Table 3. MRI Studies.
| Investigators | Domain tested | Participants | Period of abstinence | Cognitive and brain findings | Caveats |
|---|---|---|---|---|---|
| MRI | |||||
| Chang et al (2005) | Attention/psychomotor function (TMT-A, Grooved pegboard, Timed gait task, Stroop, CalCAP); Visuospatial perception (DSST); Learning/memory (AVLT, Rey–Osterrieth complex figure test); Working memory (CalCAP); Response inhibition (Stroop, CalCAP); Set-shifting/executive function (TMT-B, New adult reading test) | MA users met the DSM-IV criteria for MA dependence Cognitive testing: MA users: N=44 Controls: N=28 Imaging: MA users: N=50 Controls: N=50 | Mean 4.0±6.2 months (required 1-week minimum) | Cognitive: ↔ No differences on cognitive tests observed after co-varying for education Brain: ↔ Whole brain volumes ↑ Globus pallidus volumes ↑ Putamen volumes | Controls had higher levels of education The influence of drug use other than MA not controlled |
| Kim et al (2006) | Attention/psychomotor function (TMT-A); Response inhibition (Stroop); Set-shifting/executive function (TMT-B, WCST) | MA users met the DSM-IV criteria for MA dependence Short term (<6 months): MA users: N=11 Long term (>6 months): MA users: N=18 Controls: N=20 | Long-term: mean 30.6±39.2 months Short-term: mean 2.6±1.6 months | Cognitive: ↓ Set-shifting/executive function (WCST): short-term>long-term>controls ↔ Attention/psychomotor function ↔ Response inhibition ↔ Set-shifting/executive function Brain: ↓ GM density in R. middle frontal gyrus (short-term abstinent<long-term<controls) ↔ WM density | Controls had higher levels of education Cognitive data not compared against normative data set. Thus, the clinical importance of findings could not be determined The influence of drug use other than MA not controlled Small number of participants studied |
| Thompson et al (2004) | Immediate and delayed memory (word-recall and recognition; picture-recall and recognition); Attention/psychomotor function (TMT-A); Visuospatial perception (DSST) | MA users met the DSM-IV criteria for MA dependence: N=22 Controls: N=21 | Participants reported having used MA a majority of the past 30 days | Cognitive: Comparisons between the two groups not reported, but a significant correlation between hippocampal volume and performance on the word-recall task was noted for all participants Brain: ↓ GM in the cingulate cortex ↓ GM in the limbic cortex ↓ GM in the paralimbic cortex ↓ Hippocampal volumes ↑ WM hypertrophy ↔ Total cerebral volume ↔ Total GM | Controls had higher levels of education Clinical importance and relationship between cognitive functioning and brain activity could not be determined because limited cognitive data not reported and cognitive data not compared against normative data set The influence of drug use other than MA not controlled Small number of participants studied |
| pMRI | |||||
| Chang et al (2002) | Attention/psychomotor function (TMT-A, Grooved pegboard, Timed gait task, Stroop, CalCAP); Visuospatial perception (DSST); Learning/memory (AVLT); Working memory (CalCAP); Response inhibition (Stroop, CalCAP); Set-shifting/executive function (TMT-B, New adult reading test) | MA users met the DSM-IV criteria for MA dependence: N=20 Controls: N=20 | Mean 8.0±2.2 months | Cognitive: ↔ Regarding the standard cognitive that was compared against a normative data set, no differences on task accuracy noted for any tests CalCAP Performance: ↓Reaction time on several tasks ↓ Accuracy on 1-increment and 2-back working memory tasks Brain:↓ rCBF in bilateral putamen ↓ rCBF in bilateral insula ↓ rCBF in right lateral parietal ↑ rCBF in left temporoparietal WM↑ rCBF in left occipital ↑ rCBF in right posterior parietal | Clinical importance and relationship between cognitive functioning and brain activity could not be determined because CalCAP data was not compared against normative data set The influence of drug use other than MA not controlled Small number of participants studied |
| DTI | |||||
| Chung et al (2007) | Set-shifting/executive function (WCST) | MA users met the DSM-IV criteria for MA dependence: N=32 Controls: N=30 | Males: mean 24.3±37.5 months Females: mean 43.1±65.9 months | Cognitive: ↓ Set-shifting/executive function (WCST) Brain: ↓ FA values in bilateral frontal WM at AC–PC plane ↓ FA values in right frontal WM at 5 mm above AC–PC plane | Controls had higher levels of education Only one cognitive measure included and it was not compared against normative data set, which makes it difficult to determine the clinical importance of findings The influence of drug use other than MA not controlled |
| Salo et al (2009a) | Attention/response inhibition (Stroop) | MA users met the DSM-IV criteria for MA dependence: N=37 Controls: N=17 | Mean 20.98±31.9 months (required 3-week minimum) | Cognitive: ↓ Response inhibition Brain: ↔ FA, ADC, or diffusion along direction of axonal fiber in genu or splenium of CC | Controls had higher levels of education and IQ (NART) Only one cognitive measure included and it was not compared against normative data set, which makes it difficult to determine the clinical importance of findings The influence of drug use other than MA not controlled |
| fMRI | |||||
| Hoffman et al (2008) | Impulsivity (Delayed discounting task) | MA users met the DSM-IV criteria for MA dependence: N=19 Controls: N=17 | Mean 48±17 days | Cognitive:↓ MA users preferred smaller immediate reward, ie, discounted more steeply Brain: ↓ Bilateral precuneus ↓ Right caudate nucleus ↓ ACC ↓ DLPFC | Only one cognitive measure included and there are no normative data set for which the data can be compared, which makes it difficult to determine the clinical importance of findings The influence of drug use other than MA not controlled MA-dependent participants tested on an in-patient basis, while controls tested on an outpatient basis Small number of participants studied |
| Leland et al (2008) | Response inhibition (Go/No-go task) | MA users met the DSM-IV criteria for MA dependence: N=19 Controls: N=19 | Mean 33.9±5.9 days | Cognitive: ↔ Response inhibition Brain: ↑ Cue-related activation in two ACC ROIs | Only one cognitive measure included The influence of drug use other than MA not controlled Small number of participants studied |
| Monterosso et al (2007) | Impulsivity (Delayed discounting task) | MA users met the DSM-IV criteria for MA dependence: N=12 Controls: N=17 | Range 5–7 days | Cognitive: ↓ MA users preferred smaller immediate reward, ie, discounted more steeply Brain: ↓ Differences in activation between hard and easy choices in left DLPFC and intraparietal sulcus | Participant educational information not reported Only one cognitive measure included and there are no normative data set for which the data can be compared, which makes it difficult to determine the clinical importance of findings No correlation between delayed discounting and brain data observed The influence of drug use other than MA not controlled Small number of participants studied |
| Paulus et al (2002) | Decision-making (Two-choice prediction task) | MA users met the DSM-IV criteria for stimulant dependence: N=10 Controls: N=10 | Mean 22.4±3.5 days | Cognitive: MA users more influenced by immediately preceding outcome Brain: ↓ Activation in DLPFC during 2-choice prediction task compared to 2-choice response task ↓ No activation in ventromedial cortex in 2-choice prediction task compared to 2-choice response task | Only one cognitive measure included and there are no normative data set for which the data can be compared, which makes it difficult to determine the clinical importance of findings The influence of drug use other than MA not controlled Small number of participants studied |
| Paulus et al (2003) | Same as above | MA users met the DSM-IV criteria for stimulant dependence: N=14 Controls: N=14 | Mean 25.0±2.7 days | Cognitive: ↔ Decision-making (but greater win-stay/lose-shift consistent responses) Brain: ↓ Task-related activation in ACC, DLPFC, orbitofrontal, and parietal cortex | Controls had higher levels of education Only one cognitive measure included and there are no normative data set for which the data can be compared, which makes it difficult to determine the clinical importance of findings The influence of drug use other than MA not controlled Small number of participants studied |
| Payer et al (2008) | Affective processing (Visual matching task) | MA users met the DSM-IV criteria for MA dependence: N=12 Controls: N=12 | Mean 8.6±3.5 days | Cognitive: ↔ No difference on performance Brain: ↓ Activation in VLPFC, right fusiform gyrus, left cuneus, temporoparietal junction, anterior and posterior temporal cortex ↑ Activation in dorsal ACC ↔ Amygdalar activation | Controls had higher levels of education Only one cognitive measure included The influence of drug use other than MA not controlled Small number of participants studied |
| Salo et al (2009b) | Attention/response inhibition (Stroop) | MA users met the DSM-IV criteria for MA dependence: N=12 Controls: N=16 | Mean 4.1±2.8 months (required 3-week minimum) | Cognitive: ↔No differences on task accuracy, but MA users did not improve on response time over multiple trials Brain: ↓ Activation in the right prefrontal cortex on conditions measuring ability to use exposure to conflict to regulate behavior ↔ Within-trial conflict monitoring in ACC | Controls had higher levels of education and IQ (NART) Only one cognitive measure included and it was not compared against normative data set, which makes it difficult to determine the clinical importance of findings The influence of drug use other than MA not controlled Small number of participants studied |
Abbreviations: ACC=anterior cingulate cortex; AC–PC, anterior commissure–posterior commissure; ADC, apparent diffusion coefficient; AVLT, Rey auditory verbal learning test; CalCAP, California computerized assessment package; CC, corpus callosum; DLPFC, dorsolateral prefrontal cortex; DSM-IV, Diagnostic and Statistical Manual of Mental Disorders 4th Edition; DSST, digit-symbol substitution task; DTI, Diffusion Tensor Imaging; FA, fractional anisotropy; GM, gray matter; MA, methamphetamine; MRI, magnetic resonance imaging; NART, new adult reading test—revised; pMRI, perfusion magnetic resonance imaging; rCBF, regional cerebral blood flow; ROI, region of interest; TMT-A, Trail making test, part A; TMT-B, Trail making test, part B; VLPFC, ventrolateral prefrontal cortex; WCST, Wisconsin card sorting test; WM, white matter; WMS-III, Wechsler memory scale-III.
Cognitive performance: ↓, MA users performed more poorly than controls; ↔, MA users and controls performed equally.
Brain activity: ↓, decreased activity in MA users; ↑, increased activity in MA users; ↔, no difference in activity between MA users and controls.