Phase I/II clinical study on safety and antivascular effects of paclitaxel encapsulated in cationic liposomes for targeted therapy in advanced head and neck cancer.

BACKGROUND: The purpose of this phase I/II clinical trial was to test safety and effectiveness of 2 doses of vascular targeting cationic liposomes encapsulating paclitaxel (EndoTAG-1 [ET]) in human head and neck squamous cell carcinoma (HNSCC). METHODS: Patients with nonresectable therapy-refractory HNSCC were recruited for both ET treatment groups (3 or 4 patients per group). In cutaneous metastases, laser Doppler blood flow measurements were conducted during infusions. RESULTS: Only adverse events of grade 1 or 2 according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE version 3.0) - in particular fatigue, chills, and hypertension - occurred. Follow-up tumor volume measurements revealed stable disease in 4 of 5 cases. Reproducible dose-dependent blood flow reductions in skin metastases during ET infusions provide evidence of biological effectiveness. CONCLUSION: Infusions of ET seem to be safe and further phase II and III studies are warranted to prove efficacy in the treatment of HNSCC.

CNTNAP2 polymorphisms and structural brain connectivity: a diffusion-tensor imaging study.

CNTNAP2 is a gene on chromosome 7 that has shown associations with autism and schizophrenia, and there is evidence that it plays an important role for neuronal synchronization and brain connectivity. In this study, we assessed the relationship between Diffusion Tensor Imaging (DTI), a putative marker of anatomical brain connectivity, and multiple single nucleotide polymorphisms (SNPs) spread out over this large gene. 81 healthy controls and 44 patients with schizophrenia (all Caucasian) underwent DTI and genotyping of 31 SNPs within CNTNAP2. We employed Tract-based Spatial Statistics (TBSS) for inter-subject brain registration and computed average diffusivity values for six major white matter tracts. Analyses of Covariance (ANCOVAs) were computed to test for possible associations with genotypes. The strongest association, which survived rigorous Bonferroni correction, was between rs2710126 genotype and Fractional Anisotropy (FA) in the uncinate fasciculus (p = .00003). This anatomical location is particularly interesting given the enriched fronto-temporal expression of CNTNAP2 in the developing brain. For this SNP, no phenotype association has been reported before. There were several further genotype-DTI associations that were nominally significant but did not survive Bonferroni correction, including an association between axial diffusivity in the dorsal cingulum bundle and a region in intron 13 (represented by rs2710102, rs759178, rs2538991), which has previously been reported to be associated with anterior-posterior functional connectivity. We present new evidence about the effects of CNTNAP2 on brain connectivity, whose disruption has been hypothesized to be central to schizophrenia pathophysiology.

Inefficient neural activity in patients with schizophrenia and nonpsychotic relatives of schizophrenic patients: evidence from a working memory task.

Studies of schizophrenia with functional MRI have shown hyper- and hypoactivations in various brain regions including the prefrontal cortex. Functional anomalies have also been reported in first-degree relatives of schizophrenic patients. The aim of this study was to examine working memory related brain functions in healthy subjects, schizophrenic patients and unaffected relatives and to determine the influence of psychopathology on these processes. A parametric n-back working memory task and functional MRI were used to examine 61 patients with schizophrenia, 11 nonpsychotic relatives of schizophrenic patients and a comparison group of 61 healthy subjects. The results indicated increased as well as decreased brain functions in schizophrenic patients compared to the control group depending on the task difficulty and the performance: during the attention task (0-back), which served as control condition, behavioral responses of patients and healthy subjects hardly differed but BOLD responses were considerably enhanced in schizophrenic patients. With increasing task difficulty differences between groups in BOLD responses diminished whereas behavioral deficits of patients increased. The examination of attention-independent working memory-functions (2- vs. 0-back) produced hypoactivations in patients, especially in frontal, temporal and subcortical brain regions. Furthermore, positive symptoms were associated with parietal dysfunctions. Behavioral performance and neural responses of unaffected relatives of schizophrenic patients were intermediate between schizophrenic patients and controls indicating slight brain dysfunctions. In addition, compensatory strategies were demonstrated. These findings suggest that the genetic risk for schizophrenia is accompanied by neural inefficiency which is associated with cognitive deficits, especially in difficult tasks.

Persistence of high-capacity adenoviral vectors as replication-defective monomeric genomes in vitro and in murine liver.

Liver-based gene therapy approaches demonstrated that high-capacity adenoviral vectors (HC-AdVs) can persist life-long in mice and for 2 years or longer in rats, dogs, and nonhuman primates. However, the molecular status of episomal HC-AdV DNA molecules and the mechanism of vector genome maintenance have not been analyzed. HC-AdV lacks all viral coding sequences including early gene region 4 (E4), which prevents concatemerization in wild-type adenovirus. Therefore, we addressed whether concatemerization or circularization of HC-AdV DNA occurs in transduced cells. We employed pulsed-field gel electrophoresis and a sensitive concatemer/circle-specific polymerase chain reaction (PCR). To test for replication as a potential mechanism for maintenance, we developed a methylase/restriction endonuclease-based system using methylation-marked HC-AdV. We found that unlike DeltaE4 mutant virus, only monomers of HC-AdV genomes were observable in vitro. Using our methylase/restriction endonuclease-based system, no replication of HC-AdV was sensed in various cell lines. However, concatemer formation of HC-AdV could be induced after coinfection with an E4-deleted helper virus, indicating that linkage of genomes may be supported by replication. To examine HC-AdV DNA molecules in vivo, C57BL/6 mice were injected and vector DNA in liver was analyzed. In concordance with our in vitro results, exclusively linear monomers were detected. To sense the replication status of HC-AdV genomes, we established a sensitive real-time PCR. Our results indicated that the input transduced DNA genomes were the persistent molecules in murine liver. In summary, we demonstrated that HC-AdV genomes persist predominantly as replication-defective monomeric genomes.

A rapid protocol for construction and production of high-capacity adenoviral vectors.

High-capacity adenoviral vectors (HC-AdVs) lacking all viral coding sequences were shown to result in long-term transgene expression and phenotypic correction in small and large animal models. It has been established that HC-AdVs show significantly reduced toxicity profiles compared with early-generation adenoviral vectors. Furthermore, with capsid-modified HC-AdV becoming available, we are just starting to understand the full potential of this vector system. However, for many researchers, the wide-scale use of HC-AdV is hampered by labor-intensive and complex production procedures. Herein, we provide a feasible and detailed protocol for efficient generation of HC-AdV. We introduce an efficient cloning strategy for the generation of recombinant HC-AdV vector genomes. Infection and amplification of the HC-AdV are performed in a spinner culture system. For purification, we routinely apply cesium chloride gradients. Finally, we describe various methods for establishing vector titers. Generation of high-titer HC-AdV can be achieved in 3 weeks.

The free choice whether or not to respond after stimulus presentation.

The concept of 'willed' actions has attracted attention during the last few years. Free choices have been associated with activations on the medial frontal surface, the dorsolateral prefrontal cortex and the parietal lobe. Self-paced movements and free selection between various motor responses were typically used to investigate voluntary behavior. The aim of the present study was to determine neural correlates of voluntary motor responses and the voluntary inhibition of motor responses in a group of healthy subjects. Hence, a go/nogo/voluntary selection paradigm was used. In the voluntary selection condition subjects decided freely whether or not to respond with a button press after stimulus presentation. Functional MRI data and event-related potentials were acquired simultaneously in order to reliably investigate spatial and temporal characteristics of these responses. The results showed decision-related enhanced neural responses predominantly in the medial frontal gyrus/supplementary motor area, lateral frontal brain regions and the inferior parietal gyrus. Additional activations associated with voluntary movements were detected in the frontal eye field as well as brain regions directly linked to motor responses (e.g. somatosensory cortical areas). Altogether, decision processes were shown to be relatively independent of the kind of response chosen.

White and gray matter abnormalities in the brain of patients with fibromyalgia: a diffusion-tensor and volumetric imaging study.

OBJECTIVE: To use a combination of magnetic resonance diffusion-tensor imaging (MR-DTI) and MR imaging of voxel-based morphometry (MR-VBM) in patients with fibromyalgia syndrome (FMS) to determine microstructural and volume changes in the central neuronal networks involved in the sensory-discriminative and affective-motivational characteristics of pain, anxiety, memory, and regulation of the stress response. METHODS: Thirty female patients with FMS and 30 healthy female control subjects were studied. Predefined areas of the brain were measured for volume of gray matter by MR-VBM and for diffusivity and fractional anisotropy (FA) by MR-DTI. Higher FA values and reduced diffusivity are thought to reflect increased complexity of brain-tissue microstructure. RESULTS: MR-VBM and MR-DTI demonstrated a striking pattern of changes in brain morphology in patients with FMS. Both thalami, the thalamocortical tracts, and both insular regions showed significant decreases in FA. In contrast, increases in FA and decreases in gray matter volume were seen in the postcentral gyri, amygdalae, hippocampi, superior frontal gyri, and anterior cingulate gyri. Increased pain intensity scores were correlated with changes in MR-DTI measurements in the right superior frontal gyrus. Increased fatigue was correlated with changes in the left superior frontal and left anterior cingulate gyrus, and self-perceived physical impairment was correlated with changes in the left postcentral gyrus. Higher intensity scores for stress symptoms were correlated negatively with diffusivity in the thalamus and FA in the left insular cortex. No relationship was found between MR-VBM measurements and symptom intensity scores. CONCLUSION: MR-DTI allows the visualization of microstructural changes in the brain of patients with FMS, appears to be more sensitive than MR-VBM, and may serve as an additional diagnostic technique in FMS and probably other dysfunctional pain syndromes.

Single-trial coupling of EEG and fMRI reveals the involvement of early anterior cingulate cortex activation in effortful decision making.

While the precise role of the anterior cingulate cortex (ACC) is still being discussed, it has been suggested that ACC activity might reflect the amount of mental effort associated with cognitive processing. So far, not much is known about the temporal dynamics of ACC activity in effort-related decision making or auditory attention, because fMRI is limited concerning its temporal resolution and electroencephalography (EEG) is limited concerning its spatial resolution. Single-trial coupling of EEG and fMRI can be used to predict the BOLD signal specifically related to amplitude variations of electrophysiological components. The striking feature of single-trial coupling is its ability to separate different aspects of the BOLD signal according to their specific relationship to a distinct neural process. In the present study we investigated 10 healthy subjects with a forced choice reaction task under both low and high effort conditions and a control condition (passive listening) using simultaneous EEG and fMRI. We detected a significant effect of mental effort only for the N1 potential, but not for the P300 potential. In the fMRI analysis, ACC activation was present only in the high effort condition. We used single-trial coupling of EEG and fMRI in order to separate information specific to N1-amplitude variations from the unrelated BOLD response. Under high effort conditions we were able to detect circumscribed BOLD activations specific to the N1 potential in the ACC (t=4.7) and the auditory cortex (t=6.1). Comparing the N1-specific BOLD activity of the high effort condition versus the control condition we found only activation of the ACC (random effects analysis, corrected for multiple comparisons, t=4.4). These findings suggest a role of early ACC activation in effort-related decision making and provide a direct link between the N1 component and its corresponding BOLD signal.

Influence of trait anxiety on inhibitory control in alcohol-dependent patients: simultaneous acquisition of ERPs and BOLD responses.

Alcohol-dependence is often associated with comorbid psychiatric symptoms. However, the results concerning the influence of these symptoms on cognitive functioning in alcoholism are still inconsistent. The aim of this study was to determine performance monitoring in healthy volunteers and alcohol-dependent patients, and to assess the influence of trait anxiety on these processes. Sixteen healthy volunteers and 16 detoxified alcohol-dependent patients completed an auditory go/nogo paradigm. Functional magnetic resonance imaging, event-related potentials and behavioral data were acquired simultaneously. The patients were classified by median split based on level of self-rated trait anxiety (state-trait anxiety inventory; STAI). The results showed no significant differences regarding inhibition-associated electrophysiological and behavioral responses between alcohol-dependent patients with high-trait anxiety scores and alcohol-addicts with low-STAI scores. However, the functional MRI data revealed elevated activations during the response inhibition task especially in the middle frontal gyrus (BA 6/9), the superior frontal gyrus (BA 6/8/9) and the right inferior frontal gyrus, as well as temporo-parietal brain regions in patients with high-trait anxiety compared to non-anxious alcohol-addicts. Patients and healthy controls showed comparable results with regard to neural and behavioral responses. These results suggest that inhibitory control capacities of alcohol-dependent patients are not consistent: alcohol-addicts with high-trait anxiety ratings showed elevated neural responses compared to patients without any comorbid psychiatric symptoms. This may indicate that comorbid psychiatric symptoms need to be considered when assessing brain responses in alcohol-dependent patients.

Emerging adenoviral vectors for stable correction of genetic disorders.

Recent drawbacks in treating patients with severe combined immunodeficiency disorders with retroviral vectors underline the importance of generating novel tools for stable transduction of mammalian cells. Substantial progress has been made over the recent years which may offer important steps towards stable and more importantly safer correction of genetic diseases. This article discusses recent advances for stable transduction of target cells based on adenoviral gene transfer. There is accumulating evidence that recombinant adenoviral vectors (AdVs) based on various human serotypes with a broad cellular tropism and adenoviruses (Ads) from different species will play an important role in future gene therapy applications. In combination with recombinant AdVs for somatic integration these gene transfer vectors offer high transduction efficiencies with potentially safer integration patterns. Other approaches for persistent transgene expression include excision of stable episomes from the adenoviral vector genome, but also long-term persistence of the complete adenoviral vector genome as an episomal DNA molecule was demonstrated and exemplified by the treatment of various genetic diseases in small and large animal models. This review displays advantages but also limitations of these Ad based vector systems. This is the perfect time to pursue such approaches because alternative strategies for stable transduction of mammalian cells undergoing many cell divisions are urgently needed. Looking into the future, we believe that a combination of different components from different viral vectors in concert with non-viral vector systems will be successful in designing significantly optimized transfer vehicles for a broad range of different genetic diseases.

Influence of anxiety on electrophysiological correlates of response inhibition capacities in alcoholism.

Anxiety disorders are highly prevalent in patients with alcohol use disorder. The purpose of the present study was to examine the neural correlates of behavioral inhibition in alcohol-dependent patients (ICD-10: F 10.2), and in healthy controls and to determine the influence of anxiety on these processes. Therefore, behavioral responses (reaction times; error rates) and event-related potentials of 16 patients with alcohol dependence syndrome and 16 age-and gender-matched healthy controls were recorded while the participants performed an auditory go/no-go task. The patient group was stratified according to their self-rated trait anxiety (STAI) with scores above and below median. We hypothesized that patients suffering from alcohol dependence would show reduced no-go P3 amplitudes involved in response inhibition compared to healthy subjects. In patients with alcoholism and high trait anxiety the decline of no-go P3 amplitudes was expected to be less distinct. The estimation of effect size based on the reaction times of patients with high and low anxiety ratings revealed a cohen's d of 0.61 indicating a small effect. High trait anxiety ratings were also associated with slightly enhanced no-go P3 amplitudes in central brain regions (Mean no-go P3 amplitude at Cz: 10.43 microV) compared to patients with low anxiety scores (Mean 8.98 microV). The effect size (cohen's d) revealed a small effect. Using the Mann-Whitney-U-test for independent samples of the comparison of high- and low-anxious patients, however, did not reveal any significant differences concerning no-go P3 amplitudes. Patients with alcohol use disorder and healthy controls did not differ significantly with regard to reaction time, error rate and no-go P3 amplitudes. This study suggests that no-go P3 amplitudes in patients with alcohol use disorder might be affected to some degree by habitual anxiety. The results emphasize the importance of monitoring trait anxiety in studies regarding cognitive functions in subjects with alcohol use disorder.

Evidence of subcortical and cortical aging of the acoustic pathway: a diffusion tensor imaging (DTI) study.

RATIONALE AND OBJECTIVES: During aging, there is evidence of microstructural changes in certain cortical and subcortical brain regions. Diffusion tensor imaging (DTI) is used to study age related microstructural changes in the acoustic pathway. MATERIALS AND METHODS: Twenty healthy volunteers (mean age 28.5 years) and 15 healthy volunteers (mean age 61.3 years) were examined using a 1.5-T MR system with a high-resolution T1-weighted sequence and an integrated parallel imaging technique DTI Echo-planar-imaging (EPI) sequence. For reliability, 10 subjects underwent a second examination 2 days later. The fractional anisotropy (FA) and the apparent diffusion coefficient (ADC) were measured in six brain regions of the auditory pathway. RESULTS: We found no left/right asymmetry in the selected brain structures. There were no significant differences (P < .05) in the ADC and FA in the lateral lemniscus and medial geniculate body of young and elderly subjects. However, FA was significantly increased (P < .05) in the inferior colliculus and decreased in the auditory radiation, the superficial temporal gyrus, and the transverse temporal gyrus in the elder subjects than in the younger ones. There were no significant differences in anisotropy in subsequent examinations in the younger individuals. CONCLUSIONS: These findings suggest evidence of age-related changes in the acoustic pathway. These changes are associated with a decrease in anisotropy mainly in the cortical grey and white matter rather than in the subcortical regions. Our DTI measurements were reproducible.

Delineation of temporal bone anatomy: feasibility of low-dose 64-row CT in regard to image quality.

The aim of our present study was to evaluate the visualization of anatomical landmarks of the temporal bone using a low-dose 64-slice computed tomography (CT) technique. A total of 120 patients were evaluated, 60 patients (mean age 47.1 years; 36 male, 24 female) underwent examination with a 4-slice CT scanner: 180 mAs, 120 kV, 1 s rotation time, 2 x 0.5 mm collimation, 0.5 mm slice thickness. Another 60 consecutive patients (mean age 37.4 years; 43 male, 37 female) were examined using a 64-slice CT low-dose protocol: 140 mAs, 120 kV, 1 s rotation time, 12 x 0.6 mm collimation, 0.6 mm slice thickness. The visibility of 42 landmarks was scored by two blinded radiologists using a five-point quality rating scale. Mean equivalent dose was significantly lower for the 64-slice CT protocol (0.31 mSv +/- 0.12 mSv) compared to the 4-slice CT protocol (0.61 mSv +/- 0.08 mSv). Despite increased image noise, only 19% of the anatomical landmarks were delineated significantly better on the axial sections of the 4-slice CT and only 9.5% of the anatomical landmarks on the reformatted coronal images. The interobserver agreement did not differ significantly between the two modalities. Low-dose 64-slice CT technique facilitates temporal bone imaging with sufficient anatomical detail.

Optimization of MDCT of the wrist to achieve diagnostic image quality with minimum radiation exposure.

OBJECTIVE: This study tests various acquisition and reconstruction protocols for MDCT of the wrist to determine the optimal protocol for obtaining diagnostic image quality with minimal radiation exposure. MATERIALS AND METHODS: Thirty anatomic specimens were examined with an MDCT collimation of 4.0 x 1.0 mm and 2.0 x 0.5 mm (80, 120, and 140 kV; 80, 100, 130, 160, and 200 mA; rotation time, 0.5 0.75, 1.0 sec; pitch, 1.0, 1.3, 1.5, and 2.0). Coronal images were reconstructed using a slice thickness of 0.5, 1.0, and 2.0 mm with 60% overlap. Three observers evaluated all images independently for gross and fine anatomic detail. Diagnostic confidence was tested using Shrout-Fleiss intraclass correlation coefficients. Interobserver agreement was assessed by Kappa statistics and the Kruskal-Wallis test. RESULTS: Fine anatomic detail was best presented in 0.5-mm or 1.00-mm reconstructions based on a 2.0 x 0.5 mm acquisition. A rotation time of > or = 0.75 sec resulted in fewer artifacts; a significant dose reduction was achieved with 80 kV and 100 mA at the expense of somewhat increased noise, but without significant loss of anatomic detail in bone presentation. Artifacts were tolerable with a pitch of 1.5 or less. CONCLUSION: MDCT at the described optimal settings allows significant dosage reduction without sacrificing image quality. An acquisition and reconstruction thickness of 0.5 mm results in the best depiction of anatomic detail. A reconstruction thickness of 1.0 mm with a reconstruction interval of 0.5 mm represents a good trade-off between noise and resolution when using low-dose protocols.

Sound level dependence of the primary auditory cortex: Simultaneous measurement with 61-channel EEG and fMRI.

Sound level dependence has been investigated for years with event-related potentials (ERP). A serotonergic modulation of the sound level dependence only of the primary auditory cortex but not of the auditory association cortex has been suggested by a number of clinical and preclinical studies. Therefore, a precise covering of the activity of the primary auditory cortex seems necessary if sound level dependence is used as an indicator of the central serotonergic system. Recent fMRI studies described a pronounced sound level dependence only in the Heschl gyrus/primary auditory cortex but not in auditory association areas. In the present simultaneous 61-channel EEG and fMRI study investigating fourteen healthy subjects, we found a high correlation between the loudness-dependent change of the extent of fMRI activation (number of activated voxels) and the corresponding changes of the mean current source density within the same region of interest covering the primary auditory cortex (r = 0.84, P < 0.001). Our findings suggest a close relationship between the fMRI signal and event-related potential activity. In addition, the correspondence of the ERP-based data and the fMRI results further supports the validity of the ERP localization approach.

Formation of a novel surface structure encoded by Salmonella Pathogenicity Island 2.

The type III secretion system (T3SS) encoded by Salmonella Pathogenicity Island 2 (SPI2) is essential for virulence and intracellular proliferation of Salmonella enterica. We have previously identified SPI2-encoded proteins that are secreted and function as a translocon for the injection of effector proteins. Here, we describe the formation of a novel SPI2-dependent appendage structure in vitro as well as on the surface of bacteria that reside inside a vacuole of infected host cells. In contrast to the T3SS of other pathogens, the translocon encoded by SPI2 is only present singly or in few copies at one pole of the bacterial cell. Under in vitro conditions, appendages are composed of a filamentous needle-like structure with a diameter of 10 nm that was sheathed with secreted protein. The formation of the appendage in vitro is dependent on acidic media conditions. We analyzed SPI2-encoded appendages in infected cells and observed that acidic vacuolar pH was not required for induction of SPI2 gene expression, but was essential for the assembly of these structures and their function as translocon for delivery of effector proteins.

CT of the normal temporal bone: comparison of multi- and single-detector row CT.

PURPOSE: To evaluate multi- and single-detector row computed tomographic (CT) depiction of anatomic landmarks of temporal bone. MATERIALS AND METHODS: Institutional review board approval and written informed consent were obtained. In 50 temporal bones, transverse and coronal single-detector row CT images were compared with transverse and reformatted coronal multi-detector row CT images obtained of additional 50 temporal bones. Two radiologists evaluated images. Visibility of 50 landmarks was scored with a five-point quality rating scale. Fisher exact test, kappa statistics, and Mann-Whitney U test were used to evaluate imaging technique and landmark visibility. RESULTS: In delineating landmarks, total interobserver agreement was higher (P < .001) for transverse multi- than for single-detector row CT images. In 60% of landmarks, interobserver agreement was higher (P < .001) for transverse multi- than for single-detector row CT images. In 20% of landmarks, there was no difference, and in another 20% of landmarks, interobserver agreement was higher (P < .01) for single-detector row CT. Total interobserver agreement was higher (P < .01) for coronal multi-detector row reformations than for coronal single-detector row images. In 58% of landmarks, interobserver agreement was higher (P < .001) for coronal multi-detector row reformations than for coronal single-detector row images, while there was no difference in 8%. In 34% of landmarks, interobserver agreement was higher (P < .001) for coronal single-detector row images. Frequency of detected landmarks was higher for transverse (82%) and coronal (88%) multi-detector row images than for corresponding single-detector row images. In 72% of landmarks, transverse multi-detector row images were (P < .05) superior to corresponding transverse single-detector row images in landmark delineation. In 56% of landmarks, reformatted coronal multi-detector row images were (P < .05) superior to coronal single-detector row images in landmark delineation. CONCLUSION: Multi-detector row CT images, including reformations, better delineate temporal bone anatomy than do single-detector row CT images.

Labyrinth dysfunction 8 months after cochlear implantation: a case report.

OBJECTIVE: Investigate whether the cochleostomy is a possible port of entry for pneumolabyrinth and a resulting vertigo in patients provided with a cochlear implant. STUDY DESIGN: Retrospective case review. SETTING: Ludwig-Maximilians University of Munich, Hospital Grosshadern. PATIENT: 62-year-old patient who underwent implantation of a HiFocus II cochlear implant with positioner from Advanced Bionics (CLARION). Eight months postoperatively, the patient reported rotatory vertigo and right-side tinnitus after he had blown his nose harder than usual during an episode of rhinitis. INTERVENTIONS: Preoperative and postoperative testing of both the petrosal bone with a CT scan and of balance function. MAIN OUTCOME MEASURE: Air inclusion in the labyrinth. RESULTS: In contrast to the preoperative high resolution computed tomography (CT) scan, air inclusion was seen in the labyrinth during the episode of vertigo. At the same time, balance function tests with Frenzel glasses revealed both spontaneous and provoked horizontal nystagmus to the right side. At follow-up 8 weeks later, the level of vertigo had significantly decreased. Twelve months later, the control CT showed the cochlear implant positioned correctly and no visible air in the labyrinth. CONCLUSION: It is known that placement of the HiFocus II with Positioner from CLARION requires a relatively large cochleostomy of 1.5 mm. Moreover, in the connective tissue seal between the electrode and the positioner, the latter reaches into the tympanic cavity, and this is possibly the weak point. Further investigation will be needed to determine whether the large cochleostomy with the HiFocus II with positioner increases the predisposition to labyrinth dysfunction.

Integration of fMRI and simultaneous EEG: towards a comprehensive understanding of localization and time-course of brain activity in target detection.

fMRI and EEG are complimentary methods for the analysis of brain activity since each method has its strength where the other one has limits: The spatial resolution is thus in the range of millimeters with fMRI and the time resolution is in the range of milliseconds with EEG. For a comprehensive understanding of brain activity in target detection, nine healthy subjects (age 24.2 +/- 2.9) were investigated with simultaneous EEG (27 electrodes) and fMRI using an auditory oddball paradigm. As a first step, event-related potentials, measured inside the scanner, have been compared with the potentials recorded in a directly preceding session in front of the scanner. Attenuated amplitudes were found inside the scanner for the earlier N1/P2 component but not for the late P300 component. Second, an independent analysis of the localizations of the fMRI activations and the current source density as revealed by low resolution electromagnetic tomography (LORETA) has been done. Concordant activations were found in most regions, including the temporoparietal junction (TPJ), the supplementary motor area (SMA)/anterior cingulate cortex (ACC), the insula, and the middle frontal gyrus, with a mean Euclidean distance of 16.0 +/- 6.6 mm between the BOLD centers of gravity and the LORETA-maxima. Finally, a time-course analysis based on the current source density maxima was done. It revealed different time-course patterns in the left and right hemisphere with earlier activations in frontal and parietal regions in the right hemisphere. The results suggest that the combination of EEG and fMRI permits an improved understanding of the spatiotemporal dynamics of brain activity.

Focal epileptiform activity in the brain: detection with spike-related functional MR imaging--preliminary results.

The purpose of this study was to develop a spike-related functional magnetic resonance (MR) imaging method to detect epileptic brain activity. Correlations between simultaneous spike-related functional MR imaging and electroencephalographic (EEG) recordings were performed in 10 patients with focal epilepsy. Postprocessing techniques were implemented to eliminate contamination of the EEG recording from ballistocardiography and the echo-planar MR imaging sequence. A diagnostic EEG recording was achieved during functional MR imaging. Spike location correlated with the site of blood oxygen level-dependent signal increase. Spike-related functional MR imaging is a promising technique for detecting focal epileptic brain activity.