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A Nosology of Disorders of Attention

Article in Annals of the New York Academy of Sciences · July 2001

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A Nosology of Disorders of Attention
ALLAN F. MIRSKYa AND CONNIE C. DUNCANa,b
aSectionon Clinical and Experimental Neuropsychology, LBC,
National Institute of Mental Health, Bethesda, Maryland 20892-2615, USA
bClinicalPsychophysiology and Psychopharmacology Laboratory,
Department of Psychiatry, Uniformed Services University of the Health Sciences,
Bethesda, Maryland 20814-4799, USA

ABSTRACT: The trailblazing research on sleep mechanisms and petit mal epi-
lepsy, conducted during the period from 1940 through 1970, illuminated the
brain substrate for normal consciousness and attention, as well as their disor-
ders. This research helped inform and structure our neuropsychologically
based model of the “elements” of attention. The model has been used to assess
attention in the research laboratory and clinic, and has led to a “nosology of
disorders of attention,” which is presented here in preliminary form. The noso-
logy reviews the possible causes of the symptom(s) of impaired attention, as
well as suggesting a blueprint for future research in this area.
KEYWORDS: Attention; Nosology; Sleep; Seizure disorders; Cerebral structures;
Neuropsychological tests.

INTRODUCTION

All humans experience lapses in attention, most commonly as an accompaniment

of normal drowsiness or fatigue! To understand lapses in attention, we draw on stud-
ies of the mechanisms underlying sleep and the effects of sleep deprivation, as well
as research on certain idiopathic generalized seizure disorders. The attention lapses
following periods of sleep deprivation, in particular, have been studied extensively.
Prolonged loss of sleep may result in brief transitions from wakefulness to slow-
wave sleep (“microsleeps”) that intrude upon wakefulness.1,2 As would be expected,
the individual at the time of those intrusions is less responsive to external stimuli and
exhibits attention lapses.
The cerebral mechanisms underlying the transition from wakefulness to sleep
were provided in large part by the classic research conducted by Moruzzi, Magoun,
Lindsley and colleagues at UCLA, leading to the discovery of the ascending reticular
activating system or ARAS.3–5 This system, originating in the medial portions of the
brainstem reticular formation and pons, and ascending in the midline and reticular
nuclei of the thalamus, is the central coordinating and activating center of the brain,
with widespread connections to most of the forebrain cortical areas. It has the major

Address for correspondence: Allan F. Mirsky, Ph.D., Section on Clinical and Experimental
Neuropsychology, LBC, NIMH, NIH, MSC 2615, 5415 W. Cedar Lane, Bethesda, MD
20892-2615. Voice: 301-496-2551.
allan_mirsky@nih.gov

17
18 ANNALS NEW YORK ACADEMY OF SCIENCES

responsibility for maintaining a degree of tonic excitability (“arousal”) necessary for

all cognitive activity. In Lindsley’s words,
Wakefulness is maintained by excitation of the reticular formation and the ARAS
through collaterals from all sensory pathways, by corticofugal impulses originating in
various regions of the cortex and by humoral factors which affect particularly the ros-
tral portions of the reticular formation. . . . Attention is closely allied to arousal and
wakefulness and, like wakefulness and consciousness, appears to be a graded phenom-
enon extending from general alerting, as in the orienting reflex, to specific alerting, as
when attention is focused upon a given sense mode and dominates sensory input to the
point of exclusion of other sense modes. 5 (p. 1589)

Microsleeps, according to this formulation, represent a phasic interruption of the

capacity of the brainstem, and/or cortical structures to which they are allied, to main-
tain arousal. This is signaled, in addition to the failure of attention, by the appearance
of bursts of high voltage slow wave activity in cortical areas.1,2
Another model of lapses in attention is provided by certain seizure disorders: in
petit mal or absence epilepsy, brief interruptions of attention (“absence attacks”)
may occur at frequent intervals, particularly if the disorder has not been treated
effectively.6 Although the goal of their research was to unravel the seizure mecha-
nisms underlying this disorder, the seminal work of Penfield and Jasper6 and a group
of colleagues at the Montreal Neurological Institute led to conclusions similar to
those reached by the UCLA group. On the basis of their study of patients with sei-
zure disorders, as well as animal models, Penfield and Jasper proposed that the neu-
ral center of consciousness was located deep within the brainstem.6 In that region of
the brain, there exists a central integrating mechanism (the “centrencephalic” sys-
tem) for coordinating and regulating the activities of the two cerebral hemispheres.
The concept of the centrencephalon was supported by the results of numerous
experimental studies of the electrical activity of the brain in animals, which pointed
to a major coordinating role for midline brainstem structures. Penfield and Jasper
maintained, further, that petit mal seizures provide an example of a disorder of the
centrencephalic system: the primary symptom is a brief interruption of conscious-
ness or attention that occurs in conjunction with bilaterally symmetrical and syn-
chronous spike-and-wave EEG discharges.
In a petit mal seizure, there is a loss of consciousness which may be associated with no
other outward manifestation than a blank stare, an arrest of what one might call volun-
tary activity. The return of consciousness may likewise be without sign except for the
resumption of his previous train of thought as shown by speech or action. The patient
himself may have no knowledge of the gap unless he perceives that his position has
changed or his surroundings have altered. 6 (p. 480)

The phenomena of microsleeps and absence seizures thus provide a background

for a discussion of attention lapses in general, and the knowledge derived from
decades of sleep and epilepsy research provides a framework to support a compre-
hensive theory of the mechanisms of attention disorders. The model we have pro-
posed for assessing elements of attention relies heavily on this research base.7,8
Nevertheless, aside from the heuristic value of our knowledge of the mechanisms
underlying the microsleep and the absence attack, the question remains as to how
and whether this information can help us to understand the disorders of attention that
are more subtle, less easy to detect and therefore possibly more deleterious in their
effects on an individual’s life. In brief, our position is that all disorders of attention
MIRSKY & DUNCAN: NOSOLOGY OF DISORDERS OF ATTENTION 19

may eventually be understood in reference to the model we have developed of the

brain system that supports the elements of attention.7,8

THE ASSESSMENT OF ATTENTION: DESCRIPTION OF MEASURES

We have written extensively on the assessment of attention in normal and disor-

dered populations, beginning in 1956, and continuing to the present.7–20 During the
course of these investigations, it became apparent that disturbances of attention are
prominent symptoms of many clinical disorders. One of our goals has been to devel-
op an overarching scheme that would encompass all of these disorders and condi-
tions, one that would help us to understand how such disturbances occur. This goal
has not yet been achieved; however, in the course of our research, we have utilized
a set of measures that appear useful in defining specific types of attentional impair-
ment. These methods comprise an “attention battery,” which has helped us to con-
ceptualize five elements of attention. These elements appear to have a rough
correspondence to a set of underlying brain structures supporting attention.7,8,18,20
TABLE 1 presents a summary of the tests comprising the attention battery and the
assignment of each of them to an attentional factor or “element.” This assignment
was based on principal components analysis,8 as well as the putative supporting
brain structure or structures.7,8,18,20 It should be noted that the factor structure of the
attention battery has been replicated by a number of investigators since the analysis
of attentional elements was first published.7,21,22 The assignment of different cere-
bral structures in support of the different attentional elements is meant to be a rela-
tive specialization rather than an absolute one, as the attentional system is to some
extent equipotential. Thus, healthy components of the system may partially compen-
sate for the dysfunction of injured components.

TABLE 1. Elements of attention: summary of tests

Attentional Element Tests/Measures
Encode Digit Span (WAIS-R or WAIS-III; WISC-R or WISC-III)
Arithmetic (WAIS-R or WAIS-III; WISC-R or WISC-III)
Focus/Execute Digit Symbol Substitution (WAIS-R or WAIS-III)
Coding (WISC-R or WISC-III)
Letter Cancellation Test
Stroop Color-Word Interference Test
Trail Making Test, Parts A and B
Shift Wisconsin Card Sorting Test
Reciprocal Motor Programs Test
Sustain Visual CPT (X, AX, Other): Accuracy, Reaction Time
Auditory CPT (X, AX, Other): Accuracy, Reaction Time
Stabilize Visual CPT (X, AX, Other): Variance of Reaction Time
Auditory CPT (X, AX, Other): Variance of Reaction Time
20 ANNALS NEW YORK ACADEMY OF SCIENCES

1. The Encode Element: Tests that assess the encode element tap the capacity
to hold information in memory briefly, to enable performance of some
mental operation on the information. Our usage of encode would be equiv-
alent to the term working memory. We proposed that this factor is sup-
ported by brain structures in and around the hippocampus and amygdala.
The Digit Span (WAIS-R, WAIS-III, WISC-R, WISC-III) subtest
taps the subject’s capacity for encoding and retaining in memory a series of
numbers and repeating them immediately. There are two portions of this
test, Digits Forward and Digits Backward.
The Arithmetic (WAIS-R, WAIS-III, WISC-R, WISC-III) subtest
assesses the subjects’s capacity to encode, and retain in memory, arith-
metic word problems, and to solve them without the aid of pencil and
paper.
2. The Focus/Execute Element: Tests of the focus/execute element measure
the capacity to focus on a task in the presence of distracting stimuli, and to
execute quickly the manual or verbal responses required by the task. We
proposed that structures within the inferior parietal lobule, superior tempo-
ral gyrus and parts of the corpus striatum support this aspect of attentive
behavior.
The Digit Symbol Substitution (WAIS-R, WAIS-III) or Coding
(WISC-R, WISC-III) subtest requires the subject to transcribe the sym-
bols paired with the numbers 1 through 9 as quickly as possible, within a
given time limit. The test comprises 100 (or more) digits in random order.
Coding is an equivalent task for children and adolescents.
The Letter Cancellation Test comprises six pages of typed letters of
the alphabet, some of which are capitalized, and some of which are sepa-
rated by double spaces. The task requirements include three variations:
crossing out capital letters, crossing out the letters immediately before and
after a double space, and performing both tasks at once. There is a 60-sec-
ond time limit for each page. The Letter Cancellation Test was originally
described by Talland.23
The Stroop Color-Word Interference Test comprises three forms,
one containing color names, one containing patches of color, and the third
containing color names printed in contrasting ink colors. The subject is
required to read the words (form 1), name the colors (form 2), or name the
color of the ink (form 3) as rapidly as possible during three 45-second
intervals. The version of the Stroop test24 we employ uses stimuli and
instructions described by Golden.25
The Trail Making Test26 consists of two parts. Part A of this timed
task calls for connecting numbers in an ascending sequence, whereas Part
B requires alternation of numbers and letters in an ascending sequence
(i.e., 1-A-2-B-3-C, etc.).
3. The Shift Element: In our analysis, this attentional element is an index of
the capacity to shift attentional focus from one aspect of a complex stimu-
lus to another. The dorsolateral prefrontal cortex and anterior cingulate
gyrus are thought to support this attentional function.
MIRSKY & DUNCAN: NOSOLOGY OF DISORDERS OF ATTENTION 21

We assess this element with the Wisconsin Card Sorting Test

(WCST)27,28 and, under certain conditions, the Reciprocal Motor Pro-
grams Test (RMPT). The WCST requires the subject to sort a pack of
stimulus cards with respect to one of three stimulus qualities, i.e., color,
form or number, and to be able to shift sorting category on the basis of
feedback from the examiner. The WCST yields several scores, including
number of categories achieved, number of errors, number of perseverative
errors, etc. The RMPT is thought to have originated with Luria; it requires
the subject at first to mimic the tapping sequence of the examiner: tap once
for each single tap and twice for each double tap. The subject is then
required to do the opposite of the examiner, namely, tap twice if the exam-
iner taps once, etc. The RMPT is considered a more elementary test of the
capacity to shift, and is administered if the person is unable to achieve
more than two categories on the WCST.
4. The Sustain Element: This element represents the capacity to maintain an
attentional focus—a vigilant attitude—for an appreciable interval of time.
This capacity is measured independently in the visual and auditory modali-
ties, and, by means of a number of subtests, in increasing order of atten-
tional demands. Our own research, as well as that of others (reviewed
above), supports the view that the brainstem reticular formation as well as
midline thalamic structures are key structures supporting this element of
attentive behavior.
The Continuous Performance Test (CPT) was devised by Rosvold,
Mirsky, et al.9 as a measure of the capacity to sustain a focus of attention.
Various versions of the CPT have been devised: the standard visually pre-
sented X and AX tasks of the CPT require the subject to press a response
button to certain target stimuli (“press as quickly as possible whenever you
see the letter X” or “press for the X only if it is preceded by the letter A,”
respectively). The auditory task stimuli consist of three tones of distinctly
different pitches. Subjects must press the response button as quickly and as
accurately as possible whenever they hear the tone highest in pitch. A
homologous version to the visually presented AX task requires the subject
to press the response button whenever the high tone follows immediately
after a low tone.29 Other auditory tasks require responses to spoken letters.
5. The Stabilize Element: The stabilize element30,31 is assumed to reflect the
consistency or stability with which a person can respond to designated
“target” stimuli. It is measured by the variance of response times to cor-
rectly detected targets in the CPT. Our assumption is that this element is
supported by the same attention system that supports the other elements,
but the precise assignment is unknown.

THE NOSOLOGY

Impairment of attention—in contrast to normal fluctuations—is a common symp-

tom of neuropsychiatric disorder and merits a systematic attempt at classification.32
22 ANNALS NEW YORK ACADEMY OF SCIENCES

TABLE 2. Impaired attentional elements in four categories of etiology a

Attentional Element
Etiology Encode Focus/ Shift Sustain Stabilize Sample
Execute References
Familial/Geneticb
Absence, other IGE c Yes ? Yes Yes Yes 33
Schizophrenia d Yes Yes Yes Yes Yes 18
Autisme ? ? Yes No ? 34
Narcolepsyf Yes/? Yes/? Yes/? Yes/? Yes/? 84,85
ADD, ADHDg,h ? Yes Yes Yes Yes 20
Metabolic
Phenylketonuria ? ? ? Yes ? 35,36
Uremia ? Yes ? Yes ? 37,38
Environmental
Malnutrition No Yes Yes No No 39,40
Lead intoxication No No No Yes Yes 41,42
Pregnancy/birth ? ? ? ? ? 43,44
complications
Fetal alcohol ? Yes ? Yes Yes 45
syndrome/effect
Neurocysticercosis/ Yes Yes Yes Yes No 46,47
other parasitic
infections
Lack of intellectual ? ? Yes No No 18,32,48
stimulation
Other
Head injury ? ? Yes Yes ? 49
Brain ? ? ? Yes ? 50
infections/tumors
Sleep/breathing ? ? ? Yes ? 51
disorders
Eating disorders ? Yes ? No No 15
MIRSKY & DUNCAN: NOSOLOGY OF DISORDERS OF ATTENTION 23

TABLE 2. Footnotes
aThis is a preliminary classification, based primarily on research we have conducted, or in
which we have collaborated. The references provided are meant only to be illustrative. A full
treatment of the literature on each of these disorders is beyond the scope of this chapter. How-
ever, we believe that there is heuristic value in this preliminary nosology. In many of the disor-
ders listed in TABLE 2, there is an extensive research literature; however, we have chosen to
defer review and discussion.
bThe grouping of attention disorders into categories on the basis of etiology can be beneficial
in a number of ways: 1) It emphasizes the ubiquity of attention disorders, and their manifold cau-
sation; 2) It informs remedial efforts so that they may be maximally effective; 3) It promotes the
scientific analysis of attention disorders and of attention itself.
cIGE = idiopathic generalized epilepsies.
dThese data were derived from a sample of persons from a rural area of Ireland, who possessed
limited education, and may therefore not be representative of patients with higher levels of edu-
cation.
eThe study cited was one in which the subjects were classified as “high-functioning.” Subjects
with lower levels of functioning would be expected to perform more poorly on these tests.
fBased on a single case. We have seen one patient with a diagnosis of narcolepsy, a computer
engineer, who was impaired on virtually all of the tests of the “Attention Battery.” He was fired
from several jobs as a result of his inability to maintain wakefulness and complete assignments.
Our suspicion is that his inability to sustain attention (as evidenced by CPT scores in the
severely impaired range) was the basis of all of his other deficits. The literature suggests that
most patients with this diagnosis would be impaired on tests such as the CPT. 84,85
gAs an example of the benefits accruing to the systematic approach to disordered attention, we
cite a hypothetical case which may nevertheless be very common. A six-year-old child is
referred for evaluation of her “daydreaming and failure to pay attention in class.” In some juris-
dictions/institutions, depending on the resources and time available to the school psychologist, a
diagnosis would be made within short order that the child is suffering from some form of atten-
tion deficit disorder, with or without hyperactivity. With the compliance of a physician, the child
would be placed on stimulant medication, most likely, methylphenidate (Ritalin) or dextro-
amphetamine. After several weeks, during which time the dose of the drug would be increased, it
would be apparent that the medication was ineffective, and if anything, the child would be less
responsive and more distracted in class than ever.
In another scenario, which may follow (or replace) the one described above, the school psy-
chologist, who had been trained in neuropsychology, conducts a comprehensive and informed
evaluation of the various aspects of attention in the child. 8 The results of that examination,
which would include the Continuous Performance Test or CPT, indicate that the omission errors
made by the child suggest a failure of vigilance, rather than the impulsivity associated with
ADHD. Consequently, the school psychologist would recommend that the child be given an
EEG examination to rule out the presence of a generalized seizure disorder, such as childhood
absence epilepsy. The examination reveals the tell-tale three-per-second symmetrical and syn-
chronous spike-and-wave pattern of absence epilepsy. The child would be placed on the anticon-
vulsant medication sodium valproate, and the attention problem would improve considerably
within a few days.
This example illustrates the importance of having a more comprehensive view of the nature
and causes of attention impairment, and the value of knowledge that there can be more causes of
disordered attention than ADD/ADHD.
hThe data were derived from a population of inner-city children with ADHD, many of whom
had other diagnoses (e.g., learning disabilities, oppositional conduct disorder, etc.). The ubiqui-
tous deficits seen in this population may not be representative of what is seen in middle-class
children with this diagnosis, but nevertheless call attention to the overwhelming need for inter-
vention and remediation in this segment of our population.
24 ANNALS NEW YORK ACADEMY OF SCIENCES

The proposed nosology emphasizes the fact that all symptoms of impaired attention
do not stem from the same cause. Instead, they may have a variety of causes that
comprise a number of broad categories. It is with systematization in mind that we
began to develop a comprehensive nosology of disorders of attention.
TABLE 2 summarizes the proposed nosology of disorders of attention. It includes
relevant references, usually from our own research, concerning the specific atten-
tional elements that have been found to be impaired in the disorders.
The following caveat is in order: The evidence for the inheritance of disorders
such as schizophrenia, attention-deficit hyperactivity disorder (ADHD), and
idiopathic generalized epilepsy is clear; however, other data suggest that there may
be a genetic component in most complex human disorders—and a number of these
have the symptom of impaired attention. Therefore, the proposed categorization in
TABLE 2 will have to be altered as evidence is gathered regarding the genetic contri-
bution to other disorders.

SOME COMMENTS ON THE NOSOLOGY

Familial/Genetic Etiologies
Probably the major research effort in this field has involved the assessment of
attention in first-degree relatives of patients with schizophrenic disorders. Our stud-
ies in Ireland and Israel, as well as those from the New York High-Risk Project, have
provided ample evidence of the attentional deficit in first-degree relatives of patients
with schizophrenia. This deficit is manifest primarily in measures of sustained atten-
tion, such as the CPT.14,18,31,52
The findings of impaired attention in the relatives of patients with schizophrenia
provided a stimulus for studies in other familial/genetic disorders, such as idiopathic
generalized epilepsy.53–55 A major focus of our research effort over the past decade
has been concerned with identifying familial/genetic influences in the neuropsycho-
logical deficits seen in generalized epilepsy. We were the first to report that there is
a distinct neuropsychological deficit found in patients with absence epilepsy—man-
ifest in impaired sustained attention—a finding that we (and others) have replicated
a number of times in succeeding years.8,10–12,29,33,56,57 Lansdell and Mirsky12
reported, as well, that female patients with the disorder performed more poorly on
the CPT than male patients. Levav59 replicated this result and also found that there
is a significant tendency for female, but not male, parents of patients with absence
epilepsy to share (in milder form) the deficits seen in the probands themselves.59
This result mirrors the finding that absence epilepsy tends to be inherited in the
maternal line.53–55
Most recently, we have found that relatives of patients with juvenile myoclonic
epilepsy (JME)—another form of idiopathic generalized epilepsy—may also share
some of the deficits in visual and auditory sustained attention seen in the probands.33
We are actively pursuing the implications of these findings for the burgeoning field
of the genetic analysis of the idiopathic epilepsies (e.g., refs. 60, 61). Thus, the work
of Greenberg and colleagues suggests that there is an “epilepsy gene,” identified
through linkage analysis, which is apparently present for both probands and relatives
of probands with JME. The location of this gene is in the human lymphocyte
MIRSKY & DUNCAN: NOSOLOGY OF DISORDERS OF ATTENTION 25

antigens (HLA) region of chromosome 6p.60–64 The HLA region of chromosome 6

has also been implicated in schizophrenia65,66 and ADHD.67
Impaired attention, specifically on the CPT, has been reported in schizophrenia,
ADHD, and idiopathic generalized epilepsy.14,18,20,31,52 Moreover, a form of domi-
nant inherited deafness has been located in the HLA region of chromosome 6p.68
Our interest in this latter finding is stimulated by the fact that auditory versions of
the CPT are more sensitive than visual versions to the effects of schizophrenia,
absence epilepsy, and JME.17,18,29
The list of familial/genetic disorders also includes narcolepsy — a disorder char-
acterized by excessive daytime sleepiness and disturbances in the manifestations of
rapid eye movement sleep. Although there is a paucity of literature on the measure-
ment of attention in such patients or their relatives, it seems reasonable to assume
that they would be impaired in tests of sustained attention such as the CPT. It is nota-
ble that these patients also show abnormalities in the HLA region of chromosome 6,
as well as other possible genetic abnormalities.84,85
These genetic findings are summarized in FIGURE 1, which presents a schematic
view of chromosome 6. The question arises as to whether all of the disorders shown

FIGURE 1. The putative location of genes for schizophrenia, narcolepsy, autosomal

dominant deafness, ADHD and juvenile myoclonic epilepsy on chromosome 6p. The his-
togram at the right reflects the number of genes that have been identified at those locations
on the chromosome (adapted from Metrakos & Metrakos 83).
26 ANNALS NEW YORK ACADEMY OF SCIENCES

in the figure share a common genetic fault — a mutation or polymorphism in the

region around 6p21.3 — which is expressed as an impairment in sustained attention.
The pathophysiological mechanism underlying such an impairment could represent
abnormal firing in thalamic neurons, as is suggested by some of the neurophysiolog-
ical investigations of mouse models of absence epilepsy. The animals so afflicted
have spike-wave discharges in the EEG and a convincing murine analog of staring
spells.69,70,71 Midline thalamic nuclei are a critical component of the centrencepha-
lic system and could well be a major site of the pathophysiological process resulting
in both the behavioral and electrographic signs of absence seizures. Moreover,
abnormal subcortical tissue, as assessed by quantitative MRI, has been reported in
patients with JME.72
It is clear that considerably more work is necessary to establish whether this spec-
ulation has any validity. We assume, however, that each of the disorders shown in
FIGURE 1 must have a unique genetic signature. Thus, for example, Durner et al.73
reported that there are a number of additional chromosomal locations that may con-
tribute to vulnerability to JME or to other forms of idiopathic generalized epilepsy.
These include loci on chromosome 5, 8, 6q and 18. The following quotation is rele-
vant in this context:
One of the most difficult challenges ahead is to find genes involved in diseases that
have a complex pattern of inheritance, such as those that contribute to diabetes, asthma,
cancer and mental illness. In all these cases, no one gene has the yes/no power to say
whether a person has a disease or not. It is likely that more than one mutation is re-
quired before the disease is manifest. A number of genes may each make a subtle con-
tribution to a person’s susceptibility to a disease [italics added]; genes may also affect
how a person reacts to environmental factors. Unravelling these networks of events
will undoubtedly be a challenge for some time to come. Fifty years on, the sequence of
the human genome and the fruits it will bear will undoubtedly make a significant con-
tribution to improving the diagnosis and treatment of disease. 74

We would like to make an additional comment, on the question of the etiology of

ADHD. A convincing argument has been made that failure of inhibition is the core
deficit underlying the symptoms of ADHD.75 However, our own experience with
inner-city children with this diagnosis20 leads us to question whether such an expla-
nation fits all the data, or is applicable to all children so diagnosed. Poor performance
on some aspects of the CPT (i.e., impulsive responding to nontarget stimuli) is con-
sistent with failure of inhibition. However, other findings (i.e., errors of omission on
the CPT, impaired performance on the Wisconsin Card Sorting Test, poor scores on
tests requiring the capacity to focus on a task) suggest a more pervasive failure of
attentive processes than can be attributed solely to lack of inhibitory control.20

Metabolic Etiologies
In his studies of end-stage uremia, Murawski36 reported that patients with this
disorder exhibited impairment of sustained attention, as measured by the CPT. The
impairment of attention was particularly intriguing in view of the finding that end-
stage uremia is sometimes accompanied by an EEG pattern that resembles that seen
in absence epilepsy.76 This report encouraged the belief that the toxins associated
with kidney failure attacked the same “centrencephalic” brainstem structures impli-
cated in absence epilepsy.6 Subsequent studies of uremic patients have confirmed the
neurotoxic effects of kidney failure, including the presence of an abnormal EEG,77
and the development of convulsions that may be generalized.78,79 In addition,
MIRSKY & DUNCAN: NOSOLOGY OF DISORDERS OF ATTENTION 27

one study reported abnormal performance of dialyzed uremic patients on the Trail
Making Test.38

Environmental Etiologies

In the 1994 Herbert G. Birch Memorial Lecture to the International Neuropsy-

chological Society, the message delivered by Cravioto, DeLicardie and Birch80 was
repeated, namely that environmental conditions associated with poverty (ignorance,
malnutrition and infection) are persistent problems in underdeveloped countries.
These problems, inevitably, have resulted in impaired cognitive development for
millions, if not billions, of the world’s people. Whereas some of these problems do
not require poverty (i.e., maternal drinking, pregnancy/birth complications), there is
a greater likelihood that poor people will suffer from them. The effects of maternal
drinking on later cognitive development have been well documented by Streissguth
and colleagues.45 In the case of pregnancy/birth complications, the results of the
British studies of the 1970s indicate the catastrophic effects of poverty—as reflected
in fetal deaths and non-lethal mental defects—in the offspring of young, inexperi-
enced (and usually impoverished) mothers.43,44
The studies we conducted, in collaboration with Ecuadoran investigators, of the
residents of a small mountain village north of Quito, illuminated the effects on atten-
tion of malnutrition and parasitic infection.39,40,46,47 Whereas all parasitic infections
can act to sap energy needed for learning and development of cognition, the most vir-
ulent parasite may be the pork tapeworm or Taenia solium. This organism infests the
brain and produces a condition known as neurocysticercosis, which can be a leading
cause of cognitive decline as well as seizures.39,40,46,47
The category of environmental etiology would not be complete without reference
to lack of intellectual stimulation, or more simply, ignorance. Ignorance is not strict-
ly speaking an environmental effect, and is clearly not restricted to impoverished
populations. The fact remains, however, that in many studies of factors associated
with impaired cognitive development, maternal education and intelligence emerge as
significantly related to children’s achievement.48 We observed this relationship in
our studies in Ecuador.

Other Etiologies

Cerebral insults produce impairments in attention, and we have published find-

ings relevant to this issue.8,49 A full discussion of this research is beyond the scope
of this chapter, as is a discussion of the research on the effects of tumors and infec-
tions on attention. In this context, however, it is of interest to note that Greenblatt50
found a significant negative correlation between brainstem tumor size and measures
of CPT performance. The deleterious effects of sleep breathing disorders on atten-
tion are perhaps not unexpected, in view of the labored, interrupted sleep patterns of
persons with this disorder. What was unexpected was the severe level of impairment
on the CPT seen in a large sample of persons undergoing evaluation for treatment.51
28 ANNALS NEW YORK ACADEMY OF SCIENCES

CONCLUDING REMARKS

The data summarized in TABLE 2, especially the numerous “?” entries, indicate
that there are many aspects that remain to be investigated from the point of view of
the model of attention proposed here. The data also suggest that whereas there may
be considerable heterogeneity in the attentional deficits associated with neuropsy-
chiatric disorders, there may be a substantial degree of homogeneity as well. Thus,
of the sixteen etiologies listed in the tables, there is evidence of impaired sustained
attention, as assessed by the CPT, in eleven. The next most frequent listing is impair-
ment in the capacity to shift attention (assessed by the WCST), seen in eight of the
etiologies.
If our theorizing about the cerebral structures that support sustained attention is
correct, this would suggest that compromise of brainstem and/or midline thalamic
structures would appear to be a common feature of all the disorders in which
impaired CPT functioning is seen. This would not be subject to much discussion
with respect to absence and other forms of idiopathic epilepsy,6 possibly end-stage
uremia76–79 and perhaps some forms of schizophrenia.81,82 However, whether and
how this subcortical brain system is compromised in the other disorders remains to
be demonstrated. Nevertheless, with the imaging techniques now available to eluci-
date brain dysfunction, it may be possible to identify which cerebral structures are
implicated in the attention impairment in these common and troubling disorders.
The paper by Rosvold, Mirsky, et al. that was the first to describe the application
of the CPT to the study of impaired attention9 has been referenced in the literature
approximately 800 times. The widespread adoption of this technique for studying
sustained attention is evident in the numerous commercial versions of the CPT that
are currently on the market. The paper on the analysis of elements of attention8 has
been cited 125 times, as of the end of the last century. Those two publications would
appear to have had a salutary influence on the scientific study of attention and its
clinical application. Our hope is that this discussion of the nosology of attention dis-
orders may serve to promote further study of the disorders of attention, as well as of
our model and its applicability.

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