Cognitive Control and Comorbid Methamphetamine Abuse in Schizophrenia Patients
R
1
Salo ,
S
1
Ursu ,
1
TE Nordahl , Y Natsuaki
1,
M Leamon
1,
3
MH Buonocore & C.S.
1,2
Carter
Depts. of 1Psychiatry & 2Psychology, and Radiology 3 University of California, Davis,
Introduction
Methods
Worldwide methamphetamine abuse [MA]
surpasses that of opiates and cocaine
combined and is now impacting vulnerable
clinical populations such as patients with
schizophrenia (SZ).
MA is known to be neurotoxic to the same
I
N
T As deficits in top-down attentional control
R may promote drug seeking behavior in SZ
patients, the goal was to assess regions
O involved in cognitive control in SZ patients
D comorbid for MA abuse [SZ+MA].
U
To our knowledge, no functional imaging
C study has examined the neural correlates of
T cognitive control in SZ patients comorbid for
MA
abuse.
I
O Question 1: Will reduced cognitive control be
N observed on behavioral performance of SZ+ MA
dopaminergic rich frontostriatal brain regions
that are dysfunctional in schizophrenia
Participants: 5 SZ patients + MA abuse, 4 SZ w/out MA
abuse, 7 MA abusers and 5 Ctls.
Task: A computerized single-trial version of the Stroop
Word task (Stroop, 1935) that measures trial to trial adjustments . Subjects were instructed both for speed and accuracy and responded with a button press to colored words
that were either congruent or incongruent (see Task
panel). Stimuli were presented for 1500ms with a fixed ITI
of 2500 ms. In order to increase the level of response
conflict elicited by Incongruent stimuli, 70% of trials were
Congruent and 30% Incongruent.
Data analysis: 6 blocks of 36 trials each were acquired for
each participant.
M
E
T
H
O
D.
S
lower activity be observed in
ACC and prefrontal regions of SZ+MA abusers
compared to controls and non-using SZ patients
during the performance of the Stroop Conflict
task?
M
E
T
H
O
D
S
STROOP STIMULI
Congruent
Incongruent
GREEN
GREEN
Subject Characteristics
Group
Age
SZ
30.3
Edu
(5.9)
13.3
Yrs Use
N/A
SZ +MA
33.4 (8.6)
10.8
10.4 yrs
MA
34.8 (2.5)
12.0
12.3 yrs
CTL
32.0 (10.6)
15.1
N/A
1
R
E
S
U
L
T
S
740
700
680
660
640
620
600
PreCong
PreInc
Controls vs SZ & SZ + MA
900
PreCong
p=.07
850
n.s.
PreInc
800
750
700
650
Control
SZ
.08
.2
.04
0
Control
MA
SZ
SZ+MA
Baseline RT
900
0
Control
MA
SZ
SZ+MA
Stroop RT Effect
Incong-Cong-adj for RT diff
.2
850
.16
800
750
.12
700
650
.08
600
.04
550
500
Control
MA
SZ
SZ+MA
0
Control
Meth
SZ
SZ+MA
Results: Despite lack of group differences in Incong Error rates, group
differences emerged in RT adjustment following error trials. No sig group
differences were observed in the Stroop Effect.
EPI
Slices 36
3T Siemens Trio TR 2000 ms
3.438 x 3.438 x
TE 25 ms
3.4mm
90
FOV 220 mm
Analysis of fMRI Imaging Data
PreCong
PreInc
(BA 32,10)
R
E
S
U
L
T
S
1.75
1.5
1.25
1
.75
.5
.25
0
-.25
-.5
1
.8
.6
.4
.2
0
-.2
-.4
-.6
Control
MA
SZ
SZ+MA
SZ+MA
Controls exhibited reduced RTs to I-I sequences
(p=.07). In contrast, MA abusers, SZ or SZ+MA
failed to exhibit this pattern of cognitive regulation.
M
E
T
H
O
D
S
Statistical single-subject correlation maps were
calculated for activity in specific regions of
interest [ROIs] including ACC and DLPFC.
Covariates were used in the analysis (congruent,
incongruent and error trials, the latter as a
covariate of non-interest). To generate the
regressors used in the statistical model, each
variable of interest was convolved with a double
gamma hemodynamic response function (Friston et
al, 1995) These regressors were entered
simultaneously into a general linear model
implemented using AFNI software (Cox, 1996). This
procedure generated a semipartial correlation maps
for each subject, subsequently used to compute
differences between correlation coefficients of
conditions of interest (e.g. incongruent vs.
congruent, etc)
Control
MA
SZ
SZ+MA
Mean Difference of Beta Coefficients for Incong-Cong trials
(Averaged for each DLPFC ROI)
Left DLPFC
Right DLPFC
(BA 9,46)
R
(BA 9,46)
R
L
.6
1.8
.4
1.6
L
1.4
.2
1.2
0
1
-.2
.8
.6
-.4
780
760
740
720
700
680
660
640
620
600
720
.4
Rostral ACC
(BA 32,24)
.12
Type
Scanner
Voxel
size
Flip angle
MA Abusers
Mean Difference of Beta Coefficients for Incong-Cong trials
(Averaged for each ACC ROI)
Caudal ACC
Imaging Parameters
Rt to Incong Trials following Incong Trials [PreInc] vs Incong Trials
following Congruent Trials [PreCong]
Controls
(adjusted for RT differences)
.16
.6
Trial to Trial Reaction Time Adjustments
***ROIs were based on previous spectroscopy findings of abnormalities in MA and SZ subjects
.2
.8
R
E
S
U
L
T
S
Imaging Results
Post Error Slowing
Incongruent Error Rates
Behavioral Results (1)
abusers compared to controls and non-using SZ
patients?
Question 2: Will
Behavioral Results (2)
.4
-.6
.2
-.8
0
Control
Meth
SZ
SZ+MA
Control
Meth
SZ
SZ+MA
D  Abnormal behavioral patterns of cognitive
regulation were observed in SZ patients with
I preliminary evidence of compounded deficits in
SZ+MA subjects.
S
Rostral and Caudal regions of the ACC were more
C active in response to conflict trials in controls
compared to MA abusers and all SZ participants .
U
SZ patients comorbid for MA abuse showed
S abnormal patterns of activation in Left DLPFC
compared to other groups.
S
Preliminary data suggest that the ability of the
I DLPFC to regulate behavioral control may be
further compromised in SZ patients comorbid for
O MA abuse.
Funded by NIDA
N