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.     

Intact visual word priming in cocaine dependent subjects with and without cognitive deficit

1. The effects of semantic and repetition priming on reaction time were assessed in 27 recently abstinent cocaine and cocaine/alcohol dependent volunteers and 12 controls without substance abuse history. 2. The 27 cocaine dependent subjects were further divided into cognitively intact (N = 13) and moderate-to-severe cognitively impaired (N = 14) groups on the basis of neuropsychological testing. 3. Both cognitively intact and cognitively impaired cocaine dependent groups showed motor-response facilitation by semantic and repetition priming not significantly different from that of non-abusing controls. 4. It is proposed that both semantic and perceptually mediated visual word priming are implicit cognitive processes resilient to the sequelae of cocaine dependence which impact upon explicit cognitive systems.     

Preserved priming but insensitivity to perceptual fluency on recognition judgments in Alzheimer's disease

Background: Previous research on Alzheimer's disease (AD) has not yielded a consensus regarding the preservation of automatic memory processes, although there is a consensus that conscious recollection processes are impaired in AD. Methods: In the present study, we examined perceptual specificity effects (PSEs) in word recognition judgments (explicit memory task; Experiment 1) and word fragment completion (implicit memory task; Experiment 2) performed by individuals with mild AD and elderly adults without dementia (controls). Results: In recognition judgments, control subjects, but not individuals with AD, demonstrated PSEs (Experiment 1). In contrast, neither group showed PSEs on word fragment completion and their priming magnitudes were comparable (Experiment 2). Conclusions: The findings suggest that perceptually automatic processes in explicit memory judgments and implicit memory processes are different and that the former are specifically impaired in AD.     

Intact haptic priming in normal aging and Alzheimer's disease: evidence for dissociable memory systems

This study is the first to report complete priming in Alzheimer's disease (AD) patients and older control subjects for objects presented haptically. To investigate possible dissociations between implicit and explicit objects representations, young adults, Alzheimer's patients, and older controls performed a speeded object naming task followed by a recognition task. Similar haptic priming was exhibited by the three groups, although young adults responded faster than the two older groups. Furthermore, there was no difference in performance between the two healthy groups. On the other hand, younger and older healthy adults did not differ on explicit recognition while, as expected, AD patients were highly impaired. The double dissociation suggests that different memory systems mediate both types of memory tasks. The preservation of intact haptic priming in AD provides strong support to the idea that object implicit memory is mediated by a memory system that is different from the medial-temporal diencephalic system underlying explicit memory, which is impaired early in AD. Recent imaging and behavioral studies suggest that the implicit memory system may depend on extrastriate areas of the occipital cortex although somatosensory cortical mechanisms may also be involved.     

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.     

Spatial orienting of attention: a study of reaction time during pointing movement]

AIM: The aim of this study was to investigate how advance information both explicit and implicit provided prior to movement may affect the spatial orientation and the internal attention control processes in normal adult subjects. The originality of this work compared to the test of Posner, lies essentially in the methodology used to study the attentional systems. The use of three procedures of reaction time (RT) allowed us to study the setting concerned of the specific and non-specific components of the attention in the motor preparation. By associating of these three procedures of RT, we have evaluated the effects of the explicit and implicit components of advance information on motor preparation. The use of advance information to the movement requires the implication of the attentional systems. MATERIAL AND METHODS: Experiments were carried out using a simple reaction time (RT) procedure involving the use of an orientation cue and two choice reaction time situations: one with a neutral preparatory cue and one with a priming cue giving the likelihood of the preparatory stimulus (S1) being compatible with the imperative stimulus (S2). The mechanisms underlying the subjects' vigilance and the orientation of their attention were studied by assessing the effects on their reaction times of the preparatory signal and those of the cue giving the likelihood of S1 and S2 being compatible. The preparatory signal was designed to explicitly attract the subjects' attention towards the position of the forthcoming pointing target, whereas the cue giving the compatibility between S1 and S2 was intended to mobilize the subject's attention more implicitly. Prior to performing the pointing movement towards a visual target, the subjects' attention was therefore mobilized by the advance information containing two components: the explicit information about the position of S1 and the implicit information about the probability of S1 and S2 being compatible. RESULTS AND CONCLUSION: The results obtained here on 17 normal adult subjects show that the subjects significantly improved their RTs by using the explicit component of the information provided. The implicit information available was also used in the choice reaction situations: a priming effect was found to occur, which resulted in the shortening of the primed "compatible cue" reaction times in comparison with the "neutral cue" reaction times, and in the correlation which was found to exist between the reaction time performances and the degree of compatibility between the preparatory signal and the imperative signal. These results suggest that various components of the attentional system may participate in processing the advance information provided prior to the movement in reaction time tasks of the kind used here. The explicit information provided prior to the movement may mobilize the subject's vigilance and spatially orients his attention; whereas the implicit information available may rather subserve the internal control of the subject's attention.     

Normal attention orienting but abnormal stimulus alerting and conflict effect in combined subtype of ADHD

Recent pharmacological studies in animals and neuroimaging studies in normal humans suggest that the spatial and nonspatial cues in tasks measuring reflexive attention may be modulated by different neurotransmitter systems. The efficiency with which attention is oriented to explicit spatial cues may be altered by manipulating levels of brain acetylcholine, whereas reactions to nonspatial cues may be influenced by altering brain noradrenaline levels but not acetylcholine levels. In humans, however, previous attention studies have implicated dopamine when either explicit or implicit cueing is used. Some of the differences between animal and human work may be due to inadequate testing of nonspatial cues. To remedy this, we tested adult humans with ADHD that were primarily inattentive (ADHD/I) or combined inattentive/hyperactive (ADHD/C) and controls with the Attention Network Task that assesses both reflexive and voluntary attention and explicitly tests nonspatial cueing. Our results showed that spatial orienting in both subtypes was no different than controls. However, ADHD/C but not ADHD/I subjects had significantly slowed response times to nonspatial cues and cues with spatial conflict. Stimulant medication in a subset of ADHD/C subjects reduced these deficits to control levels. Based on these results, we conclude that ADHD/C subjects orient the focus of their attention normally but are impaired in their reactions both to abrupt visual cues and those that contain conflicting spatial cues.     

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.     

Severity of explicit memory impairment due to Alzheimer’s disease improves effectiveness of implicit learning

Background Consistent evidence from human and experimental animals studies indicates that memory is organized into two relatively independent systems with different functions and brain mechanisms. The explicit memory system, dependent on the hippocampus and adjacent medial temporal lobe structures, refers to conscious knowledge acquisition and intentional recollection of previous experiences. The implicit memory system, dependent on the striatum, refers to learning of complex information without awareness or intention. The functioning of implicit memory can be observed in progressive, gradual improvement across many trials in performance on implicit learning tasks. The influence of explicit memory on implicit memory has not been precisely identified yet. According to data from some studies, explicit memory seems to exhibit no influence on implicit memory,whereas the other studies indicate that explicit memory may inhibit or facilitate implicit memory. Objectives The analysis of performance on implicit learning tasks in patients with different severity of explicit memory impairment due to Alzheimer’s disease allows one to identify the potential influence of the explicit memory system on the implicit memory system. Patients and methods 51 patients with explicit memory impairment due to Alzheimer’s disease (AD) and 36 healthy controls were tested. Explicit memory was examined by means of a battery of neuropsychological tests. Implicit habit learning was examined on probabilistic classification task (weather prediction task). Results Patients with moderate explicit memory impairment performed the implicit task significantly better than those with mild AD and controls. Conclusion Results of our study support the hypothesis of competition between the implicit and explicit memory systems in humans.     

Investigation of serum BDNF levels in drug-naive patients with schizophrenia

The role of brain-derived neurotrophic factor (BDNF) is to promote and modulate the neuronal responses across neurotransmitter systems in the brain. Therefore, abnormal BDNF signaling may be associated with the pathophysiology of schizophrenia. Decreased BDNF levels in the brain and the serum of patients with psychotic disorders have been reported. In the present study, we assessed serum BDNF levels in a group of 14 drug-naive first-episode patients with schizophrenia (FEP), compared to 15 healthy controls. The serum BDNF levels in the sample of FEP patients was significantly reduced compared to normal controls (23.92+/-5.99 ng/ml vs. 30.0+/-8.43 ng/ml, F=5.01, df=1, p=.034). Negative correlations were shown between serum BDNF levels of the patients and the PANSS Positive and Negative subscale scores. Our findings indicate that BDNF levels at the onset of schizophrenia may reflect associated pathophysiological processes as well as the severity of positive and negative psychotic symptoms.     

Brain atrophy rates in Parkinson's disease with and without dementia using serial magnetic resonance imaging.

Increased rates of brain atrophy are seen in Alzheimer's disease, but whether rates are similarly increased in other dementias such as Parkinson's disease dementia (PDD) has not been well examined. We determined the rates of brain atrophy using serial magnetic resonance imaging (MRI) in PDD and compared this finding to rates seen in cognitively intact Parkinson's disease (PD) patients and age-matched control subjects. Thirty-one patients (PD = 18, PDD = 13) and 24 age-matched controls underwent serial volumetric 1.5 T MRI scans, approximately 1 year apart. Baseline and repeat scans were registered and quantification of the brain boundary shift integral was used to determine whole-brain atrophy rates. Rates of brain atrophy were significantly increased in PDD (1.12 +/- 0.98%/year) compared to PD (0.31 +/- 0.69%/year; P = 0.018) and control subjects (0.34 +/- 0.76%/year; P = 0.015). There were no differences in atrophy rates between controls and PD (P = 0.79). No correlations between increased atrophy rates and age or dementia severity (Mini-Mental State Examination score) were observed. Serial MRI may be a useful tool for monitoring disease progression in PDD and further studies should investigate its utility for early diagnosis.     

Attention-deficit hyperactivity disorder involves differential cortical processing in a visual spatial attention paradigm.

OBJECTIVE: Inattention is undoubtedly one of the main characteristics of Attention-deficit hyperactivity disorder (ADHD). Nevertheless, a growing corpus of evidence shows that not all attentional processes are affected in this condition. This study aimed to explore the distribution of attentional resources in children with ADHD via a spatially shifted double-oddball visual task. METHODS: We recorded event-related potentials (ERPs) for all visual stimuli. Subjects were instructed to allocate attention in a specific area of visual space while ignoring all stimuli presented outside. Ten male children (age: 9-14; mean = 11.6 +/- 2.1) who met DSM-IV criteria for the ADHD combined subtype participated in the study, along with ten age- and sex-matched healthy controls (9-14; mean = 11.2 +/- 2.3). RESULTS: ADHD subjects showed late differential cortical responses to initially suppressed irrelevant stimuli. The amplitude of early N1-P1 components were mainly modulated by stimulus location and showed no significant differences between groups, but a late P300-like positivity was clearly evoked in the ADHD group by peripheral stimuli. CONCLUSIONS: These results suggest that ADHD may not compromise the early attentional spatial filter but rather entails a different distribution of attentional resources at later stages of cortical processing. Perhaps these differences may be attributable to individual differences in attentional mechanisms. SIGNIFICANCE: ADHD may not affect initial focusing of visual attention but rather the allocation of processing resources in later stages.     

Striatal dopamine output is compromised within +/- BDNF mice.

We reported previously that mice lacking one brain-derived neurotrophic factor (BDNF) allele demonstrate elevated striatal dopamine (DA) concentrations but impaired behavioral responses involving the nigrostriatal dopaminergic (NSDA) system. To test the hypothesis that these elevated striatal DA concentrations are associated with perturbed NSDA functioning, we compared striatal DA output between heterozygous mutant (+/-) and wild-type littermate control (+/+) BDNF mice under conditions of an intact NSDA system, as well as following methamphetamine (MA)-induced neurotoxicity. Basal DA output from superfused CS tissue fragments did not differ between +/+ and +/- BDNF mice. Potassium (K+) stimulated DA outputs from intact striatal fragments of +/+ mice were significantly greater than that of +/- BDNF mice. Following MA treatment, K+ stimulated DA output of +/+ mice was statistically equivalent to +/- BDNF mice. Striatal DA concentrations of +/- BDNF mice were elevated, albeit not significantly, in both intact and MA-treated mice relative to +/+ mice. Following MA treatment, striatal DA concentrations were significantly decreased for both genotypes; however, the degree of DA depletion was significantly greater in +/+ mice. Analyzed collectively, these data show the differential effects exerted by a BDNF mutation upon striatal DA concentrations and output. Notably, lower striatal DA concentrations of +/+ vs. +/- BDNF mice can be contrasted with the significantly greater K+ stimulated DA output from the former. This difference was abolished following MA treatment. These results suggest that processes involved with the dynamics of DA release within the NSDA system may be compromised in +/- BDNF mutant mice.     

Deficient sustained attention to response task and P300 characteristics in early Huntington’s disease

Evidence for the extent and nature of attentional impairment in premanifest and manifest Huntington's disease (HD) is inconsistent. Understanding such impairments may help to better understand early functional changes in HD and could have consequences concerning care for HD patients. We investigated attentional control in both early and premanifest HD. We studied 17 early HD subjects (mean age: 51 years), 12 premanifest HD subjects (mean age: 43 years), and 15 healthy controls (mean age: 51 years), using the sustained attention to response task (SART), a simple Go/No-go test reflecting attentional and inhibitory processes through reaction time (RT) and error rates. Simultaneously recorded EEG yielded P300 amplitudes and latencies. The early HD group made more Go errors (p < 0.001) and reacted slower (p < 0.005) than the other groups. The RT pattern during the SART was remarkably different for early HD subjects compared to the other two groups (p < 0.005), apparent as significant post-error slowing. P300 data showed that for early HD the No-go amplitude was lower than for the other two groups (p < 0.05). Subjects with early HD showed a reduced capacity to effectively control attention. They proved unable to resume the task directly after having made an error, and need more time to return to pre-error performance levels. No attentional control deficits were found for the premanifest HD group.     

Developmental differences in sleep's role for implicit off-line learning: comparing children with adults

Sleep crucially contributes to the off-line consolidation of memories. Although this view was confirmed in numerous studies in adults, it is not known whether it can be generalized to sleep during development. Here, we examined effects of sleep on implicit memory formation considered of particular relevance in children, because brain structures underlying implicit learning develop earlier in ontogeny than structures supporting explicit learning. Subjects were 7- to 11-year-old children (n = 14) and 20- to 30-year-old adults (n = 12) tested on a serial reaction time task before (learning) and after (retest) equal length retention periods of overnight sleep and daytime wakefulness. At learning, after eight training blocks, all subjects had acquired implicit knowledge of the probabilistic rules underlying the sequential stimulus materials, as indicated by a substantial difference in response time to grammatical versus nongrammatical trials in two test blocks that followed the training blocks. At learning, this response time difference was greater in children (48.49 +/- 6.08 msec) than adults (28.02 +/- 3.65 msec, p < .01), but did not differ between sleep and wake retention conditions in either age group. Consistent with previous studies, retesting in the adults revealed that the reaction time differences between grammatical and nongrammatical trials increased by 9.78 +/- 4.82 msec after sleep, but decreased by -12.76 +/- 5.49 msec after the wake retention period (p < .01). Contrary to this finding in adults, sleep in children did not lead to an increase, but to a decrease in the reaction time difference averaging -26.68 +/- 12.25 msec (p < .05), whereas across the wake retention interval the reaction time difference remained nearly unchanged. The sleep-dependent deterioration in measures of implicit sequence knowledge in children was in striking contrast to the gain of such knowledge in the adults during sleep (p < .01). Our findings indicate that the functional role of sleep in implicit memory consolidation depends on age. We speculate that the overnight decrease of implicit knowledge in children reflects a preferential effect of sleep toward the enhancement of explicit aspects of task performance that interferes with implicit performance gains.     

High nitric oxide production in autistic disorder: a possible role for interferon-gamma.

BACKGROUND: Neuroimmune regulation abnormalities have been implicated in the pathophysiology of autistic disorder. Nitric oxide (NO) is involved in immune reactivity and is known to affect brain neurodevelopmental processes. Recent evidence indicates that NO, and cytokines involved in NO production, may be high in children with autism. The purpose of this study was to verify that plasma NO is high in children with autism and determine whether this elevation is related to plasma levels of cytokines involved in NO production. METHODS: The metabolites of NO, nitrite, and nitrate (NOx), along with the cytokines interferon-gamma (IFN-gamma), tumor necrosis factor-alpha, and interleukin-1beta, were measured in plasma of 29 children with autism (mean age +/- SD = 6.1 +/- 2.8 years) and 27 age- and gender-matched healthy comparison subjects using commercially available assay kits. RESULTS: Plasma levels of NOx were significantly higher in the autistic subjects (p =.006); plasma levels of the cytokines did not differ between groups. NOx and IFN-gamma levels were positively correlated in the autistic subjects (r =.51; p =.005). CONCLUSIONS: These results confirm that plasma NO is high in some children with autism and suggest that this elevation may be related to IFN-gamma activity.     

Cognitive performance in REM sleep behaviour disorder: a possible early marker of neurodegenerative disease?

BACKGROUND: Rapid eye movement [REM] sleep behaviour disorder (RBD) may herald neurodegenerative diseases. Neurobiological deficits similar to those identified in neurodegenerative diseases have been reported in idiopathic RBD. Researchers are looking for early markers supporting a possible role of RBD as a harbinger of impending neurodegenerative disease. OBJECTIVE: To examine the neuropsychological functions in idiopathic RBD subjects. Should they be found to present a neuropsychological dysfunction that overlaps that reported in neurodegenerative diseases, it would be possible to consider cognitive deficits as possible early markers of an underlying degenerative process. METHODS: Twenty-three subjects with idiopathic RBD (21 males, mean age 67.0+/-7.0 years) and a group of healthy controls matched for sex, age and education underwent a neuropsychological battery evaluating different cognitive domains. FINDINGS: Considering mean values, poorer performances were observed in the Word Span (p<.001), Rey-Osterrieth's complex figure recall (p=.003), Digit Span (p=.003) and Logic Memory (p=.003) tests. On the basis of equivalent scores, the RBD subjects performed significantly more poorly on tests of visuo-constructional learning abilities (p<.001). INTERPRETATION: Our data show the possible presence of cognitive deficits in RBD defined as idiopathic, sharing common features in particular with Lewy body disease. Neuropsychological evaluation in RBD could lead to presymptomatic identification of neurodegenerative disease, but until more prolonged long-term follow-up data are available, the true neurobiological significance of cognitive deficits in RBD will remain unknown.     

Spatial inhibition and the visual cortex: a magnetic resonance spectroscopy imaging study

Introduction

Deficits in processing spatial information have been observed in clinical populations who have abnormalities within the dopamine (DA) system. As psychostimulants such as methamphetamine (MA) are particularly neurotoxic to the dopaminergic system it was of interest to examine the performance of MA-dependent individuals on a task of spatial attention.

Method

51 MA-dependent subjects and 22 age-matched non-substance abusing control subjects were tested on a Spatial Stroop attention test. MR Spectroscopy (MRS) imaging data were analyzed from 32 MA abusers and 13 controls.

Results

No group differences in response time or accuracy emerged on the behavioral task with both groups exhibiting equivalent slowing when the word meaning and the spatial location of the word were in conflict. MRS imaging data from the MA abusers revealed a strong inverse correlation between NAA/Cr ratios in the Primary Visual Cortex (PVC) and spatial interference (p = 0.0001). Moderate inverse correlations were also seen in the Anterior Cingulate Cortex (ACC) (p = 0.02). No significant correlations were observed in the controls, perhaps due to the small sample of imaging data available (n = 13).

Discussion

The strong correlation between spatial conflict suppression and NAA/Cr levels within the PVC in the MA-dependent individuals suggests that preserved neuronal integrity within the PVC of stimulant abusers may modulate cognitive mechanisms that process implicit spatial information.     

Neural correlates of attentional deficits in Parkinson's disease patients with mild cognitive impairment

IntroductionDeficits in attentional processing observed in Parkinson's disease (PD) patients with mild cognitive impairment (MCI) increase risk of PD dementia. However, the neural basis of these attentional deficits are presently unknown. The present study aimed to explore the neural correlates of attention dysfunction in PD-MCI using the Attention Network Test (ANT) and functional Magnetic Resonance Imaging (fMRI).MethodFifteen (15) PD-MCI patients, 26 PD patients without MCI (PD-NC) and 22 healthy controls (HC) were scanned (3T Siemens PRISMA) whilst performing the ANT. Reaction time, accuracy and fMRI BOLD activation were compared between groups for the three attentional task components of 1) alerting, 2) orienting, and 3) executive control.ResultsPD-MCI patients showed an overall slower reaction time compared to PD-NC and HC, and showed less interference of reaction time in the orienting effect than HC. fMRI data demonstrated greater activation in the bilateral cerebellum crus 1 during the alerting attention condition in both PD-MCI and PD-NC compared to HC. However, activation was supressed in the left postcentral gyrus in PD-MCI compared to PD-NC and HC.DiscussionAlterations in the alerting attention functional network despite intact task performance in PD-MCI suggests that functional brain changes may precede cognitive changes in the attention domain. Furthermore, increased activation in the cerebellum may reflect an attentional compensatory mechanism unique to the PD pathology. Taken together, the findings suggest that PD has a complex effect on attentional ability that can, at least in part, be elucidated using functional neuroimaging.     

Low levels of N-acetyl aspartate in the left dorsolateral prefrontal cortex of pediatric bipolar patients

BACKGROUND: Increasing evidence suggests abnormalities in the structure, function, and neurochemistry of the frontal cortex in pediatric bipolar (BP) patients. We conducted a single-voxel proton magnetic resonance spectroscopy ((1)H MRS) of the left dorsolateral prefrontal cortex (DLPFC) of pediatric BP patients, expecting lower N-acetyl-aspartate (NAA) levels within that brain region compared to healthy comparison subjects. METHODS: We studied 35 pediatric BP (23 BP type I, 12 BP type II; mean age +/- SD = 13.2 +/- 2.9 years; 18 females) and 36 healthy controls (mean age +/- SD = 13.7 +/- 2.6 years, 17 females). A short echo time, single-voxel (1)H spectroscopy approach point-resolved spectroscopy (PRESS) sequence, measurements of metabolites was performed on a 1.5T Philips MR system. RESULTS: BP subjects had significantly lower NAA levels in the left DLPFC compared to healthy controls (F = 4.21, df = 1, 68, p = 0.04). There was not a significant difference between groups for phosphocreatine + creatine (PCr+Cr), glycerolphosphocholine + phosphocholine (GPC + PC), myo-inositol (mI), or glutamate. Further analyses revealed a significant reduction of NAA in our early puberty group compared to controls (Mann-Whitney U-test statistic = 52.00, p = 0.014), but not for BP versus controls in other pubertal groups. CONCLUSIONS: BP subjects have lower NAA levels in the left DLPFC compared to healthy subjects, suggesting neuronal dysfunction in this region.