shows that performance accuracy during the fMRI tasks was high (> 80%), and similar for cocaine and control subjects. For both groups, accuracy was significantly lower for the more demanding 2-back task as compared to the 0- and 1-back tasks (p < 0.0001; paired t-test). Accuracy on the 2-back task was lower for cocaine than for control subjects (p = 0.02; two-sample t-test) and for subjects that had positive-cocaine urine screening than for those that had negative-cocaine urine screening (p < 0.007; two-sample t-test). Reaction times (RT) were longer for cocaine than for control subjects across all conditions; and for 2-back than for 1-back, and for 1-back than for 0-back across all subjects (p < 0.006). Reaction times were not different for subjects who had positive or negative urine screening. The increased RT and the decreased performance accuracy for increased WM-load (0-, 1-, and 2-back) reflect the increased difficulty of the tasks.
Fig 1 Average performance accuracy and reaction times during fMRI of verbal working memory (WM, n-back) for control subjects (n=16; green bars) and cocaine abusers with negative (n=8; blue bars) and positive (n=8; read bars) urine toxicology screening for cocaine. (more ...)
For both groups, the 0-, 1-, and 2-back tasks activated a bilateral network ( and , “Main activation”) that included the PFC [inferior (IFG), middle (MFG), and medial (medFG) frontal gyri], and the superior parietal (SPC) and occipital [fusiform gyrus (FusG)] cortices, as well as the thalamus and the cerebellum (CER), in agreement with our previous studies (Tomasi D and E Caparelli, 2007
; Tomasi D et al., 2007
; Tomasi D et al., 2006
); the tasks deactivated the posterior cingulate gyrus (PCG) and the posterior insula (INS). Differences between the groups were observed ( and ) in 1) the precuneus (Brodmann areas, 7 and 39; PreCUN7 and PreCUN39), left cerebellum, thalamus (Tha) and mesencephalon (Mes), and the putamen (put), which were activated more in controls than in cocaine abusers; 2) the prefrontal [MFG6, MFG9, and the superior frontal gyrus (SFG8)], parietal [SPC7, inferior parietal cortex (IPC40), and the postcentral gyrus (PostCG3 and PostCG5)] and occipital [FusG19, and the lingual gyrus (LG17)] cortices, which activated more in cocaine abusers than in controls; and 3) in the ACG24, INS13, parahippocampal gyrus (PHG) and the amygdala (Amy), which deactivated more in cocaine abusers than in controls.
Table 1 Coordinates of major activation clusters in the Talairach frame of reference and average t-scores in 0.73 cc isotropic ROI centered at these coordinates. Statistical significance (corrected for multiple comparisons): Pcorr < 0.001 (bold); Pcorr (more ...)
Fig 2 Statistical maps of BOLD signals during verbal working memory (WM, conjunction analysis: 0-back + 1-back + 2-back) for cocaine abusers (n=16; positive and negative urines, combined; upper row), control subjects (n=16; second row), as well as for the differential (more ...)
Working memory activation
Brain activation during the 1- and 2-back tasks was contrasted (intra-subject) to that during the 0-back task to remove the common sensory-motor effects associated to subjects' responses (button press events). This WM effect was evaluated for each group, conjunctively for the 1- and 2-back tasks [(1-back vs. 0-back) & (2-back vs. 0-back); , “WM”]. For both groups the WM effect on brain activation was significant in the MFG9, medFG8, SPC7, and the cerebellum; the WM effect on brain deactivation was significant in the cingulate cortex, and the INS. WM-activation was larger for cocaine abusers than for controls bilaterally in the MFG9, medFG8, and in the left SPC7, LG17, and FusG19. WM-deactivation was larger for cocaine abusers than for controls in the PHG/Amy and the left PreCUN39 and right PreCUN7.
Increased WM-load from 1-back to 2-back produced larger positive fMRI signals in the PFC (MFG, and medFG) and SPC ( and ). For cocaine abusers, increased WM-load also produced larger activation in the left cerebellum and larger deactivation in the PHG/Amy (). For controls, increased WM-load also produced larger activation in the PreCUN7&39, and larger deactivation of the PCG30. Group comparisons revealed that cocaine abusers had lower WM-load activation in the MFG9 and PreCUN7 and higher WM-load activation in the cerebellum than controls (pcorr < 0.03; using a small volume correction with radius = 10 mm; two-way repeated measures ANOVA in SPM2); these regions showed group activation differences (main WM and WM-load effects).
shows the average amplitude of BOLD responses in the brain. Compared to controls (green bars) and independently for the 1- and 2-back tasks (compared to baseline), the positive BOLD responses in cocaine abusers (positive and negative urines combined) were lower in the Tha/Mes, PreCUN7, and CER (p<0.04; two-sample t-test), and larger in the prefrontal, (MFG6&9, and SFG8), parietal (IPC40, SPC7, PostCG3&5), and occipital (LG17 and FusG19) cortices (p<0.01); for cocaine abusers the negative BOLD responses (i.e. deactivation) in the ACG24, INS13, PHG/Amy, and PreCUN39 were larger than for controls (p<0.05). These abnormalities were larger in cocaine abusers with positive urine toxicology screening (red bars; ). Only the PostCG5 (1-back), PostCG3, IPC40 and PHG/Amy (2-back) demonstrated statistically significant differences between cocaine abusers with negative urine results and controls. The cocaine abusers with positive urines had larger activation in the PFC (MFG9 and MFG6), parietal cortex (PostCG5, IPC40, SPC7, and PreCUN39), and larger deactivation in the PHG/Amy than cocaine abusers with negative urines.
Fig 3 Average BOLD signals at specific ROIs () for the 1-back (top) and 2-back (bottom) conditions, and for controls (n=16; green bars) and cocaine subjects with negative (n=8; blue bars) and positive (n=8; red bars) urines for cocaine. ROI volume = (more ...)
For cocaine abusers compared to control subjects, the ROI analyses demonstrated that the differential effect of WM-load on BOLD responses (2-back – 1-back; Supplementary ) was lower in the PFC (MFG6&9, p< 0.01), parietal cortex (SPC7 and PreCUN7&39, p<0.03), and the putamen (p=0.02); only the cerebellum exhibited higher WM-load responses in cocaine abusers than in control subjects (p = 0.02). Cocaine subjects with positive urines had lower WM-load responses in the MFG9, PostCG3, and the putamen than those with negative urines (p<0.03). Cocaine subjects with negative urines had lower WM-load responses in the MFG6 and the PostCG5 than control subjects (p<0.008).
Behavior vs. brain activation
For cocaine abusers (positive and negative urine results combined), 1) higher performance accuracy during the 2-back task was associated with increased activation of the cerebellum () and lower activation of the PostCG5 (pcorr < 0.05), and 2) longer RT during the 2-back task was associated with increased activation of the PostCG5 (pcorr < 0.001, ).
Fig 4 Linear correlations between behavioral measures (performance accuracy and RT) during the 2-back condition, and average BOLD responses at specific ROIs in the cerebellum and the PostCG5 () for cocaine subjects with negative (open circles) and positive (more ...)