Abstinent Methamphetamine Abusers Research Articles

Neural basis of the attention bias during addiction stroop task in methamphetamine-dependent patients with and without a history of psychosis: an ERP study.

Attentional bias plays an important role in sustaining various types of drug addiction. No prior studies examined methamphetamine (MA)-associated psychosis (MAP) relationships between ERP time course and performance on an addiction Stroop task in MA abusers. The aim of the present study was to determine whether MA abusers with (MAP+) or without (MAP-) psychosis exhibit alterations of the ERP during the addiction Stroop task. Thirty-one healthy controls (CTRL), 14 MAP-, and 24 MAP+ participants were recruited and completed the addiction Stroop task during EEG recording using 32 electrodes. Group variations were compared on measures of behavioral task performance and event-related potentials (ERP) of performance monitoring (N200, P300, N450). The Barratt impulsiveness scores were analyzed to investigate correlations with ERP changes. MA-related word stimulus elicited a more negative N200 amplitude over left-anterior electrodes in MAP- abusers; furthermore, a positive association between the N200 amplitude and Barratt attentional scores and non-planning scores was observed, while no such differences were found in MAP+ abusers. There were no significant differences in reaction time (RT) and error rate between each group. This is the first study to examine psychosis relationships between ERP time course and performance on an addiction Stroop task in MA abusers with or without psychosis. These findings support the association between attentional bias measured by the MA addiction Stroop task and N200 component as well as indicate the possibility of using this cognitive task in combination with ERP technology to detect psychosis factors among abstinent MA abusers.

Functional connectivity abnormalities underlying mood disturbances in male abstinent methamphetamine abusers.

Anxiety and depression are the most common withdrawal symptoms of methamphetamine (METH) abuse, which further exacerbate relapse of METH abuse. To date, no effective pharmacotherapy exists for METH abuse and its withdrawal symptoms. Therefore, understanding the neuromechanism underlying METH abuse and its withdrawal symptoms is essential for developing clinical strategies and improving patient care. The aims of this study were to investigate brain network abnormalities in METH abusers (MAs) and their associations with affective symptoms. Forty‐eight male abstinent MAs and 48 age‐gender matched healthy controls were recruited and underwent resting state functional magnetic resonance imaging (fMRI). The severity of patient anxiety and depressive symptoms were measured by Hamilton anxiety and depression rating scales, which decreased across the duration of abstinence. Independent component analysis was used to investigate the brain network functional connectivity (FC) properties. Compared with healthy controls, MAs demonstrated hypo‐intra‐network FC in the cerebellar network and hyper‐intra‐network FC in the posterior salience network. A whole‐brain regression analysis revealed that FC strength of clusters located in the right rostral anterior cingulate cortex (rACC) within the ventromedial network (VMN) was associated with affective symptoms in the patients. Importantly, the intra‐network FC strength of the rACC in VMN mediated the association between abstinence duration and the severity level of affective symptoms. Our results demonstrate alterations in brain functional networks underlying METH abuse, and that the FC of rACC within VMN serve as a neural substrate in the association between abstinence length and affective symptom severity in the MAs.

Attentional bias in methamphetamine users: a visual search task study

Attentional bias for drug-related stimuli has been found in users of many types of drugs, which is closely correlated with drug use behaviors. However, such attentional bias in methamphetamine abusers has barely been addressed. The present study explored the attentional bias for methamphetamine-related stimuli in abstinent methamphetamine abusers (abstinent MA participants) and healthy participants. In Experiment 1, 32 abstinent MA participants completed a visual search task designed to assess attentional bias for methamphetamine-related (vs. neutral) pictures. In Experiment 2, 30 healthy participants with no history of drug use were recruited to complete the same task as in Experiment 1. In Experiment 3, 29 abstinent MA participants completed a similar task to examine attentional bias for methamphetamine-related (vs. neutral) pictures that were normal or scrambled. The results showed a decline of performance in MA participants when the methamphetamine-related stimulus appeared as one of the distractors in the search panel (Experiment 1). Such effect disappeared in healthy participants (Experiment 2) or when the methamphetamine-related pictures were scrambled (Experiment 3). The correlation between attentional bias and methamphetamine use behaviors was also investigated and it was found that the bias effect (indexed by response times) significantly positively correlated with years of methamphetamine use. These findings are consistent with the incentive-sensitization model of drug addiction, and support the existence of attentional bias in methamphetamine users. The cognitive task used in the present study may also have implications for intervention and prevention of methamphetamine use and relapse.

Depression and alterations in hypothalamic–pituitary–adrenal and hypothalamic–pituitary–thyroid axis function in male abstinent methamphetamine abusers

The present study was to investigate depression and alterations in the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-thyroid (HPT) axis function in methamphetamine (METH) abusers after abstinence. Depression was assessed using the 13-item Beck Depression Inventory (BDI-13) scale; blood samples from in-patients who were METH abusers and age-matched and sex-matched healthy controls were collected. The demographic characteristics and history of METH abuse also was assessed. We found that serum levels of adrenocorticotropic hormone (ACTH) and thyroxine were increased; and serum levels of cortisol, triiodothyronine, and thyroid-stimulating hormone were decreased; and the BDI score was higher in METH abusers compared with control. In addition, there was no correlation between the BDI-13 score and any of hormones of HPA and HPT axis was found. Particularly, we found abnormally higher ACTH level and mismatched with lower cortisol level in abstinent METH abusers. These results indicate that METH abusers and that their HPA and HPT functions are all altered after abstinence. Chronically using METH may destroy the regulatory function of the HPA axis, especially the feedback regulation of cortisol to ACTH.

Oxidative stress status in recently abstinent methamphetamine abusers

Methamphetamine (METH) administration is associated with excessive oxidative stress. It is not known whether the systemic oxidative stress indices would alter during early abstinence in METH abusers with positive urine testing for recent METH exposure. Sixty-four non-treatment-seeking METH abusers enrolled from a controlled environment and 60 healthy controls participated in the study. Fasting serum malondialdehyde (MDA) levels and anti-oxidant indices, including superoxide dismutase (SOD) and catalase (CAT) activity, and glutathione (GSH) levels, were measured at baseline and 2 weeks after the first measurement. We compared the differences of these oxidative stress indices between METH abusers and controls and examined the changes of the indices 2 weeks after baseline in the METH group. At baseline, the recently abstinent METH abusers had significantly higher MDA levels, lower SOD activity, and higher CAT activity and GSH levels compared to healthy controls. CAT and GSH values were positively correlated with MDA but negatively correlated with SOD. These oxidative stress indices did not significantly correlate with age, smoking amount, Alcohol Use Disorder Identification Test scores, or METH use variables. After 2 more weeks of abstinence, the indices did not alter nor normalize. Compared to controls, we found that METH abusers have persistently higher systemic oxidative stress throughout early abstinence. The compromised SOD as well as elevated CAT activity and GSH levels may act together as a compensatory mechanism to counteract excessive oxidative stress induced by METH. Whether the oxidative stress could improve after a longer period of abstinence needs to be examined in future studies.

Striatal volume increases in active methamphetamine-dependent individuals and correlation with cognitive performance.

The effect of methamphetamine (MA) dependence on the structure of the human brain has not been extensively studied, especially in active users. Previous studies reported cortical deficits and striatal gains in grey matter (GM) volume of abstinent MA abusers compared with control participants. This study aimed to investigate structural GM changes in the brains of 17 active MA-dependent participants compared with 20 control participants aged 18–46 years using voxel-based morphometry and region of interest volumetric analysis of structural magnetic resonance imaging data, and whether these changes might be associated with cognitive performance. Significant volume increases were observed in the right and left putamen and left nucleus accumbens of MA-dependent compared to control participants. The volumetric gain in the right putamen remained significant after Bonferroni correction, and was inversely correlated with the number of errors (standardised z-scores) on the Go/No-go task. MA-dependent participants exhibited cortical GM deficits in the left superior frontal and precentral gyri in comparison to control participants, although these findings did not survive correction for multiple comparisons. In conclusion, consistent with findings from previous studies of abstinent users, active chronic MA-dependent participants showed significant striatal enlargement which was associated with improved performance on the Go/No-go, a cognitive task of response inhibition and impulsivity. Striatal enlargement may reflect the involvement of neurotrophic effects, inflammation or microgliosis. However, since it was associated with improved cognitive function, it is likely to reflect a compensatory response to MA-induced neurotoxicity in the striatum, in order to maintain cognitive function. Follow-up studies are recommended to ascertain whether this effect continues to be present following abstinence. Several factors may have contributed to the lack of more substantial cortical and subcortical GM changes amongst MA-dependent participants, including variability in MA exposure variables and difference in abstinence status from previous studies.

Overlapping cognitive patterns in schizophrenia and methamphetamine dependence.

To examine whether overlapping cognitive deficits exist in currently drug-abstinent chronic methamphetamine (MA) abusers and schizophrenia (SZ) patients. Both SZ and chronic MA abuse are associated with frontostriatal disruption as well as deficits in cognitive control, such as selective attention. To identify overlapping cognitive profiles, we compared performance of the 2 groups on the Stroop attention task. Data were analyzed from 69 MA abusers who had been MA-abstinent for differing periods of time and from 23 SZ patients and 38 non-substance-abusing controls. The MA abusers in early abstinence displayed more Stroop interference than the SZ patients (P=0.004), long-term abstinent MA abusers (P=0.009), and controls (P=0.002). In the MA abusers, the magnitude of Stroop interference correlated positively with longer drug use (P=0.01) and negatively with longer drug abstinence (P=0.04). No correlations were found between psychotic symptoms and task performance. On this task of attentional selection, only the MA abusers in early stages of abstinence showed performance deficits compared with controls. More research is needed to further elucidate overlapping patterns between MA abuse and SZ.

Distributed attentional deficits in chronic methamphetamine abusers: Evidence from the Attentional Network Task (ANT)

Objective The goal of the present study was to examine distributed attentional functions in long-term but currently abstinent methamphetamine (MA) abusers using a task that measures attentional alertness, orienting, and conflict resolution. Methods Thirty currently abstinent MA abusers (1 month–5 years) and 22 healthy non-substance using adults were administered a multimodal version of the Attentional Network Task (ANT-I). In this task subjects identified the direction of a centrally presented arrow using a key press. Analyses examined the interaction between alerting tones, location cueing and congruency between the target arrows and flanking distractor stimuli. Results All participants were faster when an auditory tone preceded the trial onset ( p < 0.001), on trials in which a valid cue preceded the location of the target arrow ( p < 0.001), and on congruent trials (i.e., when all display arrows faced in the same direction) ( p < 0.001). Of primary interest was the finding that MA abusers were more influenced by the conflict between the peripheral arrows and the central target arrow ( p = 0.009). There were also correlations between length of drug sobriety and executive function as well as between drug-induced psychiatric symptoms and alertness. Conclusions These results suggest that chronic MA abusers display cognitive deficits that may reflect a specific vulnerability to distraction on a task of executive function. These findings are consistent with other studies that have reported deficits in anterior attentional systems and top-down cognitive control.

The differences in neural network activity between methamphetamine abusers and healthy subjects performing an emotion‐matching task: functional MRI study

Methamphetamine (MA) abusers commonly exhibit socially problematic behaviors, such as diminished empathy, decreased emotional regulation and interpersonal violence, which may be attributable to alterations in emotional experience. However, few studies have used functional MRI to examine directly the emotional experience of threatening or fearful non-face images in MA abusers. In this study, we investigated possible differences in neural correlates of negative emotional experiences between abstinent MA abusers and healthy subjects using complex visual scenes depicting fear or threat derived from the International Affective Picture System. In within-group analyses, healthy subjects and MA abusers activated a similarly distributed cortical network, prominently including the amygdala, fusiform gyrus, parahippocampal gyrus, ventrolateral prefrontal cortex and inferior frontal cortex. In between-group analyses, however, MA abusers showed a reduced activation in the bilateral dorsolateral prefrontal cortex and insula, and increased activation in the fusiform gyrus, hippocampus, parahippocampal gyrus and posterior cingulate cortex, relative to healthy subjects. Hypoactivation of the insula in MA abusers relative to healthy subjects suggests that the ability to have an emotional response to threatening scenes and empathy for another's pain could be compromised in MA abusers. Hyperactivity in the fusiform gyrus, parahippocampal gyrus and posterior cingulate cortex in MA abusers relative to healthy subjects indicates that threatening and fearful images from the International Affective Picture System may remind MA abusers of episodic memory related to similar experiences. Therefore, functional impairment of these neural networks in MA abusers may contribute to altered emotional experience in social interactions, which could lead to increased negative mood and stress in interpersonal communication.

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.

Glial Dysfunction in Abstinent Methamphetamine Abusers

Persistent neurochemical abnormalities in frontal brain structures are believed to result from methamphetamine use. We developed a localized (13)C magnetic resonance spectroscopy (MRS) assay on a conventional MR scanner, to quantify selectively glial metabolic flux rate in frontal brain of normal subjects and a cohort of recovering abstinent methamphetamine abusers. Steady-state bicarbonate concentrations were similar, between 11 and 15 mmol/L in mixed gray-white matter of frontal brain of normal volunteers and recovering methamphetamine-abusing subjects (P>0.1). However, glial (13)C-bicarbonate production rate from [1-(13)C]acetate, equating with glial tricarboxylic acid (TCA) cycle rate, was significantly reduced in frontal brain of abstinent methamphetamine-addicted women (methamphetamine 0.04 micromol/g per min (N=5) versus controls 0.11 micromol/g per min (N=5), P=0.001). This is equivalent to 36% of the normal glial TCA cycle rate. Severe reduction in glial TCA cycle rate that normally comprises 10% of total cerebral metabolic rate may impact operation of the neuronal glial glutamate cycle and result in accumulation of frontal brain glutamate, as observed in these recovering methamphetamine abusers. Although these are the first studies to define directly an abnormality in glial metabolism in human methamphetamine abuse, sequential studies using analogous (13)C MRS methods may determine 'cause and effect' between glial failure and neuronal injury.

Alterations in cortical activity of male methamphetamine abusers performing an empathy task: fMRI study

We investigate possible differences in neural correlates of empathy processing between abstinent methamphetamine (MA) abusers and healthy subjects using functional magnetic resonance imaging (fMRI). Nineteen abstinent MA abusers (mean age of 36.06 years, range 31-52 years) and 19 healthy subjects (mean age of 37.05 years, range 33-42 years) participated in this study. A visual fMRI activation paradigm was used, comprising a series of cartoons, each depicting a short story. There were two categories of stories: empathy (Empathy) and Physical causality (Physical). fMRI images were acquired using a 3.0 T whole-body scanner. All fMRI data were analyzed using MATLAB v. 7.2 and SPM5. Both MA subjects and controls exhibited activation in the dorsomedial prefrontal cortex. Despite this similarity in activation patterns, we found that the two groups differed in the activation of several cortical regions associated with the processing of empathy information. Hypoactivations of the orbitofrontal cortex, temporal poles, and hippocampus in MA abusers relative to healthy subjects suggests that the ability of empathic response could be compromised in abstinent MA abusers (p < 0.05, corrected for a small volume). Functional impairments in the empathic neural network caused by MA may contribute to the misunderstanding of others and to the erosion of social interactions in MA abusers.

Reduced corpus callosum white matter microstructural integrity revealed by diffusion tensor eigenvalues in abstinent methamphetamine addicts

The purpose of the current study was to determine whether abstinent methamphetamine (MA) abusers demonstrate differences in white matter (WM) integrity of the corpus callosum (CC) due to possible neurotoxic effects of long-term MA abuse, compared with control subjects. In addition to fractional anisotropy (FA), the eigenvalues of the diffusion ellipsoid were used to evaluate the microstructural source of abnormal change in abstinent MA abusers if there occurred a difference in white matter integrity of the CC between healthy controls and abstinent MA abusers. Results showed significantly reduced FA in the genu of the corpus callosum in MA-dependent subjects compared with controls. Furthermore, the eigenvalues offered a unique opportunity to assess the microstructural source of abnormal changes in the genu of the CC. The relationships between Wisconsin Card Sorting Test (WCST) performance and the values of tensor measures also suggest that altered myelination is a possible source of FA reduction observed in the genu of the CC in MA abusers.

Cognitive Control and White Matter Callosal Microstructure in Methamphetamine-Dependent Subjects: A Diffusion Tensor Imaging Study

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. 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. 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). 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.

Methamphetamine Causes Microglial Activation in the Brains of Human Abusers

Methamphetamine is a popular addictive drug whose use is associated with multiple neuropsychiatric adverse events and toxic to the dopaminergic and serotonergic systems of the brain. Methamphetamine-induced neuropathology is associated with increased expression of microglial cells that are thought to participate in either pro-toxic or protective mechanisms in the brain. Although reactive microgliosis has been observed in animal models of methamphetamine neurotoxicity, no study has reported on the status of microglial activation in human methamphetamine abusers. The present study reports on 12 abstinent methamphetamine abusers and 12 age-, gender-, and education-matched control subjects who underwent positron emission tomography using a radiotracer for activated microglia, [(11)C](R)-(1-[2-chlorophenyl]-N-methyl-N-[1-methylpropyl]-3-isoquinoline carboxamide) ([(11)C](R)-PK11195). Compartment analysis was used to estimate quantitative levels of binding potentials of [(11)C](R)-PK11195 in brain regions with dopaminergic and/or serotonergic innervation. The mean levels of [(11)C](R)-PK11195 binding were higher in methamphetamine abusers than those in control subjects in all brain regions (>250% higher; p < 0.01 for all). In addition, the binding levels in the midbrain, striatum, thalamus, and orbitofrontal and insular cortices (p < 0.05) correlated inversely with the duration of methamphetamine abstinence. These results suggest that chronic self-administration of methamphetamine can cause reactive microgliosis in the brains of human methamphetamine abusers, a level of activation that appears to subside over longer periods of abstinence.

Corticolimbic dysregulation and chronic methamphetamine abuse

This review aims to present and interpret evidence that methamphetamine dependence is associated with disorder of brain function that is required for top-down control of behavior. Presented here are findings from brain imaging studies of human research participants with histories of chronic methamphetamine abuse in the context of functional consequences and implications for treatment of their dependence on methamphetamine. Brain imaging studies have revealed differences in the brains of research participants who have used methamphetamine chronically and then abstained from taking the drug, compared with healthy control subjects. These abnormalities are prominent in cortical and limbic systems, and include deficits in markers of dopaminergic and serotonergic neurotransmitter systems, differences in glucose metabolism and deficits in gray matter. These abnormalities accompany cognitive deficits, including evidence of impaired inhibitory control. Cortical deficits in abstinent methamphetamine abusers can affect a wide range of functions that can be important for success in maintaining drug abstinence. These include but are not limited to modulation of responses to environmental stimuli as well as internal triggers that can lead to craving and relapse. Potential therapies may combine behavioral approaches with medications that can improve cognitive control.

Decreased frontal white-matter integrity in abstinent methamphetamine abusers

This study explored differences in frontal white-matter (WM) integrity between methamphetamine (MA) abusers and healthy comparison subjects using diffusion tensor imaging (DTI). Fractional anisotropy (FA) values, which indicate WM integrity, were calculated for regions-of-interest in frontal WM on diffusion tensor images of 32 MA abusers and 30 healthy comparison subjects. Frontal executive functions were also assessed by the Wisconsin Card Sorting test (WCST). MA abusers had significantly lower FA values in bilateral frontal WM at the anterior commissure-posterior commissure (AC-PC) plane and the right frontal WM 5 mm above the AC-PC plane relative to healthy comparison subjects. MA abusers had more total, perseveration and non-perseveration errors in the WCST relative to healthy comparison subjects. FA values of the right frontal WM 5 mm above the AC-PC plane negatively correlated with the number of total and non-perseveration errors in the WCST in MA abusers. In the sub-analysis for gender differences, lower FA values in frontal WM and more errors in the WCST were found only in male MA abusers, not in female MA abusers, relative to comparison subjects of the respective gender. We report that frontal WM integrity of MA abusers is compromised. This finding may also be related to impairment in frontal executive function. In addition, the neurotoxic effect of MA on frontal WM may be less prominent in women than in men, possibly due to oestrogen's neuroprotective effect.

Attentional Control and Brain Metabolite Levels in Methamphetamine Abusers

Methamphetamine abuse is associated with neurotoxicity to frontostriatal brain regions with concomitant deleterious effects on cognitive processes. 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. 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). Changes in neurochemicals within frontostriatal brain regions including ACC may contribute to deficits in attentional control among chronic methamphetamine abusers.

Relationship between N-acetyl-aspartate in gray and white matter of abstinent methamphetamine abusers and their history of drug abuse: A proton magnetic resonance spectroscopy study

Objective Altered concentrations of the brain metabolites, including N-acetyl-aspartate (NAA) and myo-inositol (MI), may indicate neurotoxicity associated with drug abuse. In this study, the authors explored differences in brain metabolites between abstinent methamphetamine (MA) abusers and healthy comparison subjects and the associations between metabolite concentrations and clinical characteristics. Method Proton magnetic resonance spectroscopy (MRS) was performed on 30 abstinent MA abusers and 20 healthy comparison subjects. Two sets of MA user subgroups were defined depending on abstinence duration (greater or less than 6 months) or the total cumulative MA dose (greater or less than 100 g lifetime). NAA and other metabolites were measured in the frontal gray and white matter and compared between MA abuser groups and healthy comparison subjects. Results MI concentrations were higher for the MA abusers relative to healthy comparison subjects. NAA concentration was lower in frontal white matter of MA abusers with a ‘large’ cumulative dose relative to those with a ‘small’ cumulative dose and to healthy comparison subjects. Additionally, in MA abusers NAA concentrations in frontal white matter correlated inversely with the cumulative MA dose. In contrast, there was no significant difference in frontal gray matter NAA concentration among the three groups. However, frontal gray matter NAA concentrations for MA abusers correlated negatively with the total cumulative MA dose and positively with the duration of abstinence. There were no differences between the different MA user groups for MI. Conclusions The current findings suggest that MA-induced metabolic alterations of frontal gray and white matter are dose-dependent, for primarily male subjects. Additionally, these findings potentially suggest that the MA-related abnormalities may, in part, recover with abstinence in gray matter, but not in the white matter regions.

Cerebral Metabolic Dysfunction and Impaired Vigilance in Recently Abstinent Methamphetamine Abusers

Methamphetamine (MA) abusers have cognitive deficits, abnormal metabolic activity and structural deficits in limbic and paralimbic cortices, and reduced hippocampal volume. The links between cognitive impairment and these cerebral abnormalities are not established. We assessed cerebral glucose metabolism with [F-18]fluorodeoxyglucose positron emission tomography in 17 abstinent (4 to 7 days) methamphetamine users and 16 control subjects performing an auditory vigilance task and obtained structural magnetic resonance brain scans. Regional brain radioactivity served as a marker for relative glucose metabolism. Error rates on the task were related to regional radioactivity and hippocampal morphology. Methamphetamine users had higher error rates than control subjects on the vigilance task. The groups showed different relationships between error rates and relative activity in the anterior and middle cingulate gyrus and the insula. Whereas the MA user group showed negative correlations involving these regions, the control group showed positive correlations involving the cingulate cortex. Across groups, hippocampal metabolic and structural measures were negatively correlated with error rates. Dysfunction in the cingulate and insular cortices of recently abstinent MA abusers contribute to impaired vigilance and other cognitive functions requiring sustained attention. Hippocampal integrity predicts task performance in methamphetamine users as well as control subjects.