Deficits in Complex Motor Functions, Despite No Evidence of Procedural
Learning Deficits, Among HIV? Individuals With History
of Substance Dependence
Raul Gonzalez, Joanna Jacobus, Anup K. Amatya,
Phillip J. Quartana, and Jasmin Vassileva
University of Illinois–Chicago
Eileen M. Martin
University of Illinois–Chicago
and Jesse Brown VA Medical Center
Human immunodeficiency virus (HIV) and drugs of abuse affect common neural systems underlying
procedural memory, including the striatum. The authors compared performance of 48 HIV seropositive
(HIV?) and 48 HIV seronegative (HIV?) participants with history of cocaine and/or heroin dependence
across multiple Trial Blocks of three procedural learning (PL) tasks: Rotary Pursuit (RP), Mirror Star
Tracing (MST), and Weather Prediction (WP). Groups were well matched on demographic, psychiatric,
and substance use parameters, and all participants were verified abstinent from drugs. Mixed model
analyses of variance revealed that the individuals in the HIV? group performed more poorly across all
tasks, with a significant main effect of HIV serostatus observed on the Mirror Star Tracing and a trend
toward significance obtained for the Rotary Pursuit task. No significant differences were observed on the
Weather Prediction task. Both groups demonstrated significant improvements in performance across all
three procedural learning tasks. It is important to note that no significant Serostatus ? Trial Block
those in the HIV? group across all trial blocks of procedural learning tasks with motor demands, but showed
no differences in their rate of improvement across all tasks. These findings are consistent with HIV?-
associated deficits in complex motor skills, but not in procedural learning.
Keywords: HIV, substance use disorders, basal ganglia, nondeclarative memory, neuropsychology
Current taxonomy of memory systems identifies multiple func-
tionally distinct components with differing neuroanatomical sub-
strates, making a primary distinction between declarative (explicit)
and nondeclarative (implicit) memory (Squire, 1992; Squire &
Zola, 1996). Briefly, declarative memory systems are responsible
for memory of facts and events that are consciously recalled and
dependent on integrity of medial temporal lobe structures. Such
abilities are usually assessed through tasks requiring memorization
of word-lists, stories, and pictures that subjects are later asked to
recall. On the other hand, nondeclarative memory includes such
functions as procedural learning (i.e., motor skills and habits),
priming, and simple classical conditioning, which do not require
conscious recollection and rely primarily on brain structures out-
side of the midtemporal lobes. Integrity of basal ganglia structures
has been deemed critical for procedural learning, which refers to
gradual, incremental learning of skills and habits that can be
demonstrated through improvements in task performance, but do
not require conscious memorization or recollection (e.g., riding a
bike, tennis swing, driving). In this study, we examined procedural
learning among individuals who were HIV-seropositive (HIV?)
and HIV-seronegative (HIV?) with history of substance use dis-
orders by using three common neurocognitive probes of proce-
Basal ganglia structures (especially caudate and putamen) have
been consistently reported as vital for procedural learning (for
reviews, see Packard & Knowlton, 2002; Salmon & Butters, 1995;
Squire et al., 1996; Yin & Knowlton, 2006). Patients with basal
ganglia abnormalities, particularly those with degenerative demen-
tias affecting subcortical brain structures, show impairments on
nondeclarative memory tasks but often demonstrate normal per-
formance on declarative memory measures compared with both
healthy controls and persons with damage involving midtemporal
structures or other brain regions outside basal ganglia (e.g.,
Knowlton, Mangels, & Squire, 1996). Conversely, densely amnes-
tic individuals with midtemporal lobe damage demonstrate ade-
quate procedural learning despite no conscious recall of the testing
situation (e.g., Knowlton, Squire, & Gluck, 1994). Other investi-
gations with human subjects support dissociable neural systems for
declarative and nondeclarative memory, with structures of the
basal ganglia supporting procedural learning (e.g., Bayley, Fras-
cino, & Squire, 2005; Poldrack & Packard, 2003).
Several tasks have been used as successful probes of procedural
learning and basal ganglia function, including the Rotary Pursuit
(RP), Star Mirror Tracing (SMT), and the Weather Prediction
(WP) task. The Rotary Pursuit task and the Star Mirror Tracing
task are measures of motor skills learning that are performed
Raul Gonzalez, Joanna Jacobus, Anup K. Amatya, Phillip J. Quartana,
and Jasmin Vassileva, Department of Psychiatry, University of Illinois–
Chicago; Eileen M. Martin, Department of Psychiatry, University of Illi-
nois–Chicago, and Jesse Brown VA Medical Center, Chicago, Illinois.
Joanna Jacobus is now at San Diego State University, University of
California–San Diego Joint Doctoral Program in Clinical Psychology.
The authors thank Drs. Rodney Eiger and Max Brito, as well as Mr. Gerald
Nunnally at the Jesse Brown VA Medical Center for their generosity in
referring participants for this investigation. This study was supported by HHS
F32 DA018522 to Dr. Gonzalez and R01 DA12828 to Dr. Martin.
Correspondence concerning this article should be addressed to Raul
Gonzalez, 1601 W. Taylor Street, MC 912, Chicago, IL 60622. E-mail:
2008, Vol. 22, No. 6, 776–786
Copyright 2008 by the American Psychological Association
abnormally by patients with disease that primarily affects the basal
ganglia, such as Parkinson’s (e.g., Heindel, Salmon, Shults, Wal-
icke, & Butters, 1989; Sarazin et al., 2002) and Huntington’s
disease (e.g., Heindel, Butters, & Salmon, 1988; Heindel et al.,
1989) compared with persons with brain disorders with relative
sparing of the basal ganglia (for review, see Salmon et al., 1995).
Similar findings have been reported using the Weather Prediction
task, a measure of procedural learning that requires participants to
make probabilistic classifications. Shohamy, Myers, Onlaor, and
Gluck (2004) found deficits in Weather Prediction task perfor-
mances as indicated by use of less effective strategies among
patients with Parkinson’s disease when compared with healthy
controls. Poldrack, Seger, and Gabrieli (1999) reported increased
basal ganglia activity in a sample of healthy subjects performing
the Weather Prediction task. Furthermore, activity in midtemporal
lobe structures and striatum differ depending on whether the task
demands are declarative or nondeclarative in nature, and activation
in these regions is inversely correlated (Poldrack, Prabhakaran,
Seger, & Gabrieli, 2001).
Damage to structures of the basal ganglia attributable to human
immunodeficiency virus (HIV) is commonly reported in the scientific
literature. The HIV virus has been reported at highest concentration in
basal ganglia of brains examined at autopsy (Navia, Cho, Petito, &
Price, 1986), with further neuropathological studies supporting pref-
erential damage to basal ganglia from HIV (Masliah, Ge, Achim,
DeTeresa, & Wiley, 1996; Nath et al., 2000; Wiley et al., 1998).
Structural magnetic resonance imaging (MRI) studies report white
matter abnormalities and decreased volume of subcortical nuclei,
particularly in the basal ganglia (Aylward et al., 1993; Jernigan et al.,
1993; Stout et al., 1998), and caudate volume is often cited as a
significant predictor of neuropsychological performance in individu-
als who are HIV? (e.g., Kieburtz et al., 1996; Paul, Cohen, Navia, &
Tashima, 2002). Biochemical abnormalities in subcortical brain struc-
tures, including basal ganglia, have been noted in both early and later
stage HIV disease using magnetic resonance spectroscopy (MRS;
e.g., Chang et al., 2004; Ernst, Itti, Itti, & Chang, 2000; Meyerhoff et
al., 1999; Paul et al., 2007). Similarly, functional abnormalities in
basal ganglia have been observed with positron emission tomography
(PET) (Rottenberg et al., 1996; van Gorp et al., 1992; von Giesen et
al., 2000; cf. Ernst et al., 2000) and functional MRI (fMRI; e.g.,
Chang et al., 2001).
HIV-related impairments on neuropsychological tests reflect dys-
function of basal ganglia and prefrontal-striatal brain circuits (e.g.,
Heaton et al., 1995; Reger, Welsh, Razani, Martin, & Boone, 2002;
Sadek et al., 2004). Neuropsychological impairments among those
infected with HIV are generally seen in attention/working memory,
information processing speed, executive functions, learning, and mo-
tor skills compared with healthy or risk-matched controls (e.g., Born-
stein et al., 1992; Hardy & Hinkin, 2002; Heaton et al., 1995; Miller
et al., 1990; Peavy et al., 1994; Reger et al., 2002).
HIV and substance use disorders are often comorbid and evi-
dence suggests additive effects on neurocognitive functioning (for
review, see Gonzalez & Cherner, 2008). HIV-associated neuro-
cognitive deficits have also been reliably detected among samples
of substance dependent individuals (Durvasula et al., 2000; Marder
et al., 1995; Rippeth et al., 2004) and studies focusing on neuro-
cognitive tasks sensitive to prefrontal-striatal dysfunction reveal
deficits in working memory (Bartok et al., 1997; Farinpour et al.,
2000; Martin et al., 2001, 2003) and decision-making (Martin et
al., 2004) among HIV-infected substance users compared with
HIV?, substance-using comparison groups. Moreover, comorbid
substance use disorders seem to worsen HIV-associated brain
dysfunction as assessed with neuropsychological tests (Basso &
Bornstein, 2000; Rippeth et al., 2004) and neuroimaging protocols
(Chang, Ernst, Speck, & Grob, 2005; Jernigan et al., 2005; Taylor,
Alhassoon, Schweinsburg, Videen, & Grant, 2000). Thus, the high
comorbidity of substance use disorders and HIV, as well as evi-
dence to suggest additive detrimental effects on neurocognitive
functioning underscores the importance of conducting studies on
effects of HIV in a substance-using population.
Dysfunction of basal ganglia structures and associated neural
pathways are considered a primary underlying cause of neuropsy-
chological impairments among individuals with HIV (with and
without history of substance use disorders), yet investigations
examining procedural learning in this population are virtually
nonexistent. Only a few studies have examined procedural learning
among persons with HIV disease or with a history of substance
abuse, and (to our knowledge) none have reported results for
individuals with both. For example, van Gorp and colleagues
(1999) found evidence of improved Rotary Pursuit performance
among abstinent cocaine users compared with healthy controls. All
participants in their investigation were HIV?. Kalechstein,
Hinkin, van Gorp, Castellon, and Satz (1998) found that mood
disorder symptoms were correlated with poorer performance on
Rotary Pursuit, but their investigation was limited only to HIV?
individuals. An early study that has been widely cited as evidence
for procedural learning deficits in HIV examined Rotary Pursuit
performance among 29 relatively high functioning nondrug-using
HIV? individuals compared with 15 HIV? controls (Martin,
Heyes, Salazar, Law, & Williams, 1993). They reported that a
subset of HIV? individuals showed significantly decreased motor-
skill learning compared with HIV? controls, consistent with basal
ganglia pathology. Furthermore, performance deficits among the
HIV? persons were associated with higher levels of the neuro-
toxin quinolinic acid in cerebrospinal fluid. Although evidence
from this initial investigation was promising, there have been
practically no follow up studies of procedural learning abilities
among HIV? patients, particularly among those with substance
use disorders despite the high comorbidity of these disorders.
In the current investigation, we compare performance of individu-
als who are HIV? and HIV? with a history of substance dependence
on three separate measures of procedural learning. We hypothesize
that the individuals in the HIV? group will perform more poorly,
overall, than those in the HIV? group across all three procedural
learning tasks consistent with general neuropsychological dysfunc-
tion. In addition, the HIV? group is expected to demonstrate a deficit
in procedural learning compared with the HIV? group by showing
decreased rate of improvement across Trial Blocks of each task.
Finally, we anticipate that HIV? subjects with more advanced dis-
ease as indexed by CD4 lymphocyte counts and HIV viral load in
plasma will show the poorest performance.
Participants were 48 HIV? and 48 enzyme-linked immunosor-
bent assay (ELISA)-verified HIV? adults enrolled in a larger
study of HIV and neurocognition among substance abusers. Sub-
HIV AND PROCEDURAL LEARNING
jects were recruited from the Chicago metropolitan area through
flyers placed throughout the community and at infectious disease
clinics and substance use treatment programs, as well as through
word-of-mouth. All participants provided informed consent for
study procedures, which were approved by the University of
Illinois Chicago Institutional Review Board and the Jesse Brown
VA Medical Center. Recent (past 3 months) CD4 T-lymphocyte
cell counts and level of HIV RNA viral load in plasma were
available for 94% of HIV? participants. Inclusion criteria in-
cluded a history of cocaine and/or heroin dependence as assessed
by the Substance Abuse Module of the Structured Clinical Inter-
view for the Diagnostic and Statistical Manual of Mental Disor-
ders, Fourth Edition (SCID-SAM; First, Spitzer, Gibbon, & Wil-
liams, 2002). Current SCID-diagnosed alcohol abuse or depen-
dence was grounds for exclusion. Subjects were instructed to
abstain from street drug use and none reported use of cocaine or
heroin for at least 7 days prior to each study visit. Those testing
positive for opiates or cocaine on urine toxicology testing (Visua-
line, SunBiomedical, Blackwood, NJ) or those with positive alco-
hol breath test (Inoxilyzer, CMI Inc., Owensboro, KY) did not
undergo study protocol and were rescheduled. Additional exclu-
sion criteria included history of head injury with loss of conscious-
ness greater than 30 minutes or open head injury of any kind,
history of schizophrenia or unmedicated bipolar disorder, and
history of neurological illness (e.g., dementia, stroke, tumor, neu-
rosyphilis). No statistically significant differences were observed
between HIV? and HIV? groups on demographic characteristics
and estimated premorbid intelligence as assessed by the American
National Adult Reading Test (AmNART; Grober & Sliwinski, 1991),
which are described in Table 1.
Trained personnel administered several structured clinical inter-
views, self-report questionnaires, and neurocognitive exams to
participants. In order to minimize participant fatigue, the assess-
ment was conducted across two study visits, each requiring one to
two hours to complete. Data were collected on substance use
history, mental health indices, and performance on several mea-
sures of procedural learning, as described below.
Substance use history.
As previously noted, participants com-
pleted the SCID-SAM to assess history of past and current depen-
dence or abuse for drugs and alcohol. In addition, a modified
version of the Kreek-McHugh-Schluger-Kellogg scale (KMSK;
Kellogg et al., 2003) was employed to index severity of alcohol
and drug use history by obtaining information on frequency,
amount, and duration of alcohol and drug use during an individ-
ual’s most intense period of drug consumption (i.e., their peak
use). Additional questions were added to the KMSK in order to
obtain information on history of cannabis use, as well as informa-
tion on drug use during the prior month for all drug classes. The
possible range of scores for peak use varies depending on the
substance queried (alcohol ? 0–13; cocaine ? 0–16; heroin ?
0–13; cannabis ? 0–16). Finally, additional information on sub-
stance use topography (e.g., years of drug use, days since last use)
was obtained via self-report. Information on participants’ sub-
stance use characteristics is presented in Table 2.
Current mental health.
Participants completed the Beck De-
pression Inventory, 2nd edition (BDI-II) to obtain information on
current severity of symptoms associated with depression (Beck,
Steer, Ball, & Ranieri, 1996). Current levels of anxiety were
assessed with the “State” portion of the State–Trait Anxiety In-
ventory (Spielberger, Gorsuch, Lushene, Vagg, & Jacobs, 1983).
Childhood symptoms of attention-deficit/hyperactivity disorder
(ADHD) were queried using the Wender-Utah Rating Scale
(WURS; Stein et al., 1995; Ward, Wender, & Reimherr, 1993).
Three separate measures were used to
assess procedural learning in our sample.
The photoelectric Rotary Pursuit task (Lafayette Instruments,
Model 30014A), is a well-studied measure of motor skills learning.
The task requires subjects to hold a plastic stylus over a rotating
disk, keeping the stylus directly over a patch of light that appears
to spin around the circumference of the disk at a set speed.
Demographic Characteristics of Sample
HIV? (n ? 48) HIV? (n ? 48)
Years of education, M (SD)
AmNART estimated IQ, M (SD)
BDI-2, Mdn (IQR)
STAI-State, M (SD)
WURS, M (SD)
Hepatitis C seropositive, %
8 (3, 14)
8 (3, 19)
National Adult Reading Test; IQR ? interquartile range; BDI-2 ? Beck
Depression Inventory–2nd Edition; STAI-State ? State-Trait Anxiety In-
ventory–State portion; WURS ? Wender-Utah Rating Scale.
HIV ? human immunodeficiency virus; AmNART ? American
Substance Use Characteristics of Sample
HIV? (n ? 48)HIV? (n ? 48)
Years of cocaine and/or
heroin use, M (SD)
Days since last use of
cocaine and/or heroin,
History of past SCID-SAM
KMSK peak, Mdn (IQR)
22.1 (7.9) 21.9 (9.1)
210 (90, 410) 276 (120, 652)
10 (8, 12)
13 (10, 16)
8 (0, 11)
10 (6, 13)
11 (8, 12)
15 (13, 15)
4 (0, 11)
11 (4, 13)
Clinical Interview for DSM-IV–Substance Abuse Module; IQR ? inter-
quartile range; KMSK ? Kreek-McHugh-Schluger-Kellogg Scale.
?p ? .05.
HIV ? human immunodeficiency virus; SCID-SAM ? Structured
GONZALEZ ET AL.
Participants were instructed to “. . .hold on to the stylus and hold
it over the light as it spins around. [They] must keep following the
light until it stops spinning.” Additional instructions were provided
as needed until it was evident to the examiner that the participant
understood the instructions. Based on data from previous studies
(e.g., see Table 1 in Weickert et al., 2002), the age of our partic-
ipants, and our own pilot investigations, the speed of the turntable
was set at 55 rpm for all participants across all trials given. This
approach allowed us to use a standardized setting with all partic-
ipants that showed minimal “floor” and “ceiling” effects. This
method also obviated the need for practice trials, and ensured that
all improvements in performance were captured during testing
trials, as all participants would be starting the task with no prior
exposure or training. Eight trials lasting 20 seconds each were
conducted. The time (in seconds) that the stylus was kept on the
target during each trial was recorded. Participants were allowed to
rest for approximately 20 seconds between each trial, with a
15-min break halfway through the task between the fourth and fifth
The Mirror Star Tracing task (Lafayette Instruments, Model
58024A) requires participants to trace within an outline of a
six-point star on a flat metallic plate using a metal stylus similar in
shape to a pen. Participants are unable to see the actual star (or
their hand) as they are tracing the star, but rather see only a mirror
image of the two. The subjects are instructed to maintain contact
between the stylus and the surface of the apparatus and to trace
within the black outline of the star, trying not to stray from within
the outline. They are told to trace as quickly as they can, while
trying to remain within the outline of the star. Eight trials were
conducted and the amount of time required for the participant to
trace the full outline of the star, one time, was recorded for each
trial. If 240 s elapsed during a trial, the participant would be asked
to stop, the trial would be discontinued, and a time of 241 s would
be recorded for that participant on that trial. Participants were
allowed to rest for approximately 20 s between trials, except
between the fourth and fifth trials where they had a 5-min break.
Participants also completed the Weather Prediction task, a 200-
trial two-choice probabilistic classification task (Knowlton et al.,
1994). On each trial, the participant views a display that contains
one, two, or three cards (from a set of four cards, each with a
distinct abstract design). As the cards are presented, participants
must press one of two keys on a computer keyboard to indicate if
they think the cards are associated with an outcome of “sunshine”
or “rain.” Each card display (pattern) has a fixed probability of
each outcome that is not told to participants. They are only
informed that they may have to “guess at first” but that they should
try “to get better at predicting the weather” as the task goes on. We
administered the Weather Prediction task with the method put
forth in Experiment 2 of Gluck, Shohamy, and Myers (2002),
which employs the same procedures of Knowlton et al. (1994), but
uses a probability structure that is somewhat easier to learn and
would thus have a difficulty level more appropriate for our sample
of inner-city substance users with relatively low levels of educa-
tional attainment. As in previous studies, responses were classified
as “correct” if participants chose the response that was more
strongly associated with the cards presented. The percentage of
correct responses made during each of four 50-trial blocks was
used as the dependent variables.
There was one noteworthy difference in our method for admin-
istering the Weather Prediction task. Instead of allowing partici-
pants up to 5 s to make their responses, we set the task parameters
to allow participants up to 10 s to respond. This was done to
minimize the impact of processing speed problems (that are com-
mon in HIV and sometimes observed in substance use disorders)
on the participants’ ability to perform the task. Our data suggest
that the response time limit we employed was sufficiently lengthy
to prevent possible deficits in processing speed from interfering
with task performance, as HIV? and HIV? groups did not differ
significantly in their response times (p ? .15; HIV?, M ? 1.31s,
SD ? 0.51; HIV?, M ? 1.45s, SD ? 0.43). Moreover, groups did
not differ in the total number of trials in which they failed to
provide a response within the 10s time limit (p ? .76; HIV?,
Mdn ? 0, range ? 0–2; HIV?, Mdn ? 0, range ?0–2). Indeed,
only four HIV? and five HIV? participants failed to provide a
response within the time limit on any one trial.
General Statistical Procedures
Distributions of data for each variable and all statistical analyses
were examined for outliers and violations of statistical assump-
tions (e.g., nonnormal distribution, heterogeneity of variance).
Nonnormal data underwent transformation when appropriate. Stu-
dent’s t tests were used for between-groups (HIV? and HIV?)
comparisons with one continuous dependent variable, whereas ?2
tests were employed when the single dependent variable was
categorical. Analyses were deemed statistically significant when p
values were less than or equal to .05. In order to reduce the number
of dependent variables in analyses and to reduce variability, data
reduction techniques were used for data from the Rotary Pursuit
task and the Mirror Star Tracing task. Specifically, performance on
the eight trials of the task were reduced to four trial blocks for each
of these two measures, such that each trial block represented the
average performance across two successive trials (i.e., Trial Block
1 ? average of Trial 1 and Trial 2; Trial Block 2 ? average of
Trial 3 and Trial 4; and so forth).
Groups (HIV? and HIV?) were well matched on demographic
factors, with no statistically significant differences observed in
age, years of education, gender, handedness, race/ethnicity, esti-
mated IQ, and hepatitis C serostatus (see Table 1). HIV? and
HIV? groups were also matched on self-reported symptoms of
depression (BDI-II), anxiety (STAI-State), and attention-deficit/
hyperactivity disorder (WURS) (see Table 1). Similarly, no statis-
tically significant differences were observed on various measures
of substance use (see Table 2), with the exception of higher
prevalence of past heroin dependence among HIV? participants
and a higher prevalence of past stimulant dependence in the HIV?
group. More of the participants in the HIV? group were on
methadone treatment (HIV? ? 21%, HIV? ? 4%; Fisher’s exact
test, n ? 96, p ? .004) and reported using heroin more recently
(HIV?, n ? 35, Mdn ? 229 days ago; HIV?, n ? 28, Mdn ? 425
days ago; Kruskal-Wallis Test, p ? .02). Despite this, groups did
not differ significantly in severity of peak substance use for all
substances assessed by the KMSK, including for heroin (see Table 2).
HIV AND PROCEDURAL LEARNING
Among HIV? participants, only 18% had an immunological
acquired immune deficiency (AIDS) diagnosis (CD4 count:
Mdn ? 359 cells/mL, interquartile range: 249, 555) and 44% of the
HIV? sample had undetectable HIV RNA viral load in plasma
(Mdn ? 352 copies/mL, IQR: 75, 4206). Exactly half of the
individuals in the HIV? sample reported being prescribed highly
active antiretroviral (ARV) treatment, with 86% of HIV? partic-
ipants reporting use of any ARV treatment.
Performance on Measures of PL by HIV Serostatus
Study hypotheses were examined using 2 (Group: HIV?;
HIV?) ? 4 (Trial Block: Block 1, Block 2, Block 3, Block 4)
mixed-model analyses of variance (ANOVAs), with Group as the
between-subjects factor and Trial-Block as the within-subjects
factor. The dependent variable for each ANOVA model tested was
performance for each of the four Trial Blocks associated with each
PL task: RPT ? Rotary Pursuit seconds on target, SMT ? Star
Mirror Tracing seconds to complete, WPT ? Weather Prediction
percentage of correct selections. For each model tested, we em-
ployed a Greenhouse-Geiser correction to control for violation of
the assumption of sphericity.
Because individuals in the HIV? and HIV? groups differed
significantly on prevalence of heroin dependence, stimulant de-
pendence, and methadone treatment status, we examined (individ-
ually) if any of these factors was associated with performance on
any of the procedural learning tasks to determine whether they
should be included as covariates in analyses. Briefly, each factor
was included as the sole independent variable in a mixed-model
ANOVA using the same procedures just described. No statistically
significant effects were observed (all p values ?.05) for each of
these variables; thus, they were not included as covariates in
Performance of HIV? and HIV? groups on PL tasks are depicted
in Figures 1 through 3 and in Table 3. For each mixed-model
ANOVA, we observed a statistically significant main effect for Trial
Blocks, indicating that overall participant performance improved
across task trials (all p values ?.001). There were no significant
Group ? Trial Block interaction effects for any PL task; SMT:
F(1.83, 171.59) ? 0.43, p ? .63; RPT: F(2.63, 247.56) ? 1.35, p ?
.26; WPT: F(2.77, 255.03) ? 0.34, p ? .78, suggesting that both
HIV? and HIV? groups demonstrated similar rates of improvement
in performance across Trial Blocks. However, HIV? participants
performed worse overall than HIV? participants on all tasks. A
statistically significant main effect for Group was observed for the
SMT, F(1, 94) ? 11.32, p ? .001, such that HIV? participants
Star Mirror Tracing
Block 1Block 2 Block 3Block 4
seconds to complete
represent mean performance and SE for each trial block.
Star mirror tracing performance by human immunodeficiency virus (HIV) serostatus. Data points
Performance of Groups on Procedural Learning Measures
HIV? (n ? 48),
HIV? (n ? 48),
Star Mirror Tracing task (SMT)
Trial Block 1
Trial Block 2
Trial Block 3
Trial Block 4
Overall mean performance
Rotary Pursuit task (RPT)
Trial Block 1
Trial Block 2
Trial Block 3
Trial Block 4
Overall mean performance
Weather Prediction task (WPT)
Trial Block 1
Trial Block 2
Trial Block 3
Trial Block 4
Overall mean performance
are seconds to complete task (lower value is better); RPT values are
seconds on target (higher value is better); WPT values are percentage of
correct choices (higher value is better).
All data presented in this table is not transformed. Values for SMT
GONZALEZ ET AL.
performed more poorly overall compared to HIV? participants. A
similar pattern of data was observed on RPT performance, although
the main effect of Group failed to reach conventional levels of
significance, F(1, 94) ? 3.73, p ? .057. In contrast, a statistically
significant main effect of Group was not observed on the WPT, F(1,
94) ? 1.13, p ? .29. Overall mean differences in performances
between HIV? and HIV? groups on the SMT and RPTs evidenced
effect sizes of medium to large (hedges g ? 0.68) and small to
medium magnitude (hedges g ? 0.39), respectively. In summary,
these data suggest that the HIV? and HIV? groups evidenced no
differences in their rate of PL across all tasks. However, HIV?
participants performed worse, overall, on two of the three tasks.
In order to analyze asymptotes in performance across Trial
Blocks, a quadratic function was fitted separately for each PL task.
Point-of-asymptote was calculated for all three tasks using data
from all four Trial Blocks. As in previous analyses, a significant
main effect of Trial Block was observed for all tasks (p values
?.05). There were no significant Group ? Trial Block interac-
tions, indicating that point-of-asymptote did not differ between
HIV? and HIV? groups on any of the tasks. Participants were
found to reach asymptote slightly before or during the fourth Trial
Block (point-of-asymptote: RPT ? 4.28, SMT ? 3.95, WPT
? 3.74). Mean performance level at the point-of-asymptote was
calculated for the HIV? and HIV? group on each of the three PL
Block 1Block 2Block 3 Block 4
seconds on target
represent mean performance and standard error for each trial block.
Rotary pursuit performance by human immunodeficiency virus (HIV) serostatus. Data points
Block 1 Block 2Block 3 Block 4
represent mean performance and standard error for each trial block.
Weather prediction performance by human immunodeficiency virus (HIV) serostatus. Data points
HIV AND PROCEDURAL LEARNING
tasks. Consistent with results from our previous analyses, t tests
revealed that the HIV? group performed significantly better than
the HIV? group at asymptote on the SMT (p ? .001), but not the
Weather Prediction (p ? .32). Difference in Group performance at
point-of-asymptote for the RP approached significance (p ? .056).
Effects of HIV Disease Severity and Treatment Factors on
Additional analyses were conducted with the HIV? sample to
determine whether biomarkers of disease severity (i.e., HIV RNA
viral load in plasma and CD4 counts) or current treatments (on
antiretrovirals or highly active antiretroviral therapy, HAART) influ-
enced performance on measures of procedural learning.
Using a median split, HIV? participants were stratified into those
with low (?359, n ? 23) and high (?359, n ? 22) CD4 counts. As
in previous analyses, three separate mixed-model ANOVAs were
conducted (one for each procedural learning task), with CD4 group as
the between-subjects factor and Trial Blocks as the within-subjects
factor. As with all prior analyses, a significant main effect of Trial
Block was observed for each procedural learning task, indicating
significant improvements in performance over time (p values ?
.01). No other statistically significant main effects or interaction
effects were observed (p values ? .10).
Using the same statistical methods previously described, three
separate mixed-model ANOVAs (one for each procedural learning
measure) were conducted with presence of HIV RNA viral load in
plasma serving as the between-subjects factor and Trial Blocks on
procedural learning tasks as the within-subjects factor. Of the 45
HIV? participants for which plasma viral load levels were avail-
able, 25 had detectable and 20 had undetectable HIV viral load. As
with our previous analyses, all models demonstrated a significant
main effect for Trial Blocks across all procedural learning tasks,
indicating improvements in performance over time (p values
?.001). A statistically significant Group main effect for viral load
was only observed on the Weather Prediction task, with HIV?
participants with detectable viral load performing worse, overall,
compared to those without detectable viral load, F(1, 43) ? 4.90,
p ? .03. Statistically significant Group main effects were not
observed for performance on the Star Mirror Tracing or Rotary
Pursuit tasks (p values ? .10). Similarly, no statistically signifi-
cant Group ? Trial Block effects were observed, regardless of
procedural learning task (p values ?.10).
For the final set of analyses, the between-subjects factor was
whether HIV? participants were on ARV medications (ARV?;
n ? 41; ARV?; n ? 7). Again, three separate mixed-model
ANOVAs were conducted. Consistent with prior analyses, statis-
tically significant effects for Trial Blocks were observed across all
tasks, indicating improved performance over Trial Blocks (p val-
ues ? .001). No significant Group main effect or Group ? Trial
Block effects were observed for any of the procedural learning
tasks (p values ?.05).
The primary goal of this investigation was to determine if a
positive HIV serostatus was associated with poorer procedural
learning in a sample of individuals with a history of substance
dependence. Several important conclusions emerged. First, com-
pared with individuals in the HIV? group, HIV? individuals
showed evidence of poorer overall performance on procedural
learning tasks, particularly on the two measures with complex
motor demands (i.e., Rotary Pursuit and Star Mirror Tracing).
Second, both HIV? and HIV? participants evidenced signifi-
cant improvements in performance across trial blocks of all
three tasks, suggesting successful procedural learning. Finally,
there was no evidence to substantiate a specific deficit in
procedural learning among HIV? compared with HIV? par-
Our findings are consistent with deficits in complex motor
functions and processing speed (typically indexed by slowed per-
formance) among HIV? participants, which have been well doc-
umented in the scientific literature (e.g., Hardy et al., 2002; Heaton
et al., 1995; Martin, Sorensen, Edelstein, & Robertson, 1992) and
are often referred to as a “hallmark” neurocognitive feature result-
ing from known abnormalities in white matter and subcortical
nuclei of HIV? participants. Of the tasks that our participants
were administered, the Rotary Pursuit task and Star Mirror Tracing
task both place time demands on participant performance and
depend on intact complex motor functions whereas the Weather
Prediction task does not. Although in theory our subjects’ perfor-
mance might be influenced in part by peripheral neuropathy, some
evidence argues against this explanation. Peripheral neuropathies
are reported in 10% to 15% of HIV? patients and are more
common in advanced disease stages, typically affect the lower
extremities first and often do not produce objective motor deficits
in the upper limbs (for reviews, see Verma, 2001; Wulff, Wang, &
Simpson, 2000). Given the low prevalence of immunological
AIDS diagnoses in our ambulatory community sample of HIV?
participants, we do no think that peripheral neuropathies (if
present) would be of sufficient severity to affect performance on
the measures we employed. However, future studies may benefit
from detailed evaluation of peripheral neuropathy, particularly
among subjects with more advanced disease. Furthermore, inclu-
sion of additional neuropsychological tests assessing specifically
simple motor skills and processing speed would help to understand
better the mechanisms for the complex motor deficits that we
observed in the HIV? sample.
It is important to note that multiple structures in addition to the
caudate and putamen contribute to performance of both motor and
nonmotor tasks of procedural learning, including prefrontal, oc-
cipital, parietal cortex, and cerebellum (e.g., Grafton et al., 1992;
Jenkins, Brooks, Nixon, Frackowiak, & Passingham, 1994;
Poldrack et al., 2001, 1999). Procedural learning tests of motor
skills may rely more heavily on different structures (e.g., putamen
and cerebellum) in these systems when compared with procedural
learning measures without motor demands (e.g., Weather Predic-
tion task). Furthermore, neural mechanisms that may prove com-
pensatory for Weather Prediction task may not necessarily gener-
alize to Star Mirror Tracing and Rotary Pursuit tasks. Recent
literature suggests that in some conditions individuals may recruit
medial temporal lobe structures and partially rely on declarative
memory to perform the Weather Prediction task (e.g., Foerde,
2006; Moody, 2004). Additional evidence indicates that individual
elements of the circuitry supporting procedural learning might
compensate for possible dysfunction in other structures in the
network. For example, Fera and colleagues (2005) compared per-
formance of young and older healthy adults on the Weather Pre-
GONZALEZ ET AL.
diction task and found no significant group differences in task
performance. However, older adults demonstrated much greater
activation of parietal cortex on fMRI.
HIV-associated neurocognitive deficits were detected in our
sample of individuals with history of substance dependence on two
of three procedural learning tasks, and our finding of significant
improvements across Trial Blocks on all tasks indicate that the
measures employed in this investigation were sensitive indicators
of procedural learning in our sample. However, despite evidence
of poorer performance on the Rotary Pursuit and Star Mirror
Tracing tasks, our findings did not demonstrate specific procedural
learning deficits among HIV? substance dependent individuals
compared with HIV? controls. Contrary to our hypothesis, both
HIV? and HIV? individuals demonstrated significant improve-
ments in performance across Trial Blocks and their rate of im-
provement across Trial Blocks did not differ significantly across
all three procedural learning tasks. However, the absence of a
nonsubstance using HIV? control group and a group of healthy
controls precludes coming to definitive conclusions on whether
performance among our HIV? subjects was “within normal lim-
its” or whether there are possible interactions between substance
use and HIV on procedural learning performance. Recruitment of
such groups is currently underway in our laboratory to address
these questions in future studies.
At first glance, our findings may appear to contradict those
presented in the seminal paper by Martin and colleagues (1993),
that is widely cited as providing evidence for procedural learning
deficits associated with HIV infection. However, findings from
these two studies are considerably less discrepant with careful
comparison of their investigation with ours. Martin et al. (1993)
found that a small subset of approximately 24% of the HIV?
group in their study and 7% of HIV? controls (ns ? 7 and 1,
respectively) could be characterized as “poor learners” on the basis
of minimal improvement in performance from the first to last
Rotary Pursuit trial. The level of the neurotoxin quinolinic acid in
CSF among five HIV? “poor learners” was significantly higher
than in 18 HIV? “good learners” and quinolinic acid levels were
correlated with improvements in Rotary Pursuit performance.
However, they also found that HIV? subjects, as a group, did not
show a deficit in rate of improvement across Trial Blocks on the
Rotary Pursuit and the majority of subjects performed in the
normal range. Thus, analyses of task performance in both the A.
Martin study subjects and our groups showed no significant HIV
serostatus by Trial Block interactions, which we deem necessary to
establish a specific procedural learning deficit from HIV. In fact,
despite significant differences in sample characteristics and our use
of individuals with history of substance dependence, the results of
both investigations are remarkably similar. Further, our conclu-
sions are bolstered by our larger study sample and use of three
separate procedural learning tasks. Therefore, although both in-
vestigations found evidence for complex motor problems among
HIV? participants as a whole, neither investigation substantiates
specific procedural learning deficits, per se, among HIV? persons.
To our knowledge, no study has demonstrated this latter type of
impairment among HIV? participants. One can speculate that the
paucity of published investigations on HIV-associated procedural
learning deficits may stem, in part, from a “file drawer” effect, as
other studies with negative outcomes may have gone unpublished
Several findings from more detailed studies of the neural sys-
tems underlying procedural learning help to clarify our results.
Most initial investigations suggesting that procedural learning is
dependent on integrity of striatum were conducted with clinical
populations with known basal ganglia disease (i.e., Parkinson’s
and Huntington’s disease). However, the pattern of neuropathol-
ogy associated with these diseases typically extends well beyond
striatum and are much more severe than in HIV. The caudate is
often noted as a critical structure for procedural learning, but
widespread circuitry beyond striatum is often shown to be active in
neuroimaging studies of procedural learning (e.g., Grafton et al.,
1992; Jenkins et al., 1994; Poldrack et al., 2001, 1999,). Thus,
some researchers have postulated that the caudate is an important,
but not essential, structure for procedural learning (e.g.,
Schmidtke, Manner, Kaufmann, & Schmolck, 2002). As we noted
earlier, several studies have suggested that individuals may rely on
brain systems outside striatum to perform some procedural learn-
ing tasks. It is possible that neuropathology in striatum must reach
a threshold level of severity or must extend substantially to addi-
tional brain regions for frank deficits in procedural learning to
emerge. Brain functioning in our HIV? sample was compromised
enough to manifest with deficits in complex motor skills, but it
may be that injury to neural systems that support procedural
learning was insufficient to produce detectable deficits.
We acknowledge that HIV has been shown to disrupt basal
ganglia preferentially, but HIV-associated neuropathology is dif-
fuse and affects additional brain systems, including white matter,
prefrontal cortex, and hippocampus (e.g., Jernigan et al., 1993;
Pomara, Crandall, Choi, Johnson, & Lim, 2001; Reyes, Mohar,
Mallory, Miller, & Masliah, 1994). Furthermore, correlations be-
tween basal ganglia neuropathology and neurocognitive perfor-
mance are not always detected, suggesting that there is not an
invariable relationship between striatal integrity and neuropsycho-
logical performance in the HIV literature (cf. Paul et al., 2002). For
example, Moore and colleagues (2006) found significant correla-
tions between a global index of neuropsychological performance
obtained shortly before death of HIV? participants and postmor-
tem measures of neurodegeneration in hippocampus and midfron-
tal cortex, but not putamen. Striatal pathology in HIV may not be
of sufficient severity, in most cases, to produce deficits in proce-
dural learning as have been reported with disorders that severely
damage basal ganglia and associated circuits (e.g., Parkinson’s and
With one exception, we found no consistent evidence to suggest
that markers of immune status related to performance in our
sample. Weather Prediction task performance was significantly
worse among HIV? participants with detectable viral load in
plasma, compared to those with undetectable viral load (p ? .03).
However, performance on the Weather Prediction task did not
differ significantly as a consequence of CD4 count or ARV status.
Furthermore, performance on the Star Mirror Tracing and Rotary
Pursuit tasks, which differed based on HIV serostatus, did not
differ significantly when HIV? groups were stratified by CD4
count, plasma viral load, or ARV status. Although the observed
differences in Weather Prediction task performance might have
resulted from Type-I error, one might speculate that HIV effects
may first manifest on tests involving complex motor skills (e.g.,
Star Mirror Tracing and Rotary Pursuit tasks) and then progress to
more “cognitive” tasks (e.g., Weather Prediction task). Therefore,
HIV AND PROCEDURAL LEARNING
participants with more advanced disease would be more likely to
demonstrate differences in performance on the Weather Prediction
task, in addition to the Rotary Pursuit and Star Mirror Tracing
tasks. However, only 18% of HIV? participants in the current
study met criteria for an immunological AIDS diagnosis, 44% had
undetectable HIV viral load in plasma, and 86% were on ARV
medications, with 50% on HAART. Future studies may benefit
from including HIV? participants with more advanced disease
and from examination of additional medical markers of HIV
disease severity (e.g., biomarkers of neuroinflammation, viral load
in cerebrospinal fluid, or neuroimaging data).
Our sample consisted predominantly of African American men
with a high school education, most of who were in their fourth
decade of life and were recruited from the Chicago greater met-
ropolitan area; thus, our results may not generalize to participants
of differing demographics. Nonetheless, our findings are very
similar to those of Martin et al. (1993), who tested a sample of men
recruited from the U.S. military that was generally younger, more
highly educated, and of higher estimated IQ than our sample.
Additional studies that include more diverse samples will be better
poised to systematically examine possible interactions with demo-
graphic variables, including possible gender effects.
In summary, the results from the current investigation showed
evidence of poorer performance on procedural learning tasks that
were consistent with general difficulties in complex motor skills
among HIV? individuals with substance dependence compared to
matched HIV? controls. However, there was no evidence for
specific procedural learning deficits among the HIV? group, as
both groups showed significant and comparable improvements in
performance across Trial Blocks on motor and nonmotor tasks of
procedural learning. Although our results suggest that both groups
achieved asymptote within the trials we administered, future in-
vestigations may examine if HIV? individuals may achieve levels
of performance comparable to controls on motor skills tasks if they
receive additional training. Overall, our findings contribute new
knowledge to an initially promising but understudied research area
within the literature on HIV and neurocognition. Furthermore, the
current study is unique in its use of multiple measures of proce-
dural learning (with and without motor demands), a fairly large
sample size, and its focus on examining the effects of HIV among
individuals with history of substance dependence. The ability to
implicitly acquire skills gradually and incrementally may impact
an individual’s ability to learn and implement new tasks at work,
efficiently complete routine tasks at home, and carry out skills
taught in clinical treatment programs. Understanding procedural
learning in HIV? substance dependent individuals will help to
more accurately characterize the impact of HIV and substance use
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Received December 11, 2007
Revision received April 18, 2008
Accepted May 21, 2008 ?
Correction to Myers et al. (2008)
In the article “Learning and Generalization Deficits in Patients With Memory Impairments Due to
Anterior Communicating Artery Aneurysm Rupture or Hypoxic Brain Injury,” by Catherine E.
Myers, Ramona O. Hopkins, John DeLuca, Nancy B. Moore, Leo J. Wolansky, Jennifer M. Sumner,
and Mark A. Gluck (Neuropsychology, 2008, Vol. 22, No. 5, pp. 681–686), author Ramona O.
Hopkins’s name was misspelled as Romona O. Hopkins.
GONZALEZ ET AL.