetic source
imaging: Validation based on the Wada test. Epilepsia 2009;50:2242–8.
[109] Hamalainen M, Hari R, Ilmoniemi RJ, Knuutila J, Lounasmaa OV. Magnetoencephalo-
graphy: theory, instrumentation, and applications to non-invasive studies of the
working human brain. Rev Mod Phys 1993;65:413–97.
[110] Ver Hoef LW, Sawrie S, Killen J, Knowlton RC. Left mesial temporal sclerosis and verbal
memory: A magnetoencephalography study. J Clin Neurophysiol 2008;25:1–6.
[111] Fletcher JM, Taylor HG. Neuropsychological approaches to children: towards a
developmental neuropsychology. J Clin Exp Neuropsychol 1984;6:39–56.
[112] Porter BE, Judkins AR, Clancy RR, Duhaime A, Dlugos DJ, Golden JA. Dysplasia: A
common finding in intractable pediatric temporal lobe epilepsy. Neurol 2003;61:365–8.
[113] Duchowny MS. Developmental lesions in epilepsy. ASIM 2001;1:147–52.
[114] Smith ML. Presurgical neuropsychological assessment. In: Lassonde M, Jambaque I,
Dulac O, editors. The neuropsychology of childhood epilepsy. New York: Plenum
Press; 2001. p. 207–14.
[115] Fastenau PS, Johnson CS, Perkins SM, et al. Neuropsychological status at seizure onset in
children: risk factors for early cognitive deficits. Neurology 2009;18(73):526–34.
[116] Tatum W, French JA, Faught E, et al. Post marketing experience with topiramate and
cognition. Epilepsia 2001;42:1134–40.
[117] Baker GA, Goldstein LH. The dos and don'ts of neuropsychological assessment in
epilepsy. Epilepsy Behav 2004;5(Suppl 1):S77–80.
[118] Motamedi GK, Meador KJ. Antiepileptic drugs and memory. Epilepsy Behav 2004;5:
435–9.
[119] Aldenkamp AP, Baker GA. Systematic review of the effects of lamotrigine on cognitive
function and quality of life. Epilepsy Behav 2001;2:85–91.
[120] Cramer JA. ILAE Subcommission on Outcome Measurement in Epilepsy (Camfield C,
Carpay H, Helmstaedter C, Langfitt J, Malmgren K, Wiebe S). Principles of health-
related quality of life: assessment in clinical trials. Epilepsia 2002;43:1084–95.
[121] Giovagnoli A, Avanzini G. Quality of life and memory performance in patients with
temporal lobe epilepsy. Acta Neurol Scand 2000;101:295–300.
[122] Perrine K, Hermann BP, Meador KJ, et al. The relationship of neuropsychological
functioning to quality of life in epilepsy. Arch Neurol 1995;52:997–1003.
[123] Surmeijer TP, Reuvekamp MF, Aldenkamp BP. Social functioning, psychological
functioning and quality of life in epilepsy. Epilepsia 2001;42:1160–8.
[124] Wong T.M, Strickland T.L, Fletcher-Janzen E.F, Ardila A, Reynolds C.R. Theoretical and
practical issues in the neuropsychological assessment and treatment of culturally
dissimilar patients. In Fletcher-Janzen E.F, Strickland T.L, and Reynolds CR, editors.
Handbook of cross-cultural neuropsychology. New York: Kluwer Academic, Plenum
Publishers; 2000.
[125] Pérez-Arce P. The influence of culture on cognition. Arch Clin Neuropsychol 1999;14:
581–92.