Table 2. PET Studies.
| Investigators | Domain tested | Participants | Period of abstinence | Cognitive and brain findings | Caveats |
|---|---|---|---|---|---|
| Dopamine-related (DAT, D2/D3 receptor, VMAT-2) ligands | |||||
| Boileau et al (2008) | Attention/psychomotor function (TMT-A, Grooved pegboard); Immediate and delayed memory (CVLT); Working memory (Letter-Number Sequencing and Visual Memory Span—backwards subtests of WMS-III); Set-shifting/executive function (TMT-B) Note that the complete test battery was not reported | MA users met the DSM-IV criteria for a MA-use disorder: N=16 Controls: N=14 | Mean: 19±24 days | Cognitive: ↓ Attention/psychomotor functioning ↓ Delayed memory ↔ Working memory ↔Set-shifting/executive function Brain: ↑ VMAT-2 BP in caudate, putamen, and ventral striatum | 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 |
| Johanson et al (2006) | Attention/psychomotor function (TMT-A, Grooved pegboard, Finger-tapping task, Rapid visual information processing (CANTAB)); Visuospatial perception (DSST); Immediate and delayed memory (CVLT, PAL); Working memory (Spatial working memory and Delayed match to sample tasks (CANTAB)); Set-shifting/executive function (TMT-B, Verbal fluency test: FAS, Animal fluency, Intra/extradimensional shift and Stocking of Cambridge tasks (CANTAB)) | MA users met the DSM-IV criteria for MA dependence: N=16 Controls: N=18 | Mean: 3.4 years, range 3 months–18 years (required 3-month minimum) | ↓ Visuospatial perception ↓ Immediate and delayed memory (CVLT only) ↔ Attention/psychomotor function (3 out of 4 tests) ↔ Working memory ↔Set-shifting/executive function Brain: ↓ DAT BP in all regions of the striatum (including caudate, putamen, and ventral striatum) ↓ VMAT-2 BP in the striatum overall (including caudate and anterior putamen) | MA users' cognitive performance on all tests fell within the normal range when data compared against normative data set The influence of drug use other than MA not controlled The influence of comorbid psychiatric disorders such as ADHD and depression not controlled No relationship between imaging data and cognitive deficits was observed Small number of participants studied |
| Lee et al (2009) | Cognitive testing not included | MA users met the DSM-IV criteria for MA dependence: N=22 Controls: N=30 | All had positive urine tests upon entry | Cognitive: Not included Brain: ↓ D2/D3 BP in the striatum (caudate nucleus, putamen, and ventral striatum) | Participant educational information not reported Relationship between cognitive functioning and brain activity could not be determined because no cognitive measure was included The influence of drug use other than MA not controlled |
| McCann et al (1998) | Cognitive testing not included | MA users (diagnostic information not provided): N=6 Controls: N=10 | Range 4–65 months | Cognitive: Not included Brain: ↓ DAT BP in the caudate nucleus and putamen | Relationship between cognitive functioning and brain activity could not be determined because no cognitive measure was included The influence of drug use other than MA not controlled Small number of participants studied |
| McCann et al (2008) | Attention/psychomotor function (TMT-A, Grooved pegboard, Finger-tapping task, Stroop); Learning/memory (WMS-III Logical Memory); Working memory (Letter-Number Sequencing and Visual Memory Span-backwards subtests of WMS-III); Response inhibition (Stroop); Set-shifting/executive function (TMT-B, WCST, Boston naming task, Verbal concept attainment scale, New adult reading test, Controlled oral word association test) | Cognitive testing: MA users (diagnostic information not provided): N=22 Controls: N=17 Imaging subset: MA users: N=7 Controls: N=16 | Cognitive testing: mean 28.90±64.77 months, range 0.5–300 months Imaging subset: mean 77.43±102.21 months, range 8–300 months | ↔ Attention/psychomotor function (3 out of 4) ↔ Learning/memory (3 out of 5) ↔ Working memory ↔ Set-shifting/executive function Brain: ↓ DAT BP in the bilateral caudate and left putamen | 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 The influence of comorbid psychiatric disorders such as ADHD and depression not controlled Small number of participants studied |
| Sekine et al (2001) | Cognitive testing not included | MA users (diagnostic information not provided): N=11 Controls: N=9 | Range 7 days–1.5 years | Cognitive: Not included Brain: ↓ DAT BP in the striatum (caudate, putamen, and ventral striatum) and PFC | Relationship between cognitive functioning and brain activity could not be determined because no cognitive measure was included Small number of participants studied |
| Volkow et al (2001b) | Attention/psychomotor function (TMT-A, Grooved pegboard, Timed gait task, Stroop, CalCAP); Visuospatial perception (DSST); Learning/memory (AVLT) | MA users met the DSM-IV criteria for MA dependence: N=15 Controls: N=18 | Mean 5.9±9.0 months (required 2-week minimum) | Cognitive: Comparisons between the two groups not reported, but significant correlations between striatal DAT and performance in some cognitive domains were noted for the MA group (ie, psychomotor function, learning/memory) Brain: ↓ DAT BP in the caudate and putamen | Participant educational information not reported 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 |
| Volkow et al (2001c) | Cognitive testing not included | MA users met the DSM-IV criteria for MA dependence: N=15 Controls: N=20 | Data not reported | Cognitive: Not included Brain: ↓ D2 BP in the caudate and putamen | Participant educational information not reported Relationship between cognitive functioning and brain activity could not be determined because no cognitive measure was included The influence of drug use other than MA not controlled Small number of participants studied |
| Volkow et al (2001d) | Psychomotor function (Grooved pegboard, Timed gait task); Learning/memory (AVLT) | MA users met the DSM-IV criteria for MA dependence: N=5 evaluated twice (early and protracted abstinence); N=5 additional Controls: N=11 | Early: mean 3±1.6 months Protracted (9 months later): 14±2 months Other group: mean 17±10 months | Cognitive: Comparisons between the MA and control groups not reported ↔ Cognitive performance was not altered as a function of abstinence status Brain:↓ DAT BP in the caudate and putamen in early abstinence, relative to controls ↑ DAT BP in the caudate and putamen with protracted abstinence | Participant educational information not reported 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 |
| FDG ligand | |||||
| Berman et al (2008) | Vigilance (auditory vigilance task) | MA users met the DSM-IV criteria for MA dependence: N=10 Controls: N=12 | Test 1: mean 6.7±1.6 days Test 2: mean 27.6±0.96 days | Cognitive: ↔ Vigilance (auditory vigilance task) Brain: ↑ rCMRglc between tests 1 and 2 in the neocortex (in MA users) ↔ rCMRglc between tests 1 and 2 in subcortical regions (in MA users) | Only one cognitive measure included The influence of drug use other than MA not controlled Small number of participants studied |
| Kim et al (2005) | Set-shifting/executive function (WCST) | MA users met the DSM-IV criteria for an MA-use disorder: N=35 Controls: N=21 | Mean 19.14±27.20 months (required 4-week minimum) | Cognitive: ↓ Set-shifting/executive function: males ↔ Set-shifting/executive function: females Brain: ↔ rCMRglc levels in the right superior frontal WM (females) ↓ rCMRglc levels in the right superior frontal WM (males) | 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 |
| Kim et al (2009) | Same as above | MA users met the DSM-IV criteria for an MA-use disorder: N=24 Controls: N=21 | Mean 20.5±8.3 days (required 1-week minimum) | Cognitive:↓ Set-shifting/executive function Brain: ↓ Metabolism in the left inferior frontal WM | 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 Performance on the WCST was not correlated with brain activity |
| London et al (2004) | Attention/vigilance (CPT) | MA users (diagnostic information not provided): N=14 Controls: N=13 | Range 4–7 days | Cognitive: ↔ Attention/vigilance Brain: ↔ No difference in global glucose metabolism ↓ Relative rCMRglc in infragenual ACC ↑ Activity in one cluster extending from middle to posterior portions of dorsal cingulate gyrus ↑ Relative rCMRglc in the ventral striatum | 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 |
| London et al (2005) | Same as above | MA users (diagnostic information not provided): N=17 Controls: N=16 | Range 4–7 days | Cognitive:↓ Attention/vigilance Brain: MA users: Negative correlations between error rates and relative activity in anterior and middle cingulate gyrus and insula Controls: Positive correlations between error rates and activity in the cingulate cortex | 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 Small number of participants studied |
| Volkow et al (2001a) | Attention/psychomotor function (TMT-A, Grooved pegboard, Timed gait task, Stroop, CalCAP); Visuospatial perception (DSST); Learning/memory (AVLT) | MA users met the DSM-IV criteria for MA dependence: N=15 Controls: N=21 | Required 2-week minimum | Cognitive: Results not reported Brain: ↓ Glucose metabolism in the thalamus, caudate, and putamen ↑ Glucose metabolism in parietal cortex | Participant educational information not reported Clinical importance and relationship between cognitive functioning and brain activity could not be determined because no cognitive results not reported The influence of drug use other than MA not controlled Small number of participants studied |
| Wang et al (2004) | Same as above | MA users met the DSM-IV criteria for MA dependence: N=5 evaluated twice (short and protracted abstinence); N=8 additional Controls: N=11 | Short: mean 3±1.6 months Protracted: Original 5 MA users: mean 14±2 months Additional 8 MA users: mean 17±10 months | Cognitive: Comparisons between the two groups not reported, but significant correlations between thalamic activity changes and performance in some cognitive domains were noted for the MA group (ie, psychomotor function (timed gait), learning/memory (delayed recall)) Brain: MA users evaluated twice: ↑ Thalamic metabolism in protracted abstinence relative to short abstinence ↔ Global metabolism or absolute metabolic measures in the striatum, thalamus, or occipital cortex between short (<6 months) and protracted (12–17 months) abstinence ↔ Striatal metabolism in protracted abstinence relative to short abstinence Comparison with controls: ↓ Striatal metabolism in protracted abstinence and short abstinence relative to controls ↓ Thalamic metabolism in short abstinence relative to controls ↔ Absolute global brain metabolism among short and protracted abstinence and controls ↔ Thalamic metabolism in protracted abstinence relative to controls | Participant educational information not reported 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 |
Abbreviations: ACC, anterior cingulate cortex; AVLT, Rey auditory verbal learning test; BP, binding potential; CalCAP, California computerized assessment package; CANTAB, Cambridge automated neuropsychological assessment battery; CPT, continuous-performance task; CVLT, California verbal learning task; DAT, dopamine transporter; DSM-IV, Diagnostic and Statistical Manual of Mental Disorders 4th Edition; DSST, digit-symbol substitution task; FDG, [18F]fluorodeoxyglucose; MA, methamphetamine; PAL, paired associates learning task; PET, positron emission tomography; PFC, prefrontal cortex; rCMRglc, regional cerebral metabolic rate for glucose; TMT-A, Trail making test, part A; TMT-B, Trail making test, part B; VMAT-2, vesicular monoamine transporter-2; 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.