Procedural Learning among HIV+ and HIV- individuals with Substance Dependence

R. Gonzalez, J. Jacobus, J.W. Rodriguez,

E.H. Fakhoury, E.M. Martin

Brief Background

• HIV is associated with striatal damage

• Substance use affects striatal systems

• Striatum is critical for procedural learning

• Procedural learning in HIV & substance use – A. Martin et al., (1993)– Kalechstein et al., (1998)– Van Gorp et al., (1999)– Waldrop et al., (2001)

PL Measures

Pursuit Rotor (PR)

• Trace star seeing only mirror image– Go quickly, stay inside lines

– 4 trial blocks, 2 trials each

– DV = time to complete

• Follow light around circle– 55 rpm

– 4 trial blocks, 2 20s trials each

– DV = seconds on target

Mirror Tracing (MT)

Weather Prediction (WP)

• Try to guess “sun” or “rain” based on cards – Participants are not told probability structure

– 4 trial blocks, 50 cards each

Performance on PL Tasks

Performance Indices

| General Deficit(Main Effect)

| PL Deficit(Group X Time)

| # Errors

Time (Trial Blocks)

Per

form

ance

Control Group

Clinical Group

Lea

rnin

g

Hypotheses

• HIV+ participants:– poorer performance, overall, on measures of PL

• General Deficit

– less improvement in performance over time on PL tasks• PL Deficit

• More severe substance use:– poorer performance overall and with poorer PL

• Interaction between HIV and substance use

Participants

• 79 adults with history of cocaine and/or heroin dependence– HIV- : n = 33– HIV+: n = 46

• Negative u-tox & alcohol breath test

• No cocaine or heroin use in last 7 days

• No current abuse or dependence for EtOH and other drugs

• No history of severe thought disorder or unmedicated bipolar disorder

• No history of significant loss of consciousness or neurological problems

Demographics HIV – (n = 33) HIV + (n = 46)

Age 45.8 (7.9) 44.2 (6.6) yrs of education 12.3 (1.8) 11.9 (1.7) AmNART 102.6 (9.3) 100.6 (7.6) % men 87.9% 71.7% Ethnicity/Race Caucasian 9% 2% Hispanic 3% 5% African American 88% 91% Other 0 2%

Psychiatric & Medical HIV – (n = 33) HIV + (n = 46) BDI-2 12 (10.6) 14 (12.6) STAI 38.8 (13.3) 37.7 (13.5) WURS 32.8 (19.1) 30.6 (16.6) % on psych meds 21% 36% HCV+ 30% 43% On methadone 36% 4% CD4 | 396 (206) %AIDS (CD4) | 16% plasma viral load (Md, IQR) | 399 [75, 4970] % detectable viral load | 58% on HAART | 48%

Substance Use Parameters

HIV – (n = 33) HIV + (n = 46) yrs drug use 22.5 (9.1) 22.0 (8.7) dys since last use 120 [64, 263] 182 [86, 373] History of SCID-SAM Dx Alcohol 88% 91% Cocaine 91% 96% Heroin 79% 46% Cannabis 94% 72% Stimulants 7% 24% Hallucinogens 10% 24% Sedatives 17% 29% Injection drug use 42% 46% KMSK (peak) Cocaine + Heroin M, SD 19.5 (6.2) 18 (5.6) Md, Range 19 [6, 29] 16 [9, 28] dys since peak use (Md, IQR) 1095 [240, 2980] 1095 [365, 2351]

Summary of Results

Pursuit Rotor Mirror Tracing Weather Prediction Main Effects HIV .16 < .01 .12 KMSK ns ns ns Time < .01 < .01 ns Interactions HIV x KMSK ns ns ns HIV x Time ns ns ns KMSK x Time ns .08 ns HIV x KMSK x Time .03 .01 .10

5

7

9

11

13

15

Block 1 Block 2 Block 3 Block 4

Pursuit Rotor

se

co

nd

s

HIV- HIV+

10

12

14

16

18

20

22

24

Block 1 Block 2 Block 3 Block 4

Mirror Tracing

se

co

nd

s

HIV- HIV+

Mirror Tracing HIV Main Effect: Hedges ES = 0.65, 95%CI [0.20, 1.11]Significant 3-way interactions

25

27

29

31

33

Block 1 Block 2 Block 3 Block 4

Weather Prediction

# c

orr

ec

t

HIV- HIV+

PR Interaction Effect

-4

-2

0

2

4

6

8

10

12

PR

4/4-

PR

1/1

5 10 15 20 25 30KMSKpeak-tobalcmj

-4

-2

0

2

4

6

8

10

12

PR

4/4-

PR

1/1

5 10 15 20 25 30KMSKpeak-tobalcmjKMSK KMSK

PR

ch

an

ge

PR

ch

an

ge

HIV – HIV +

n = 33 n = 46R2 = .16, p = .02 R2 = .03, p = .24

↑ improvement in PR was associated with history of ↑ severe drug use[only for HIV- subjects]

0

5

10

15

20

ST

Mt1

/4-4

/4

5 10 15 20 25 30KMSKpeak-tobalcmj

MT Interaction Effect

0

5

10

15

20

ST

Mt1

/4-4

/4

5 10 15 20 25 30KMSKpeak-tobalcmj

HIV – HIV +

n = 33 n = 46R2 = .12, p = .05 R2 = .03, p = .26

KMSK

MT

ch

an

ge

MT

ch

an

ge

↑ improvement in MT was associated with history of ↑ severe drug use [only for HIV- subjects]

KMSK

Summary• HIV+ subjects generally performed worse,

overall, on PL tasks– Significant differences on Mirror Tracing– Evidence suggests general deficit

• History of substance use severity and HIV serostatus interacted to affect procedural learning

Possible Explanations• Supersensitivity of striatal dopamine receptors

– Process disrupted by HIV

• HIV+ participants fairly “healthy”

• Control group consisted of individuals with substance dependence

• Amount of striatal damage not sufficient for functional deficits

• HIV deficits are “spotty” affecting multiple systems

Acknowledgements• NIDA

– F32 DA018522 (RG)– R01 DA12828 (EMM)

• University of Illinois Chicago, Dept. of Psychiatry

• HIV & Addictions Neuroscience– Eileen Martin, PhD– Jasmin Vassileva, PhD– Pyrai Vaughn– Elizabeth Walczak– Leslie Ladd– Sarah Wicks