Biomedical subjects

Thomas E Nordahl

Publications and source records attributed to Thomas E Nordahl.

11 recordsLinked to original sources

PubMed2006

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.

Adult↗

PubMed2005

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.

Adult↗

PubMed2005

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.

Adult↗

PubMed2003

Sex differences in the corpus callosum of patients with schizophrenia.

The corpus callosum (CC) has been of interest in schizophrenia research because of its possible role in reduced lateralization and because of its sexually dimorphic characteristics. The literature has been replete with structural brain studies that have yielded equivocal results because of failure to address sex differences, handedness, and overall reductions in total brain volume (TBV) associated with schizophrenia. We performed midsagittal corpus callosum area MRI measurements on 71 chronically ill patients with schizophrenia (52 males, 19 females) and 67 controls (49 males, 18 females) using a semiautomated analytic technique subdividing the corpus callosum into five segments. Consistent with a meta-analysis [J. Neurol., Neurosurg. Psychiatry 58 (1995) 457], reductions in total CC area (after controlling for TBV and age) were found in schizophrenia patients relative to controls. However, our effect size, though not statistically significant, was -0.33 compared to -0.18 for the meta-analysis, indicating greater reductions in total CC area in our group of patients. Statistical significance was achieved only in male patients versus male controls (effect size=-0.50). The effect size remained the same when only right-handers were included in the analysis; thus, handedness did not account for this result. CC size was not related to psychiatric symptoms nor cognitive functioning in this group of patients.

Adult↗

PubMed2003

Neuropsychological effects of chronic methamphetamine use on neurotransmitters and cognition: a review.

Methamphetamine use is on the rise, with an imminent upsurge of abuse and dependence reported across the United States. Currently, preliminary evidence suggests that methamphetamine dependence may cause long-term neural damage in humans, with concomitant deleterious effects on cognitive processes such as memory and attention. This selective review provides an outline and synthesis of studies that assess the neurotoxic mechanisms of methamphetamine, as well as those that evaluate the cognitive sequelae of methamphetamine abuse.

Central Nervous System Stimulants↗

PubMed2002

Low N-acetyl-aspartate and high choline in the anterior cingulum of recently abstinent methamphetamine-dependent subjects: a preliminary proton MRS study. Magnetic resonance spectroscopy.

Studies based on animal models report that methamphetamine (MA) abuse diminishes dopamine (DA) and serotonin innervation in frontal brain regions. In this in vivo human study, we used proton magnetic resonance spectroscopy (MRS), which yields measures of N-acetyl-aspartate (NAA), a marker of living neurons, to examine frontal brain regions possibly affected by methamphetamine dependence (MD). We tested the hypothesis that MD subjects would exhibit abnormally low levels of NAA, referenced to creatine (Cr), in anterior cingulate gray matter. We further hypothesized that the primary visual cortex, which receives relatively less DA innervation than the frontal brain regions, would show normal NAA/Cr ratios in MD subjects. Subjects included nine MD men (mean+/-standard deviation (S.D.)=32.5+/-6.4 years) and nine age-matched control men (mean+/-S.D.=32.7+/-6.8 years). The MD subjects were MA-free for 4-13 weeks. Proton MRS metabolites were expressed as ratios of creatine; the absolute values of which did not distinguish controls and MD subjects. With regard to metabolite ratios, the MD men had significantly lower NAA/Cr in the cingulum (mean+/-standard error (S.E.): control=1.46+/-0.03; MD=1.30+/-0.03; Mann-Whitney P=0.01) but not in the visual cortex (mean+/-S.E.: control=1.64+/-0.06; MD=1.69+/-11; Mann-Whitney P=0.52) relative to controls. These results provide evidence for NAA/Cr deficit that is selective to the anterior cingulum, at least with respect to visual cortex, in MD subjects. The neuronal compromise that these changes reflect may contribute to the attentional deficits and dampened reward system in MD.

Adult↗

PubMed2002

Preliminary evidence of reduced cognitive inhibition in methamphetamine-dependent individuals.

Chronic methamphetamine abuse is associated with disruption of frontostriatal function involving serotonin and dopamine circuitry. Clinically, methamphetamine-dependent (MD) individuals are highly distractible and have difficulty focussing. Here, we used a computerized single-trial version of the Stroop Test to examine selective attention and priming in MD. Subject groups comprised eight MD men (31.7+/-7.2 years of age), who had used methamphetamine for 15.75+/-8.4 years but were currently abstinent for 2-4 months, and 12 controls (35.7+9.7 years of age). Compared with the control group, the MD group exhibited significantly greater interference (P<0.05) despite intact priming. Error rates did not differ between the groups. This preliminary finding of reduced cognitive inhibition in MD individuals is consistent with the distractibility they show clinically. Furthermore, the dissociation between explicit attentional performance and priming effects suggests that some attentional functions are not as affected by long-term methamphetamine use as others.

Adult↗

PubMed2002

Attentional control and word inhibition in schizophrenia.

Previous studies have suggested that schizophrenia patients do not utilize contextual information efficiently to modulate attentional performance. The goal of the current study was to compare the utilization of context in modulating responses to irrelevant information on the Stroop task between a group of schizophrenia outpatients and matched controls. A single-trial version of the Stroop task was used to investigate performance on the Stroop task under three expectancy conditions. Eleven schizophrenia outpatients (on and off antipsychotic medication) and sixteen matched controls were tested. The schizophrenia patients showed: (1) augmented facilitation; (2) interference comparable to normals; and (3) normal ability to reduce interference under certain experimental circumstances. Schizophrenia patients were able to utilize contextual information under certain conditions and could modulate the magnitude of irrelevant word interference, although they were not able to overcome the prepotent tendency to read the word during the Stroop task as effectively as normals, which was reflected in greater Stroop facilitation. This suggests that the integrity or impairment of cognitive control functions in schizophrenia is related to the complexity of the context representation required to support that function.

Adult↗

PubMed2002

Immediate versus sustained processing in schizophrenia.

A Stroop negative priming (NP) task was used to assess immediate selective attention and priming in schizophrenia and schizoaffective disorder. Subject groups were comprised of 12 state hospital inpatients (41.8 +/- 7.5 years of age), 11 outpatients (39.8 +/- 7.5 years of age), and 16 controls (36.4 +/- 11.7 years of age). Compared with the control group and the outpatients, inpatients failed to exhibit NP [F(2,36) = 6.09, p < .01], despite exhibiting equivalent Stroop RT interference (p > .05). Error rates did not differ significantly between the 3 groups. Although medication types and dosages were similar between the 2 patient groups, length of illness was significantly longer in the inpatients (19.8 years) than in the outpatients (12.4 years; p < .05). Positive symptom ratings were also significantly higher in the inpatients. The finding of reduced NP in the state hospital patients appears to be related to severity of symptomatology and chronicity of illness.

Adult↗

PubMed2002

Time course of inhibition and facilitation in patients with schizophrenia.

INTRODUCTION: Negative priming (NP) paradigms have been used extensively to understand the nature and time course of inhibitory deficits in patient populations. A majority of these studies have reported abnormal NP effects, with patients showing faster reaction times on NP sequences compared to the slowing displayed by controls. METHODS: A Stroop NP task was employed to measure immediate (within-trial) attentional processing as well as the sustainment (between-trial) of these processes in 12 medicated schizophrenia inpatients and 13 matched controls. Two response stimulus intervals (RSIs) were presented (500 ms and 2000 ms). Within-trial Stroop effects (interference and facilitation) and between-trial priming effects (negative and positive priming) were measured. Clinical symptomatology and duration of illness were also examined. RESULTS: At short RSIs of 500 ms, chronically ill state hospital schizophrenia patients failed to exhibit NP. In contrast, the control subjects exhibited normal NP at the short RSI but this priming faded at the long 2000 ms RSI and was no longer significant. The facilitatory priming effects remained stable across time in both groups. CONCLUSIONS: These results suggest that schizophrenia patients are better able to inhibit irrelevant stimuli that are immediate, but the sustainment of inhibition across very short time intervals (500 ms) may fade compared to controls.

Journal Article↗

PubMedDate not supplied

No effect of age and estrogen on aromatic L- amino acid decarboxylase activity in rhesus monkey brain.

A variety of studies have shown an effect of estrogen on dopamine function and suggest that estrogen may modulate central dopaminergic activity. Positron emission tomography (PET) and the dopamine metabolism tracer, [18F]6-fluoro-L-m-tyrosine (FMT) were used to evaluate dopaminergic function in the frontal cortex and striatum in six aged, but pre-menopausal, female monkeys before and after ovariectomy (OVX). Dynamic PET brain uptake data and metabolite-corrected blood input functions were fit to a three-compartment model for FMT uptake. Prior to OVX, all animals showed preferential accumulation of the tracer bilaterally in the striatum and less but measurable activity in the frontal cortex. Paired comparisons showed that there were no significant differences in FMT uptake (K(i)) in either brain region before and after OVX. In addition, FMT uptake did not differ from a group of young adult female monkeys at either time point. These findings may represent a compensatory up-regulation of aromatic L- amino acid decarboxylase (AADC) activity.

Age Factors↗