An anatomical landmark for the supplementary eye fields in human revealed with functional magnetic resonance imaging.
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Together with the frontal and parietal eye fields, the supplementary eye field (SEF) is involved in the performance and control of voluntary and reflexive saccades and of ocular pursuit. This region was first described in non-human primates and is rather well localized on the dorsal surface of the medial frontal cortex. In humans the site of the SEF is still ill-defined. Functional imaging techniques have allowed investigation of the location and function of the SEF. However, there is great variability with regard to the published standardized coordinates of this area. We used here the spatial precision of functional magnetic resonance imaging (fMRI) in order to better localize the SEF in individuals. We identified as the SEF a region on the medial wall that was significantly activated when subjects executed self-paced horizontal saccades in darkness as compared to rest. This region appeared to be predominantly activated in the left hemisphere. We found that, despite a discrepancy of >2 cm found in the standardized Talairach coordinates, the location of this SEF-region could be precisely and reliably described by referring to a sulcal landmark found in each individual: the upper part of the paracentral sulcus. (+info)
Differences in frontal cortical activation by a working memory task after substitution of risperidone for typical antipsychotic drugs in patients with schizophrenia.
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Antipsychotic drug treatment of schizophrenia may be complicated by side effects of widespread dopaminergic antagonism, including exacerbation of negative and cognitive symptoms due to frontal cortical hypodopaminergia. Atypical antipsychotics have been shown to enhance frontal dopaminergic activity in animal models. We predicted that substitution of risperidone for typical antipsychotic drugs in the treatment of schizophrenia would be associated with enhanced functional activation of frontal cortex. We measured cerebral blood oxygenation changes during periodic performance of a verbal working memory task, using functional MRI, on two occasions (baseline and 6 weeks later) in two cohorts of schizophrenic patients. One cohort (n = 10) was treated with typical antipsychotic drugs throughout the study. Risperidone was substituted for typical antipsychotics after baseline assessment in the second cohort (n = 10). A matched group of healthy volunteers (n = 10) was also studied on a single occasion. A network comprising bilateral dorsolateral prefrontal and lateral premotor cortex, the supplementary motor area, and posterior parietal cortex was activated by working memory task performance in both the patients and comparison subjects. A two-way analysis of covariance was used to estimate the effect of substituting risperidone for typical antipsychotics on power of functional response in the patient group. Substitution of risperidone increased functional activation in right prefrontal cortex, supplementary motor area, and posterior parietal cortex at both voxel and regional levels of analysis. This study provides direct evidence for significantly enhanced frontal function in schizophrenic patients after substitution of risperidone for typical antipsychotic drugs, and it indicates the potential value of functional MRI as a tool for longitudinal assessment of psychopharmacological effects on cerebral physiology. (+info)
Neural representation of a rhythm depends on its interval ratio.
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Rhythm is determined solely by the relationship between the time intervals of a series of events. Psychological studies have proposed two types of rhythm representation depending on the interval ratio of the rhythm: metrical and nonmetrical representation for rhythms formed with small integer ratios and noninteger ratios, respectively. We used functional magnetic resonance imaging to test whether there are two neural representations of rhythm depending on the interval ratio. The subjects performed a short-term memory task for a seven-tone rhythm sequence, which was formed with 1:2:4, 1:2:3, or 1:2.5:3.5 ratios. The brain activities during the memory delay period were measured and compared with those during the retention of a control tone sequence, which had constant intertone intervals. The results showed two patterns of brain activations; the left premotor and parietal areas and right cerebellar anterior lobe were active for 1:2:4 and 1:2:3 rhythms, whereas the right prefrontal, premotor, and parietal areas together with the bilateral cerebellar posterior lobe were active for 1:2.5:3.5 rhythm. Analysis on individual subjects revealed that these activation patterns depended on the ratio of the rhythms that were produced by the subjects rather than the ratio of the presented rhythms, suggesting that the observed activations reflected the internal representation of rhythm. These results suggested that there are two neural representations for rhythm depending on the interval ratio, which correspond to metrical and nonmetrical representations. (+info)
Null mutation of c-fos causes exacerbation of methamphetamine-induced neurotoxicity.
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Methamphetamine neurotoxicity has been demonstrated in rodents and nonhuman primates. These neurotoxic effects may be associated with mechanisms involved in oxidative stress and the activation of immediate early genes (IEG). It is not clear, however, whether these IEG responses are involved in a methamphetamine-induced toxic cascade or in protective mechanisms against the deleterious effects of the drug. As a first step toward clarifying this issue further, the present study was thus undertaken to assess the toxic effects of methamphetamine in heterozygous and homozygous c-fos knock-out as well as wild-type mice. Administration of methamphetamine caused significant reduction in [(125)I]RTI-121-labeled dopamine uptake sites, dopamine transporter protein, and tyrosine hydroxylase-like immunohistochemistry in the striata of wild-type mice. These decreases were significantly exacerbated in heterozygous and homozygous c-fos knock-out mice, with the homozygous showing greater loss of striatal dopaminergic markers. Moreover, in comparison with wild-type animals, both genotypes of c-fos knock-out mice showed more DNA fragmentation, measured by the number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeled nondopaminergic cells in their cortices and striata. In contrast, wild-type mice treated with methamphetamine demonstrated a greater number of glial fibrillary acidic protein-positive cells than did c-fos knock-out mice. These data suggest that c-fos induction in response to toxic doses of methamphetamine might be involved in protective mechanisms against this drug-induced neurotoxicity. (+info)
FTDP-17 tau mutations decrease the susceptibility of tau to calpain I digestion.
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Frontal temporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17) is caused by splice site and missense mutations in the tau gene, and characterized by the accumulation of filamentous tau in cerebral neurons and glia. The missense mutations reduce the ability of tau to promote microtubule assembly and increase the ability of tau to form filaments. In this report we demonstrate that mutants V337M and R406W are less susceptible than mutant P301L or corresponding wild type tau to degradation by calpain I. The differences were at least in part due to changes in accessibility of a cleavage site located about 100 amino acids off the carboxy-terminus. The results suggest that the pathogenesis of some forms of FTDP-17 may involve tau accumulation due to decreased proteolytic degradation. (+info)
Changes in cerebral blood oxygenation of the frontal lobe induced by direct electrical stimulation of thalamus and globus pallidus: a near infrared spectroscopy study.
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OBJECTIVE: Blood oxygenation level dependent (BOLD) contrast functional MRI images show activated cortical areas by detecting a reduced concentration of deoxyhaemoglobin (deoxy-Hb) during neuronal activity; however, near infrared spectroscopy (NIRS) has shown various patterns of cerebral blood oxygenation (CBO) changes in the frontal lobe during cognitive tasks. To determine if various patterns of CBO changes occur in the frontal lobe when the brain is directly stimulated, changes in CBO in the frontal lobe induced by deep brain stimulation in patients with implanted electrodes were evaluated. METHODS: Six patients were studied, including five with Parkinson's disease and one with essential tremor. To reduce tremor or rigidity, the electrodes were implanted at the thalamic nucleus ventralis intermedius (VIM: three Parkinson's disease and one essential tremor) or the globus pallidus internus (GPi: two Parkinson's disease). Using NIRS, changes of deoxy-Hb, oxyhaemoglobin (oxy-Hb) and total haemoglobin (total Hb) were measured in the bilateral frontal lobes during various stimulus conditions. RESULTS: High frequency (120 Hz) GPi stimulation consistently increased oxy-Hb and total Hb with a decrease of deoxy-Hb in an intensity and time dependent manner. Oxy-Hb and total Hb increased immediately after the onset of stimulation and then gradually decreased when stimulation was continued. By contrast, high frequency (120 Hz) VIM stimulation decreased oxy-Hb, deoxy Hb and total Hb in an intensity dependent manner. In the severe tremor patient with VIM stimulation, frequency response was examined by decreasing stimulus frequencies; deoxy-Hb increased at high frequencies (70-40 Hz), and then decreased below the control level at low frequencies (30-0 Hz), whereas oxy-Hb and total Hb increased consistently at high and low frequencies. CONCLUSION: The electrical stimulation of GPi and VIM caused various CBO changes in the frontal lobe, which were similar to those found during cognitive tasks. Such a multiplicity of CBO changes in the frontal lobe may be caused by complex neuronal circuits in the frontal lobe which has many neuronal connections to other cortical areas or the basal ganglia. (+info)
Studies on the acute and chronic effects of reboxetine on extracellular noradrenaline and other monoamines in the rat brain.
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1 The effect of reboxetine, a novel antidepressant drug that potently and selectively inhibits neuronal noradrenaline (NA) uptake, on brain extracellular monoamines was studied by microdialysis. 2 Fifteen mg kg-1 i.p. reboxetine raised extracellular NA in the frontal cortex (by 242%) and dorsal hippocampus (by 240%). 3 Idazoxan (1 mg kg-1 s.c.), given 60 min after 15 mg kg-1 reboxetine, markedly potentiated the effect on extracellular NA in the frontal cortex (by 1580%) and dorsal hippocampus (by 1360%), but had no effect by itself. 4 Twenty-four hours after the last injection of a chronic schedule (15 mg kg-1 i.p. once daily for 14 days) reboxetine had no effect on basal extracellular concentrations of NA in the dorsal hippocampus and a challenge dose of reboxetine (15 mg kg-1) raised extracellular NA similarly in rats treated chronically with reboxetine (by 353%) and saline (by 425%). 5 Ten and 20 microg kg-1 i.p. clonidine dose-dependently reduced hippocampal extracellular NA similarly in rats given chronic reboxetine (by 32% and 57%) and saline (by 42% and 56%). 6 Extracellular concentrations of dopamine and 5-HT in the striatum were similar in rats treated chronically with reboxetine and saline. A challenge dose of reboxetine (15 mg kg-1) had no effect on striatal extracellular dopamine and slightly increased striatal extracellular 5-HT to a similar extent in rats treated chronically with reboxetine (by 137%) and saline (by 142%). 7 The results suggest that combining reboxetine with an alpha2-adrenoceptor antagonist may facilitate its antidepressant activity. Repeated treatment confirmed that reboxetine is fairly selective for the noradrenergic system but provided no evidence of adaptive changes in that system that could facilitate its effect on extracellular NA. (+info)
A functional imaging study of translation and language switching.
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The neural systems underlying translation and language switching were investigated using PET. Proficient German-English adult bilinguals were scanned whilst either translating or reading visually presented words in German (L1), English (L2) or alternating L1/L2. We refer to alternating L1/L2 as 'switching'. The results revealed contrasting patterns of activation for translation and switching, suggesting at least partially independent mechanisms. Translation, but not switching, increased activity in the anterior cingulate and subcortical structures whilst decreasing activation in several other temporal and parietal language areas associated with the meaning of words. Translation also increased activation in regions associated with articulation (the anterior insula, cerebellum and supplementary motor area) arguably because the reading response to the stimulus must be inhibited whilst a response in a different language is activated. In contrast, switching the input language resulted in activation of Broca's area and the supramarginal gyri, areas associated with phonological recoding. The results are discussed in terms of the cognitive control of language processes. (+info)