Attention deficit

Review Article

Attention Deficit Peter B. R o s e n b e r g e r , M D

Attention deficit, among the most commonly diagnosed functional deficits in pediatric neurology, is, like epilepsy, most often idiopathic. It can also be a symptom of many neuropathologic states. Although a lifelong problem, attention deficit is most troublesome during school years, because, like asthma, it is highly sensitive to environmental influence. The neurologist can consider attention deficit in its own right, apart from hyperkinesis and other associated behavior disorders, as a cognitive limitation and handicap to academic progress. Rosenberger PB. Attention deficit. Pediatr Neurol 1991;7: 397-405.

Introduction An important challenge to the child beginning school is to learn to sit still in a group of peers, resist a deluge of distractions from the surroundings, pay attention to an instructor who does not reciprocate constantly, and concentrate on a task that does not necessarily command attention. Relative failure to acquire this skill is commonly referred to as attention deficit (AD) and is responsible for a substantial portion of the practice of pediatric neurology.

Definitions AD in children is commonly approached as part of a syndrome defined by a consensus of clinicians and researchers, mostly psychiatrists [1], which includes motor overactivity and problems with behavioral adjustment and emotional stability. Controversies regarding the definition of AD have been reviewed in detail elsewhere [2].

Evolution of the Clinical Syndrome The concept that a brain disorder may be associated with AD appears to have taken root at the turn of the century. English proposed that children suffer such serious after-effects from brain trauma because the injuries occur during the time of development of the intellectual capacities [3]. Leahly and Sands initially reported behavioral distur-

From the Learning Disorders Unit and Division of Child Neurology; Massachusetts General Hospital; and Department of Neurology; Harvard Medical School; Boston, Massachusetts.

bances in children following recovery from epidemic encephalitis [4]. In a more complete report Ebaugh reviewed 17 patients, 10 of whom had, in varying degrees, "a total change in character and disposition with characteristic hyperkinetic states, leading to behavior oddities consisting of emotional lability, sexual precocity, general incorrigibility, etc." [5]. He made no specific mention of AD, but reported that although psychotherapy was of little use, occupational therapy appeared to be helpful in "channeling" the child's energies. Strecker and Ebaugh reviewed 30 children with post-traumatic encephalopathy and discussed the similarity of the hyperkinetic states and affective disorders to those encountered in post-encephalitic children [6]. In 10 of these patients, they measured distractibility by recording the number of attempts required for the children to learn a string of digits one digit longer that their baseline digit spans, and found a substantial increase over that required by normal children of the same age. Kahn and Cohen termed the "surplus of inner impulsion" in many patients following epidemic encephalitis as "organic drivenness" and suggested that this disorder may reflect dysfunction of the brainstem, although admitting that they had no neuropathologic evidence to support such a hypothesis [7]. They also appear to have been the first to recognize distractibility as part of this syndrome. Strauss proposed a conceptual framework that is remarkably relevant to today's studies of AD [8]. He recalled Kanner's classification of the child's learning process in the 4 categories of (1) goal-awareness, (2) vigilance, (3) selectivity, and (4) tenacity: a more adequate schema, in my view, than more modem distinctions between "selective" and "sustained" attention. Strauss suggested that for the brain-injured child the most serious handicap is in the function of selectivity or discrimination of essential from nonessential details [8]. He reported that goal-awareness and vigilance usually were normal and that some brain-injured children were, in fact, hypervigilant. Tenacity usually was impaired secondarily. More recent precursors of contemporary research in AD were reviewed in a symposium of the Oxford International Study Group in Child Neurology in 1962 [9] and in the proceedings of a conference sponsored in 1972 by the New York Academy of Sciences [10]. The latter brought to-

Communications should be addressed to: Dr. Rosenberger; ACC 705; Massachusetts General Hospital; Boston, MA 02114. Received September 13, 1991; accepted October 31, 1991.

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gether reports from 50 researchers, many of whom remain active to the present.

Table 1.

Measures of attention*

Direct

Specification of AD Attempts to specify AD have been hampered by a lack of consensus regarding the nature of attention. It has long been recognized to be a process basic to the organism's effective interaction with the environment; many different brain structures play a role. Kinsbourne suggested that lateral attention, in the form of the orienting response, is critical in the defense of the primitive organism from predators and probably bilaterally directed [ 11 ]; higher order focal attention may not only depend upon hemispheric specialization but also, to some extent, be involved in its development. A similar approach to attention as an orienting response was suggested by Posner [12]. Mesulam suggested a functional specialization for the right cerebral hemisphere for all "directed" attention [ i 3]. Also contributing to confusion is the fact that attention has several facets. A basic distinction upon which most psychologists agree is between arousal attention, sometimes called intention [14,15], and selective attention [16]. The former refers to the probability that the organism will respond to a stimulus of a given strength, the latter to the probability that, under the same conditions, other competing "irrelevant" stimuli will be rejected or ignored. Physiologically, the distinction may be largely arbitrary because no stimulus occurs in a background totally devoid of "noise;" however, it recognizes the inhibitory character of selective attention. A further distinction may be made between immediate and sustained attention. The latter has long been the subject of interest as a physiologic property [17], although it has also been recognized to depend upon more than just stimulus intensity and arousal state [18]. The important point is that these classifications are not mutually exclusive (i.e., either arousal or selective attention may be considered in either the immediate or sustained context). There is considerable disagreement as to whether the AD commonly found in poorly functioning schoolchildren is chiefly of the arousal or selective variety and whether such deficits amount to a "vigilance decrement" from the starting point or are to be found only over time [15,19,20], Deficits in all of the above have been found with abundance in laboratory studies. What the teacher observes in the classroom is probably best understood in terms of the selective aspect of attention functioning over time (sustained).

Measurement of AD Measures of AD may be initially classified into 2 basic types: direct (i.e., observations of the child) and indirect (i.e., questionnaires to parents and/or teachers). Direct observations may be categorized in 3 ways: physiologic, psychophysical, and psychometric. Table 1 lists the different measures.

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(A) Physiologic Alpha rhythm Contingent negative variation P-300 (B) Psychophysical - experimental Reaction time Continuous performance tests Paired associate learning Selective reminding Matching familiar figures test (impulsivity) (C) Psychometric - clinical Wechsler I Q - Freedom from Distractibility factor Stanford-Binet IQ - Short-term Memory Quotient Wechsler Memory Scale - compare with full-scale IQ Stroop Color and Word Test Knox Cubes Detroit Test - attentiveness quotient Reading achievement compare structured and unstructured Key Math - mental computations subtest

Indirect (questionnaire) Conners's scales Child behavior checklist Yale Children's Inventory DSM-oriented scales SNAP (DSM II1) SNAP-R (DSM III-R) * See text for references.

Physiologic measures, of relevance almost exclusively in research, consist mainly of brain electrical potentials. Alpha activity recorded in the resting electroencephalogram has long been recognized to reflect a state of relative inattention to the surroundings which recently was demonstrated systematically [21 ]. Evoked potentials have been measured in experimental animals in a wide variety of brain structures, including thalamus, superior colliculus, basal ganglia, and sensory cortex, particularly visual. Colby provided an up-to-date review [22]. In humans, 2 types of evoked potentials have proved to be of special interest to attention. The contingent negative variation or "expectancy wave" ]23] is generated in the frontal cortex, after training, by a warning stimulus that heralds a second imperative stimulus requiring a motor response. The longlatency or P300 wave [24] is generated by a variety of stimulus parameters having in common the evoking of a cogitative response by the observer. Increases in the latency of this wave have been demonstrated to correlate with other indices of organic cognitive impairment in children [25]. Psychophysical measures have the greatest relevance for basic and clinical research, with limited applications in practice. Among the oldest is simple reaction time which has been widely used to study both experimental animals [261 and brain-damaged humans [27]. Reaction time was the method of choice for many of the earlier studies of

drug response (for review [28]). It was used by Sprague et al. to illustrate that stimulants have an effect opposite that of phenothiazine tranquilizers [29] and by Rapaport et al. to demonstrate that the cognitive improvement after stimulant administration can be observed in normal and hyperactive children [30]. In behavioral research using operant conditioning, concurrent schedules of reinforcement have been employed to monitor divided attention to multiple stimuli [31]. Stimulus generalization [32] has proved to be a useful method of quantifying attention to specific stimulus dimensions. I employed this technique to study visual hemi-inattention in unilateral parietal lobe dysfunction [33]. The continuous performance test (CPT), initially used by Rosvold et al. [34], monitors ongoing awareness of an intermittent change in a recurring stimulus. It was used in early studies by Conners [35] and by numerous investigators since. Errors of commission (i.e., false-positive responses) appear to be more reliably affected by therapeutic intervention than are errors of omission (i.e., misses). Barkley et al. studied the correlation between CPT scores and other measures of AD [36]. Impulsivity, although not encountered in every inattentive child, clearly contributes to AD. In addition to commission errors on the CPT, the Matching Familiar Figures Test has been used frequently to assess this factor [37]. Barkley et al. reported that error rates on this test correlate better with other measures of AD than do test completion times, suggesting that impulsivity may not be the critical variable [36]. Paired associate learning (PAL) has proved to be a particularly useful measure of the effect of AD on learning. It is the skill tapped by the coding or digit symbol subtest, which loads for the factor of freedom from distractibility [38] and, more than any other single Wechsler subtest, distinguishes specifically learning-disabled from normal children. PAL was measured in early studies by Conners et al. [39] and has been used extensively by Kinsboume's group (for partial review [15]). Especially in the continuous-measure modification [40], PAL tests present a uniformly demanding task that is sensitive to inattention and resistant to practice effects on repeated assessments. Using this modification, Kinsbourne confirmed in the laboratory [15] what classroom teachers have long known, namely, that attention variability at different times is a hallmark of the attention-deficient child. Because attention is a necessary condition for memorization, standard memory tests should be sensitive to attentional variables. The Selective Reminding Task of Buschke distinguishes between immediate recall (probably mostly an attention function) and other components of the memory process [41]. Evans et al. reported that performance on this task by AD children is improved by stimulant medications [42]; however, this finding was not confirmed by Barkley et al. who demonstrated that AD children without hyperactivity have more difficulty with this type of verbal learning than do their hyperactive

counterparts, who tend to make more errors on vigilance tasks [36]. Psychometric measures attempt to determine to what extent AD interferes with cognitive abilities as they relate to school function. Attention is part of leaming ability and adequate measures of learning capacity or aptitudes shouM be sensitive, to some extent, to attentional variables. Some measures are clearly more affected than others. References for individual tests are available elsewhere [43]. Factor-analytic studies of the Wechsler Intelligence Scale for Children (WISC) demonstrated covariance of 3 subtests - arithmetic, digit span, and coding - in what has been termed the freedom from distractibility factor [38]. Studies have demonstrated this factor to be low in hyperactive children [44,45], providing dramatic documentation that AD actually interferes with learning ability. The Stroop Color and Word Test, which measures "cognitive flexibility" through introduction of an artificial distractor, has been useful in the analysis of frontal lobe function, and documents an "interference factor" in some but not all children with AD. The Knox Cubes Test, which requires the subject to reproduce serial position sequences of multiple taps on 4 cubes in linear arrangement, is sensitive to attention in much the same way as the digit span test. On the revised form of the Stanford-Binet Intelligence Scale, the Short-term Memory Quotient should differ from the full-scale IQ when inattentiveness is a factor. The same applies to the comparison of the memory quotient from the Wechsler Memory Scale with the Wechsler full-scale IQ. The newly revised version of the Detroit Test of Learning Aptitudes provides a calculation of an attentiveness quotient from the subtests of sentence imitation, word sequences, oral directions, and object sequences. On standard tests of scholastic achievement, reading comprehension on tasks of independent, silent reading (e.g., GatesMacGinitie Reading Test) is frequently poorer than that on more highly structured tasks (e.g., Woodcock Reading Mastery Test) when inattention interferes with performance. On the Key Math Diagnostic Arithmetic Test, the mental computations subtest score is frequently affected preferentially by AD. Questionnaires to parents and teachers are the oldest and most widely used instruments for clinical assessments of AD. Their use was recently reviewed by Voeller [2]. The tests vary in length from 10 items [46] to over 100 [47,48]. The earliest scale [49], as well as most of those that followed, heavily emphasized disorders of discipline, socialization, and emotional stability in children with AD. More recent scales [50] allowed distinction among the factors of hyperactivity, inattention, impulsivity, and peer interactions. A simpler scale of just 14 items, developed by Deutsch (personal communication), is taken directly from the criteria specified by the latest version of the DSM III-R [1] for the diagnosis of the attention deficit hyperactivity disorder. It uses the original 4-point rating system by Conners and also allows distinction among the abovementioned factors. Although lacking in firmly established

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Table 2. Relation between epilepsy and attention deficit

(A) A shared etiology (B) The seizure (1) Aura (2) Ictus (a) Disturbanceof consciousness (b) Confusion-disorientation (c) "Petit mal status" (3) Post-ictalstate (C) Cerebral dysrhythmiawithout seizure (D) "Epilepticdementia" (E) Antiepilepticdrugs norms, it is most useful in assessing the effects of therapeutic intervention. A D and Other Learning Disabilities

Clinicians have long recognized that specific learning disabilities and ADs coexist with greater than chance frequency, both in the same individual and in the same family. The nature of the relationship between the two has been the subject of considerable investigative interest. The subject was recently reviewed by Felton et al. [51] and Shaywitz and Shaywitz [52]. It appears that AD and learning disabilities exert different influences on classroom performance, and, although they aggravate one another, are causally unrelated. In a recent study, however, I reported that evidence of AD is found more commonly among dyscalculic than dyslectic children [53]; this report called attention to the long-recognized fact that math is the academic skill most sensitive to AD and also suggested, along with Ackerman et al. [54], that much apparent dyscalculia may simply represent poor math performance secondary to AD. However, it is also possible that both dyscalculia and AD are manifestations of right hemisphere dysfunction [55,56]. A D and Brain Disease

Colby observed that attention is a widely distributed process in brain [22]. This fact probably accounts for frustrations encountered in attempts to assign a particular anatomic locus to AD. By the same token, as has long been recognized by clinicians, acquired brain damage in any one of many loci, or indeed diffuse damage with no particular locus, may have AD as a prominent clinical feature. Examples include diffuse trauma [57], hypoxia [58,59], lead intoxication [60,61 ], CNS leukemia and its treatments [62], maternal smoking during pregnancy [63], and maternal alcohol ingestion during pregnancy [64]. The relationship between epilepsy and cognitive function is complex (for review [65]). The different ways in

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which AD can be involved are summarized in Table 2. Most earlier studies failed to distinguish adequately among epileptic seizures, the encephalopathies causing them, general intelligence, and antiepileptic drugs as independent variables. A recent study demonstrated that AD is a prominent feature of cognitive deficits in epileptic children [66]. A follow-up study of the school performance of children of very low birth weight reported a correlation of head circumference at age 8 months with IQ scores, basic skills achievement, and hyperactivity scores [67]; further study may demonstrate that AD is an important factor in this group as well. Finally, AD is an important side effect of several medications commonly prescribed for children, including antiepileptic drugs, most notably barbiturates [68], and antihistamines, of which the phenothiazines [29] are a special case. Neuroanatomy

Despite the fact that early students regarded hyperkinesis and AD as trademarks of the "brain-damaged" or "brain-crippled" developmentally disabled child, remarkably little consensus has emerged over the past 50 years regarding the anatomic localization of these deficits. The two locations that have been found to be most likely in recent speculations are (1) the basal ganglia or striate cortex and (2) the frontal lobes and their connections (for review [69]). The striate cortex came under scrutiny in early studies, partly because of the fact that this area was prominently involved in epidemic encephalitis. Five of 17 patients reported by Ebaugh had choreiform movements and 2 others had "twitches" [5]. Although they described "organic drivenness" as a brainstem syndrome, Kahn and Cohen reported either choreiform movements or twitches in all of their patients [7]. Bender also discussed the extrapyramidal nature of the movement disorder, commenting that it was sometimes progressive in postencephalitic patients [70]. A degree of hyperkinesis with attention and/or behavior disorder is found in the majority of patients with Sydenham chorea. Lou et al. [71], using emission tomography after xenon inhalation, reported hypoperfusion of striatal regions, mostly on the right, which was partially reversible with methylphenidate, in children with ADHD. The role of the frontal lobes, while more intuitively direct [72], has been difficult to document. The early experiments by Ruch and Shenkin from Fulton's laboratory [73] producing hyperkinesis in the monkey involved bilateral lesions of the orbitofrontal cortex. Furthermore, the frontal lobes, along with the striate cortex, are known to be involved in circuits utilizing both dopamine (DA) and norepinephrine (NE), substances believed to be important to the ADHD mechanism. Recently, Zametkin et al. employed positron emission tomography to demonstrate reduced cerebral glucose metabolism, particularly in the su-

perior prefrontal and premotor cortex, during an auditory continuous-performance task by a group of adults who had been hyperactive since childhood [74]. Kinsbourne recently suggested that 3 different frontal areas may be involved in the distinct aspects of cognitive behavior: the ventromedial area in selective attention, the lateral orbitofrontal area in "cognitive flexibility" or ability to shift set, and the dorsomedial area in spontaneity and overcoming of mental inertia (personal communication).

Biochemistry The biochemistry of AD and hyperkinesis has been mostly derived from pharmacologic considerations, proceeding from the evidence for efficacy of specific drugs. The substances most widely studied in this regard include dopamine (DA) and norepinephrine (NE). The amphetamine stimulants and methylphenidate are powerful dopaminergic agonists and the DA system's involvement in ADHD has been studied extensively. Shaywitz et al. demonstrated hyperactivity during the first 30 days of life in rats fed from birth with 6-hydroxy DA which increases DA turnover and, presumably, selectively depletes brain DA [75]. They then measured the cerebrospinal fluid concentration of homovanillic acid (HVA), a principal metabolite of DA, in hyperactive and normal children following treatment with probenecid, and found a decreased ratio of HVA to probenecid in the hyperactive subjects [76]. Shekim et al. studied urinary HVA concentration in hyperactive children treated with dexedrine; HVA was lower than normal in those who responded favorably to medication [77]. Less solid evidence is available for involvement of NE in MBD. Shekim et al. reported decreased urinary excretion of the NE metabolite, MHPG, in hyperactive boys compared to normal controls [78]. Urinary MHPG excretion was decreased by d-amphetamine in hyperactive boys classified as favorable responders, but not in the nonresponders [77]. Finally, levels of enzymes involved in the metabolism of both of the above substances have been studied. Rapoport et al. reported higher levels of DA-[3-hydroxylase (DBH), the enzyme responsible for conversion of DA to NE, in hyperactive children with minor physical anomalies than in those without [79]. This finding was confirmed by Deutsch [80]; however, Deutsch compared both monamine oxidase and DBH in hyperactive children and normal controls and found no significant differences.

Epidemiology, Genetics AD was thought, in the "brain damage" model, to be sporadic; however, hyperactive children seen in child guidance centers in the 1920s through the 1950s frequently had affected family members. The long-term follow-up studies by Robins supported this observation and stimulated numerous further efforts [81]. Cantwell found a

retrospective diagnosis of hyperactivity in significant numbers of families of hyperactive children as compared with controls [82]. Fathers were affected 4 times as often as mothers. Morrison and Stewart found significantly more hyperactivity in the biologic parents of adopted, hyperactive children than in their adoptive parents [83]. Willerman [84], using questionnaires filled out by mothers, found a higher correlation of activity level in monozygotic than in dizygotic twins. Safer reported more hyperactivity among full siblings of hyperactive children than among half siblings (same father) [85]. Deutsch et al. examined the histories of 200 children satisfying the DSM-III criteria for AD disorder (ADD) and found a 17% rate of nonrelative adoption [86], 8 times that found in a nonhyperactive control group or estimated for the general population. The suggestion is that the circumstances leading to adoption may be the result of behaviors inherited by the child and expressed as "ADD." All of the above-mentioned studies have been performed on clinical populations selected more for behavioral maladjustment than for school dysfunction. It is unknown whether the same is true for AD as an isolated abnormality, although, in view of the strong relationship between AD and other specific learning disorders, it would be surprising if this were not true.

Therapeutic Intervention The trailblazing study of drug therapy of children with learning difficulties was published by Bradley [87]. Sargant and Blackburn had already reported that Benzedrine ®, an amphetamine stimulant, facilitates learning to the extent of improving scores on intelligence tests [88]. Bradley gave the medication to children who were resident patients in a home for the behavior-disordered. His findings provided a remarkably accurate catalogue of what may be described to parents today as the benefits to be anticipated from stimulant medications in AD children. Fourteen of his 21 patients responded in what he termed a "spectacular fashion," exhibiting greatly increased interest in schoolwork, a "drive to accomplish as much as possible," and increase in speed of comprehension and accuracy of performance, usually with insight on the child's part. He also mentioned most of the side effects experienced by children on small doses of stimulants, including initial anorexia and insomnia, occasional nausea, and mild depression and emotional lability. The report by Conners and Eisenherg was among the first to examine systematically the effect of stimulant drugs on leaming ability [89]. Further studies of neuropsychologic tests as measures of drug effect were pursued by Millichap and Boldrey [90] and Millichap et al. [91]; a research review was provided by Conners [35], along with further data from Conners's laboratory which referred to drug effects on standard psychometric tests. A great deal of attention has been given to the question of how stimulant medications affect learning. Sprague

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et al. demonstrated that in two important respects stimulants have an effect opposite to that of major tranquilizers [29]; in comparison with placebo, stimulants reduce reaction time and increase the accuracy of response, while major tranquilizers do the opposite. Flintoff et al., using a visual scanning task, demonstrated a direct effect of stimulants on selective attention in hyperactive children [92]. Evans et al. [42], using the Selective Reminding Test [41 ], reported beneficial effects on storage and retrieval without improvement in immediate recall. They interpreted this finding to be an effect on memory, independent of attention; however, Barkley et al., using the same test, have since demonstrated that AD children in the nonmedicated state have more problems with storage and retrieval than with recall [36]. Rapaport et al. reported that the learning performance of normal, as well as hyperactive boys, is improved by amphetamines [30]. The question of dosage has been a difficult one. Numerous earlier studies measured the therapeutic effect (usually by behavioral questionnaire) as a linear function of the dose; however, Sprague et al., using laboratory tests of learning, demonstrated that the dose-response curve of methylphenidate related to accuracy of response is an "inverted U" function, peaking at about 0.3 mg/kg, not linear as it is for reaction time [93]. A later report from their laboratory made a similar comparison between response accuracy and teacher ratings of behavior [94]. Kinsbourne and Swanson found a preferential response to lower doses in some but not all patients [95]. A more recent study by Barkley et al. [36], comparing the effects of 3 different doses on hyperactive versus nonhyperactive AD children, disclosed first that the nonhyperactive group, who exhibited less impulsivity but greater difficulty with verbal learning, benefited most from the low dose; and second, that school behavior was as much improved by the low dose as by moderate or high doses, whereas home behavior responded better to higher doses. Other medications have been administered in recent years with some success, including the tricyclic antidepressants imipramine [79] and desipramine [96], as well as magnesium pemoline [97]. They are of greatest use in patients in whom stimulants are poorly tolerated, even though the latter are more effective as attention expanders. A number of nonpharmacologic interventions have been considered in recent years. Food additives were studied extensively during the 1970s and early 1980s. This experience was reviewed by Swanson and Kinsbourne [98[. Two principles appear to have remained unchanged during the intervening years. First, food sensitivities are many and highly variable from patient to patient. Second, the effect of food additives on attention, if any, is pharmacologic (i.e., dose-related), rather than allergic. Although it is sensible to avoid large amounts of the suspect substance, laborious review of the contents of every prepared foodstuff is not necessary. Psychotherapy and counseling are enormously helpful, sometimes critical, in the management of behavioral mal-

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adjustment and emotional instability in hyperactive children. I am aware of no evidence that they improve attention. Behavior modification techniques have been attempted in a number of laboratories, including my own [99]. Although of proved efficacy in the laboratory, behavior modification techniques are difficult to validate in the field and are cumbersome and expensive in clinical practice.

Long-term Follow-up and Prognosis Although the consensus at present is that AD is a lifelong problem, little is known of its natural history beyond the school years. The original concept by Bradley that the effect of stimulant medications on children is "paradoxical" and the conclusion therefrom that they are no longer effective after puberty [87], now are generally agreed to have been inaccurate. However, nearly all long-term follow-up studies to date have focused upon various aspects of behavioral maladjustment frequently found in the presence of AD. The monograph by Robins described a follow-up of children referred to a child guidance clinic for school maladjustment that almost certainly included AD and focused on the emergence of sociopathic personality in adulthood [81 ]. Another oft-cited earlier study by Menkes et al. provided a 25-year follow-up, but was retrospective and depended upon previous diagnoses of "minimal brain dysfunction" for ascertainment [100]. The follow-up studies by Weiss et al. [101,102] also based in a psychiatric clinic and using hyperkinesis as the ascertainment criterion, disclosed a rather poor prognosis for social development after 5 years, but much better prospects after 10 years; the principal differences from controls showed up in high school grade performance, number of court referrals, and job status relative to that of the father. Barkley et al., in a prospective study using stricter diagnostic criteria, found that symptoms of oppositional defiant disorder apparent at initial diagnosis accounted for most of the differences between hyperactive patients and controls on measures of behavioral and social adjustment 8 years later [103]. Few studies have focused on the cognitive aspects of AD in follow-up measures. From Weiss's group, Hopkins et al. [104], examining previously diagnosed hyperactive patients in a 15-year follow-up, documented poor performance on the Matching Familiar Figures Test (MFFT) and Stroop tests, also on the Embedded Figures Test, a measure of selective attention to complex stimuli. Fischer et al. in an 8-year follow-up study reported poor scores on tests of academic achievement, classroom function, and vigilance (continuous-performance), but not on the MFFT, Selective Reminding Test, or Wisconsin Card Sorting Test [105]. Little information is available from properly controlled studies regarding the long-term effects of treatment on cognition. A report on the cohort by Weiss et al. disclosed no difference in IQ test performance 5 years later among hyperactive children treated with methylphenidate, chlorpromazine, and no drug [106]; however, patients were not

randomly selected for treatment, leaving the possibility that treatment varied with severity. DeLong described a subset of hyperactive children whose behavior prominently featured antisocial elements, such as lying, stealing, and fire setting, along with emotional outbursts, hateful attitudes, and in some cases unusual food cravings [107]. He presented family history evidence of manic-depressive illness; lithium carbonate administration was partly successful. Summary The precise nature of the relationship among AD, hyperkinesis, and specific learning disabilities remains a mystery. They are encountered in one another's company with far greater than chance frequency. It is clear that AD and learning disability aggravate one another; that is, that which is difficult to learn is more difficult to attend to, and vice versa. Furthermore, in children at least, attending ability and activity level have a reciprocal relationship; that is, improvement of attention tends to reduce activity level and vice versa. Conversely, each of these disorders is observed in isolation with sufficient frequency to assure us that none of the three is simply a by-product of one or both of the other two. It is unlikely that a single etiology will be identified to account for a significant number of AD patients; therefore, it is unlikely that a "cure" or even a mode of prevention will be found. A change in the attitude of the culture toward formal education would reduce the morbidity of the syndrome, but this is also unlikely to occur in the near future. Further research does promise to yield medications that improve attention span with fewer side effects and, perhaps more importantly, more workable techniques for changing behavior and engineering environments to encourage academic productivity in the face of this important aptitude deficit.

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