Deep Brain Stimulation Does Not Modulate Auditory-Motor Integration of Speech in Parkinson's Disease.

Deep brain stimulation (DBS) has significant effects on motor symptoms in Parkinson's disease (PD), but existing studies on the effect of DBS on speech are rather inconclusive. It is assumed that deficits in auditory-motor integration strongly contribute to Parkinsonian speech pathology. The aim of the present study was to assess whether subthalamic DBS can modulate these deficits. Twenty PD patients (15 male, 5 female; 62.4 ± 6.7 years) with subthalamic DBS were exposed to pitch-shifted acoustic feedback during vowel vocalization and subsequent listening. Voice and brain activity were measured ON and OFF stimulation using magnetoencephalography (MEG). Vocal responses and auditory evoked responses time locked to the onset of pitch-shifted feedback were examined. A positive correlation between vocal response magnitude and pitch variability was observed for both, stimulation ON and OFF (ON: r = 0.722, p < 0.001, OFF: r = 0.746, p < 0.001). However, no differences of vocal responses to pitch-shifted feedback between the stimulation conditions were found [t (19) = -0.245, p = 0.809, d = -0.055]. P200m amplitudes of event related fields (ERF) of left and right auditory cortex (AC) and superior temporal gyrus (STG) were significantly larger during listening [left AC P200m: F (1, 19) = 10.241, p = 0.005, f = 0.734; right STG P200m: F (1, 19) = 8.393, p = 0.009, f = 0.664]. Subthalamic DBS appears to have no substantial effect on vocal compensations, although it has been suggested that auditory-motor integration deficits contribute to higher vocal response magnitudes in pitch perturbation experiments with PD patients. Thus, DBS seems to be limited in modulating auditory-motor integration of speech in PD.

Rapid temporal recalibration to visuo-tactile stimuli.

For a comprehensive understanding of the environment, the brain must constantly decide whether the incoming information originates from the same source and needs to be integrated into a coherent percept. This integration process is believed to be mediated by temporal integration windows. If presented with temporally asynchronous stimuli for a few minutes, the brain adapts to this new temporal relation by recalibrating the temporal integration windows. Such recalibration can occur even more rapidly after exposure to just a single trial of asynchronous stimulation. While rapid recalibration has been demonstrated for audio-visual stimuli, evidence for rapid recalibration of visuo-tactile stimuli is lacking. Here, we investigated rapid recalibration in the visuo-tactile domain. Subjects received visual and tactile stimuli with different stimulus onset asynchronies (SOA) and were asked to report whether the visuo-tactile stimuli were presented simultaneously. Our results demonstrate visuo-tactile rapid recalibration by revealing that subjects' simultaneity reports were modulated by the temporal order of stimulation in the preceding trial. This rapid recalibration effect, however, was only significant if the SOA in the preceding trial was smaller than 100 ms, while rapid recalibration could not be demonstrated for SOAs larger than 100 ms. Since rapid recalibration in the audio-visual domain has been demonstrated for SOAs larger than 100 ms, we propose that visuo-tactile recalibration works at shorter SOAs, and thus faster time scales than audio-visual rapid recalibration.

Beamformer source analysis and connectivity on concurrent EEG and MEG data during voluntary movements.

Electroencephalography (EEG) and magnetoencephalography (MEG) are the two modalities for measuring neuronal dynamics at a millisecond temporal resolution. Different source analysis methods, to locate the dipoles in the brain from which these dynamics originate, have been readily applied to both modalities alone. However, direct comparisons and possible advantages of combining both modalities have rarely been assessed during voluntary movements using coherent source analysis. In the present study, the cortical and sub-cortical network of coherent sources at the finger tapping task frequency (2-4 Hz) and the modes of interaction within this network were analysed in 15 healthy subjects using a beamformer approach called the dynamic imaging of coherent sources (DICS) with subsequent source signal reconstruction and renormalized partial directed coherence analysis (RPDC). MEG and EEG data were recorded simultaneously allowing the comparison of each of the modalities separately to that of the combined approach. We found the identified network of coherent sources for the finger tapping task as described in earlier studies when using only the MEG or combined MEG+EEG whereas the EEG data alone failed to detect single sub-cortical sources. The signal-to-noise ratio (SNR) level of the coherent rhythmic activity at the tapping frequency in MEG and combined MEG+EEG data was significantly higher than EEG alone. The functional connectivity analysis revealed that the combined approach had more active connections compared to either of the modalities during the finger tapping (FT) task. These results indicate that MEG is superior in the detection of deep coherent sources and that the SNR seems to be more vital than the sensitivity to theoretical dipole orientation and the volume conduction effect in the case of EEG.

Multi-modal causality analysis of eyes-open and eyes-closed data from simultaneously recorded EEG and MEG.

Owing to the recent advances in multi-modal data analysis, the aim of the present study was to analyze the functional network of the brain which remained the same during the eyes-open (EO) and eyes-closed (EC) resting task. The simultaneously recorded electroencephalogram (EEG) and magnetoencephalogram (MEG) were used for this study, recorded from five distinct cortical regions of the brain. We focused on the 'alpha' functional network, corresponding to the individual peak frequency in the alpha band. The total data set of 120 seconds was divided into three segments of 18 seconds each, taken from start, middle, and end of the recording. This segmentation allowed us to analyze the evolution of the underlying functional network. The method of time-resolved partial directed coherence (tPDC) was used to assess the causality. This method allowed us to focus on the individual peak frequency in the 'alpha' band (7-13 Hz). Because of the significantly higher power in the recorded EEG in comparison to MEG, at the individual peak frequency of the alpha band, results rely only on EEG. The MEG was used only for comparison. Our results show that different regions of the brain start to `disconnect' from one another over the course of time. The driving signals, along with the feedback signals between different cortical regions start to recede over time. This shows that, with the course of rest, brain regions reduce communication with each another.

Longitudinal deformation-based morphometry reveals spatio-temporal dynamics of brain volume changes in patients with corticobasal syndrome.

BACKGROUND/OBJECTIVE: Corticobasal syndrome (CBS) is a rare neurodegenerative disorder characterized by a progressive and asymmetric manifestation of cortical and basal-ganglia symptoms of different origin. The spatio-temporal dynamics of cerebral atrophy in CBS is barely known. This study aimed to longitudinally quantify the individual dynamics of brain volume changes in patients with CBS as compared to healthy controls. METHODS: We used deformation-field-based morphometry (DFM) to study volumetric changes of each individual brain in short intervals of a few months. DFM enabled the quantitative analysis of local volume changes without predefining regions of interest in MR images of 6 patients with CBS and 11 matched healthy controls. A total of 64 whole brain 3D-MR-scans were acquired two to eight times over periods of 14 to 26 months. Based on repeated registrations of MR observations to the initial scan, maps of local volume ratio changes were computed. RESULTS: Compared to controls patients showed significant and increasing volume loss over time in premotor and primary-motor-cortices, somatosensory area 3a, superior parietal areas BA 5/7, and corticospinal tract. Furthermore, significant and asymmetric atrophy was identified in the caudate nucleus head, putamen, pallidum, motor-thalamus and substantia nigra. Temporal lobe was affected in those patients who presented progressive cognitive impairment. CONCLUSIONS: The analysis revealed localized, pathological changes in brains of patients with CBS, which differed significantly from those occurring during aging in healthy controls. As compared to age- and sex-matched controls, brains of CBS patients showed a common degenerating neural network comprising the motor circuit with basal ganglia and motor thalamic nuclei as well as the premotor and primary-motor-cortex.

Echoes from childhood--imitation in Gilles de la Tourette Syndrome.

BACKGROUND: Tourette syndrome patients are reported to show automatic imitation (echopraxia), but this has not yet been proven experimentally. METHODS: Video clips showing either tics of other Tourette patients or spontaneous movements of healthy subjects were presented to Tourette patients and healthy subjects. Participants' responses were assessed using blinded review of video recordings by 2 independent raters and related to stimuli presented. RESULTS: Both raters detected more echoes in patients. In a permutation analysis, no healthy subject had echoes above chance level. In contrast, 6 and 5 patients were classified as echoers according to rater 1 and rater 2, respectively, in 1 analysis, and 9 patients were so classified in a second analysis (according to rater 2 only). Concordance between raters was high. Patients echoed both following stimuli showing tics and following stimuli showing spontaneous movements. Most echoes were part of patients' individual tic repertoire. CONCLUSIONS: Echopraxia is a hallmark of Tourette syndrome.

Characterisation of tremor-associated local field potentials in the subthalamic nucleus in Parkinson's disease.

We simultaneously recorded local field potentials (LFPs) in the subthalamic nucleus (STN) and surface electromyographic signals (EMGs) from the extensor and flexor muscles of the contralateral forearm in eight patients with idiopathic tremor-dominant Parkinson's disease (resting tremor) during the bilateral implantation of deep brain stimulation electrodes. Recordings were made at different heights (in 0.5- to 2.0-mm steps beginning outside the STN) using up to five concentrically configured macroelectrodes (2 mm apart). The patients were instructed to relax their contralateral forearm (rest condition). We analysed the coherence between tremor EMGs and STN LFPs, which showed significant tremor-associated coupling at single tremor and double tremor frequencies. Moreover, the EMG-LFP coherences were characterised by differences between antagonistic muscles (flexor, extensor) and by the spatial distribution of LFPs within the STN. Coherence at single and double tremor frequencies occurred significantly more frequently within STN than above STN (in the zona incerta). In this study, we were able to show that, within STN, tremor-associated LFP activity varied with spatial distribution and with the contralateral antagonistic forearm muscles. These findings suggest the existence of distribution- and muscle-specific tremor-associated LFP activity at different tremor frequencies and an organisation of tremor-related subloops within the STN.

Degradation of the endocrine disrupting chemicals (EDCs) carbamazepine, clofibric acid, and iopromide by corona discharge over water.

Common wastewater treatment plants often do not eliminate endocrine disrupting chemicals (EDCs). Aqueous solutions of three EDCs were treated with an enhanced corona discharge technology. The three EDCs were clofibric acid, a blood lipid regulator, carbamazepine, an antiepileptic drug, and iopromide, a contrast media. To simulate real conditions, EDC solutions containing landfill leachate were also used. In our setup, two barrier electrodes provided an atmospheric pressure corona discharge over a thin water film, in which the counter-electrode was submerged. Clofibric acid, carbamazepine, and iopromide were effectively removed from a single solution. After a treatment of 15min, there were no traces of iopromide estrogen activity either as a single substance or as degradation products when using an E-Screen Assay. Continuous treatment was compared with pulsed treatment using carbamazepine solutions mixed with pretreated landfill leachate. Best degradation results were achieved with a 500 W continuous duty cycle treatment. Counter-electrodes from materials such as boron doped diamond (BDD), titanium iridium oxide, and iron were investigated for their influences on the process effectivity. Significant improvements were achieved by using an enclosed reactor, BDD electrodes, and circulating only a fresh air or argon/air mixture as cooling gas through the barrier electrodes.

Differential effects of levodopa and subthalamic nucleus deep brain stimulation on bradykinesia in Parkinson's disease.

Cardinal symptoms of Parkinson's disease (PD) respond well to treatment with levodopa and deep brain stimulation (DBS) of the subthalamic nucleus (STN). However, it has remained unclear whether levodopa and STN-DBS have differential effects on bradykinesia. We investigated 8 PD-patients with STN-electrodes in four conditions: STN-DBS and levodopa (ON(MED)/ON(STIM)), STN-DBS only (OFF(MED)/ON(STIM)), levodopa only (ON(MED)/OFF(STIM)), without STN-DBS/levodopa (OFF(MED)/OFF(STIM)). Fourteen volunteers served as controls. Subjects performed fastest possible (1) pronation/supination of the forearm (diadochokinesia) and (2) flexion and extension of the index finger (finger movements). Movements were recorded using a 3D-ultrasound-system. Maximum frequency, amplitude, and smoothness of movements were determined. During OFF(MED)/OFF(STIM), all parameters were worser than in all other conditions. In proximal diadochokinesia, OFF(MED)/ON(STIM) significantly improved the amplitude and frequency, whereas ON(MED)/OFF(STIM) had no significant effect. In contrast, we found a stronger effect of levodopa (ON(MED)/OFF(STIM)) on amplitudes of distal finger movement than on amplitudes of diadochokinesia. Combination of treatments during ON(MED)/ON(STIM) further improved both movements. However, maximum frequency remained lower in PD-patients during ON(MED)/ON(STIM) compared with controls. This study demonstrates a better effect of levodopa on distal finger movements and STN-DBS on proximal diadochokinesia. Furthermore, a complementary effect of both therapies on brain areas involved in bradykinesia can be assumed.

Biochip reader with dynamic holographic excitation and hyperspectral fluorescence detection.

A highly parallel microarray scanner for functional genomic research using a dynamically reconfigurable holographic excitation and hyperspectral fluorescence detection is described. The light from two laser sources (405 and 532 nm) is split into an arbitrary number of focused spots on the biochip using a pair of spatial light modulators and a novel imaging system. The parallel optical scanner includes a hyperspectral detection unit with a high-sensitivity CCD camera to detect and analyze the emitted fluorescence spectra (from 430 to 800 nm) of all illuminated spots simultaneously. By using an xy scanner, the spectra of all spots on an entire array can be read out line by line.

Replicated, high-aspect-ratio micro-optical components fabricated from inorganic solgel materials.

A replication process for the fabrication of refractive microlenses from a purely inorganic solgel material based on tetraethoxysilane is presented. The geometrical dimensions and optical properties of the inorganic microlenses are characterized and compared with those of microlenses replicated in a hybrid xerogel containing organic additives. By a reduced solvent content in the sol composition, together with modifications in the replication process, it was possible to obtain inorganic xerogel lenses with exceptionally high sagittal height values of as much as 28 microm. Compared with the hybrid xerogel, the inorganic xerogel has the advantage of an absorption coefficient that is five times lower in the visible spectral range and exhibits optical transparency in the near-ultraviolet range for wavelengths down to 200 nm.

[Patient and consumer information centres according to 65b Social Security Code V--means for high-quality information exchange and counselling]. / Patienten- und Verbraucherberatungsstellen nach 65b SGB V--Wege zu einer qualitativ hochwertigen Informationsvermittlung und Beratung.

Counsellors of Independent Health Information Centres according to 65b Social Security Code V provide the public with comprehensive information on health and disease-related themes, as well as on their financial, service, and legal aspects; they also provide extensive counselling and psychosocial support. The counsellors mostly have a university background in educational, social, medical, or legal disciplines; they usually have long-term experience in counselling as well as additional professional qualifications. In addition to the provision of information, independent health information centres must also be active in assuring and promoting their own quality control. Different measures are applied for this purpose, however at this time there are no standardised, high-quality activities of the independent health information centres to ensure quality.

Effects of sympathetic nerves and angiotensin II on renal sodium and water handling in rats with common bile duct ligature.

We tested the hypothesis that angiotensin II is likely to be mandatory for the neurogenic sodium and volume retention in cirrhotic rats with common bile duct ligature (BDL) following an acute volume load. To assess the neural control of volume homeostasis, 21 days after common BDL rats underwent volume expansion (0.9% NaCL; 10% body wt over 30 min) to decrease renal sympathetic nerve activity. Untreated animals, rats with renal denervation or pretreated with a nonhypotensive dose of an angiotensin II type 1 receptor antagonist were studied. The renal renin-angiotensin system was assessed by immunohistochemistry and RT-PCR. Rats with BDL excreted only 71 +/- 4% of the administered volume load. In cirrhotic rats pretreated with an angiotensin II AT1 inhibitor or after renal denervation, these values ranged significantly higher from 98 to 103% (P < 0.05 for all comparisons). Renal sympathetic nerve activity decreases by volume expansion were impaired in BDL rats (P < 0.05) but unaffected by angiotensin II receptor inhibition. In kidneys of BDL animals, renin mRNA was increased, and immunohistochemistry revealed increased staining for peritubular angiotensin II. Renal denervation in BDL animals reduced renin expression within 5 days to control levels. In conclusion, the impaired excretion of an acute volume load in rats with liver cirrhosis is due to effects of an increased renal sympathetic nerve activity that are likely to be dependent on intrarenal angiotensin II and renin. We speculate that similar changes may contribute to long-term volume retention in liver cirrhosis.

Hypertension, sodium retention, calcium excretion and osteopenia in Dahl rats.

BACKGROUND: Salt-sensitive hypertension in the Dahl rat is associated with abnormalities in both calcium (Ca2+) and sodium (Na) homeostasis. OBJECTIVE: To test the hypothesis that salt-induced abnormal Ca(2+) handling in Dahl salt-sensitive (DSS) rats is associated with negative Ca(2+) balance and bone disease. METHODS: Ca(2+) excretion in acute and chronic Na(+) loading and electrolyte and water balance were determined by balance studies in Dahl salt-resistant (DSR) and salt-sensitive (DSS) rats fed 8 or 0.1% NaCl for 4 weeks. A dry ashing procedure was used to determine Na(+), Ca(2+), and water content and their association with blood pressure in the rats. RESULTS: When fed 8% NaCl, DSS rats initially maintained a positive Ca(2+) balance and showed decreased natriuresis compared with DSR rats. During the course of Na(+) loading, DSS rats increased natriuresis and calciuresis. After 4 weeks of salt loading, cumulative Na balance was greater and cumulative Ca(2+) balance was less in DSS than in DSR rats. In addition, DSS rats developed osteopenia. Bone mineral content correlated inversely with blood pressure in DSS rats. Acute saline volume expansion in DSS rats demonstrated their ability to excrete the Na load fully, but led to an exaggerated renal loss of Ca(2+) compared with DSR rats. CONCLUSION: DSS, but not DSR, develop Ca(2+) loss and ostopenia during chronic Na(+) loading. We speculate that Na retention in DSS rats fed a high Na diet may be in part a compensatory mechanism to maintain Ca(2+) balance.

An MRI-compatible surgical robot for precise radiological interventions.

OBJECTIVE: A variety of medical robots have been developed in recent years. MRI, including MR angiography and morphological imaging, with its excellent soft-tissue contrast is attractive for the development of interventional MRI-guided therapies and operations. This paper presents a telerobotic device for use in CT- and/or MR-guided radiological interventions. A robotic device for precise needle insertion during MR-guided therapy of spinal diseases will be briefly described. MATERIALS AND METHODS: Actuation of robots in an MRI environment is difficult due to the presence of strong magnetic fields. Therefore, the robot was constructed of nonmagnetic materials. The system frame was built from polyether ether ketone (PEEK) and fiber-reinforced epoxy, and actuated using ultrasonic and pneumatic motors. Completely MR-compatible sensors were developed for positioning control. RESULTS: Accuracy evaluation procedures and phantom tests were performed, with the required accuracy of approximately 1 mm being achieved and no significant artifacts being caused by the robotic device during MR image acquisition.

Reduced osmotically inactive Na storage capacity and hypertension in the Dahl model.

Recent evidence suggested that Na can be stored in an osmotically inactive form. We investigated whether osmotically inactive Na storage is reduced in a rat model of salt-sensitive (SS) hypertension. SS and salt-resistant (SR) Dahl-Rapp rats as well as Sprague-Dawley (SD) rats were fed a high (8%)- or low (0.1%)-NaCl diet for 4 wk (n = 10/group). Mean arterial pressure (MAP) was measured at the end of the experiment. Wet and dry weights, water content, total body Na (TBS), and bone Na content were measured by dessication and dry ashing. MAP was higher in both Dahl strains than in SD rats. In SS rats, 8% NaCl led to Na accumulation, water retention, and hypertension due to impaired renal Na excretion. There was no dietary-induced Na retention in SR and SD rats. TBS was variable; nevertheless, TBS was significantly correlated with body water and MAP in all strains. However, the extent of Na-associated volume and MAP increases was strain specific. Osmotically inactive Na in SD rats was threefold higher than in SS and SR rats. Both SS and SR Dahl rat strains displayed reduced osmotically inactive Na storage capacity compared with SD controls. A predisposition to fluid accumulation and high blood pressure results from this alteration. Additional factors, including impaired renal Na excretion, probably contribute to hypertension in SS rats. Our results draw attention to the role of osmotically inactive Na storage.