Variability in color-choice Stroop performance within and across EEG and MRI laboratory contexts.

To examine the reproducibility of the Stroop effect, behavioral data from 22 healthy female individuals were repeatedly (three-month interval between two separate measurement sessions) obtained while performing a color-choice Stroop task under realistic magnetic resonance imaging (MRI) and electroencephalography (EEG) laboratory conditions. At the group statistical level, the Stroop effect, indicated by longer response times for incongruent than for congruent stimulus conditions, was consistently present for almost all examined measurement levels. However, differential effects of laboratory contexts on retest reproducibility were observed across repeated measurement levels, both within and between sessions. These results challenge existing theories about the underlying nature of Stroop interference processing. It appears necessary to apply a multitheoretical approach, because intraindividual variability within and across measurement sessions suggests potential fluctuations in the individual mental strategies applied, recruitment of varying memory resources, the influence of mediator variables such as working memory capacity and/or attention, and many more possible variations. Single-observation studies run the risk of favoring a single theoretical concept and therefore underestimating the individual factor. We further conclude that dependent analysis-of-variance statistics are a more fit test for reproducibility than are correlative reliability estimations.

"Silent event-related" fMRI reveals reduced sensorimotor activation in laryngeal dystonia.

OBJECTIVE: To study with fMRI the pattern of sensorimotor activation in patients with spasmodic dysphonia (laryngeal dystonia) compared to healthy controls. METHODS: The authors performed fMRI measurements during vocal motor tasks in 12 patients with laryngeal dystonia and compared them with those of 12 healthy volunteers. Patients were scanned before (pre) and after (post) treatment with local injections of botulinum toxin (BTX). They examined two different motor tasks: simple vocalization inducing dystonia and whispering without appearance of dystonic symptoms. To avoid movement artifacts with oral motor tasks, the authors used a silent event-related fMRI approach involving noncontinuous sampling with no data acquisition during task performance. RESULTS: They found reduced activation of primary sensorimotor as well as of premotor and sensory association cortices during vocalization in patients with laryngeal dystonia pre-BTX. This was partly observed also during the asymptomatic whispering task. BTX treatment did not result in reversal of reduced cortical activation. CONCLUSION: fMRI signal is reduced in sensorimotor cortices associated with movement of the affected body part in laryngeal dystonia, supporting a dystonic basis for this voice disorder.

Transmodal sensorimotor networks during action observation in professional pianists.

Audiovisual perception and imitation are essential for musical learning and skill acquisition. We compared professional pianists to musically naive controls with fMRI while observing piano playing finger-hand movements and serial finger-thumb opposition movements both with and without synchronous piano sound. Pianists showed stronger activations within a fronto-parieto-temporal network while observing piano playing compared to controls and contrasted to perception of serial finger-thumb opposition movements. Observation of silent piano playing additionally recruited auditory areas in pianists. Perception of piano sounds coupled with serial finger-thumb opposition movements evoked increased activation within the sensorimotor network. This indicates specialization of multimodal auditory-sensorimotor systems within a fronto-parieto-temporal network by professional musical training. Musical ''language,'' which is acquired by observation and imitation, seems to be tightly coupled to this network in accord with an observation-execution system linking visual and auditory perception to motor performance.

Hypothalamic activation in trigeminal autonomic cephalgia: functional imaging of an atypical case.

We report headache induced BOLD changes in an atypical case of trigeminal autonomic cephalgia (TAC). A 68-year-old patient was imaged using fMRI during three attacks of a periorbital head-pain with a average duration of 3 min. During the attacks, left sided conjunctival injection, rhinorrhea, lacrimation, facial sweating and hypersalivation were apparent. These attacks were usually partly responsive to oxygen administration but otherwise refractory to any drug. The patient described either attacks with a duration of one minute or less or longer attacks persisting for maximum of 20 min with headaches occurring up to 100 times a day. When considering the symptoms, frequency, duration and therapeutic response of the patient's headache, no clear-cut classification to one of the subtypes of trigeminal autonomic cephalgias (cluster headache, paroxysmal hemicrania, SUNCT) or trigeminal neuralgia was possible. The cerebral activation pattern was similar but not identical to those previously observed in cluster headache and SUNCT with a prominent activation in the hypothalamic grey matter. This case study underlines the conceptual value of the term TAC for the group of headaches focusing around the trigeminal-autonomic reflex. Our results emphasize the importance of the hypothalamus as key region in the pathophysiology of this entity.

Neural correlates associated with impaired disgust processing in pre-symptomatic Huntington's disease.

Disturbances in recognizing facial expressions of disgust have been reported previously in pre-symptomatic and manifest Huntington's disease. Given the substantial role of the insula and basal ganglia in the perception of disgust as revealed by functional imaging, lesion studies and intracerebral recordings, we propose dysfunction within the insula and/or basal ganglia as the underlying neural substrate. Using functional MRI (fMRI), we studied a group of nine pre-symptomatic Huntington's disease gene carriers and nine healthy controls, matched for age, gender, intelligence and years of education, while they were viewing disgusted facial expressions. As control conditions, surprised and neutral expressions were presented. Compared with healthy controls, Huntington's disease gene carriers showed reduced responses within the left dorsal anterior insula during processing of disgusted facial expressions. Moreover, processing of disgust was associated with significant activation of the left dorsal anterior insula and putamen in healthy controls, but not in Huntington's disease gene carriers. Furthermore, behavioural assessment revealed a selective impairment in recognizing facial expressions displaying disgust in Huntington's disease gene carriers. Our finding of dysfunctional decreased insula activation in pre-symptomatic Huntington's disease provides an explanation for the clinical deficit in recognizing facial expression of disgust. Furthermore, it underscores the role of the insula in the emotion of disgust.

Subthalamic nucleus stimulation affects striato-anterior cingulate cortex circuit in a response conflict task: a PET study.

The subthalamic nucleus (STN) has generally been considered as a relay station within frontal-subcortical motor control circuitry. Little is known about the influence of the STN on cognitive networks. Clinical observations and studies in animals suggest that the STN participates in non-motor functions which can now be probed in Parkinson's disease patients with deep brain stimulation of the STN, allowing selective and reversible modulation of this nucleus. Using PET, we studied changes in regional cerebral blood flow (rCBF) associated with a response conflict task (Stroop task) in Parkinson's disease patients ON and OFF bilateral STN stimulation. The Stroop task requires subjects to name the font colour of colour words (e.g. "blue") printed in an incongruent colour ink (e.g. yellow). During STN stimulation, impaired task performance (prolonged reaction times) was associated with decreased activation in both right anterior cingulate cortex (ACC) and right ventral striatum. Concomitant increased activation in left angular gyrus indicative of ongoing word processing during stimulation is consistent with an impairment to inhibit habitual responses. ACC and ventral striatum are part of the ACC circuit associated with response conflict tasks. The decreased activation during STN stimulation in the ACC circuit, while response conflict processing worsened, provides direct evidence of STN modulating non-motor basal ganglia-thalamocortical circuitry. Impairment in ACC circuit function could account for the subtle negative effects on cognition induced by STN stimulation.

Time-resolved fMRI of activation patterns in M1 and SMA during complex voluntary movement.

The aim of this study was to use time-resolved functional magnetic resonance imaging (fMRI) to investigate temporal differences in the activation of the supplementary motor area (SMA) and the primary motor cortex (M1). We report data from eight human volunteers who underwent fMRI examinations in a 1.5T Philips Gyroscan ACS-NT MRI scanner. While wearing a contact glove, subjects executed a complex automated sequence of finger movements either spontaneously or in response to external auditory cues. Based on the result of a functional scout scan, a single slice that included the M1 and the SMA was selected for image acquisition (echo planar imaging, repetition time 100 ms, echo time 50 ms, 64 x 64 matrix, 1,000 images). Data were analyzed with a shifting cross-correlation approach using the STIMULATE program and in-house programs written in Interactive Data Language (IDL(TM)). Time-course data were generated for regions of interest in the M1 as well as in the rostral and caudal SMA. Mean time between onset of the finger movement sequence and half-maximum of the signal change in M1 was 3.6 s for the externally cued execution (SD 0.5) and 3.5 s for the spontaneous execution (SD 0.6). Activation in the rostral section of the SMA occurred 0.7 s earlier than it did in the M1 during the externally cued execution and 2.0 s earlier during the spontaneous execution, a difference significant at the P < 0.01 level. Our results indicate that rostral SMA activation precedes M1 activation by varying time intervals in the sub-second range that are determined by the mode of movement initialization. By applying a paradigm that exerts a differential influence on temporal activation, we could ensure that the observed timing differences were not the result of differences in hemodynamic response function.

Event-related functional magnetic resonance imaging in Parkinson's disease before and after levodopa.

Event-related functional MRI (fMRI) was used to study blood oxygen level dependent cortical signal changes associated with volitional limb movements off and on levodopa in Parkinson's disease. Eight patients with early stage akinetic Parkinson's disease and eight healthy volunteers underwent three functional imaging runs (high speed echo planar imaging with 600 scans/run) while performing paced single joystick movements in a freely chosen direction every 7-15 s. The non-magnetic joystick was linked to a monitoring system for on-line registration of performance parameters along with timing of the pacing tones and fMRI-scan acquisition parameters. This allowed correlation of movement onset, i.e. event-onset, to scanning time. We repeated the scanning procedure in the Parkinson's disease patients when akinesia improved 30 min after oral levodopa. Compared with the control group, patients both off and on levodopa showed movement-related impaired activation in the rostral supplementary motor area and increased activation in primary motor cortex (M1) and the lateral premotor cortex bilaterally. Levodopa led to a relative normalization of the impaired activation in the mesial premotor cortex and decreased signal levels in M1, lateral premotor and superior parietal cortex. We conclude that levodopa improves impaired motor initiation in the supplementary motor area and decreases hyperfunction of lateral premotor and M1 associated with Parkinson's disease during simple volitional movements.

A functional magnetic resonance imaging study of the role of left posterior superior temporal gyrus in speech production: implications for the explanation of conduction aphasia.

Conduction aphasia, characterized by good auditory comprehension and fluent but disordered speech production, is classically viewed as a disconnection syndrome. We review recent evidence which suggests that at least one form of conduction aphasia results from damage to cortical fields in the left posterior superior temporal gyrus which participate not only in speech perception, but also in phonemic aspects of speech production. As a test of this hypothesis, we carried out a 4T functional magnetic resonance imaging study in which subjects named visually presented objects sub-vocally. Group-based analyses showed that a majority of participants showed activation in two regions on the dorsal portion of the left posterior superior temporal gyrus.

Mechanisms for the formation of glycoxidation products in end-stage renal disease.

BACKGROUND: Advanced glycation end products (AGEs) accumulate on tissue and plasma proteins in patients with renal failure far in excess of normal aging or diabetes. The aim of these studies was to elucidate the nature of the precursors and the pathways that lead to an accelerated formation of two structurally identified AGEs [pentosidine and Nepsilon(carboxymethyl)lysine (CML)] in the uremic milieu. METHODS: Serum levels of the glycoxidation products, pentosidine and CML, were quantitated by high-performance liquid chromatography in uremic patients treated by dialysis. The formation of early glycation products (as furosine) and late glycoxidation products was modeled in uremic serum and in spent peritoneal dialysate. RESULTS: Clinical factors that affect circulating levels of AGEs included dialysis clearance and dialyzer membrane pore size, but not the presence or absence of diabetes. Both pentosidine and CML form at an accelerated rate in serum from uremic patients. Chelating agents most effectively slow the formation in vitro. In uremic fluids, the primary mechanism of formation of pentosidine is through the Amadori pathway. The primary mechanism of formation of CML is through metal-chelated autoxidation of reducing sugars generating reactive carbonyl precursors. In uremic serum, the presence of an unidentified reactive low molecular weight precursor accelerates the formation of pentosidine. CONCLUSIONS: The formation of the two glycoxidation products, pentosidine and CML, proceeds by different pathways and is enhanced by different precursors in the uremic milieu. The formation of both AGEs is markedly enhanced by metal-catalyzed reactions, evidence for the presence of increased metal-ion mediated oxidant stress in uremia.

Analysis of non enzymatic glycosylation in vivo: impact of different dialysis solutions.

BACKGROUND: Glucose-containing dialysis solutions in peritoneal dialysis (PD) patients induce non enzymatic glycosylation (NEG) within the peritoneal cavity. The subsequent formation of advanced glycosylation end-products (AGEs) may be implicated in the functional deterioration of the peritoneal membrane in long-term PD patients. AIM OF THE STUDY AND PARAMETERS: Measurement of NEG by the determination of percent glycation of albumin and IgG (GP), and of AGEs by measuring pentosidine content of protein in 4-hour effluents (Peff) and serum. SUBJECTS: In 5 patients each, a comparison was made between 3.86% glucose and 1.36% glucose (GP and Peff), and between 3.86% glucose and 7.5% icodextrin (Peff). Nine patients with clinically severe ultrafiltration failure (UFF) were compared to nine patients treated with PD for 1 month. Six of the patients with UFF were treated with non glucose dialysis solutions and Peff was studied again after 6 weeks. RESULTS: No difference was found between Peff comparing 3.86% glucose to either 1.36% glucose or icodextrin. GP were higher in 3.86% glucose than in 1.36%. Glycated/non glycated (G/NG) protein clearance ratios were 1.29 for albumin and 1.12 for IgG (p = 0.003). In contrast to GP, both Peff and serum pentosidine were higher in the UFF patients than in the recently started patients. Peff, but not GP, correlated with duration of PD (r = 0.67, p = 0.04). In 5 of 6 patients treated with non glucose dialysate, Peff decreased while serum pentosidine was stable. DISCUSSION: These data show that 4-hour Peff contents are not influenced by glucose concentration or osmolality, in contrast to GP. The relation between Peff and duration of PD, and the effect of non glucose dialysate on Peff, suggest that long-term glucose exposure is an important determinant of membrane glycosylation. Thus Peff probably reflects the long-term effects of intraperitoneal glycosylation of peritoneal membrane proteins. Treatment with non glucose dialysis solutions may result in "washout" of glycosylated proteins from the peritoneal membrane.

Human hippocampal long-term sustained response during word memory processing.

Temporal behavior of activation associated with the neural substrate of human memory function was investigated during and after an auditorily instructed word memory task using multislice functional magnetic resonance imaging. The hippocampal formation, which is involved in human memory function, displayed a long-term sustained response that persisted significantly (approximately 90 s) beyond the duration of the memory task. This sustained period was approximately two-fold longer than the duration of the post-task activation observed in auditory areas and Broca's area, which are involved in the phonological loop of the verbal working memory. These observations suggest that the hippocampal memory processing involves sustained activation in the transitional function for the long-term memory over the working memory period.

Kinetics of high-energy phosphates in allopurinol-pretreated ischaemic and post-ischaemic skeletal muscle: an in vivo magnetic resonance spectroscopy study.

Allopurinol (AP) protects skeletal muscle function against ischaemia-induced injury, but the mechanism is not yet clear. As AP acts as a competitive xanthine oxidase inhibitor, both a reduction of oxygen-derived free radicals and an enhancement of purine resynthesis (salvage pathway) might be involved. We investigated the in vivo kinetics of high-energy phosphates in skeletal muscle after AP pretreatment using 31P-magnetic resonance spectroscopy during 2 h of ischaemia and 3 h of reperfusion in rat hindlimbs. Three animals (group A) were pretreated with a total of 160 mg/kg AP i.p., 3 control animals (group B) received the same amount of 0.9% saline solution. ATP decreased to 18.6 +/- 1.3% of the pre-ischaemic value in group A and to 17.3 +/- 2.8% in group B after 2 h of ischaemia, and rose to only 47.7 +/- 1.5 and 50.5 +/- 1.8%, respectively, after 3 h of reperfusion. Phosphocreatine fell to 7.2 +/- 2.9 and 7.6 +/- 2.2% of pre-ischaemic values after 2 h of ischaemia and rose again to 36.5 +/- 12.9 and 45.4 +/- 20.4% after 3 h of reperfusion. Inorganic phosphate (Pi) increased 5-fold after 2 h of ischaemia, irrespective of the treatment. After 3 h of reperfusion, Pi was still 4 times the pre-ischaemic value. The kinetics of ATP, PCr, and Pi levels were not statistically different between the two groups. These results indicate that the ATP salvage pathway does not play an important role in AP-induced attenuation of ischaemia/reperfusion-induced muscle damage.

Age-related changes of glycosidases in human retinal pigment epithelium.

This study was undertaken to determine whether there are age-related changes in the specific activities of several glycosidases in fresh retinal pigment epithelial cells (RPE) isolated from the posterior pole of human donor eyes. One hundred and twenty-one pairs of eyes from human donors, between the ages of 43 and 95 years, were obtained from the National Disease Research Interchange (NDRI, Philadelphia, PA) and the Cleveland Ohio Eye Bank within 18 to 24 h of death. None had histories of diabetes, hepatitis, HIV infection, intraocular surgery, or documented age-related macular degeneration, although several older donors with evidence of drusen were included in the study. RPE cells were isolated from the posterior third of the retina using the conventional rush method and homogenized with a glass, Broeck tissue grinder. All post-nuclear supernatants were analyzed for glycosidase activity; a smaller number of nuclear pellets were assayed to verify that the majority of the enzyme activity was associated with the post-nuclear sypernatants. Glycosidase activity was quantitated fluorometrically by measuring the enzymatic release of umbelliferone from synthetic substrate preparations, specific for each enzyme. Total protein was determined by a micro BCA protein assay. Regression analysis revealed statistically significant age-related decreases for the specific activities of alpha-mannosidase (p = 0.0001), beta-galactosidase (p = 0.0001), N-acetyl-beta-glucosaminidase (p = 0.0001), and N-acetyl beta galactosaminidase (p = 0.0001) in fresh human donor RPE cells taken from the region of the posterior third of the retina that included the macula. Mannose and N-acetyl-glucosamine are major carbohydrate monomers of the oligosaccaride chains of human rhodopsin, and a relatively high percentage of the oligosaccharide chains are galactosylated. Defects in their degradation may lead to the accumulation of undigested residual material in the RPE.

[Effects of allopurinol on damage caused by ischemia and reperfusion of skeletal muscles: an in vivo spectroscopic analysis (31P-MR) in rats]. / Effetto dell'allopurinolo sui danni causati da ischemia e riperfusione nella muscolatura scheletrica: un'analisi spettroscopica (31P-RM) in vivo nel ratto.

The effect of allopurinol on energetic metabolism (reutilization of hypoxanthine) has been studied in vivo by mean of 31P-RM spectroscopy on skeletal muscle in the rat in conditions of ischemia and reperfusion. The treatment with allopurinol demonstrates of on benefit or phosphocreatine and ATP kinetics. These results outline that reutilization of hypoxanthine doesn't represent a protective mechanism of allopurinol on skeletal muscles. The role of hypoxanthine reutilization has to be investigated with further researches.

Retrospective estimation and correction of physiological fluctuation in functional MRI.

Image-to-image fluctuation due to physiological motion is a major limitation to the accurate detection of neuronal activity with functional MRI. In this paper, a new and general technique for the estimation and compensation of the physiological effects is presented. By simultaneously monitoring the respiration and heart beat during the acquisition of imaging data, and retrospectively synchronizing the imaging data with physiological activity, physiological effects are estimated and removed. This technique does not rely on the periodicity of the respiration or the heart beat, does not affect the signal changes arising from neuronal activation, and is beneficial to images acquired with any speed. Experimental studies performed with FLASH and EPI sequences have demonstrated that the new technique is effective in reducing physiological fluctuation and improving the sensitivity of functional MRI and is generally applicable.

1H-2H exchange in the perfused rat liver metabolizing [3-13C]alanine and 2H2O as detected by multinuclear NMR spectroscopy.

The exchange of individual protons of hepatic metabolites against the solvent deuterons has been investigated in perfused rat liver. Livers from starved rats were perfused for 20 min with a 10 mM solution of unlabeled or 3-13C-labeled L-alanine in Krebs Ringer bicarbonate buffer, with or without 50% deuterium oxide (2H2O). High resolution 13C NMR analysis of deuterium-induced isotopic shifts and of 2H-13C couplings revealed a differential 1H-2H exchange depending on the chemical nature of the metabolite and on the site of 13C labeling. [3-13C]Aspartate isotopomers showed similar 2H/1H ratios in the C3 and in the C2 carbons while [2-13C]aspartate isotopomers had much smaller 2H/1H ratios in the C2 than in the C3 carbons. Similarly, [2-13C]glutamate isotopomers had 2H/1H ratios significantly smaller in the C2 than in the C3 carbon. These results suggest that the hydration-dehydration reactions of the citric acid cycle, which result in exchange at the C3 carbons of aspartate and glutamate, approach equilibrium with the perfusate faster than the aminotransferases of aspartate and alanine, which induce exchange at the C2 carbons of these amino acids. Taken together, the results obtained are consistent with a heterogeneous solvent exchange environment in the perfused liver.

[Modification of ischemia and reperfusion damage of skeletal muscles with allopurinol: in vivo 31P MR spectroscopy of the posterior limb of the rat]. / Beeinflussung von Ischämie- und Reperfusionsschaden der Skelettmuskulatur mit Allopurinol: In-vivo-31P-MR-Spektroskopie am Hinterlauf der Ratte.

The effect of Allopurinol on energy metabolism (re-utilisation of hypoxanthine) was studied in a in vivo skeletal muscle ischemia rat model by 31-P-MR spectroscopy. Allopurinol-treatment showed no benefit to the kinetics of PCr/(Pi + PCr) and ATP/(Pi + PCr). The role of re-utilisation of hypoxanthine has to be further investigated.