Multimodal Fingerprints of Resting State Networks as assessed by Simultaneous Trimodal MR-PET-EEG Imaging.

Simultaneous MR-PET-EEG (magnetic resonance imaging - positron emission tomography - electroencephalography), a new tool for the investigation of neuronal networks in the human brain, is presented here for the first time. It enables the assessment of molecular metabolic information with high spatial and temporal resolution in a given brain simultaneously. Here, we characterize the brain's default mode network (DMN) in healthy male subjects using multimodal fingerprinting by quantifying energy metabolism via 2- [18F]fluoro-2-desoxy-D-glucose PET (FDG-PET), the inhibition - excitation balance of neuronal activation via magnetic resonance spectroscopy (MRS), its functional connectivity via fMRI and its electrophysiological signature via EEG. The trimodal approach reveals a complementary fingerprint. Neuronal activation within the DMN as assessed with fMRI is positively correlated with the mean standard uptake value of FDG. Electrical source localization of EEG signals shows a significant difference between the dorsal DMN and sensorimotor network in the frequency range of δ, θ, α and ß-1, but not with ß-2 and ß-3. In addition to basic neuroscience questions addressing neurovascular-metabolic coupling, this new methodology lays the foundation for individual physiological and pathological fingerprints for a wide research field addressing healthy aging, gender effects, plasticity and different psychiatric and neurological diseases.

Spatiotemporal properties of auditory intensity processing in multisensor MEG.

Loudness dependence of auditory evoked potentials (LDAEP) evaluates loudness processing in the human auditory system and is often altered in patients with psychiatric disorders. Previous research has suggested that this measure may be used as an indicator of the central serotonergic system through the highly serotonergic innervation of the auditory cortex. However, differences among the commonly used analysis approaches (such as source analysis and single electrode estimation) may lead to different results. Putatively due to discrepancies of the underlying structures being measured. Therefore, it is important to learn more about how and where in the brain loudness variation is processed. We conducted a detailed investigation of the LDAEP generators and their temporal dynamics by means of multichannel magnetoencephalography (MEG). Evoked responses to brief tones of five different intensities were recorded from 19 healthy participants. We used magnetic field tomography in order to appropriately localize superficial as well as deep source generators of which we conducted a time series analysis. The results showed that apart from the auditory cortex other cortical sources exhibited activation during the N1/P2 time window. Analysis of time courses in the regions of interest revealed a sequential cortical activation from primary sensory areas, particularly the auditory and somatosensory cortex to posterior cingulate cortex (PCC) and to premotor cortex (PMC). The additional activation within the PCC and PMC has implications on the analysis approaches used in LDAEP research.

The temporal dynamics of the Müller-Lyer illusion.

By attaching arrows to a line's ends, the Müller-Lyer illusion can be used to modulate perceived line length. In the present study, we investigated the dynamics of the brain processes underlying this illusion using magnetoencephalography. Subjects were presented with a horizontal line with arrows attached to its ends. Across trials, the angles formed by the arrows were repeatedly changed such that 2 variants of the Müller-Lyer length illusion were either induced or not. The onset of both variants of the illusion revealed consistent activations in visual areas between 85 and 130 ms after stimulus onset, as well as strong and longer lasting activations along the ventral visual processing stream including inferior occipital, inferior temporal, and fusiform gyrus within the range of 195-220 ms. Subsequent neural activation was observed in the right superior temporal cortex, as well as in the right inferior parietal and the right inferior frontal cortex. The time course and the location of the activations suggest that the mechanisms involved in generating the Müller-Lyer illusion are closely linked to the ones associated with object perception, consistent with theories considering a relevant contribution of higher visual areas to the generation of the Müller-Lyer illusion.

Neural correlates of subliminal and supraliminal letter processing--an event-related fMRI study.

One problem of interpreting research on subconscious processing is the possibility that participants are weakly conscious of the stimuli. Here, we compared the fMRI BOLD response in healthy adults to clearly visible single letters (supraliminal presentation) with the response to letters presented in the absence of any behavioural evidence of visibility (subliminal presentation). No letter catch trials served as a control condition. Forced-choice responses did not differ from chance when letter-to-background contrast was low, whereas they were almost 100% correct when contrast was high. A comparison of fMRI BOLD signals for supraliminal and subliminal letters with the control trials revealed a signal increase in left BA 37 (fusiform gyrus). Comparison of supraliminal with subliminal letters showed a significant increase in the right inferior frontal gyrus (BA 44, partly extending to BA 9 and BA 45, as well as BA 46). Finally, a comparison of subliminal with supraliminal letters showed increases in the left middle temporal gyrus (BA 21) and the right extrastriate cortex (BA 19).

Optimized mismatch negativity paradigm reflects deficits in schizophrenia patients. A combined EEG and MEG study.

Mismatch negativity (MMN) and its neuromagnetic analog (MMNm) are event-related brain responses elicited by changes in a sequence of auditory events and indexes early cognitive processing. It consistently detects neural processing deficits in schizophrenia. So far MMN is assessed with different methods (electroencephalography, EEG; magnetoencephalography, MEG) and with different paradigms: the "traditional" oddball design with rare deviants (20%) or the "optimum" design with 50% deviants varying in one of five parameters each. These MMN measures may not reflect one unitary mechanism which is equally affected in schizophrenia. We compared both designs in 12 patients with schizophrenia and controls using MEG and EEG. Automated, observer-independent data analysis rendered the procedures suitable for clinical applications. The optimum design was fastest to detect MMN and MEG had the best signal-to-noise ratio. In addition MMN was mostly reduced in schizophrenia if measured with MEG in the optimum paradigm. Optimized paradigms improve sensitivity and speed for the detection of schizophrenia endophenotypes. Dysfunctions in this disorder may lie primarily in the fast and automatic encoding of stimulus features at the auditory cortex.

Synchronization tomography: a method for three-dimensional localization of phase synchronized neuronal populations in the human brain using magnetoencephalography.

We present a noninvasive technique which allows the anatomical localization of phase synchronized neuronal populations in the human brain with magnetoencephalography. We study phase synchronization between the reconstructed current source density (CSD) of different brain areas as well as between the CSD and muscular activity. We asked four subjects to tap their fingers in synchrony with a rhythmic tone, and to continue tapping at the same rate after the tone was switched off. The phase synchronization behavior of brain areas relevant for movement coordination, inner voice, and time estimation changes drastically when the transition to internal pacing occurs, while their averaged amplitudes remain unchanged. Information of this kind cannot be derived with standard neuroimaging techniques like functional magnetic resonance imaging or positron emission tomography.

Synthesis and antiviral activity of 7-O-(omega-substituted)-alkyl-3-O-methylquercetin derivatives.

3',4'-Di-O-benzyl-3-O-methylquercetin (2), the precursor in the synthesis of an important antivirally active flavone 3-O-methylquercetin (1), was regioselectively alkylated at the 7-OH position by a series of 1,omega-dihaloalkanes and omega-bromoalkanols. Dimerization of the flavone had to be avoided by applying strict reaction conditions. Subsequent debenzylation was carried out by catalytic transfer hydrogenolysis, affording quantitatively the 7-O-(omega-haloalkyl)-3-O-methylquercetin (11-14) and 7-O-(omega-hydroxyalkyl)-3-O-methylquercetin derivatives (15, 16). All compounds were tested for their antiviral activity against poliomyelitis- and HIV-viruses.