Extended findings of brain metabolite normalization in MA-dependent subjects across sustained abstinence: a proton MRS study.

OBJECTIVE: The goal of the present study was to extend our previous findings on long-term methamphetamine (MA) use and drug abstinence on brain metabolite levels in an expanded group of MA-dependent individuals. METHODS: Seventeen MA abusers with sustained drug abstinence (1-5 years), 30 MA abusers with short-term drug abstinence (1-6 months) and 24 non-substance using controls were studied using MR spectroscopy (MRS). MRS measures of NAA/Cr, Cho/Cr and Cho/NAA were obtained in the anterior cingulate cortex (ACC) and in the primary visual cortex (PVC). RESULTS: ACC-Cho/NAA values were abnormally high in the short-term abstinent group compared to controls [F(1,52) = 18.76, p < 0.0001]. No differences were observed between controls and the long-term abstinent group [F(1,39) = 0.97, p = 0.97]. New evidence of lower ACC-NAA/Cr levels were observed in the short-term abstinent MA abusers compared to controls [F(1,52) = 23.05, p < 0.0001] and long-term abstinent MA abusers [F(1,45) = 7.06, p = 0.01]. No differences were observed between long-term abstinent MA abusers and controls [F(1,39) = 0.48, p = 0.49]. CONCLUSIONS: The new findings of relative NAA/Cr normalization across periods of abstinence suggest that adaptive changes following cessation of MA abuse may be broader than initially thought. These changes may contribute to some degree of normalization of neuronal function in the ACC.

Drug abstinence and cognitive control in methamphetamine-dependent individuals.

Chronic methamphetamine (MA) abuse is associated with disruption of frontostriatal function as well as deficits in cognitive control. To examine the relationship between drug use patterns and cognitive deficits, we pooled previously published behavioral data with new data collected using the Stroop Attention Test. Subject groups are composed of 38 MA-abusing individuals who recently initiated abstinence (36.1 +/- 8.8 years of age), 27 MA-abusing individuals who had initiated abstinence more than 1 year prior to study (38.7 +/- 7.7 years of age), and 33 non-substance-abusing controls (33.9 +/- 8.5 years of age). The recently abstinent MA-abusing individuals exhibited greater Stroop reaction time (RT) interference compared with both the control group (p = .001) and the long-term abstinent MA-abusing individuals (p = .01). No difference was seen between long-term abstinent MA-abusing individuals and controls (p = .87). Stroop RT interference correlated positively with both duration of drug use (p = .003) and drug abstinence (p = .05). The data in the current study provide evidence that cognitive function may improve with protracted drug abstinence.

Cognitive control and white matter callosal microstructure in methamphetamine-dependent subjects: a diffusion tensor imaging study.

BACKGROUND: Methamphetamine (MA) abuse causes damage to structures within the human cerebrum, with particular susceptibility to white matter (WM). Abnormalities have been reported in anterior regions with less evidence of changes in posterior regions. Methamphetamine abusers have also shown deficits on attention tests that measure response conflict and cognitive control. METHODS: We examined cognitive control with a computerized measure of the Stroop selective attention task and indices of WM microstructure obtained from diffusion tensor imaging (DTI) in the callosal genu and splenium of 37 currently abstinent MA abusers and 17 non-substance abusing control subjects. Measurements of fractional anisotropy (FA), apparent diffusion coefficient (ADC) of callosal fibers, and diffusion tensor eigenvalues were obtained in all subjects. RESULTS: The MA abusers exhibited greater Stroop reaction time interference (i.e., reduced cognitive control) (p = .04) compared with control subjects. After correcting for multiple comparisons, FA within the genu correlated significantly with measures of cognitive control in the MA abusers (p = .04, Bonferroni corrected) but not in control subjects (p = .26). Group differences in genu but not splenium FA were trend significant (p = .09). CONCLUSIONS: Methamphetamine abuse seems to alter anterior callosal WM microstructure with less evidence of change within posterior callosal WM microstructure. The DTI indices within the genu but not splenium correlated with measures of cognitive control in chronic MA abusers.

Preliminary evidence of behavioral predictors of recurrent drug-induced psychosis in methamphetamine abuse.

The goal of this study was to examine behavioral characteristics of currently drug-abstinent methamphetamine (MA)-dependent subjects (n=39) who experienced psychotic symptoms associated with MA abuse. All participants completed the Wender Utah Rating Scale (WURS), which retrospectively assesses Attention Deficit Hyperactivity Disorder-relevant childhood behaviors. The results suggest the existence of possible behavioral markers reflecting an early cognitive vulnerability to the development of frequent MA-induced psychotic symptoms as well as increased vulnerability associated with a family history of psychiatric illness.

Findings of preserved implicit attention in methamphetamine dependent subjects.

Long-term methamphetamine (MA) abuse is associated with a wide range of deficits on explicit tasks of selective attention. Less is known however about the effects of MA abuse on implicit measures of attention. Accordingly, we used a computerized spatial priming task to assess implicit attentional processes in 54 MA dependent subjects (mean age=37.04+/-8.9 years) and 32 healthy controls without history of any form of substance abuse (mean age=33.63+/-7.05 years). The MA dependent subjects had been drug-abstinent a minimum of 3 weeks with a mean duration of MA use of 13.27+/-7.75 years. The MA dependent subjects did not differ significantly from controls on either inhibitory priming [p=.37] or facilitory priming) [p=.69]. This result comports with our earlier findings of intact object-based priming in MA dependent individuals and suggests that intact priming effects extend across spatial domains. Further, this pattern of sparing suggests that cortical brain systems typically supporting implicit attentional functioning are relatively intact in long-term MA dependent individuals whereas brain systems supporting explicit attentional processes are affected.

Attentional control and brain metabolite levels in methamphetamine abusers.

BACKGROUND: Methamphetamine abuse is associated with neurotoxicity to frontostriatal brain regions with concomitant deleterious effects on cognitive processes. METHODS: By using a computerized measure of selective attention and single-voxel proton magnetic resonance spectroscopy, we examined the relationship between attentional control and brain metabolite levels in the anterior cingulate cortex (ACC) and primary visual cortex (PVC) in 36 currently abstinent methamphetamine abusers and 16 non-substance-using controls. RESULTS: The methamphetamine abusers exhibited reduced attentional control (i.e., increased Stroop interference) compared with the controls (p = .04). Bonferroni-adjusted comparisons revealed that ACC levels of N-acetyl aspartate (NAA)-creatine and phosphocreatine (Cr) were lower and that levels of choline (Cho)-NAA were higher in the methamphetamine abusers compared with the controls, at the adjusted p value of .0125. Levels of NAA-Cr, but not of Cho-NAA, within the ACC correlated with measures of attentional control in the methamphetamine abusers (r = -.41; p = .01) but not in controls (r = .22; p = .42). No significant correlations were observed in the PVC (methamphetamine abusers, r = .19; p = .28, controls, r = .38; p = .15). CONCLUSIONS: Changes in neurochemicals within frontostriatal brain regions including ACC may contribute to deficits in attentional control among chronic methamphetamine abusers.

Methamphetamine users in sustained abstinence: a proton magnetic resonance spectroscopy study.

BACKGROUND: Abnormal patterns of metabolite levels have been detected by magnetic resonance spectroscopy in frontostriatal regions of individuals meeting DSM-IV criteria for methamphetamine dependence, but less is known about the effects of drug abstinence on metabolite levels. OBJECTIVE: To assess the effects of long-term methamphetamine use and drug abstinence on brain metabolite levels. DESIGN: To assess regional specific metabolite levels using magnetic resonance spectroscopy imaging techniques in 2 groups of currently abstinent methamphetamine users: methamphetamine users who recently initiated abstinence and methamphetamine users who had initiated abstinence more than 1 year prior to study. SETTING: Participants were recruited from outpatient substance abuse treatment centers. PARTICIPANTS: Eight methamphetamine users with sustained abstinence (1 year to 5 years) and 16 recently abstinent methamphetamine users (1 month to 6 months) were compared with 13 healthy, non-substance-using controls. MAIN OUTCOME MEASURES: Magnetic resonance spectroscopy measures of N-acetylaspartate-creatine and phosphocreatine (NAA/Cr), choline-creatine and phosphocreatine (Cho/Cr), and choline-N-acetylaspartate (Cho/NAA) ratios were obtained in the anterior cingulate cortex as well as in the primary visual cortex, which served as a control region. RESULTS: The absolute values of Cr did not differ between controls and methamphetamine users. Methamphetamine users had abnormally low NAA/Cr levels within the anterior cingulate cortex, regardless of the time spent abstinent (F(2,34) = 12.61; P<.001). No NAA/Cr group differences were observed in the primary visual cortex (F(2,33) = 0.29; P = .75). The Cho/NAA values for the anterior cingulate cortex were abnormally high in the methamphetamine users who recently initiated abstinence but followed a normal pattern in the methamphetamine users who had initiated abstinence more than 1 year prior to study (F(2,34) = 7.31; P = .002). CONCLUSIONS: The relative choline normalization across periods of abstinence suggests that following cessation of methamphetamine use, adaptive changes occur, which might contribute to some degree of normalization of neuronal structure and function in the anterior cingulum. More research is needed to elucidate the mechanisms underlying these adaptive changes.

A dissociation in attentional control: evidence from methamphetamine dependence.

BACKGROUND: Selective attention comprises multiple, dissociable component processes, including task shifting and selective inhibition. The goal of this study was to test whether task-shifting, selective inhibition, or both processes were impaired in long-term but currently abstinent methamphetamine-dependent individuals. METHODS: Participants were 34 methamphetamine-dependent subjects and 20 nonsubstance abusing controls who were tested on an alternating-runs switch task with conflict sequences that required subjects to switch tasks on every second trial (AABBAABB). RESULTS: Methamphetamine-dependent individuals committed more errors on trials that required inhibition of distracting information compared with controls (methamphetamine = 17%; controls = 13%; p = .02). By contrast, error rates did not differ between the groups on switch trials (methamphetamine = 7%; controls = 6%; p = .68). CONCLUSIONS: These results indicate that selective inhibition, but not task switching, is selectively compromised by methamphetamine.