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.

[Simultaneous EEG-fMRI measurements: insights in applications and challenges]. / Simultane EEG-fMRT-Messungen : Ein Einblick in Anwendungsmöglichkeiten und Herausforderungen.

BACKGROUND: The following article presents an introduction to simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI) measurements which have undergone a huge development during the last few years. OBJECTIVES: The idea behind combining both non-invasive methods is to join the excellent temporal resolution of EEG (ms) together with the superior spatial resolution of fMRI (mm). In this article the status quo of the method and perspectives regarding multimodal imaging are discussed. MATERIAL AND METHODS: Simultaneous EEG-fMRI measurements are affected by scanner and cardioballistic artifacts. We present common artifact subtraction methods in order to achieve a feasible data quality and outline what to consider when planning and recording EEG and fMRI simultaneously. Moreover, we discuss different analysis strategies. RESULTS: Combined EEG-fMRI measurements have already increased our knowledge about the underlying relationships between the blood oxygenation level-dependent (BOLD) response and the EEG signal and are applied to answer widespread research questions. Simultaneous measurements are an essential part of multimodal imaging in investigating the underlying processing mechanisms of the brain as well as in advancing our understanding of neuropsychiatric diseases. CONCLUSIONS: Current developments in multimodal imaging focus on the combination of electrophysiological and MRI parameters within ultra-high field MRI as well as on positron emission tomography (PET) in a trimodal approach.

Predicting performance in attention by measuring key metabolites in the PCC with 7T MRS.

The posterior cingulate cortex (PCC) is a key hub of the default mode network and is known to play an important role in attention. Using ultra-high field 7 Tesla magnetic resonance spectroscopy (MRS) to quantify neurometabolite concentrations, this exploratory study investigated the effect of the concentrations of myo-inositol (Myo-Ins), glutamate (Glu), glutamine (Gln), aspartate or aspartic acid (Asp) and gamma-amino-butyric acid (GABA) in the PCC on attention in forty-six healthy participants. Each participant underwent an MRS scan and cognitive testing, consisting of a trail-making test (TMT A/B) and a test of attentional performance. After a multiple regression analysis and bootstrapping for correction, the findings show that Myo-Ins and Asp significantly influence (p < 0.05) attentional tasks. On one hand, Myo-Ins shows it can improve the completion times of both TMT A and TMT B. On the other hand, an increase in aspartate leads to more mistakes in Go/No-go tasks and shows a trend towards enhancing reaction time in Go/No-go tasks and stability of alertness without signal. No significant (p > 0.05) influence of Glu, Gln and GABA was observed.

High resolution BrainPET combined with simultaneous MRI.

UNLABELLED: After the successful clinical introduction of PET/CT, a novel hybrid imaging technology combining PET with the versatile attributes of MRI is emerging. At the Forschungszentrum Jülich, one of four prototypes available worldwide combining a commercial 3T MRI with a newly developed BrainPET insert has been installed, allowing simultaneous data acquisition with PET and MRI. The BrainPET is equipped with LSO crystals of 2.5 mm width and Avalanche photodiodes (APD) as readout electronics. Here we report on some performance characteristics obtained by phantom studies and also on the initial BrainPET studies on various patients as compared with a conventional HR+ PET-only scanner. MATERIAL, METHODS: The radiotracers [18F]-fluoro-ethyl-tyrosine (FET), [11C]-flumazenil and [18F]-FP-CIT were applied. RESULTS: Comparing the PET data obtained with the BrainPET to those of the HR+ scanner demonstrated the high image quality and the superior resolution capability of the BrainPET. Furthermore, it is shown that various MR images of excellent quality could be acquired simultaneously with BrainPET scans without any relevant artefacts. DISCUSSION, CONCLUSION: Initial experiences with the hybrid MRI/BrainPET indicate a promising basis for further developments of this unique technique allowing simultaneous PET imaging combined with both anatomical and functional MRI.

[Neurobiology, clinical characteristics and therapy in Tourette's syndrome]. / Neurobiologische Grundlagen, Klinik und Therapie des Tourette-Syndroms.

Tourette's syndrome (TS) is characterised by motor and vocal tics. The clinical manifestation during childhood and the frequent remission during early adulthood point to a dysregulation in the maturation of neuronal pathways. As a neurobiological correlate, the cortico-striato-thalamo-cortical circuit is the main focus of research. Two main features of a movement, the speed and direction of a movement, are controlled by the basal ganglia. Both features are dysregulated in TS.  Besides the motor symptoms, patients with TS suffer from comorbidities such as attention deficit hyperactivity syndrome, depression and obsessive compulsive disorders. Tics are modified in frequency and intensity by actions that require a high level of concentration such as reading or by distress, e.g., teasing by peers. The results of structural and functional imaging data support the hypothesis of altered signal transmission in the basal ganglia and a dysfunction in the limbic system. They also point to a complex interaction between cortical motor areas, the anterior cingulum, prefrontal regions and the basal ganglia.

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.

Quantitative thermal perception testing in 225 children and juveniles.

Quantitative Thermotesting evaluates peripheral small nerve fiber function. The method of limits is a widely used algorithm of perception threshold determination. Normative data are needed to apply the method of limits in children and juveniles. In 225 healthy boys and girls, aged 7 to 17.9 years, warm and cold perception thresholds were established with the method of limits at the volar distal forearm, the thenar eminence, the lower medial calf, the lateral dorsal foot, and the cheek. A 1 degree C/s stimulus velocity, a 32 degrees C thermode baseline, and a 1.5-cm x 2.5-cm Thermotest stimulator were used. Accuracy of stimulus perception was studied by comparing the lowest to the highest response of five consecutive stimuli. The influence of different stimulator sizes on thresholds was tested at the lower calf and distal forearm with an additional 2.5-cm x 5.0-cm thermode. To determine the impact of the pretest skin temperature on thresholds, skin temperature was correlated with thresholds. Results showed good intratrial reproducibility of thresholds. The large thermode yielded lower thresholds than the small probe. Skin temperature had only minor influence on thresholds. The large probe should be used at body sites where it adjusts planely.

Highly abnormal thermotests in familial dysautonomia suggest increased cardiac autonomic risk.

OBJECTIVE: Patients with familial dysautonomia have an increased risk of sudden death. In some patients with familial dysautonomia, sympathetic cardiac dysfunction is indicated by prolongation of corrected QT (QTc) interval, especially during stress tests. As many patients do not tolerate physical stress, additional indices are needed to predict autonomic risk. In familial dysautonomia there is a reduction of both sympathetic neurons and peripheral small nerve fibres which mediate temperature perception. Consequently, quantitative thermal perception test results might correlate with QTc values. If this assumption is correct, quantitative thermotesting could contribute to predicting increased autonomic risk. METHODS: To test this hypothesis, QTc intervals were determined in 12 male and eight female patients with familial dysautonomia, aged 10 to 41 years (mean 21.7 (SD 10.1) years), in supine and erect positions and postexercise and correlated with warm and cold perception thresholds assessed at six body sites using a Thermotest. RESULTS: Due to orthostatic presyncope, six patients were unable to undergo erect and postexercise QTc interval assessment. The QTc interval was prolonged (>440 ms) in two patients when supine and in two additional patients when erect and postexercise. Supine QTc intervals correlated significantly with thermal threshold values at the six body sites and with the number of sites with abnormal thermal perception (Spearman's rank correlation p<0.05). Abnormal Thermotest results were more frequent in the four patients with QTc prolongation and the six patients with intolerance to stress tests. CONCLUSION: The results suggest that impaired thermal perception correlates with cardiac sympathetic dysfunction in patients with familial dysautonomia. Thus thermotesting may provide an alternative, albeit indirect, means of assessing sympathetic dysfunction in autonomic disorders.