1. RESULTS RESULTSRESULTS RESULTSRESULTS Cognitive Control and Comorbid Methamphetamine Abuse in Schizophrenia Patients R Salo 1, S Ursu 1, TE Nordahl 1, Y Natsuaki 1, M Leamon 1, MH Buonocore 3 & C.S. Carter 1,2 Depts. of 1 Psychiatry & 2 Psychology, and Radiology 3 University of California, Davis,  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 dopaminergic rich frontostriatal brain regions that are dysfunctional in schizophrenia  As deficits in top-down attentional control may promote drug seeking behavior in SZ patients, the goal was to assess regions involved in cognitive control in SZ patients comorbid for MA abuse [SZ+MA].  To our knowledge, no functional imaging study has examined the neural correlates of cognitive control in SZ patients comorbid for MA abuse.  Question 1: Will reduced cognitive control be observed on behavioral performance of SZ+ MA abusers compared to controls and non-using SZ patients?  Question 2: Will 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?I IINTNTRODUCTRODUCTIIONONIINTNTRODUCTRODUCTIIONONI Congruent GREEN Congruent GREEN IncongruentGREEN IncongruentGREENMETHODS  Abnormal behavioral patterns of cognitive regulation were observed in SZ patients with preliminary evidence of compounded deficits in SZ+MA subjects.  Rostral and Caudal regions of the ACC were more active in response to conflict trials in controls compared to MA abusers and all SZ participants.  SZ patients comorbid for MA abuse showed abnormal patterns of activation in Left DLPFC compared to other groups.  Preliminary data suggest that the ability of the DLPFC to regulate behavioral control may be further compromised in SZ patients comorbid for MA abuse.DISCUSSION 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 adjust- ments. Subjects were instructed both for speed and accur- acy 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.. Subject CharacteristicsMETHODS TypeEPISlices36 Scanner3T Siemens TrioTR2000 ms Voxel size 3.438 x 3.438 x 3.4mm TE25 ms Flip angle90FOV220 mm METHODSMETHODSMETHODSMETHODS Imaging ParametersRESULTS Imaging Results GroupAgeEduYrs Use SZ 30.3 (5.9)13.3 N/A SZ +MA 33.4 (8.6) 10.8 10.4 yrs MA 34.8 (2.5)12.012.3 yrs CTL 32.0 (10.6)15.1 N/A Analysis of fMRI Imaging Data 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) 650 700 750 800 850 900 Control SZ SZ+MA PreInc PreCong ***ROIs were based on previous spectroscopy findings of abnormalities in MA and SZ subjects Rostral ACC (BA 32,10) 600 620 640 660 680 700 720 740 PreCongPreInc 600 620 640 660 680 700 720 740 760 780 PreCongPreInc Trial to Trial Reaction Time Adjustments Rt to Incong Trials following Incong Trials [PreInc] vs Incong Trials following Congruent Trials [PreCong] ControlsMA Abusers Controls vs SZ & SZ + MA Caudal ACC (BA 32,24) Post Error Slowing (adjusted for RT differences) Stroop RT Effect Incong-Cong-adj for RT diff p=.07 n.s. -.6 -.4 -.2 0.2.4.6.8 1 ControlMASZSZ+MA -.5 -.25 0.25.5.75 1 1.25 1.5 1.75 ControlMASZSZ+MA Left DLPFC (BA 9,46) -.8 -.6 -.4 -.2 0.2.4.6 ControlMethSZSZ+MA STROOP STIMULI 0.2.4.6.8 1 1.2 1.4 1.6 1.8 ControlMethSZSZ+MA Right DLPFC (BA 9,46) Funded by NIDA 0.04.08.12.16.2 ControlMASZSZ+MA 0.2.4.6.8 1 ControlMASZSZ+MA Incongruent Error Rates RL RL Mean Difference of Beta Coefficients for Incong-Cong trials (Averaged for each ACC ROI) Mean Difference of Beta Coefficients for Incong-Cong trials (Averaged for each DLPFC ROI) 0.04.08.12.16.2 ControlMethSZSZ+MA Behavioral Results (2) 500 550 600 650 700 750 800 850 900 ControlMASZSZ+MA IntroductionMethods Baseline RT 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. 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. Behavioral Results (1)