The effects of methylphenidate on cognitive control in active methamphetamine dependence using functional magnetic resonance imaging

Abstract

Methamphetamine (MA) dependence is associated with cognitive deficits. Methylphenidate (MPH) has been shown to improve inhibitory control in healthy and cocaine-dependent subjects. This study aimed to understand the neurophysiological effects before and after acute MPH administration in active MA-dependent and control subjects. Fifteen MA-dependent and 18 control subjects aged 18-46 years were scanned using functional magnetic resonance imaging before and after either a single oral dose of MPH (18 mg) or placebo while performing a color-word Stroop task. Baseline accuracy was lower (p = 0.026) and response time (RT) was longer (p < 0.0001) for the incongruent compared to congruent condition, demonstrating the task probed cognitive control. Increased activation of the dorsolateral prefrontal cortex (DLPFC) and parietal cortex during the incongruent and Stroop effect conditions, respectively was observed in MA-dependent compared to control subjects (p < 0.05), suggesting the need to recruit neural resources within these regions for conflict resolution. Post- compared to pre-MPH treatment, increased RT and DLPFC activation for the Stroop effect were observed in MA-dependent subjects (p < 0.05). In comparison to MPH-treated controls and placebo-treated MA-dependent subjects, MPH-treated MA-dependent subjects showed decreased activation of parietal and occipital regions during the incongruent and Stroop effect conditions (p < 0.05). These findings suggest that in MA-dependent subjects, MPH facilitated increased recruitment of the DLPFC for Stroop conflict resolution, and a decreased need for recruitment of neural resources in parietal and occipital regions compared to the other groups, while maintaining a comparable level of task performance to that achieved pre-drug administration. Due to the small sample size, the results from this study are preliminary; however, they inform us about the effects of MPH on the neural correlates of cognitive control in active MA-dependent subjects.

Keywords: BOLD; Stroop; cognitive control; drug dependence; fMRI; methamphetamine; methylphenidate.

Figure 1

Whole-brain two-sample t-test results for the incongruent condition showing pre-drug MA-dependent > control group differences in activation of: (A) the right superior frontal gyrus [peak voxel MNI co-ordinates (mm): (28, 4, 60); T₃₁ = 5.73, p < 0.05 cluster-corrected], and (B) the right middle frontal gyrus [peak voxel MNI co-ordinates (mm): (30, 10, 46); T₃₁ = 3.84, p < 0.05 cluster-corrected]. The scale represents the color (from red to yellow) of the cluster corresponding to the increasing t-statistic. The structural image represents the IXI550 average normal brain which has been registered to the MNI152 space with corresponding inferior–superior co-ordinates.

Figure 2

Whole-brain two-sample t-test results for the Stroop effect condition showing pre-drug MA-dependent > control group differences in activation of: (A) the left inferior parietal lobule [peak voxel MNI co-ordinates (mm): (−46, −54, 58); T₃₁ = 3.81, p < 0.05 cluster-corrected], (B) the right inferior parietal lobule [peak voxel MNI co-ordinates (mm): (48, −48, 52); T₃₁ = 4.62, p < 0.05 cluster-corrected], and (C) Plot of the mean ± standard error parameter estimates representing the percentage blood-oxygen-level-dependent signal change within the right inferior parietal lobule. The scale represents the color (from red to yellow) of the cluster corresponding to the increasing t-statistic. The structural image represents the IXI550 average normal brain which has been registered to the MNI152 space with corresponding inferior–superior co-ordinates.

Figure 3

Whole-brain 2 × 2 between-subject ANOVA results for the incongruent condition showing post- minus pre-drug “MA placebo” > “MA MPH” group differences in activation of: (A) the right superior occipital gyrus [peak voxel MNI co-ordinates (mm): (17, −92, 34); T₂₉ = 3.53, p < 0.05 cluster-corrected], (B) the left superior parietal gyrus [peak voxel MNI co-ordinates (mm): (−8, −82, 52); T₂₉ = 4.49, p < 0.05 cluster-corrected], and (C) Plot of the mean ± standard error parameter estimates representing the percentage blood-oxygen- level-dependent signal change post- compared to pre-drug administration within the left superior parietal gyrus. The scale represents the color (from red to yellow) of the cluster corresponding to the increasing t-statistic. The structural image represents the IXI550 average normal brain which has been registered to the MNI152 space with corresponding inferior–superior co-ordinates.

Figure 4

(A) Whole-brain 2 × 2 between-subject ANOVA results for the incongruent condition showing post- minus pre-drug “Control MPH” > “MA MPH” group differences in activation of the right inferior parietal lobule [peak voxel MNI co-ordinates (mm): (56, −36, 54); T₂₉ = 3.34, p < 0.05 cluster-corrected], and (B) Plot of the mean ± standard error parameter estimates representing the percentage blood-oxygen-level-dependent signal change post- compared to pre-drug administration within the right inferior parietal lobule. The scale represents the color (from red to yellow) of the cluster corresponding to the increasing t-statistic. The structural image represents the IXI550 average normal brain which has been registered to the MNI152 space with corresponding inferior–superior co-ordinates.

Figure 5

Whole-brain 2 × 2 between-subject ANOVA results for the Stroop effect condition showing post- minus pre-drug “control MPH” > “MA MPH” group differences in activation of: (A) the left middle occipital gyrus [peak voxel MNI co-ordinates (mm): (−32, −82, 30); T₂₉ = 4.18, p < 0.05 cluster-corrected], and (B) the right middle occipital gyrus [peak voxel MNI co-ordinates (mm): (45, −80, 24); T₂₉ = 3.79, p < 0.05 cluster-corrected]. The scale represents the color (from red to yellow) of the cluster corresponding to the increasing t-statistic. The structural image represents the IXI550 average normal brain which has been registered to the MNI152 space with corresponding inferior–superior co-ordinates.