Mood disturbances and regional cerebral metabolic abnormalities in recently abstinent methamphetamine abusers

BACKGROUND: Mood disturbances in methamphetamine (MA) abusers likely influence drug use, but the neurobiological bases for these problems are poorly understood. OBJECTIVE: To assess regional brain function and its possible relationships with negative affect in newly abstinent MA abusers. DESIGN: Two groups were compared by measures of mood and cerebral glucose metabolism ([18F]fluorodeoxyglucose positron emission tomography) during performance of a vigilance task. SETTING: Participants were recruited from the general community to a research center. PARTICIPANTS: Seventeen abstaining (4-7 days) MA abusers (6 women) were compared with 18 control subjects (8 women). MAIN OUTCOME MEASURES: Self-reports of depressive symptoms and anxiety were measured, as were global and relative glucose metabolism in the orbitofrontal, cingulate, lateral prefrontal, and insular cortices and the amygdala, striatum, and cerebellum. RESULTS: Abusers of MA provided higher self-ratings of depression and anxiety than control subjects and differed significantly in relative regional glucose metabolism: lower in the anterior cingulate and insula and higher in the lateral orbitofrontal area, middle and posterior cingulate, amygdala, ventral striatum, and cerebellum. In MA abusers, self-reports of depressive symptoms covaried positively with relative glucose metabolism in limbic regions (eg, perigenual anterior cingulate gyrus and amygdala) and ratings of state and trait anxiety covaried negatively with relative activity in the anterior cingulate cortex and left insula. Trait anxiety also covaried negatively with relative activity in the orbitofrontal cortex and positively with amygdala activity. CONCLUSIONS: Abusers of MA have abnormalities in brain regions implicated in mood disorders. Relationships between relative glucose metabolism in limbic and paralimbic regions and self-reports of depression and anxiety in MA abusers suggest that these regions are involved in affective dysregulation and may be an important target of intervention for MA dependence.     

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.     

Brain serotonin transporter density and aggression in abstinent methamphetamine abusers

CONTEXT: In animals, methamphetamine is known to have a neurotoxic effect on serotonin neurons, which have been implicated in the regulation of mood, anxiety, and aggression. It remains unknown whether methamphetamine damages serotonin neurons in humans. OBJECTIVE: To investigate the status of brain serotonin neurons and their possible relationship with clinical characteristics in currently abstinent methamphetamine abusers. DESIGN: Case-control analysis. SETTING: A hospital research center. PARTICIPANTS: Twelve currently abstinent former methamphetamine abusers (5 women and 7 men) and 12 age-, sex-, and education-matched control subjects recruited from the community. INTERVENTIONS: The brain regional density of the serotonin transporter, a structural component of serotonin neurons, was estimated using positron emission tomography and trans-1,2,3,5,6,10-beta-hexahydro-6-[4-(methylthio)phenyl]pyrrolo-[2,1-a]isoquinoline ([(11)C](+)McN-5652). Estimates were derived from region-of-interest and statistical parametric mapping methods, followed by within-case analysis using the measures of clinical variables. MAIN OUTCOME MEASURES: The duration of methamphetamine use, the magnitude of aggression and depressive symptoms, and changes in serotonin transporter density represented by the [(11)C](+)McN-5652 distribution volume. RESULTS: Methamphetamine abusers showed increased levels of aggression compared with controls. Region-of-interest and statistical parametric mapping analyses revealed that the serotonin transporter density in global brain regions (eg, the midbrain, thalamus, caudate, putamen, cerebral cortex, and cerebellum) was significantly lower in methamphetamine abusers than in control subjects, and this reduction was significantly inversely correlated with the duration of methamphetamine use. Furthermore, statistical parametric mapping analyses indicated that the density in the orbitofrontal, temporal, and anterior cingulate areas was closely associated with the magnitude of aggression in methamphetamine abusers. CONCLUSIONS: Protracted abuse of methamphetamine may reduce the density of the serotonin transporter in the brain, leading to elevated aggression, even in currently abstinent abusers.     

Evidence for long-term neurotoxicity associated with methamphetamine abuse: A 1H MRS study

OBJECTIVE: To determine whether proton MRS (1H MRS) can detect long-term metabolite abnormalities in abstinent methamphetamine users. BACKGROUND: Methamphetamine is toxic to dopaminergic and serotonergic neurons in rodents; however, little data are available on the toxic effects of methamphetamine on the human brain. METHODS: 1H MRS was performed in 26 abstinent methamphetamine abusers with a history of methamphetamine dependence (median total cumulative lifetime exposure, 3,640 g; median recency of last methamphetamine use, 4.25 months) and 24 healthy subjects without a history of drug abuse. Cerebral metabolite concentrations on 1H MRS were measured in the frontal cortex, frontal white matter, and basal ganglia. RESULTS: The concentration of N-acetylaspartate ([NA]), a neuronal marker, was reduced significantly (-5 to -6%) in the basal ganglia and frontal white matter of methamphetamine users compared with control subjects. The frontal white matter [NA] correlated inversely with the logarithm of the lifetime methamphetamine use. The methamphetamine users also showed significantly reduced total creatine in the basal ganglia (-8%), and increased choline-containing compounds ([CHO], +13%) and myo-inositol ([MI], +11%) in the frontal grey matter. CONCLUSIONS: The reduced [NA] on 1H MRS provides evidence for long-term neuronal damage in abstinent methamphetamine users.     

Methamphetamine Enhances the Development of Schizophrenia in First-Degree Relatives of Patients With Schizophrenia

Objective:

Although there is some evidence that methamphetamine (MA) abuse may play a causative role in the development of schizophrenia, studies directly linking these 2 are rare.

Methods:

In our study, the effect of MA abuse on the development of schizophrenia was investigated in 15 MA abusers who are offspring of patients with schizophrenia and 15 siblings of MA abusers without a history of drug abuse. Cognitive deficits and resting-state brain function were evaluated in all participants. Correlations between cognitive deficits and schizophrenia development were investigated.

Results:

Significantly more cognitive impairments were observed in MA abusers, compared with their siblings without a history of drug use. Significant abnormalities in regional homogeneity (ReHo) signals were observed in resting brain in MA abusers. Decreased ReHo was found to be distributed over the bilateral cingulate gyrus, right Brodmann area 24, and bilateral anterior cingulate cortex. Seven MA abusers were diagnosed with schizophrenia, while 1 control sibling was diagnosed with schizophrenia during the 5-year follow-up. The cognitive scores correlated with the development of schizophrenia in MA abusers.

Conclusion:

Our study provides direct evidence for the causative role of MA use in the etiology of schizophrenia and highlights the role of MA-induced brain abnormalities in cognitive deficiency and development of schizophrenia.     

Prefrontal hypoactivation during cognitive control in early abstinent methamphetamine-dependent subjects

Individuals who abuse methamphetamine (MA) perform at levels below those of healthy controls on tests that require cognitive control. As cognitive control deficits may influence the success of treatment for addiction, we sought to help clarify the neural correlates of this deficit. MA-dependent (n = 10, abstinent 4–7 days) and control subjects (n = 18) performed a color-word Stroop task, which requires cognitive control, during functional MRI (fMRI). The task included a condition in which participants were required to respond to one stimulus dimension while ignoring another conflicting dimension, and another condition without conflict. We compared the groups on performance and neural activation in the two conditions. MA-dependent subjects made more errors and responded more slowly than controls. Controlling for response times in the incongruent condition, voxel-wise mixed effects analyses (whole-brain corrected) demonstrated that MA-dependent subjects had less activation than control subjects in the right inferior frontal gyrus, supplementary motor cortex/anterior cingulate gyrus and the anterior insular cortex during the incongruent condition only. MA-dependent subjects did not exhibit greater activation in any brain region in either of the Stroop conditions. These preliminary findings suggest that hypofunction in cortical areas that are important for executive function underlies cognitive control deficits associated with MA dependence.     

EEG of chronic marijuana users during abstinence: relationship to years of marijuana use, cerebral blood flow and thyroid function.

OBJECTIVE: Marijuana abuse is associated with neurological changes including increases in frontal EEG alpha during abstinence. Research is needed to assess to what extent these EEG patterns are indicative of cerebral perfusion deficits. METHODS: We recorded the resting eyes closed EEG of 75 abstinent marijuana users and 33 control subjects. Fifty-six marijuana users used marijuana for less than eight years and 19 used for eight years or more. The EEG evaluation occurred within 72h of admission to an inpatient unit. Fifty-nine marijuana users remained abstinent for a month and were tested twice. Supplemental psychological and physiological data were also collected. RESULTS: Log alpha2 and beta2 power at posterior sites were significantly lower for the marijuana abusers that used eight years or more than the other marijuana abusers and the control subjects. These EEG changes continued for the month of abstinence. The marijuana users who used marijuana for more than eight years, also, had lower heart rates and thyroid function (T4) compared to the other marijuana users and the control subjects. CONCLUSIONS: Chronic marijuana use was also associated with reduced EEG power in alpha and beta bands at posterior sites. These reductions in EEG power appear to be related to cerebral perfusion deficits and/or thyroid function in marijuana abusers. SIGNIFICANCE: Our results suggest EEG, cerebral blood flow velocity, cardiovascular and thyroid function alterations in marijuana abuser with an extended period of use. These alterations reflect under arousal in these systems.     

Risky decision making and the anterior cingulate cortex in abstinent drug abusers and nonusers

Risky decision making is a hallmark behavioral phenotype of drug abuse; thus, an understanding of its biological bases may inform efforts to develop therapies for addictive disorders. A neurocognitive task that measures this function (Rogers Decision-Making Task; RDMT) was paired with measures of regional cerebral perfusion to identify brain regions that may underlie deficits in risky decision making in drug abusers. Subjects were abstinent drug abusers (> or =3 months) and healthy controls who underwent positron emission tomography scans with H(2)(15)O. Drug abusers showed greater risk taking and heightened sensitivity to rewards than control subjects. Both drug abusers and controls exhibited significant activations in a widespread network of brain regions, primarily in the frontal cortex, previously implicated in decision-making tasks. The only significant group difference in brain activation, however, was found in the left pregenual anterior cingulate cortex, with drug abusers exhibiting less task-related activation than control subjects. There were no significant correlations between neural activity and task performance within the control group. In the drug abuse group, on the other hand, increased risky choices on the RDMT negatively correlated with activation in the right hippocampus, left anterior cingulate gyrus, left medial orbitofrontal cortex, and left parietal lobule, and positively correlated with activation in the right insula. Drug abuse severity was related positively to right medial orbitofrontal activity. Attenuated activation of the pregenual ACC in the drug abusers relative to the controls during performance on the RDMT may underlie the abusers' tendency to choose risky outcomes.     

Partial recovery of brain metabolism in methamphetamine abusers after protracted abstinence

OBJECTIVE: Methamphetamine is a highly addictive drug of abuse that is neurotoxic to dopamine terminals. The authors recently reported that decreases in dopamine transporters (used as markers of dopamine terminals) in the striatum of methamphetamine abusers recover with protracted abstinence and that relative to comparison subjects, recently detoxified methamphetamine abusers have lower metabolism in the striatum and thalamus. In this study, the authors assessed whether metabolism recovers with protracted abstinence. METHOD: Brain glucose metabolism was measured with positron emission tomography and [18F]fluorodeoxyglucose in five methamphetamine abusers who were evaluated after both a short (<6 months) and protracted (12-17 months) abstinence interval, eight methamphetamine abusers tested only after protracted abstinence, and 11 comparison subjects who were not drug users. RESULTS: Significantly greater thalamic, but not striatal, metabolism was seen following protracted abstinence relative to metabolism assessed after a short abstinence interval, and this increase was associated with improved performance in motor and verbal memory tests. Relative to the comparison subjects, the methamphetamine abusers tested after protracted abstinence had lower metabolism in the striatum (most accentuated in the caudate and nucleus accumbens) but not in the thalamus. CONCLUSIONS: The persistent decreases in striatal metabolism in methamphetamine abusers could reflect long-lasting changes in dopamine cell activity, and decreases in the nucleus accumbens could account for the persistence of amotivation and anhedonia in detoxified methamphetamine abusers. The recovery of thalamic metabolism could reflect adaptation responses to compensate for the dopamine deficits, and the associated improvement in neuropsychological performance further indicates its functional significance. These results suggest that while protracted abstinence may reverse some of the methamphetamine-induced alterations in brain function, other deficits persist.     

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.     

Persistent cognitive and dopamine transporter deficits in abstinent methamphetamine users

BACKGROUND: Studies in abstinent methamphetamine (METH) users have demonstrated reductions in brain dopamine transporter (DAT) binding potential (BP), as well as cognitive and motor deficits, but it is not yet clear whether cognitive deficits and brain DAT reductions fully reverse with sustained abstinence, or whether behavioral deficits in METH users are related to dopamine (DA) deficits. This study was conducted to further investigate potential persistent psychomotor deficits secondary to METH abuse, and their relationship to brain DAT availability, as measured using quantitative PET methods with [(11)C]WIN 35428. METHODS: Twenty-two abstinent METH users and 17 healthy non-METH using controls underwent psychometric testing to test the hypothesis that METH users would demonstrate selective deficits in neuropsychiatric domains known to involve DA neurons (e.g., working memory, executive function, motor function). A subset of subjects also underwent PET scanning with [(11)C]WIN 35428. RESULTS: METH users were found to have modest deficits in short-term memory, executive function, and manual dexterity. Exploratory correlational analyses revealed that deficits in memory, but not those in executive or motor function, were associated with decreases in striatal DAT BP. CONCLUSIONS: These results suggest a possible relationship between DAT BP and memory deficits in abstinent METH users, and lend support to the notion that METH produces lasting effects on central DA neurons in humans. As METH can also produce toxic effects on serotonin (5-HT) neurons, further study is needed to address the potential role of brain 5-HT depletion in cognitive deficits in abstinent METH users.     

Association of dopamine transporter reduction with psychomotor impairment in methamphetamine abusers

OBJECTIVE: Methamphetamine is a popular and highly addictive drug of abuse that has raised concerns because it has been shown in laboratory animals to be neurotoxic to dopamine terminals. The authors evaluated if similar changes occur in humans and assessed if they were functionally significant. METHOD: Positron emission tomography scans following administration of [(11)C]d-threo-methylphenidate (a dopamine transporter ligand) measured dopamine transporter levels (a marker of dopamine cell terminals) in the brains of 15 detoxified methamphetamine abusers and 18 comparison subjects. Neuropsychological tests were also performed to assess motor and cognitive function. RESULTS: Methamphetamine abusers showed significant dopamine transporter reduction in the striatum (mean differences of 27.8% in the caudate and 21.1% in the putamen) relative to the comparison subjects; this reduction was evident even in abusers who had been detoxified for at least 11 months. Dopamine transporter reduction was associated with motor slowing and memory impairment. CONCLUSIONS: These results provide evidence that methamphetamine at dose levels taken by human abusers of the drug leads to dopamine transporter reduction that is associated with motor and cognitive impairment. These results emphasize the urgency of alerting clinicians and the public of the long-term changes that methamphetamine can induce in the human brain.     

Impairments of facial emotion recognition and theory of mind in methamphetamine abusers

Chronic use of methamphetamine is related to behavioral disturbances including depression, aggressive behavior, and social isolation. These alterations of social behavior may be attributable to impairments in social cognition. However, few studies have evaluated social cognition in methamphetamine (MA) abusers. Therefore, the aim of the present study was to investigate whether MA abusers exhibit social cognition deficits in terms of facial emotion recognition and theory of mind (ToM). We also assessed cognitive flexibility by using the Wisconsin Card Sorting Test (WCST) to evaluate the impact of this function on social cognition. Twenty-eight MA abusers and twenty-seven healthy subjects enrolled in this study. All participants performed the Facial Emotion Recognition Task and advanced ToM tasks such as the Eye Test and Hinting Task. The Korean Wechsler Adult Intelligence Scale—Revised and computerized versions of the WCST were also administrated. The performances of MA abusers on the Facial Emotion Recognition Task and Eyes Test were lower than those of healthy subjects. In the WCST, MA abusers completed significantly fewer categories and made more total and perseverative errors than healthy subjects did. In addition, impairments in cognitive flexibility are correlated with impairments in facial emotion recognition and ToM within MA abusers. These findings lend further support to the assertion that the capacity to identify emotions from facial expression and infer mental state of others is impaired in MA abusers. Therefore, treatment and rehabilitation for MA abusers must consider role of social cognition and include relearning social interactions and behaviors.     

Frontoparietal cortical activity of methamphetamine-dependent and comparison subjects performing a delay discounting task

Relative to individuals who do not have addictive disorders, drug abusers exhibit greater devaluation of rewards as a function of their delay ("delay discounting"). The present study sought to extend this finding to methamphetamine (MA) abusers and to help understand its neural basis. MA abusers (n = 12) and control subjects who did not use illicit drugs (n = 17) participated in tests of delay discounting with hypothetical money rewards. We then used a derived estimate of each individual's delay discounting to generate a functional magnetic resonance imaging probe task consisting of three conditions: "hard choices," requiring selections between "smaller, sooner" and "larger, later" alternatives that were similarly valued given the individual's delay discounting; "easy choices," in which alternatives differed dramatically in value; and a "no choice" control condition. MA abusers exhibited more delay discounting than control subjects (P < 0.05). Across groups, the "hard choice > no choice" contrast revealed significant effects in the ventrolateral prefrontal cortex, dorsolateral prefrontal cortex (DLPFC), dorsal anterior cingulate cortex, and areas surrounding the intraparietal sulcus (IPS). With group comparisons limited to these clusters, the "hard choice > easy choice" contrast indicated significant group differences in task-related activity within the left DLPFC and right IPS; qualitatively similar nonsignificant effects were present in the other clusters tested. Whereas control subjects showed less recruitment associated with easy than with hard choices, MA abusers generally did not. Correlational analysis did not indicate a relationship between this anomaly in frontoparietal recruitment and greater degree of delay discounting exhibited by MA abusers. Therefore, while apparent inefficiency of cortical processing related to decision-making in MA abusers may contribute to the neural basis of enhanced delay discounting by this population, other factors remain to be identified.     

Behavioral regulation in methamphetamine abusers: An fMRI study

The goal of this study was to extend our previous findings of abnormal prefrontal function in methamphetamine (MA) abusers and controls and to link the imaging data to behavioral, demographic and drug use variables. We used a fast event-related functional magnetic resonance imaging (fMRI) design to examine trial-to-trial reaction time (RT) adjustments in 30 MA abusers and 30 controls. A variant of the Stroop task was employed to measure influence of response conflict on RT, including the level of trial-to-trial RT adjustments seen after conflict trials. Compared to control subjects, MA abusers exhibited reduced RT adjustments and reduced activation in the prefrontal cortex (PFC) after conflict trials. RT adjustment correlated negatively with PFC brain activity in the MA group, while a trend for a positive correlation was observed in controls. No correlations were observed between task performance or brain activity and age, education or drug use variables. These data support our previous findings that the ability to adapt a behavioral response based on prior experience is compromised in MA abusers. Interestingly, these impairments do not appear to be linked to drug use patterns or to educational levels.     

Implications of chronic methamphetamine use: a literature review

Methamphetamine (MA) abuse is increasing to epidemic proportions, both nationally and globally. Chronic MA use has been linked to significant impairments in different arenas of neuropsychological function. To better understand this issue, a computerized literature search (PubMed, 1964-2004) was used to collect research studies examining the neurobiological and neuropsychiatric consequences of chronic MA use. Availability of MA has markedly increased in the United States due to recent technological improvements in both mass production and clandestine synthesis, leading to significant public health, legal, and environmental problems. MA intoxication has been associated with significant psychiatric and medical comorbidity. Research in animal models and human subjects reveals complicated mechanisms of neurotoxicity by which chronic MA use affects catecholamine neurotransmission. This pathology may underlie the characteristic cognitive deficits that plague chronic MA users, who experience impairments in memory and learning, psychomotor speed, and information processing. These impairments have the potential to compromise, in turn, the ability of MA abusers to engage in, and benefit from, psychosocially based chemical-dependency treatment. Development of pharmacological interventions to improve these cognitive impairments in this population may significantly improve the degree to which they may be able to participate in treatment. Atypical antipsychotics may have some promise in this regard.     

Perfusion MRI and computerized cognitive test abnormalities in abstinent methamphetamine users

This study aims to determine possible persistent abnormalities in regional cerebral blood flow (relative rCBF) and cognitive function in abstinent methamphetamine (METH) users. Twenty METH-dependent subjects (abstinent for 8+/-2 months) and 20 age- and gender-matched controls were evaluated with perfusion magnetic resonance imaging (pMRI) and neuropsychological tests. METH users showed decreased relative rCBF bilaterally in putamen/insular cortices (right: -12%; left: -10%) and the right lateral parietal brain region (-11%), but increased relative rCBF bilaterally in the left temporoparietal white matter (+13%), the left occipital brain region: (+10%) and the right posterior parietal region (+24%). Interaction effects were observed between METH and gender in the right occipital cortex and a midline brain region; female METH users showed increased relative rCBF (+15% both regions) whereas the male METH users had decreased relative rCBF (-10% and -18%, respectively). METH users performed within normal ranges on standard neuropsychological tests; however, they were slower on several tasks on the California Computerized Assessment Package (CalCAP), especially tasks that required working memory. These findings suggest that METH abuse is associated with persistent physiologic changes in the brain, and these changes are accompanied by slower reaction times on computerized measures of cognitive function.     

Reduced cerebral glucose metabolism in patients at risk for Alzheimer's disease

While significantly reduced glucose metabolism in fronto-temporo-parietal and cingulate cortices has been demonstrated in Alzheimer's disease (AD) compared with controls, cerebral glucose metabolism in patients with mild cognitive impairment who subsequently develop AD is less well-defined. In the present study we measured cerebral glucose metabolism by positron emission tomography (PET) with (18)F-2-fluoro-2-deoxy-D-glucose in 14 patients with aging-associated cognitive decline (AACD), 44 patients with AD, and 14 healthy control subjects at baseline. The AACD patients were clinically followed up, and conversion to AD was determined. Compared with controls, AACD patients had significantly reduced glucose metabolism in the right precuneus, posterior cingulate, right angular gyrus, and bilateral middle temporal cortices, while the respective deficits were more pronounced in AD patients and also involved the frontal cortices. AACD patients who subsequently converted to AD (AACD-converters) showed more extended metabolic changes which also involved the frontal and temporal cortices, right cingulate gyrus, right thalamus, and bilateral precuneus.     

Decreased conflict- and error-related activity in the anterior cingulate cortex in subjects with schizophrenia

OBJECTIVE: People with schizophrenia have exhibited reduced functional activity in the anterior cingulate cortex during the performance of many types of cognitive tasks and during the commission of errors. According to conflict theory, the anterior cingulate cortex is involved in the monitoring of response conflict, acting as a signal for a need for greater cognitive control. This study examined whether impaired conflict monitoring in people with schizophrenia could underlie reduced anterior cingulate activity during both correct task performance and error-related activity. METHOD: Functional activity in the anterior cingulate of 13 schizophrenia patients and 13 healthy comparison subjects was investigated by using event-related fMRI and a Stroop task that allowed simultaneous examination of activity during both conflict (incongruent trials) and error (commission of error trials). RESULTS: In the presence of comparable reaction time measures for conflict as well as comparable error rates, the schizophrenia subjects showed both decreased conflict- and error-related activity in the same region of the anterior cingulate cortex. Moreover, those with schizophrenia did not exhibit significant post-conflict or post-error behavioral adjustments. CONCLUSIONS: Concurrently reduced conflict- and error-related activity in the anterior cingulate cortex along with reduced trial-to-trial adjustments in performance has not previously been reported in schizophrenia. The current results suggest that impaired conflict monitoring by the anterior cingulate cortex might play an important role in contributing to cognitive control deficits in patients with schizophrenia.