Influence of antiresorptive/antiangiogenic therapy on the extension of experimentally induced peri-implantitis lesions.

OBJECTIVES: To investigate the extension of experimentally induced peri-implantitis lesions under various antiresorptive and antiangiogenic medications. MATERIAL AND METHODS: Fourty-eight albino rats had randomly received the following medications (dual application, n = 8 each): (1) amino-bisphosphonate (zoledronate) (Zo), (2) RANKL inhibitor (denosumab) (De), (3) antiangiogenic (bevacizumab) (Be), (4) Zo+Be, (5) De+Be, or (6) no medication (Co). Ligature- and lipopolysaccharide-induced peri-implantitis lesions were established at 2 maxillary implants over a period of 16 weeks. Histological (e.g., apical extension and surface area of the inflammatory cell infiltrate-aICT, ICT; defect length; defect width; CD68 positive cells) and bone micromorphometric (µCT) outcomes were assessed. The animal was defined as a statistical unit. RESULTS: A total of n = 38 animals (Zo = 6, De = 6, Be = 8, Zo + Be = 6, De + Be = 5, Co = 7) were analyzed. ICT's were commonly marked by a positive CD68 antigen reactivity. Comparable median aICT (lowest-Zo: 0.53 mm; highest-Be: 1.22 mm), ICT (lowest-De + Be: 0.00 mm2; highest-Co: 0.49 mm2), defect length (lowest-Zo: 0.90 mm; highest-Co: 1.93 mm) and defect width (lowest-De+Be: 1.27 mm; highest-Be: 1.80 mm) values were noted in all test and control groups. Within an inner (diameter: 0.8 mm) cylindric volume of interest, the bone microstructure did not significantly differ between groups. CONCLUSIONS: The present analysis did not reveal any marked effects of various antiresorptive/ antiangiogenic medications on the extension of experimentally induced peri-implantitis lesions. CLINICAL RELEVANCE: The extension of peri-implantitis lesions may not be facilitated by the antiresorptive and antiangiogenic medications investigated.

Peptidoglycan as major binding motif for Uranium bioassociation on Magnetospirillum magneticum AMB-1 in contaminated waters.

The U(VI) bioassociation on Magnetospirillum magneticum AMB-1 cells was investigated using a multidisciplinary approach combining wet chemistry, microscopy, and spectroscopy methods to provide deeper insight into the interaction of U(VI) with bioligands of Gram-negative bacteria for a better molecular understanding. Our findings suggest that the cell wall plays a prominent role in the bioassociation of U(VI). In time-dependent bioassociation studies, up to 95 % of the initial U(VI) was removed from the suspension and probably bound on the cell wall within the first hours due to the high removal capacity of predominantly alive Magnetospirillum magneticum AMB-1 cells. PARAFAC analysis of TRLFS data highlights that peptidoglycan is the most important ligand involved, showing a stable immobilization of U(VI) over a wide pH range with the formation of three characteristic species. In addition, in-situ ATR FT-IR reveals the predominant strong binding to carboxylic functionalities. At higher pH polynuclear species seem to play an important role. This comprehensive molecular study may initiate in future new remediation strategies on effective immobilization of U(VI). In combination with the magnetic properties of the bacteria, a simple technical water purification process could be realized not only for U(VI), but probably also for other heavy metals.

Microscopic and spectroscopic bioassociation study of uranium(VI) with an archaeal Halobacterium isolate.

The safe disposal of high-level radioactive waste in a deep geological repository is a huge social and technical challenge. So far, one of the less considered factors needed for a long-term risk assessment, is the impact of microorganisms occurring in the different host rocks. Even under the harsh conditions of salt formations different bacterial and archaeal species were found, e. g. Halobacterium sp. GP5 1-1, which has been isolated from a German rock salt sample. The interactions of this archaeon with uranium(VI), one of the radionuclides of major concern for the long-term storage of high-level radioactive waste, were investigated. Different spectroscopic techniques, as well as microscopy, were used to examine the occurring mechanisms on a molecular level leading to a more profound process understanding. Batch experiments with different uranium(VI) concentrations showed that the interaction is not only a simple, but a more complex combination of different processes. With the help of in situ attenuated total reflection Fourier-transform infrared spectroscopy the association of uranium(VI) onto carboxylate groups was verified. In addition, time-resolved laser-induced luminescence spectroscopy revealed the formation of phosphate and carboxylate species within the cell pellets as a function of the uranium(VI) concentration and incubation time. The association behavior differs from another very closely related halophilic archaeon, especially with regard to uranium(VI) concentrations. This clearly demonstrates the importance of studying the interactions of different, at first sight very similar, microorganisms with uranium(VI). This work provides new insights into the microbe-uranium(VI) interactions at highly saline conditions relevant to the long-term storage of radioactive waste in rock salt.

Uranium and neptunium retention mechanisms in Gallionella ferruginea/ferrihydrite systems for remediation purposes.

The ubiquitous ß-Proteobacterium Gallionella ferruginea is known as stalk-forming, microaerophilic iron(II) oxidizer, which rapidly produces iron oxyhydroxide precipitates. Uranium and neptunium sorption on the resulting intermixes of G. ferruginea cells, stalks, extracellular exudates, and precipitated iron oxyhydroxides (BIOS) was compared to sorption to abiotically formed iron oxides and oxyhydroxides. The results show a high sorption capacity of BIOS towards radionuclides at circumneutral pH values with an apparent bulk distribution coefficient (Kd) of 1.23 × 104 L kg-1 for uranium and 3.07 × 105 L kg-1 for neptunium. The spectroscopic approach by X-ray absorption spectroscopy (XAS) and ATR FT-IR spectroscopy, which was applied on BIOS samples, showed the formation of inner-sphere complexes. The structural data obtained at the uranium LIII-edge and the neptunium LIII-edge indicate the formation of bidentate edge-sharing surface complexes, which are known as the main sorption species on abiotic ferrihydrite. Since the rate of iron precipitation in G. ferruginea-dominated systems is 60 times faster than in abiotic systems, more ferrihydrite will be available for immobilization processes of heavy metals and radionuclides in contaminated environments and even in the far-field of high-level nuclear waste repositories.

Comparative analysis of uranium bioassociation with halophilic bacteria and archaea.

Rock salt represents a potential host rock formation for the final disposal of radioactive waste. The interactions between indigenous microorganisms and radionuclides, e.g. uranium, need to be investigated to better predict the influence of microorganisms on the safety assessment of the repository. Hence, the association process of uranium with two microorganisms isolated from rock salt was comparatively studied. Brachybacterium sp. G1, which was isolated from the German salt dome Gorleben, and Halobacterium noricense DSM15987T, were selected as examples of a moderately halophilic bacterium and an extremely halophilic archaeon, respectively. The microorganisms exhibited completely different association behaviors with uranium. While a pure biosorption process took place with Brachybacterium sp. G1 cells, a multistage association process occurred with the archaeon. In addition to batch experiments, in situ attenuated total reflection Fourier-transform infrared spectroscopy was applied to characterize the U(VI) interaction process. Biosorption was identified as the dominating process for Brachybacterium sp. G1 with this method. Carboxylic functionalities are the dominant interacting groups for the bacterium, whereas phosphoryl groups are also involved in U(VI) association by the archaeon H. noricense.

Multistage bioassociation of uranium onto an extremely halophilic archaeon revealed by a unique combination of spectroscopic and microscopic techniques.

The interactions of two extremely halophilic archaea with uranium were investigated at high ionic strength as a function of time, pH and uranium concentration. Halobacterium noricense DSM-15987 and Halobacterium sp. putatively noricense, isolated from the Waste Isolation Pilot Plant repository, were used for these investigations. The kinetics of U(VI) bioassociation with both strains showed an atypical multistage behavior, meaning that after an initial phase of U(VI) sorption, an unexpected interim period of U(VI) release was observed, followed by a slow reassociation of uranium with the cells. By applying in situ attenuated total reflection Fourier-transform infrared spectroscopy, the involvement of phosphoryl and carboxylate groups in U(VI) complexation during the first biosorption phase was shown. Differences in cell morphology and uranium localization become visible at different stages of the bioassociation process, as shown with scanning electron microscopy in combination with energy dispersive X-ray spectroscopy. Our results demonstrate for the first time that association of uranium with the extremely halophilic archaeon is a multistage process, beginning with sorption and followed by another process, probably biomineralization.

The Sorption Processes of U(VI) onto SiO2 in the Presence of Phosphate: from Binary Surface Species to Precipitation.

The ternary system containing aqueous U(VI), aqueous phosphate and solid SiO2 was comprehensively investigated using a batch sorption technique, in situ attenuated total reflection Fourier-transform infrared (ATR FT-IR) spectroscopy, time-resolved luminescence spectroscopy (TRLS), and surface complexation modeling (SCM). The batch sorption studies on silica gel (10 g/L) in the pH range 2.5 to 5 showed no significant increase in U(VI) uptake in the presence of phosphate at equimolar concentration of 20 µM, but significant increase in U(VI) uptake was observed for higher phosphate concentrations. In situ infrared and luminescence spectroscopic studies evidence the formation of two binary U(VI) surface species in the absence of phosphate, whereas after prolonged sorption in the presence of phosphate, the formation of a surface precipitate, most likely an autunite-like phase, is strongly suggested. From SCM, excellent fitting results were obtained exclusively considering two binary uranyl surface species and the formation of a solid uranyl phosphate phase. Ternary surface complexes were not needed to explain the data. The results of this study indicate that the sorption of U(VI) on SiO2 in the presence of inorganic phosphate initially involves binary surface-sorption species and evolves toward surface precipitation.

Short-Term Effects of Blood Transfusions on Hepcidin in Preterm Infants.

BACKGROUND: Hepcidin, a key regulatory peptide hormone in iron homeostasis, may in future serve as a non-invasive iron status parameter for monitoring iron supplementation in preterm infants. For this, coexisting influencing factors should be taken into account. OBJECTIVES: To evaluate the short-term effects of red blood cell (RBC) transfusions on hepcidin concentrations in serum (HepS) and urine (HepU) of preterm infants. METHODS: This was a prospective, observational study conducted between May 2009 and September 2010 at a single neonatal unit (Tübingen University Hospital, Tübingen, Germany) in very preterm infants, i.e. with a gestational age (GA) of <32 weeks, who received clinically indicated RBC transfusions. The concentration of the mature, 25 amino-acid form of hepcidin was determined in serum und urine by competitive enzyme-linked immunosorbent assay together with cellular indices before and after transfusion. RESULTS: Twenty preterm infants born at a median GA of 26 + 0/7 (interquartile range: 24 + 6/7 to 27 + 3/7) weeks received 27 RBC transfusions at a median corrected age of 31 + 3/7 (29 + 6/7 to 34 + 5/7) weeks. When measured shortly after transfusion (mean time: 10 h), haematocrit values increased from a mean of 26.6% (SD 2.8) to 40.9% (SD 3.2); p < 0.0001. HepS also increased [geometric mean: 44.3 (95% confidence interval 30.8-63.8) ng/ml vs. 58.0 (35.7-94.3) ng/ml; p < 0.05] but HepU remained unaffected. CONCLUSION: The data indicate that HepS concentrations increase shortly after RBC transfusion in preterm infants. Long-term observational studies are needed to understand the dynamics of hepcidin regulation in preterm infants.

Use of prestudy heparin did not influence the efficacy and safety of rivaroxaban in patients treated for symptomatic venous thromboem-bolism in the EINSTEIN DVT and EINSTEIN PE studies.

OBJECTIVES: In the EINSTEIN DVT and EINSTEIN PE studies, the majority of patients received heparins to bridge the period during venous thromboembolism (VTE) diagnosis confirmation and the start of the study. In contrast to vitamin K antagonists (VKAs), rivaroxaban may not require initial heparin treatment. METHODS: To evaluate the effect of prestudy heparin on the efficacy and safety of rivaroxaban relative to enoxaparin/VKA, the 3-month incidence of recurrent VTE, and the 14-day incidence of major and nonmajor clinically relevant bleeding were compared in patients who did and did not receive prestudy heparin. RESULTS: Of the 8,281 patients randomized, 6,937 (83.8%) received prestudy heparin (mean ± SD duration = rivaroxaban: 1.04 [± 0.74] days; enoxaparin 1.03 [± 0.42] days), and 1,344 (16.2%) did not. In patients who did not receive prestudy heparin, the incidences of recurrent VTE were similar in rivaroxaban (15 of 649, 2.3%) and enoxaparin/VKA (13 of 695, 1.9%) patients (adjusted hazard ratio [HR] = 1.11; 95% confidence interval [CI] = 0.52 to 2.37). The incidences of recurrent VTE were also similar in rivaroxaban (54 of 3,501, 1.5%) and enoxaparin/VKA (69 of 3,436, 2.0%) patients who did receive prestudy heparin (adjusted HR = 0.74; 95% CI = 0.52 to 1.06; pinteraction  = 0.32). The incidences of major or nonmajor clinically relevant bleeding with rivaroxaban were not significantly different from those with enoxaparin/VKA, either with (105 of 3,485, 3.0% vs. 104 of 3,428, 3.0%; adjusted HR = 0.98; 95% CI = 0.75 to 1.29) or without (24 of 645, 3.7% vs. 30 of 688, 4.4%; adjusted HR = 0.81; 95% CI = 0.46 to 1.40; pinteraction  = 0.68) prestudy heparin. CONCLUSIONS: Although the majority of patients in the EINSTEIN studies received prestudy heparin, there were no notable differences in treatment effect of rivaroxaban versus enoxaparin/VKA in those who did and did not receive it.

In situ spectroscopic identification of neptunium(V) inner-sphere complexes on the hematite-water interface.

Hematite plays a decisive role in regulating the mobility of contaminants in rocks and soils. The Np(V) reactions at the hematite-water interface were comprehensively investigated by a combined approach of in situ vibrational spectroscopy, X-ray absorption spectroscopy and surface complexation modeling. A variety of sorption parameters such as Np(V) concentration, pH, ionic strength, and the presence of bicarbonate was considered. Time-resolved IR spectroscopic sorption experiments at the iron oxide-water interface evidenced the formation of a single monomer Np(V) inner-sphere sorption complex. EXAFS provided complementary information on bidentate edge-sharing coordination. In the presence of atmospherically derived bicarbonate the formation of the bis-carbonato inner-sphere complex was confirmed supporting previous EXAFS findings.1 The obtained molecular structure allows more reliable surface complexation modeling of recent and future macroscopic data. Such confident modeling is mandatory for evaluating water contamination and for predicting the fate and migration of radioactive contaminants in the subsurface environment as it might occur in the vicinity of a radioactive waste repository or a reprocessing plant.

Effect of supplementation with long-chain ω-3 polyunsaturated fatty acids on behavior and cognition in children with attention deficit/hyperactivity disorder (ADHD): a randomized placebo-controlled intervention trial.

OBJECTIVE: To determine whether supplementation with the long-chain omega-3 polyunsaturated fatty acids eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) affects behavioral symptoms and cognitive impairments in children 6-12 years of age diagnosed with attention-deficit/hyperactivity disorder (ADHD). STUDY DESIGN: The randomized, double-blind placebo-controlled 16 weeks trial was conducted with 95 children diagnosed with ADHD according to DSM-IV criteria. Behavior was assessed by parents, teachers and investigators using standardized rating scales and questionnaires. Further outcome variables were working memory, speed of information processing and various measures of attention. For a subgroup of 81 participants, erythrocyte membrane fatty acid composition was analyzed before and after the intervention. RESULTS: Supplementation with the omega-3 fatty acid mix increased EPA and DHA concentrations in erythrocyte membranes and improved working memory function, but had no effect on other cognitive measures and parent- and teacher-rated behavior in the study population. Improved working memory correlated significantly with increased EPA, DHA and decreased AA (arachidonic acid).

Temperature impact on the sorption of selenium(VI) onto anatase.

The impact of temperature (298 K, 313 K, and 333 K) on the sorption of selenium(VI) onto anatase was investigated for the first time. At a macroscopic level, batch experiments showed a decrease of selenium(VI) retention with both increasing pH (3.5-7.0) and temperature. The thermodynamic parameters of the sorption reaction, i.e. the enthalpy Δ(R)H, entropy Δ(R)S, and the Gibbs free energy Δ(R)G, were determined from the temperature dependence sorption data using the van't Hoff equation. The sorption process was found to be exothermic. Neither significant phase transformation nor a significant increase of anatase solubility could be detected with increasing temperature by XRD and ICP-MS. However, electrophoretic mobility measurements showed that both the zeta potential as well as the isoelectric point (pH(IEP)) of anatase were shifted to lower values with increasing temperature, leading to a decreased selenium(VI) sorption. At a microscopic level, the sorption mechanism of selenium(VI) onto anatase was elucidated at the three investigated temperatures by means of in situ Attenuated Total Reflection Fourier-Transform Infrared spectroscopy (ATR FT-IR). Results evidenced the formation of outer-sphere surface complexes, with no significant structural changes within the investigated temperature range.

Activation of thalamus in motor imagery results from gating by hypnosis.

The ability to mentally imagine the performance of automatic movements has been well-established being employed in sports and physiotherapy as a tool for motor learning and rehabilitation. This is probably mediated by engagement of the same brain areas as during real motor performance. Here we investigated the effect of hypnotic trance on the cerebral activation pattern engaged in motor imagery in 16 healthy, right-handed subjects using fMRI. Motor imagery as compared with rest was related to activations in the left medial frontal areas (preSMA/SMA), prefrontal- and frontal areas, putamen and inferior parietal areas. When compared with performance of the same movements motor imagery resulted in activation of the left middle frontal cortex, precuneus, and posterior cingulate. Under hypnotic trance there was one extra-activation in the left thalamus which occurred specifically in the motor imagery condition. The regional beta indices were highly correlated among the areas of the cortical-subcortical motor network. Our data accord with the notion that hypnotic trance enhances the motor control circuit engaged in motor imagery by modulating the gating function of the thalamus.

The facilitating effect of clinical hypnosis on motor imagery: an fMRI study.

Hypnosis is increasingly being employed in therapy of neurologically impaired patients. In fact, reports from neuropsychological practice point out that neurological patients with a loss of motor abilities achieve successful rehabilitation by means of motor imagery during hypnosis. This approach was shown to be effective even if the patients' ability to imagine movements was impaired or lost. The underlying mechanisms of "how" and "where" hypnosis affects the brain, however, are largely unknown. To identify the brain areas involved in motor imagery under hypnosis, we conducted an fMRI study in which we required healthy human subjects either to imagine or to execute repetitive finger movements during a hypnotic trance. We observed fMRI-signal increases exclusively related to hypnosis in the left superior frontal cortex, the left anterior cingulate gyrus and left thalamus. While the superior frontal cortex and the anterior cingulate were active related more to movement performance than to imagery, the thalamus was activated only during motor imagery. These areas represent central nodes of the salience network linking primary and higher motor areas. Therefore, our data substantiate the notion that hypnosis enhances motor imagery.

Uranium sorption on various forms of titanium dioxide--influence of surface area, surface charge, and impurities.

Titanium dioxide (TiO(2)) has often served as a model substrate for experimental sorption studies of environmental contaminants. However, various forms of Ti-oxide have been used, and the different sorption properties of these materials have not been thoroughly studied. We investigated uranium sorption on some thoroughly characterized TiO(2) surfaces with particular attention to the influence of surface area, surface charge, and impurities. The sorption of U(VI) differed significantly between samples. Aggressive pretreatment of one material to remove impurities significantly altered the isoelectric point, determined by an electroacoustic method, but did not significantly impact U sorption. Differences in sorption properties between the various TiO(2) materials were related to the crystallographic form, morphology, surface area, and grain size, rather than to surface impurities or surface charge. In-situ attenuated total reflection Fourier-transform infrared (ATR FT-IR) spectroscopic studies showed that the spectra of the surface species of the TiO(2) samples are not significantly different, suggesting the formation of similar surface complexes. The data provide insights into the effect of different source materials and surface properties on radionuclide sorption.

Aqueous uranium(VI) hydrolysis species characterized by attenuated total reflection Fourier-transform infrared spectroscopy.

The speciation of uranium(VI) in micromolar aqueous solutions at ambient atmosphere was studied by attenuated total reflection Fourier-transform infrared (ATR FT-IR) spectroscopy and by speciation modeling applying the updated NEA thermodynamic database. It can be shown that reliable infrared spectra of micromolar U(VI) solutions are obtained abolishing the restrictions of previous spectroscopic investigations to millimolar concentrations and, consequently, to the acidic pH range. A significant change of the U(VI) speciation can be derived from the spectral alterations of the absorption band representing the antisymmetric stretching mode (nu3) of the UO2(2+) ion observed upon lowering the U(VI) concentration from the milli- to the micromolar range at a constant pH 4 value. The acquisition of spectra of diluted U(VI) solutions allows the increase of the pH up to 8.5 without the risk of formation of colloidal or solid phases. The infrared spectra are compared to the results of the computed speciation patterns. Although a complete interpretation of the spectra can not be given at this state of knowledge, the spectral data strongly suggest the presence of monomeric U(VI) hydroxo species already showing up at a pH value > or = 2.5 and dominating the speciation at pH 3. This is in contradiction to the predicted speciation where the fully hydrated UO2(2+) is expected to represent the main species at pH values below 4. At ambient pH, a more complex speciation is suggested compared to the results of the computational modeling technique. The predicted dominance of the UO2(CO3)3(4-) complex at pH > or = 8 was not confirmed by the infrared data. However, the infrared spectra indicate the formation of hydroxo complexes obviously containing carbonate ligands.

Mental practice improves hand function after hemiparetic stroke.

PURPOSE: In a multiple baseline design, we tested the hypothesis that imagery of finger movements is a specific strategy to improve hand function. METHODS: The effect of mental training of sequential finger movements (n=6) on hand function was compared to the repetitive execution of the same movements (n=6) and conventional physical therapy (n=5) in 17 patients after their first hemiparetic stroke. The behavioral outcome measures consisted of peak force of the pinch grip using a force transducer and manipulation functions of the upper extremity (Jebsen-test). In addition, activities of daily living (Barthel Index) were acquired to describe the population. RESULTS: Mental training resulted in an increase in the peak force of the pinch grip and generalized in a better functionality of the upper extremity (Jebsen-test). This effect was similar to the repetitive execution of the movements and superior to conventional physiotherapy. CONCLUSIONS: Our results suggest that the control of finger movements benefits from mental training of sequential finger movements and, thus, may be employed as a strategy in post-stroke rehabilitation.

The cerebral oscillatory network associated with auditorily paced finger movements.

Motor tasks involve neural activity in a spatially distributed network. It is assumed that coherent activity between these brain structures reflects functional connectivity. The aim of the present study was to investigate brain areas associated with a unimanual auditorily paced finger-tapping task and to characterize their dynamic interplay. We examined cerebromuscular and cerebrocerebral coupling in 10 right-handed subjects using recordings of continuous brain activity with a 122-channel whole-head neuromagnetometer while subjects performed the task with both hands consecutively. Additionally, surface EMG of the first dorsal interosseus was measured. Our data demonstrate that an oscillatory network composed of primary sensorimotor cortex, lateral as well as mesial premotor areas, the posterior parietal cortex and thalamus contralateral, and cerebellum and primary auditory cortex ipsilateral to the tapping hand subserves task execution. Connectivity between these areas and direction of coupling agree well with anatomical findings. During the right-hand condition, additional oscillatory activity in the primary sensorimotor cortex ipsilateral to the tapping hand was evident. This result suggests an asymmetric motor control in right-handers. Cerebrocerebral coupling predominantly occurs at 8-12 Hz. Therefore, our data support the hypothesis that coupling at 8-12 Hz in a cerebello-thalamic-cortical network represents a fundamental characteristic of the motor system and provides evidence for the significance of 8-12 Hz oscillations in a large scale network during the execution of simple motor tasks.

The role of the primary somatosensory cortex in an auditorily paced finger tapping task.

It has been suggested that a simple auditorily paced finger tapping task is associated with three tap-related neuromagnetic sources in the primary sensorimotor cortex contralateral to the tapping hand. Since a first source peaking at approximately 100 ms before tap-onset most likely represents activation of the primary motor cortex (M1) due to the motor command, a second source localized in the primary somatosensory cortex (S1) peaking around tap-onset could be due to kinesthetic feedback of the finger movement. A third source peaking at approximately 100 ms after tap-onset is also localized in the primary somatosensory cortex but inferior to the first S1 source (S1 inferior). The functional meaning of this source is still under debate. On the one hand it has been argued that S1 inferior represents the neuromagnetic correlate of tactile-kinesthetic feedback due to finger-taps and movements. On the other hand the functional meaning of this source could go beyond the sole processing of somatosensory feedback monitoring the temporal distance between tap and pacer (click) to keep the subject in time with the external event. This hypothesis is based on the observation that (1). S1 inferior seems to be coupled equally well to tap and click and (2). that this source might be triggered by the last event (i.e. tap or click). In the present study we re-examined this hypothesis by using a 122-channel whole-head neuromagnetometer. Eight healthy subjects synchronized their right index finger taps to an auditory pacing signal presented with a constant interstimulus interval of 800 ms. To test the hypothesis that the last event triggers S1 inferior we compared neuromagnetic activity following the tap as the first and the last event. In the auditorily paced finger tapping task usually the tap leads over the click (negative asynchrony). Therefore, the tap usually occurs as the first event. Since it has been shown that delivering additional feedback at the time of tap-onset results in a reduced negative asynchrony, in a second run auditory feedback was presented at tap-onset to enhance the number of positive asynchronies (i.e. the tap is the last event). Since no latency differences of S1 inferior associated with positive and negative asynchronies were found, results from the present study do not support the assumption that S1 inferior is triggered by the last event. Moreover, the amplitude of S1 inferior is significantly reduced following positive asynchronies as compared to negative asynchronies. Additionally, tap duration (i.e. the time between tap-onset and tap-offset) is significantly reduced while subjects produce positive asynchronies. Therefore, the amplitude of S1 inferior seems to be modulated by movement kinematics. This observation agrees well with the idea that activation of S1 is solely associated with the processing of somatosensory information. To conclude, our data contradict the hypothesis of an evaluation process localized in the primary somatosensory cortex and substantiate the idea that S1 inferior exclusively represents the processing of somatosensory feedback information.

Cortical activations associated with auditorily paced finger tapping.

We investigated neuromagnetic responses during an auditorily paced synchronization task using a 122-channel whole-head neuromagnetometer. Eight healthy right handed subjects were asked to synchronize left and right unilateral finger taps to a regular binaural pacing signal. Synchronization of the right hand with an auditory pacing signal is known to be associated with three tap-related neuromagnetic sources localized in the contralateral primary sensorimotor cortex. While the first source represents the neuromagnetic correlate of the motor command the second one reflects somatosensory feedback due to the finger movement. The functional meaning of the third source, which is also localized in the primary somatosensory cortex is still unclear. On the one hand this source represents a neuromagnetic correlate of somatosensory feedback due to the finger tap. On the other hand it has been suggested that the function of this source could additionally represent a cognitive process, which enables the subject to monitor the time distance between taps and clicks. The aim of the present study was to elucidate the function of this source, which would fundamentally reform the meaning of the primary somatosensory cortex in the timing of movements with respect to external events. The data of the present study demonstrate that the three sources in the contralateral sensorimotor cortex are stronger related to the tap than to the click. This result contradicts the assumption of a cognitive process localized in the primary somatosensory cortex. Thus, activation in the primary somatosensory cortex most likely represents exclusively somatosensory feedback and no further cognitive processes.