Attentional functioning in abstinent cocaine abusers

Drug and Alcohol Dependence 54 (1999) 19 – 33

Attentional functioning in abstinent cocaine abusers Michael David Horner a,b,* b

a Department of Psychiatry and Beha6ioral Sciences, Medical Uni6ersity of South Carolina, Charleston, SC, USA Mental Health Ser6ice, Ralph H. Johnson Department of Veterans Affairs Medical Center, 109 Bee Street, Charleston, SC 29401 -5799, USA

Received 16 December 1997; accepted 2 August 1998

Abstract The effect of chronic cocaine use on attention is directly relevant to the treatment of cocaine dependence, since attention underlies most other cognitive processes, and thus the ability to profit from cognitively-based interventions. This paper reviews 17 studies examining attention in patients with cocaine abuse or dependence. Findings have been inconsistent, largely due to various methodological difficulties. There has been some suggestion of reduced cognitive speed, while focused and sustained attention have generally been unimpaired. Divided attention has been largely unexplored. Thus, there is insufficient evidence either to accept or reject the hypothesis of attentional dysfunction associated with chronic cocaine use. © 1999 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Cocaine; Neuropsychology; Attention; Cognition

1. Rationale Cocaine use has been associated with a variety of neurological complications, including seizures, ischemic stroke, subarachnoid and intracerebral hemorrhage, cerebral vasculitis and vascular spasm, and transient ischemic attacks (Volkow et al., 1992; Weber et al., 1993; Mena et al., 1994; Strickland and Stein, 1995; Rosselli and Ardila, 1996). Various studies have also shown abnormalities in regional cerebral blood flow and brain metabolic activity among cocaine-dependent patients (Volkow et al., 1988; Tumeh et al., 1990; Holman et al., 1991, 1992; Volkow et al., 1992; Strickland et al., 1993; Weber et al., 1993). Chronic cocaine use might, therefore, also be expected to affect cognitive functioning adversely (Hoff et al., 1996). However, despite the incidence of cocaine dependence in the United States and the high demand for its treatment, surprisingly little is known about its effects on cognition. * Tel.: +1 803 5775011, ext. 7131; fax: + 1 803 8055782; e-mail: [email protected]

Such neuropsychological data are of direct relevance to the clinical treatment of cocaine dependence. Comprehensive, psychosocial treatment of addictions typically involves interventions that are fundamentally cognitive, such as examining and altering maladaptive behavior patterns, learning new strategies for managing stress, and learning and applying strategies for preventing relapse (Miller, 1985; Donovan et al., 1987; Meek et al., 1989; Fals-Stewart and Schafer, 1992; Weinstein and Shaffer, 1993). The ability to comprehend, learn, and apply the information presented in treatment thus entails numerous cognitive functions, so that substance abuse patients with cognitive deficits are likely to be at risk for treatment failure. The effect of chronic cocaine use on attention is of particular relevance to clinical treatment, since patients who have difficulty attending to substance abuse interventions might be less likely to profit from them. Furthermore, attention underlies most other cognitive functions, such as memory and problem-solving (Lezak, 1995), which are also required for successful substance abuse treatment and for countless other aspects of everyday functioning.

0376-8716/99/$ - see front matter © 1999 Elsevier Science Ireland Ltd. All rights reserved. PII: S0376-8716(98)00141-0

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M.D. Horner / Drug and Alcohol Dependence 54 (1999) 19–33

There are several reasons to hypothesize an association between chronic cocaine use and attentional impairment. Difficulty concentrating is among the most frequently cited cognitive complaints among cocaine users (Siegel, 1982; Washton et al., 1984). Further, as attention underlies other cognitive functions, its impairment can be manifested as difficulty in various cognitive domains; it is thus possible that the wide variation in cognitive deficits previously reported in cocaine-dependent patients is partially due to an underlying attentional deficit. Thus, considering the inconsistent empirical evidence of cognitive impairment in cocaine dependence, examination of attentional functions is a logical starting point. Various investigators have called for further study of this issue (O’Malley and Gawin, 1990; Strickland et al., 1993; Hoff et al., 1996; Rosselli and Ardila, 1996), but the evidence has yet to be specifically examined. The present paper examines the currently available data on attentional functioning in patients with cocaine abuse or dependence. As the effects of chronic cocaine use, rather than acute intoxication, are of primary interest in this review, only studies of abstinent cocainedependent patients are included. The following sections address current conceptions of attention and its measurement, methodological issues, and existing data on attentional functioning in cocaine-abusing patients.

ignoring distractors (Keith, 1994); (c) sustained attention, exemplified by vigilance, is the ability to maintain alertness and to focus on target stimuli over longer periods of time (van Zomeren and Brouwer, 1994); and (d) divided attention is the ability to attend simultaneously to multiple sources of information, or to execute two or more attention-demanding cognitive operations simultaneously (Kahnemann, 1973; Keele, 1973; Wickens, 1980). While some authors have discussed the ability to shift cognitive set as an aspect of attention, it is inextricably related to ‘higher-level’ executive functions and is difficult to assess in the absence of complex, non-attentional operations (Mirsky et al., 1991; van Zomeren and Brouwer, 1994); it will therefore not be considered in the present discussion. Furthermore, there are other, basic attentional processes that have been the subject of much research in the non-clinical, cognitive psychology literature. These include orienting to sensory events (e.g. by foveation of the stimulus), covert attentional shifts (i.e. prior to orienting movements of the eyes), and detecting signals for conscious processing (Posner and Petersen, 1990; Kinchla, 1992). However, as these processes have rarely been examined in cocaine-abusing patients, they are not discussed in the following review.

3. Clinical assessment of attention 2. Subtypes of attention

3.1. General considerations

While attention has been the subject of much investigation, it remains a rather poorly-defined term that has been used to label a complex set of processes. There is general agreement that attention is not a unitary phenomenon, but encompasses a variety of subcomponent processes (Posner, 1978; Parasuraman and Davies, 1984; Schiffrin, 1988). Until relatively recently, limited interdisciplinary integration existed between findings in experimental cognitive psychology and clinical neuropsychology. However, several recent attempts have been made to bridge this gap and to provide a taxonomy of attentional subcomponent processes applicable to the evaluation of clinical samples (Mirsky et al., 1991; van Zomeren and Brouwer, 1994). Using common clinical neuropsychological tests, Mirsky et al. (1991) provided evidence from principal components analysis for four discrete elements of attention: the abilities to encode, focus/execute, sustain, and shift attention. However, using a theoretically based approach, van Zomeren and Brouwer (1994) classified attentional tasks as requiring the following abilities: (a) information processing speed is the rate at which cognitive operations are executed; (b) focused attention, also called selective attention, is the capacity to select target information from the array of available stimuli, while

Many tests in common clinical neuropsychological use do not selectively assess a single one of the attentional subtypes discussed above (van Zomeren and Brouwer, 1994). Most place demands on two or more types of attention or on other cognitive functions, hampering uncontaminated evaluation of discrete attentional processes. This situation results partially from the historical development of clinical neuropsychology, in which many tests were originally designed to detect the presence of cognitive dysfunction, rather than to evaluate a specific, theoretically or empirically derived cognitive domain. Thus, impaired performance on many clinical measures of attention can actually reflect impairment of other, non-attentional functions. Nevertheless, principal components and factor analyses have consistently shown that common attentional tests load on similar factors, providing support for their construct validity (Mirsky et al., 1991; Larrabee and Curtiss, 1995).

3.2. Attentional tests used in studies of cocaine-abusing patients Numerous tests have been used to assess attentional functions, both in clinical practice and in empirical

M.D. Horner / Drug and Alcohol Dependence 54 (1999) 19–33

21

investigations. The following list includes the measures used in the studies described in the present review. It is not grouped by the specific subtype of attention assessed by each test, as many tests are sensitive to deficits in more than one subcomponent process.

pants are given forms printed with rows of digits, and are instructed to mark as many instances of a target digit as possible within a specified time limit. Various other versions of letter and digit cancellation tasks are also in common use.

3.2.1. Arithmetic subtest of the Wechsler Adult Intelligence Scale— Re6ised (WAIS-R; Wechsler, 1981) In this test, orally presented arithmetic problems are solved without pencil or paper. While it is often considered a measure of focused attention (Mirsky et al., 1991), successful performance also requires calculation ability and information processing speed.

3.2.7. Paced Auditory Serial Addition Test (PASAT; Gronwall, 1977) In this sensitive test, participants listen to a tape recording of a series of one-digit numbers, and each time add the number just presented to the one immediately preceding it. Four sets of 50 numbers are presented at increasing speed. This test requires sustained, focused, and divided attention, as well as speeded information processing.

3.2.2. Digit Span subtest of the WAIS-R (Wechsler, 1981) and Digit Span subtest of the Wechsler Memory Scale— Re6ised (WMS-R; Wechsler, 1987) These tests involve recitation of auditorily presented digit strings in forward and reverse order, and are considered indices of focused attention (Mirsky et al., 1991; van Zomeren and Brouwer, 1994; Lezak, 1995). 3.2.3. Digit Symbol subtest of the WAIS-R (Wechsler, 1981) A timed task of transcribing coded symbols, this sensitive but relatively non-specific measure involves sustained attention, divided attention, and information processing speed, as well as motor persistence, motor speed, visual scanning, and visuomotor coordination (van Zomeren and Brouwer, 1994; Lezak, 1995). 3.2.4. Gordon Diagnostic System (GDS; Gordon et al., 1986) In the Vigilance condition, a relatively unconfounded measure of sustained attention, participants watch numbers displayed sequentially on a screen, and respond only when a specified sequence appears. The Distractibility condition additionally requires focused attention, as participants perform the same task while ignoring distractor numbers appearing in other parts of the screen. 3.2.5. Mental Control subtest of the WMS-R (Wechsler, 1987) This very brief test includes three timed tasks of ‘concentration’: counting backward, reciting the alphabet, and performing serial addition. It is considered a test of focused attention (Mirsky et al., 1991; van Zomeren and Brouwer, 1994; Lezak, 1995). 3.2.6. Numerical Attention Test (O’Malley et al., 1992) This cancellation task is an abbreviated form of the Digit Vigilance Test (Lewis and Rennick, 1979), which assesses sustained attention in addition to visual scanning, cognitive and psychomotor speed, and inhibition of rapid responses (Lezak, 1995). Partici-

3.2.8. Sternberg task (Sternberg, 1966, 1969) This task was designed to assess speed of information processing, while controlling for variations in motor speed. Primarily an experimental paradigm, its clinical utility has recently been questioned (Becker et al., 1995). Participants are presented with a target list of letters or digits, and a single probe item is then presented. The task is to indicate as rapidly as possible whether or not the probe item was a member of the target list. 3.2.9. Stroop Color and Word Test (Golden, 1978 ; MacLeod, 1991) This test consists of three conditions. In the Word condition, participants are shown a page with the words ‘red’, ‘green’ and ‘blue’ recurring in random order, and read aloud as many of the words as possible in 45 s. In the Color condition, the task is to name as quickly as possible the color of ink (red, green or blue) in which Xs are printed. In the Interference condition, the words ‘red’, ‘green’ and ‘blue’ are printed in discordant colors of ink (e.g. ‘red’ printed in green ink), and the task is to name the ink color while ignoring the word. The Color and Word conditions have been considered measures of information processing speed or sustained attention (Orsini et al., 1988; Mirsky et al., 1991; van Zomeren and Brouwer, 1994). While the Interference condition is properly classified as a response inhibition task, some authors (van Zomeren and Brouwer, 1994) have pointed to its additional requirements of divided attention or ignoring distracting stimuli (focused attention). 3.2.10. Symbol Digit Modalities Test (Smith, 1982) This test is similar to the Digit Symbol subtest of the WAIS-R, except that participants provide the numbers associated with symbols rather than vice versa. As such, it requires many of the same cognitive

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M.D. Horner / Drug and Alcohol Dependence 54 (1999) 19–33

functions as the Digit Symbol subtest (van Zomeren and Brouwer, 1994). Performance on these two tests is highly correlated, although their interchangeability has been questioned (Morgan and Wheelock, 1992).

3.2.11. 3RT Test (Teng, 1990) These computer-administered tasks measure reaction time (RT) under three conditions. In the Simple RT task, participants respond as soon as an arrow appears on a computer screen. In the Choice task, participants respond by pressing one of two possible keys, depending on the direction in which the arrow points. In the Conditional task, the correct response is determined by a signal presented concurrently with the target stimulus. Like many RT tasks, the 3RT is likely to be sensitive to variations in speed of perceptual and motor functions, as well as information processing speed. 3.2.12. Trail Making Test (Reitan and Wolfson, 1985) Part A is a timed psychomotor task of connecting numbers on a page sequentially; it is considered sensitive to deficits in sustained attention or information processing speed, but also requires various other functions including visual scanning and psychomotor speed (Orsini et al., 1988; Mirsky et al., 1991; Spreen and Strauss, 1991; van Zomeren and Brouwer, 1994). In Part B, numbers are alternated with letters, thus requiring simultaneous tracking of two sequences; it has been variously cited as a measure of focused, sustained, and divided attention as well as processing speed, but is in fact sensitive to many types of neuropsychological impairment (Lezak, 1983; Orsini et al., 1988; Mirsky et al., 1991; Spreen and Strauss, 1991; van Zomeren and Brouwer, 1994; Gaudino et al., 1995). 3.2.13. Other 6igilance or monitoring tasks (6an Zomeren and Brouwer, 1994) Various versions of these measures of sustained attention exist, in addition to the Vigilance condition of the GDS. In visual vigilance or monitoring tasks, participants watch a display for several minutes and respond when a particular target stimulus appears on the screen. Auditory tasks have also been used, in which participants respond to occurrences of a specified target stimulus presented among a sequence of non-target stimuli.

4. Methodological issues in neuropsychological studies of cocaine abusers Several methodological issues have complicated the study of attentional functions in cocaine-abusing patients, or have limited the conclusions that can be drawn across studies.

4.1. Specific tests used to measure attention As noted above, many common, clinical tests of attention do not specifically assess a single attentional subcomponent. Further, many of these tests are sensitive to dysfunction in non-attentional cognitive domains, such as perceptual, motor, or executive functions. Very few of the studies reviewed in this paper had as their primary purpose the assessment of attention; thus, most have included only a limited number of attentional measures.

4.2. Sample size In the attempt to identify neuropsychological sequelae of chronic cocaine use, many studies have examined cocaine-abusing patients without other substance use disorders. However, as most cocaine-dependent patients seeking treatment also abuse alcohol or other drugs (Jatlow et al., 1991; Brown et al., 1994), recruitment of large groups of patients with uncomplicated cocaine dependence has often been problematic. Thus, many of the studies have used relatively small samples.

4.3. Length of abstinence at time of e6aluation The length of abstinence from cocaine prior to neuropsychological evaluation has varied considerably both within and across studies. Some have examined patients after several days or weeks of abstinence, while others have examined patients abstinent for several months. The relationship between cognitive functioning and length of abstinence from cocaine remains unclear; while it has been well established that alcoholic patients should be abstinent for at least several weeks prior to neuropsychological evaluation (Grant, 1987; Orsini et al., 1988), the length of abstinence from cocaine at which cognitive findings can be considered stable and reliable has yet to be determined.

4.4. Monitoring of abstinence A related question is whether abstinence has been monitored prior to neuropsychological evaluation. Some studies have required participants to undergo urine drug screening (UDS) in the weeks prior to evaluation, so that the length of abstinence from cocaine and other substances can be determined with more certainty; some have also employed periodic breathalyzer readings to measure blood alcohol level (BAL) and thus detect recent alcohol use. Other studies have examined individuals in controlled environments (e.g. long-term inpatient treatment, prison) in which access to substances of abuse was restricted. In some studies, however, abstinence was not rigorously monitored, so that data on length of abstinence at the time of evaluation might be less reliable.

M.D. Horner / Drug and Alcohol Dependence 54 (1999) 19–33

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4.5. Se6erity of cocaine abuse

4.8. Comparability of control groups

Study samples have differed in the severity, amount, and duration of cocaine use. Most studies that have reported the amount of cocaine used by their subjects have examined individuals who used at least 3 g/week; however, many studies have not reported such data, and accurate quantification of amount of cocaine use has been difficult. Further, some studies have simply reported that patients abused cocaine for at least 6 months prior to evaluation, while others examined patients with 10-year histories of cocaine use; still others failed to report duration data. There has also been some variation across studies in route of administration; most have examined patients who ‘freebase’ or smoke ‘crack’, but others have included intravenous or intranasal users. While variation across studies on all of these dimensions constitutes another potential confound that might limit the comparability of findings, the relationship between these factors and neuropsychological variables remains unclear.

The comparability of control to cocaine groups in these studies has also varied widely. Clearly, the most definitive results would be obtained if cocaine-abusing patients were compared with a control group that was matched as closely as possible on demographic variables, and that was subject to rigorous exclusion criteria such as those noted in the preceding section (e.g. history of psychiatric or neurological illness, ADHD, etc.). It is also important to rule out current or previous substance abuse history among control subjects. Some studies have applied rigorous inclusion and exclusion criteria to carefully matched control groups, and have ensured control participants’ abstinence by UDS and breathalyzer readings. On the other hand, several studies have not used a control group, instead comparing patients’ scores with normative data; in such instances, the comparability of the cocaine abusers to the test’s normative sample can be questionable.

4.6. Concurrent abuse of other substances

5. Empirical findings

Studies have also differed on whether patients have used substances other than cocaine. Some studies have excluded cocaine-dependent patients with other, concurrent substance use disorders, while other studies have used less rigorous exclusion criteria. It is thus possible that some of the neurocognitive deficits found in studies of cocaine-dependent patients with concurrent alcohol dependence could be attributable to alcohol rather than cocaine use, as the neuropsychological sequelae of chronic alcoholism are well known (Grant, 1987; Parsons, 1987; Wilkinson, 1987; Orsini et al., 1988; Goldman, 1990; Parsons, 1994).

Of the existing studies of neuropsychological sequelae of chronic cocaine use, 17 have included attentional tests. (Other cognitive functions assessed in these studies are not considered in the present review.) While many potentially confounding factors have been listed in the preceding section, some of these are more salient than others to the question of attentional dysfunction in abstinent cocaine abusers. In particular, the findings considered most definitive are those in which cocaine abusers’ performance was compared to that of matched controls, and in which abstinence was rigorously monitored by laboratory assays such as UDS; these studies are discussed in Section 5.1. Where abstinence was not thus monitored, findings are considered more definitive if patients were in controlled environments (inpatient hospitalization, incarceration) in which access to cocaine and other drugs was restricted; these are discussed in Section 5.2. Studies whose findings are considered most likely to be confounded are those in which access to cocaine was not monitored or restricted (Section 5.3), or in which cocaine abusers were not compared to matched controls (Section 5.4). The studies are summarized in Table 1.

4.7. Neuromedical and psychiatric illness Premorbid characteristics could also influence attentional findings among cocaine-abusing patients, as well as control subjects. For example, history of traumatic brain injury has been an exclusion criterion in some, but not all, studies, so that deficits observed in some studies might actually be attributable to this factor rather than to substance abuse. The same is true for other previous or current neurological illness (e.g. seizures), medical illness (e.g. hepatic dysfunction), and psychiatric illness, all of which could affect cognitive performance. Of particular relevance, many studies have failed to assess for premorbid history of attentiondeficit/hyperactivity disorder (ADHD), which could clearly affect performance on attentional measures. In fact, there is evidence that ADHD is over-represented among cocaine-dependent patients (Wilens et al., 1994; Beatty et al., 1995).

5.1. Controlled studies of patients with monitored abstinence Five studies to date have compared cocaine-dependent patients to a matched control group, and have regularly monitored abstinence from substances by laboratory techniques such as UDS. Berry et al. (1993) compared 16 cocaine-dependent inpatients abstinent for

Number of cocaine patients

Controlled environment?

Days abstinent

Yes

No

16

12

33

Berry et al. (1993)

Roberts and Bauer (1993)

Van Gorp et al. (1995)

21

7–10, 16–21, 94–100 (repeated)

14–18

7–10, 16–21, 94–100 (repeated)

210

Yes

Yes

Yes

20

O’Malley et al. (1992)

61 Rosselli and Ardila (1996)

Selby and 60 Azrin (1998)

Yes

12

Herning et al. (1990)

Yes

23

Beatty et al. (1995)

1076

78

24

Up to 21 (repeated testing)

21–40

Controlled studies of patients living in controled environments

Yes

No

11

Bauer (1994)

No

30

Azrin et al. (1995)

Controled studies of patients with monitored abstinence

Study

No

No

No

No

No

Yes

Yes

Yes

Yes

Yes

Abstinence monitored?

Table 1 Summary of perfommance of cocaine-abusing patients on attentional tasks

]0.5

]4.0

8.6

?

?

6.7

3.0

12.5

10.3

4.2

3.7

7.1

Dependence

B5.0

2.4

Yes, if 521 drinks/week in prior 6 months

No, except alcohol abuse in remission

Yes

No, except alcohol dependence in remission

Yes

No

Other substance abuse?

Current alcohol abuse and dependence excluded

Yes, as long as not dependent

Abuse or de- No pendence

Dependence

Dependence

Abuse or de- ? pendence

No minimum requirements

Dependence

Dependence

?

]0.5

Dependence

Severity

Dependence

5.6

Duration of cocaine use/ abuse (years)

?

3.0

5.3

Grams of cocaine per week

Yes

No

Yes

No

Yes

Yes

Yes

Yes

Yes

Yes

Neuromedical and psychiatric confounds excluded?

PASAT; Trails A; Trails B

PASAT; Trails A

Vigilance (auditory)

Digit Span; Mental Control

Tasks unimpaired

Arithmetic; Digit Span; Digit Symbol

Arithmetic; Symbol Digit

Stemberg task

Stroop Interference; Trails A; Trails B

Mental Control; Trails A; Trails B

Numerical Attention Test; Trails A; Trails B

Vigilance (auditory); vigilance (visual)

Arithmetic; GDS DistractiDigit Symbol; bility Trails A; Trails B

Reaction time

Trails B

Reaction time

Tasks impaired

24 M.D. Horner / Drug and Alcohol Dependence 54 (1999) 19–33

Number of cocaine patients

Controlled environment?

Days abstinent

Abstinence monitored?

Grams of cocaine per week

32

19

Horner (1997)

Waid et al. (1994)

No

No

No

Yes

Volkow et al. (1988)

20

Yes

Strickland et al. 8 (1993)

Studies without control groups Ardila et al. 37 Yes (1991)

38

Hoff et al. (1996)

?

Yes

] 180 ?

No

?

No

No

27

?

17

25

4.0

12.6

9.3

?

?

]4.0

Controlled outpatient studies in which abstinence was not consistently monitored Brown et al. 82 No 28 No ? (1994)

Study

Table 1 (Continued)

]0.5

2.4

1.4

?

?

0.5

?

Duration of cocaine use/ abuse (years)

No

Neuromedical and psychiatric confounds excluded?

Yes

No

Yes, as long as Yes not dependent

Yes

Other substance abuse?

Abuse

Dependence

Dependence

Yes

?

Yes, before cocaine dependence

Yes

Yes

Yes

Abuse or de- Yes, as long as No pendence not dependent

Dependence

Dependence

‘‘Significant problems’’ with cocaine and alcohol on ASI

Severity

Arithmetic; Digit Span

Stroop Interference; Trails B?

3RT errors; Stroop Word; Trails B

Trails B

Tasks impaired

Digit Span; Mental Control

Reaction time; Stroop Color; Stroop Interference; Trails A

Digit Span; Symbol Digit

Cancellation Test; Stroop; Symbol Digit; Trails A

Digit Span; Digit Symbol

Tasks unimpaired

M.D. Horner / Drug and Alcohol Dependence 54 (1999) 19–33 25

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M.D. Horner / Drug and Alcohol Dependence 54 (1999) 19–33

2 weeks to well-matched control subjects who had no history of substance abuse. Subjects were excluded if they had a history of other major psychiatric disorders, head injury with significant loss of consciousness, learning disability, or various other medical conditions that could affect cognition. Subjects were also excluded if recent use of alcohol or marijuana, or lifetime use of phencyclidine, exceeded predetermined amounts; however, cocaine-dependent patients with alcohol dependence in remission were apparently eligible for participation. Abstinence was monitored by regular UDS. Cocaine-dependent patients performed more poorly than controls on Part B of the Trail Making Test, but were unimpaired on Part A. Cocaine-dependent patients were also unimpaired on the PASAT. A follow-up study by van Gorp et al. (1995) used similarly rigorous methods for selecting subjects and monitoring abstinence. Preliminary findings from this study, however, were negative. After 3 weeks of monitored abstinence, no decrements were found in a larger sample of non-alcoholic, cocaine-dependent patients, compared to drug-free controls, on the PASAT or the Trail Making Test. Bauer (1994; Roberts and Bauer, 1993) examined cocaine-dependent patients serially at 1 week, 3 weeks, and 3 months of abstinence. None of the patients were alcohol-dependent, but four abused alcohol. Smoking was the predominant route of cocaine administration, and no subjects self-administered it intravenously. Subjects were excluded for history of alcohol or opiate dependence, other Axis I psychiatric disorders, head injury with loss of consciousness exceeding 10 min, seizures (including drug-related), cardiovascular or liver disease, or current use of psychoactive medication. Abstinence was monitored by UDS and breathalyzer; while these were performed only once per week, subjects were given less than 2 days’ notice each time in order to minimize undetected drug use. A matched control group, who did not meet criteria for any substance abuse/dependence category, underwent UDS and breathalyzer readings only on the three testing occasions. Cocaine-dependent patients consistently demonstrated slower reaction times than control subjects, even after 3 months of abstinence; but sustained attention, assessed by a 30-min, auditory vigilance task, was consistently unimpaired. Azrin et al. (1995) examined 30 cocaine-dependent patients in outpatient treatment whose abstinence was verified by weekly UDS. Length of abstinence varied widely, but was considerably greater than in the studies described above, with a mean of 7 months. The sample included patients who abused crack, powder cocaine, and both. Patients were excluded for history of other Axis I psychiatric disorders (including other substance abuse), head injury and other neurological disorders, various medical conditions, learning disability, ADHD

and other developmental disorders, and current use of psychoactive medication. These criteria were also applied to 30 control subjects with no history of substance abuse, who were matched at the group level on demographic indices. The cocaine-dependent patients showed no deficit on the Digit Span and Mental Control subtests of the WMS-R, both of which are relatively brief measures that might not be sensitive to subtle attentional dysfunction.

5.2. Controlled studies of patients li6ing in controlled en6ironments Several other studies, while not continuously monitoring abstinence, have examined patients in controlled environments in which access to drugs was restricted. These include individuals who were hospitalized, in rehabilitation centers, or incarcerated. A potential drawback of these studies is that, when substance-free control subjects from the community were used as comparison groups, their abstinence was not monitored, so it is at least possible that some of them might have been using substances at the time of their examination. In addition, it is possible that even some of the individuals in controlled environments might have had access to substances of abuse during their period of presumed abstinence. Beatty et al. (1995) studied 23 cocaine-abusing (mostly ‘freebasing’) inpatients who had been abstinent for several weeks. Patients were excluded if they consumed more than 21 drinks per week in the 6 months prior to treatment, although those with prior histories of alcohol dependence were presumably eligible for participation; patients with current or previous use of other substances that was ‘more than experimental in nature’ were also excluded. Subjects were also excluded for limited education or verbal intelligence, significant depressive symptomatology, major psychiatric or medical disorders, history of neurological illness or injury, and current use of psychoactive medication. A healthy control group met similar inclusion and exclusion criteria, and generally matched the cocaine group on demographic variables. However, self-report and retrospective questionnaires revealed higher incidences of childhood behavioral disorders, adult-residual ADHD, and current depressive symptoms among the cocaine group. Cocaine-abusing patients performed more poorly than controls on Trails A and B, and on the Digit Symbol and Arithmetic subtests of the WAISR; however, they were unimpaired on a less confounded measure of sustained and focused attention, the Distractibility condition of the GDS. While the group differences on indices of ADHD and depression could suggest that the findings be interpreted cautiously, these indices were not significantly correlated with performance on attentional tasks.

M.D. Horner / Drug and Alcohol Dependence 54 (1999) 19–33

O’Malley et al. (1992) studied 20 middle-class, mostly Caucasian, cocaine-dependent inpatients after approximately 3 weeks of abstinence. Seventy percent smoked freebase cocaine, while the others self-administered intranasally. Exclusion criteria included history of alcohol or other drug dependence, history of head trauma with loss of consciousness, major medical and psychiatric disorders, significant perinatal or developmental problems, learning disorders, and current use of psychoactive medication. Two groups of control subjects were used, as no single control group had taken the entire battery of neuropsychological tests; one of these groups was drawn from the tests’ normative sample. While these groups were well matched to the cocaine group on demographic variables, they were drawn from different geographical regions and, potentially, different populations, raising some concern about their comparability to the cocaine group. Results of attentional tests were inconsistent: cocaine patients performed more poorly on the Symbol Digit Modalities Test and the Arithmetic subtest of the WAIS-R, but there were no group differences on the Trail Making Test and Numerical Attention Test. In another early study, Herning et al. (1990) compared 12 cocaine-abusing inpatients to nine age- and education-matched control subjects, using a repeated testing paradigm over the first 3 weeks of abstinence. Eleven of the cocaine patients used cocaine intravenously, while one used intranasally; apparently they met diagnostic criteria for cocaine abuse, but not necessarily dependence. Inclusion and exclusion criteria were not clearly specified; the authors noted that one cocaine patient met diagnostic criteria for depression and seven met criteria for antisocial personality disorder, which might itself be associated with cognitive deficits (Miller, 1987; Kandel and Freed, 1989; Gillen and Hesselbrock, 1992), but that ‘no subjects had medical problems’. Information processing speed, as measured by the Sternberg task, was slower in the cocaine group; sustained attention, assessed by both visual and auditory vigilance tasks, was unimpaired. However, the small sample size, the lack of clearly specified inclusion and exclusion criteria in the published report, and psychiatric differences between groups suggest that the findings be considered tentative. Two other studies examined patients in controlled environments who had maintained much longer periods of abstinence. Rosselli and Ardila (1996) studied 61 Colombian, cocaine-dependent patients who smoked ‘basuco’ (a base of cocaine similar to crack) and/or who used cocaine powder intranasally, and who had been abstinent for nearly 3 months. No patients met criteria for concurrent alcohol abuse or dependence, although it is unclear whether patients with previous histories of these diagnoses were excluded. Other exclusion criteria were also somewhat less stringent than in some of the

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above studies; patients were excluded for history of neurological illness or psychiatric hospitalization, but evidently not for other medical or psychiatric disorders. The degree to which the 63 age- and education-matched control subjects were free from substances of abuse, and met the other exclusion criteria, is unclear. Further, various premorbid differences were identified between groups, including histories of anxiety, self-aggression, and suicide attempts, as well as family history of substance abuse. On neuropsychological examination, cocaine-dependent patients were impaired on the subtests of the WAIS (in Spanish translation) most sensitive to attentional impairment: Digit Span, Arithmetic, and Digit Symbol. However, there were no group differences on the Trail Making Test and the Mental Control subtest of the WMS. Incarcerated males with cocaine abuse or dependence who had maintained several years of abstinence were examined by Selby and Azrin (1998). These patients had no history of other substance abuse or dependence (other than caffeine or nicotine), psychiatric disorder other than substance abuse, head injury with loss of consciousness exceeding 5 min, or major medical or neurological disorder. Control subjects were 138 incarcerated felons who met the same criteria, except that they had no diagnosis of substance abuse or dependence. Route of cocaine administration was not reported. There were no differences between the cocaine and the control groups on the Trail Making Test or the Interference condition of the Stroop Test. (A group of subjects with polysubstance abuse including alcohol, cocaine, and other drugs performed more poorly than controls on these measures.)

5.3. Outpatient studies in which abstinence was not consistently monitored Some studies have compared cocaine-dependent patients to healthy control subjects on attentional measures, even though abstinence from substances prior to evaluation was not monitored and patients were not living in controlled environments. Hoff et al. (1996) studied 38 cocaine-dependent men; length of abstinence was quite variable, with a mean of 25 days. Patients were excluded for dependence on substances other than caffeine or nicotine, use of more than 12 ounces of alcohol per week, history of enrollment in special education classes, and ‘medical, neurological, or psychiatric problems other than those related to cocaine abuse’. Fifty-four male volunteers from the community served as controls; exclusion criteria were the same, but data on their current and previous substance use were not provided. The cocaine patients had lower education and socioeconomic status, were more depressed, and had a much higher proportion of African–American individuals than the control group. Cocaine-dependent

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patients performed more poorly than controls on Trails B, but there were no group differences on a variety of other attentional measures, including Trails A, a cancellation task, the Stroop Test, and the Symbol Digit Modalities Test. Even their poorer performance on Trails B should be interpreted cautiously, in light of the non-specificity of this test, the demographic and psychiatric differences between groups, the fact that abstinence from substances was not monitored for either group, and the possibility of confounding medical or psychiatric conditions that were not excluded. Other studies have compared cocaine abusers to groups other than healthy controls. For example, noting the frequency of alcohol dependence among cocaine-dependent patients seeking treatment, Horner (1997) compared cocaine-dependent, alcoholic patients to alcoholic patients without cocaine abuse or dependence. That is, in a sample of alcoholic patients seeking treatment, 32 with cocaine dependence were compared to 55 without cocaine abuse or dependence. Smoking was the primary route of administration for all cocainedependent patients. Length of abstinence varied widely, with a mean of approximately 2 weeks for both groups. Subjects whose self-report indicated abuse or dependence on other substances were excluded. The sample included both inpatients and outpatients; while all were subject to random UDS and breathalyzer readings, these were not performed on all subjects on a regular basis. Other potential confounds were also not rigorously controlled; for example, while all subjects were medically stable at the time of evaluation, data on prior or comorbid neurological and other medical illnesses were not systematically recorded. Subjects were not excluded for other psychiatric diagnoses, but the groups did not differ significantly on this dimension. Data on other premorbid characteristics (e.g. learning disabilities, ADHD) were also not available. Only two attentional measures, Digit Span and the Symbol Digit Modalities Test, were included in the test battery, and the groups did not differ on them. In light of the various potential confounds in this study, and the limited range of attentional measures administered, the negative finding should be interpreted cautiously. One other published study also compared alcohol-dependent patients with and without concurrent cocaine abuse. Brown et al. (1994) compared 82 patients with cocaine and alcohol problems to 64 patients with alcohol dependence alone. Patients were not excluded for comorbid psychiatric, neurological, or other medical conditions; other premorbid factors were also not controlled. Furthermore, cannabis use was prominent in the cocaine-and-alcohol, but not the alcohol-only, group. Patients were tested within the first 5 days of treatment, and again 4 weeks later, at which time UDS was performed. As the focus of the study was not primarily neurocognitive, only two attentional mea-

sures, the Digit Span and Digit Symbol subtests of the WAIS were administered; after controlling for the higher age of the alcohol-only group, performance of the groups did not differ. An unpublished study by Waid et al. (1994) reported preliminary findings in 19 outpatients with crack abuse or dependence, compared to 46 mildly to moderately alcohol-dependent outpatients. Exclusion criteria included other substance dependence and various psychiatric and medical conditions; data on history of learning disability, ADHD, and similar premorbid factors were not reported. The study did not specify subjects’ length of abstinence at the time of evaluation, or whether this was monitored. The cocaine group was younger than the alcoholic group, with lower estimated IQ and level of education. Group comparisons on specific cognitive measures controlled for this difference in IQ; apparently the other factors were controlled by using age- and education-stratified norms for some, but not all, of the tests. A complex pattern of findings emerged: cocaine abusers performed more slowly than alcoholic subjects on the Word condition of the Stroop Test, but not on the Color or Interference conditions. Cocaine abusers also performed more slowly than alcoholics on Trails B, but not on Trails A. While these findings might suggest reduced speed of information processing in the cocaine group, these patients actually demonstrated ‘faster’ reaction times on the 3RT than alcoholic patients, but made more errors of commission, suggesting difficulty with impulse control rather than cognitive speed. Thus, while there was some suggestion of reduced cognitive speed among the cocaineabusing patients, the lack of a substance-free comparison group precludes straightforward interpretation of the results.

5.4. Studies without control groups Finally, several studies have reported results of attentional tests in cocaine-abusing patients, but have compared the results to the tests’ published norms, rather than to the performance of a matched comparison group. This approach, while useful for hypothesis generation, can preclude definitive interpretation of the results, since the similarity of the experimental group to the tests’ normative samples often cannot be assumed. One such study (Volkow et al., 1988) reported a selective performance decrement on the Digit Span and Arithmetic subtests of the WAIS in 20 inpatient cocaine abusers free of other substance dependence and medical or psychiatric illness. However, neither of these scores fell in the impaired range, and the length of abstinence at the time of evaluation is unclear, so that these findings do not constitute strong evidence for attentional impairment.

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Strickland et al. (1993) examined eight cocaine-dependent, long-term inpatients abstinent for at least 6 months, as monitored by random UDS. No specific or unconfounded measures of attention were administered. Most of the patients performed in the impaired range on the Interference condition of the Stroop Test, and two performed poorly on Trails B. (Trails A and the other Stroop conditions were not administered.) The relatively non-specific nature of these tests, lack of a control group, small sample size, and possibility of premorbid neuropsychological impairment in the sample preclude definitive interpretation. Similarly, Ardila et al. (1991) compared the performance of 37 cocaine-dependent inpatients after 1 month of abstinence to tests’ normative data. Scores on the Digit Span and Mental Control subtests of the WMS were well within 1 S.D. of the normative mean, suggesting that the aspects of attention measured by these tasks were not grossly impaired, but leaving open the possibility of more subtle impairment that might have been evident in a controlled study.

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in two others (O’Malley et al., 1992; Van Gorp et al., 1995). These inconsistencies are not easily ascribed to severity of cocaine abuse, or other methodological factors; (c) most tasks on which cocaine abusers were impaired require other non-attentional functions (e.g. motor speed, executive functions, or calculation ability) in addition to cognitive speed; only the Sternberg task provides a relatively unconfounded measure, and it was employed in only one study which failed to exclude some neuromedical and psychiatric confounds (Herning et al., 1990); (d) while six of these studies (Herning et al., 1990; O’Malley et al., 1992; Berry et al., 1993; Roberts and Bauer, 1993; Bauer, 1994; Beatty et al., 1995) reported deficits in cocaine abusers, participants in all of these except the study by Berry et al. (1993) might have been using other substances (e.g. alcohol, as long as consumption did not exceed a certain level) at the time of evaluation. As chronic alcoholism is known to affect performance of speeded psychomotor tasks such as the Trail Making Test and Digit Symbol subtest (Grant, 1987; Orsini et al., 1988), deficits on such tasks in some of these studies might have reflected the effects of chronic alcoholism rather than cocaine use.

6. Conclusions

6.2. Focused attention The preceding discussion, summarized in Table 1, reflects inconsistent findings, partially attributable to various methodological confounds and to methodological differences across studies. Nevertheless, some trends can be seen to emerge. The most definite conclusions are to be drawn from studies in which cocaine-dependent patients were compared to matched, healthy control subjects, and in which abstinence was consistently monitored or in which controlled environments prevented access to cocaine. The seven such studies that examined patients after several weeks of abstinence (Herning et al., 1990; O’Malley et al., 1992; Berry et al., 1993; Roberts and Bauer, 1993; Bauer, 1994; Beatty et al., 1995; Van Gorp et al., 1995) permit the following conclusions.

6.1. Information processing speed All of the tasks on which cocaine-dependent patients demonstrated impairment in these seven studies are sensitive to deficits in speed of information processing. Nevertheless, several considerations indicate that the results do not ‘consistently’ suggest a cocaine-associated decrement in cognitive speed: (a) the PASAT, which also requires cognitive speed, was unimpaired in the two studies which included it; (b) performance on identical tests differed across studies: performance on Trails A was impaired in one study (Beatty et al., 1995) but intact in three (O’Malley et al., 1992; Berry et al., 1993; Van Gorp et al., 1995); Trails B was impaired in two studies (Berry et al., 1993; Beatty et al., 1995) but intact

Cocaine abusers’ ability to process target information while ignoring distractor stimuli (focused attention) was rarely explored explicitly in these studies. Simple ‘concentration’ tasks (e.g. Digit Span, Arithmetic, and Mental Control subtests) which presumably tap this construct (Mirsky et al., 1991; van Zomeren and Brouwer, 1994; Lezak, 1995) produced mixed results. Cocaine abusers were impaired on the Arithmetic subtest of the WAIS-R in all three controlled studies that included it; Mental Control was unimpaired in both studies that included it. Digit Span was intact in one of these studies and impaired in another, and was also intact in two other controlled studies in which abstinence was not consistently monitored. Other tasks which require focused attention in addition to sustained attention (GDS Distractibility condition, PASAT) were generally unimpaired. It thus appears likely that the deficit on the Arithmetic subtest is due to other task requirements, such as information processing speed or task demands unique to this test.

6.3. Sustained attention Performance on relatively ‘pure’, unconfounded measures of sustained attention was consistently unimpaired. These were primarily vigilance tasks, such as the GDS. This finding was also generally true of less specific measures with a sustained attention component, including the PASAT, Numerical Attention Test, and Trails A.

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6.4. Di6ided attention No unconfounded measures of divided attention were used in these studies. Several studies included tasks which apparently require divided attention, but the other attentional and non-attentional demands of these tasks limit firm conclusions. Performance on the PASAT was unimpaired in both studies that included it, and the Stroop Interference task was unimpaired in one study. The findings on the more non-specific measures with putative demands for divided attention (Digit Symbol, Symbol Digit, Trails B) were inconsistent, but as noted above, impairment on these tasks could be attributable to deficits in numerous cognitive domains other than divided attention, or to concurrent alcoholism among cocaine-abusing subjects.

6.5. Summary of findings Thus, among the best-controlled studies of cocaine abusers abstinent for several weeks, sustained attention was generally intact. There were inconsistent suggestions of reduced cognitive speed, but many of these findings could also be attributable to the non-attentional demands of the various tasks. Divided attention remains unexplored. In general, a similar pattern of results is reflected in controlled outpatient studies in which abstinence was ‘not’ consistently monitored: tasks on which cocaine abusers were impaired required speeded information processing, but other tasks requiring this same factor were unimpaired, and no unconfounded measures of divided attention were administered. Controlled studies of patients with several ‘months’ of abstinence yielded inconclusive findings. There have been five such controlled studies, three of patients with monitored abstinence (Roberts and Bauer, 1993; Bauer, 1994; Azrin et al., 1995) and two of patients in controlled environments (Rosselli and Ardila, 1996; Selby and Azrin, 1998). Two of these studies (Azrin et al., 1995; Selby and Azrin, 1998) found no attentional deficit among chronic cocaine users, although the range of attentional tests administered was somewhat limited. In contrast, Rosselli and Ardila (1996) reported relatively impaired performance on several WAIS subtests with attentional components; however, these findings should be interpreted cautiously in light of the relatively less stringent inclusion and exclusion criteria, and the demonstrated premorbid differences between the cocaine and control groups. Bauer (1994; Roberts and Bauer, 1993) reported persisting decrements in reaction time in cocaine-dependent patients, possibly suggestive of decreased speed of information processing. Several reasons can be identified for the inconsistency of findings in studies of patients with both shorter and longer periods of abstinence. The methodological issues

listed in Section 4 undoubtedly account for a significant portion of the variation across studies. In particular, even limiting the analysis to those studies which monitored abstinence or examined patients in controlled environments, several methodological difficulties have complicated the collection and interpretation of data: First, most of the attentional measures used in these studies are confounded by various factors, including task demands in non-attentional domains (e.g. motor speed, executive functions). Second, significant differences undoubtedly exist across the samples examined in these studies. For example, study populations ranged from incarcerated individuals (Selby and Azrin, 1998) to patients seeking treatment at a VA Medical Center (Berry et al., 1993; Van Gorp et al., 1995) to middle class individuals (O’Malley et al., 1992). Further, most studies examined patients who smoked cocaine, but several (O’Malley et al., 1992; Azrin et al., 1995) included patients who self-administered intranasally, and one (Herning et al., 1990) primarily studied intravenous users; the effect of route of cocaine administration on cognitive functioning remains largely unknown. Third, some of the studies did not rigorously control for potential confounds among experimental and cocaine groups, including prior or concurrent use of other psychoactive substances, various medical and psychiatric disorders (e.g. depressive symptoms that do not meet criteria for major depressive disorder), and developmental deficits of attention or other functions. In addition, some studies (Herning et al., 1990; O’Malley et al., 1992; Rosselli and Ardila, 1996) used control groups which differed from the cocaine patients on demographic, psychiatric, premorbid, or other variables. Thus, based on the evidence accumulated to date, it would be premature either to accept or to reject the hypothesis of attentional impairment associated with cocaine dependence.

6.6. Directions for future research The above findings indicate that further research is needed to clarify the existence, nature, and severity of attentional impairment among chronic cocaine users. Future studies will produce the most definitive results when abstinence is consistently monitored for all subjects, when stringent inclusion and exclusion criteria are applied to eliminate potential confounds (e.g. psychiatric, neurological, or other medical illness, history of ADHD, concurrent use of other substances), and when experimental and control groups are as closely matched as possible on relevant variables (e.g. age, education, socioeconomic status). Clearly, however, such experimental designs are not easily implemented. Suitable patients can be difficult to recruit (especially when cocaine-dependent patients with other substance use

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disorders are to be excluded), and monitoring of abstinence can be time-consuming and expensive. Most previous studies have employed only a handful of attentional tests, many of which have been confounded by non-attentional task demands. Resolution of the question of attentional functioning in cocaine dependence appears unlikely until more specific and sensitive measures are used to examine each subtype of attention. For example, relatively unconfounded measures of information processing speed would include reaction time tasks and the Sternberg paradigm. Focused attention could be assessed using various ‘concentration’ tasks, such as Mental Control and Digit Span, as well as tasks which require that distractor stimuli be ignored, such as the Distractibility condition of the GDS. Vigilance tasks, including the GDS and various other continuous performance tasks, provide relatively unconfounded measures of sustained attention. Divided attention, which has remained largely unexplored in cocaine-abusing patients, could be assessed with a dichotic listening test; visual divided attention tasks and dual-task paradigms have frequently been employed in the non-clinical, cognitive psychology literature (Hartley, 1992), and could also be applied in this context. In fact, in light of the non-specific nature of many clinical measures of attention, further use of attentional tasks and concepts from the rich literature in non-clinical cognitive psychology (Johnston and Dark, 1986; Posner and Petersen, 1990; Kinchla, 1992) would likely prove fruitful. More definitive findings would also be obtained from studies that include several measures of each subtype of attention. Even if some of these measures are confounded by non-attentional factors, the results obtained from a more comprehensive battery of attentional tests would indicate more clearly the presence and nature of any impairment. Finally, many of the well-controlled studies to date have examined cocaine-dependent patients without other, concurrent substance use disorders. As noted above, the advantages of this design for detecting neuropsychological effects of chronic cocaine use are readily apparent. Nevertheless, as the incidence of other substance abuse, particularly alcoholism, is very high among cocaine-dependent patients seeking treatment (Jatlow et al., 1991; Brown et al., 1994; Higgins et al., 1994), the generalizability of many previous findings might be limited. Future studies could focus on attention and other cognitive functions among patients who abuse both cocaine and alcohol.

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