Speaking in gestures: Left dorsal and ventral frontotemporal brain systems underlie communication in conducting.

Conducting constitutes a well-structured system of signs anticipating information concerning the rhythm and dynamic of a musical piece. Conductors communicate the musical tempo to the orchestra, unifying the individual instrumental voices to form an expressive musical Gestalt. In a functional magnetic resonance imaging (fMRI) experiment, 12 professional conductors and 16 instrumentalists conducted real-time novel pieces with diverse complexity in orchestration and rhythm. For control, participants either listened to the stimuli or performed beat patterns, setting the time of a metronome or complex rhythms played by a drum. Activation of the left superior temporal gyrus (STG), supplementary and premotor cortex and Broca's pars opercularis (F3op) was shared in both musician groups and separated conducting from the other conditions. Compared to instrumentalists, conductors activated Broca's pars triangularis (F3tri) and the STG, which differentiated conducting from time beating and reflected the increase in complexity during conducting. In comparison to conductors, instrumentalists activated F3op and F3tri when distinguishing complex rhythm processing from simple rhythm processing. Fibre selection from a normative human connectome database, constructed using a global tractography approach, showed that the F3op and STG are connected via the arcuate fasciculus, whereas the F3tri and STG are connected via the extreme capsule. Like language, the anatomical framework characterising conducting gestures is located in the left dorsal system centred on F3op. This system reflected the sensorimotor mapping for structuring gestures to musical tempo. The ventral system centred on F3Tri may reflect the art of conductors to set this musical tempo to the individual orchestra's voices in a global, holistic way.

Fully automated detection of focal cortical dysplasia: Comparison of MPRAGE and MP2RAGE sequences.

OBJECTIVE: The detection of focal cortical dysplasia (FCD) in magnetic resonance imaging is challenging. Voxel-based morphometric analysis and automated FCD detection using an artificial neural network (ANN) integrated into the Morphometric Analysis Program (MAP18) have been shown to facilitate FCD detection. This study aimed to evaluate whether the detection of FCD can be further improved by feeding this approach with magnetization prepared two rapid acquisition gradient echoes (MP2RAGE) instead of magnetization-prepared rapid acquisition gradient echo (MPRAGE) datasets. METHODS: MPRAGE and MP2RAGE datasets were acquired in a consecutive sample of 32 patients with FCD and postprocessed using MAP18. Visual analysis and, if available, histopathology served as the gold standard for assessing the sensitivity and specificity of FCD detection. Out-of-sample specificity was evaluated in a cohort of 32 healthy controls. RESULTS: The sensitivity and specificity of FCD detection were 82.4% and 62.5% for the MPRAGE and 97.1% and 34.4% for the MP2RAGE sequences, respectively. Median volumes of true-positive voxel clusters were .16 ml for the MPRAGE and .52 ml for the MP2RAGE sequences compared to .08- and .04-ml volumes of false-positive clusters. With regard to cluster volumes, FCD detection was substantially improved for the MP2RAGE data when the estimated optimal threshold of .23 ml was applied (sensitivity = 72.9%, specificity = 83.0%). In contrast, the estimated optimal threshold of .37 ml for the MPRAGE data did not improve FCD lesion detection (sensitivity = 42.9%, specificity = 79.5%). SIGNIFICANCE: In this study, the sensitivity of FCD detection by morphometric analysis and an ANN integrated into MAP18 was higher for MP2RAGE than for MPRAGE sequences. Additional usage of cluster volume information helped to discriminate between true- and false-positive MP2RAGE results.

"Within a minute" detection of focal cortical dysplasia.

PURPOSE: To evaluate a MRI postprocessing tool for the enhanced and rapid detection of focal cortical dysplasia (FCD). METHODS: MP2RAGE sequences of 40 consecutive, so far MRI-negative patients and of 32 healthy controls were morphometrically analyzed to highlight typical FCD features. The resulting morphometric maps served as input for an artificial neural network generating a FCD probability map. The FCD probability map was inversely normalized, co-registered to the MPRAGE2 sequence, and re-transferred into the PACS system. Co-registered images were scrolled through "within a minute" to determine whether a FCD was present or not. RESULTS: Fifteen FCD, three subcortical band heterotopias (SBH), and one periventricular nodular heterotopia were identified. Of those, four FCD and one SBH were only detected by MRI postprocessing while one FCD and one focal polymicrogryia were missed, respectively. False-positive results occurred in 21 patients and 22 healthy controls. However, true positive cluster volumes were significantly larger than volumes of false-positive clusters (p < 0.001). The area under the curve of the receiver operating curve was 0.851 with a cut-off volume of 0.05 ml best indicating a FCD. CONCLUSION: Automated MRI postprocessing and presentation of co-registered output maps in the PACS allowed for rapid (i.e., "within a minute") identification of FCDs in our clinical setting. The presence of false-positive findings currently requires a careful comparison of postprocessing results with conventional MR images but may be reduced in the future using a neural network better adapted to MP2RAGE images.

T2* Relaxometry in Patients with Parkinson's Disease : Use of an Automated Atlas-based Approach.

BACKGROUND: Magnetic resonance (MR) relaxometry is of increasing scientific relevance in neurodegenerative disorders but is still not established in clinical routine. Several studies have investigated relaxation time alterations in disease-specific areas in Parkinson's disease (PD), all using manually drawn regions of interest (ROI). Implementing MR relaxometry into the clinical setting involves the reduction of time needed for postprocessing using an investigator-independent and reliable approach. The aim of this study was to evaluate an automated, atlas-based ROI method for evaluating T2* relaxation times in patients with PD. METHOD: Automated atlas-based ROI analysis of quantitative T2* maps were generated from 20 PD patients and 20 controls. To test for the accuracy of the atlas-based ROI segmentation, we evaluated the spatial overlap in comparison with manually segmented ROIs using the Dice similarity coefficient (DSC). Additionally, we tested for group differences using our automated atlas-based ROIs of the putamen, globus pallidus, and substantia nigra. RESULTS: A good spatial overlap accuracy was shown for the automated segmented putamen (mean DSC, 0.64 ± 0.04) and was inferior but still acceptable for the substantia nigra (mean DSC, 0.50 ± 0.17). Based on our automated defined ROI selection, a significant decrease of T2* relaxation time was found in the putamen as well as in the internal and external globus pallidus in PD patients compared with healthy controls. CONCLUSION: Automated digital brain atlas-based approaches are reliable, more objective and time-efficient, and therefore have the potential to replace the time-consuming manual drawing of ROIs.

Mesoscopic imaging of glioblastomas: Are diffusion, perfusion and spectroscopic measures influenced by the radiogenetic phenotype?

The purpose of this study was to identify markers from perfusion, diffusion, and chemical shift imaging in glioblastomas (GBMs) and to correlate them with genetically determined and previously published patterns of structural magnetic resonance (MR) imaging. Twenty-six patients (mean age 60 years, 13 female) with GBM were investigated. Imaging consisted of native and contrast-enhanced 3D data, perfusion, diffusion, and spectroscopic imaging. In the presence of minor necrosis, cerebral blood volume (CBV) was higher (median ± SD, 2.23% ± 0.93) than in pronounced necrosis (1.02% ± 0.71), pcorr = 0.0003. CBV adjacent to peritumoral fluid-attenuated inversion recovery (FLAIR) hyperintensity was lower in edema (1.72% ± 0.31) than in infiltration (1.91% ± 0.35), pcorr = 0.039. Axial diffusivity adjacent to peritumoral FLAIR hyperintensity was lower in severe mass effect (1.08*10-3 mm2/s ± 0.08) than in mild mass effect (1.14*10-3 mm2/s ± 0.06), pcorr = 0.048. Myo-inositol was positively correlated with a marker for mitosis (Ki-67) in contrast-enhancing tumor, r = 0.5, pcorr = 0.0002. Changed CBV and axial diffusivity, even outside FLAIR hyperintensity, in adjacent normal-appearing matter can be discussed as to be related to angiogenesis pathways and to activated proliferation genes. The correlation between myo-inositol and Ki-67 might be attributed to its binding to cell surface receptors regulating tumorous proliferation of astrocytic cells.

Integrative Network-based Analysis of Magnetic Resonance Spectroscopy and Genome Wide Expression in Glioblastoma multiforme.

The goal of this study was to identify correlations between metabolites from proton MR spectroscopy and genetic pathway activity in glioblastoma multiforme (GBM). Twenty patients with primary GBM were analysed by short echo-time chemical shift imaging and genome-wide expression analyses. Weighed Gene Co-Expression Analysis was used for an integrative analysis of imaging and genetic data. N-acetylaspartate, normalised to the contralateral healthy side (nNAA), was significantly correlated to oligodendrocytic and neural development. For normalised creatine (nCr), a group with low nCr was linked to the mesenchymal subtype, while high nCr could be assigned to the proneural subtype. Moreover, clustering of normalised glutamine and glutamate (nGlx) revealed two groups, one with high nGlx being attributed to the neural subtype, and one with low nGlx associated with the classical subtype. Hence, the metabolites nNAA, nCr, and nGlx correlate with a specific gene expression pattern reflecting the previously described subtypes of GBM. Moreover high nNAA was associated with better clinical prognosis, whereas patients with lower nNAA revealed a shorter progression-free survival (PFS).

Oxytocin attenuates neural reactivity to masked threat cues from the eyes.

The neuropeptide oxytocin has recently been shown to modulate covert attention shifts to emotional face cues and to improve discrimination of masked facial emotions. These results suggest that oxytocin modulates facial emotion processing at early perceptual stages prior to full evaluation of the emotional expression. Here, we used functional magnetic resonance imaging to examine whether oxytocin alters neural responses to backwardly masked angry and happy faces while controlling for attention to the eye vs the mouth region. Intranasal oxytocin administration reduced amygdala reactivity to masked emotions when attending to salient facial features, ie, the eyes of angry faces and the mouth of happy faces. In addition, oxytocin decreased neural responses within the fusiform gyrus and brain stem areas, as well as functional coupling between the amygdala and the fusiform gyrus specifically for threat cues from the eyes. Effects of oxytocin on brain activity were not attributable to differences in behavioral performance, as oxytocin had no impact on mere emotion detection. Our results suggest that oxytocin attenuates neural correlates of early arousal by threat signals from the eye region. As reduced threat sensitivity may increase the likelihood of engaging in social interactions, our findings may have important implications for clinical states of social anxiety.

Who needs a Wada test? Present clinical indications for amobarbital procedures.

INTRODUCTION: The Wada test has been the gold standard for testing cerebral language localisation during presurgical investigation in the past decades. However, during the last few years a shift has occurred in epilepsy surgery programmes towards the use of non-invasive methods, predominantly functional MRI (fMRI). However, Wada tests are still performed, albeit in a considerably smaller number of patients at many epilepsy centres. METHODS: A retrospective monocentric analysis of remaining clinical indications for performing a Wada procedure was undertaken. The clinical data of patients who participated in Wada tests (42 hemispheric and 8 superselective procedures) during recent years were retrospectively evaluated. RESULTS: Reasons for conducting a Wada test were (1) a patient's inability to perform the fMRI task due to agitation, mental disablement, or perceptual impairment, (2) validation of atypical, inconclusive or not clearly lateralised language activation shown with fMRI, (3) evaluation of propagation of ongoing interictal bilateral epileptiform EEG activity, (4) region selective testing of language and other cognitive functions, or (5) assessment of motor localisation. Patients who were not able to perform the fMRI task or in whom fMRI did not provide interpretable results were significantly younger (p<0.05). CONCLUSION: It is argued that fMRI is eligible to replace Wada tests in the majority of patients who are compliant with clearly lateralised language localisation, but in patients who are agitated or mentally impaired as well as in the case of the above-mentioned specific clinical indications and bilateral fMRI activations, Wada tests still provide additional information. Additionally, non-invasive methods less sensitive to movement artefacts are discussed as possible alternatives for these patients.

Dynamic gray matter changes within cortex and striatum after short motor skill training are associated with their increased functional interaction.

Gray matter (GM) changes have been described after short learning tasks that lasted for 7 days or after external stimulation that lasted for 5 days. However, the early time course of training-dependent GM changes is still unknown. We investigated whether shorter motor training sessions (four times of 30 min training) would induce GM changes. Therefore, T1-weighted MRIs were acquired daily. Because reported GM changes were induced by learning, a close relationship was assumed between the functional activity and the GM changes. Therefore, fMRI was performed in addition to daily T1-weighted MRIs. At the end of the four training sessions (at time point "post"), the test results of the trained motor skill were associated with an increase of GM in secondary cortical motor areas (dPMC(right), dPMC(left), SMA(left) and the right inferior parietal lobule, IPL(right)). The earliest time point at which a GM change was detected was 1day before in the right ventral striatum (by contrasting daily T1-weighted MRI vs. baseline). To analyze whether this very early GM change within the right ventral striatum is associated with those GM changes at time point post (which were associated with motor skill performance), their functional connectivity was investigated over the time period of motor skill training. This analysis revealed an increase of functional coupling between these regions (striatum and cortex) over the training days. The current data demonstrate training-induced short GM plasticity is paralleled by their temporally dynamical process of functional interaction between the cortex and the striatum in response to a motor skill training.

Late-onset autosomal dominant limb girdle muscular dystrophy and Paget's disease of bone unlinked to the VCP gene locus.

The broadwide spectrum of differential diagnoses of autosomal dominant muscular dystrophies in adults can be specified by additional features. The combination of late-onset muscular dystrophy, rimmed vacuoles and inclusion bodies in the muscle biopsy, and Paget's disease of bone suggests a mutation in the Valosin-containing protein gene (VCP, p97 or CDC48) even without dementia. We report on a German family with late-onset autosomal dominant muscular dystrophy starting in the pelvic girdle about age 40years, a subsequent rapidly-progressing course, high alkaline phosphatase and Paget's disease of bone. Clinical examination revealed no cognitive impairment. Histology showed myopathic changes with rimmed vacuoles and inclusion bodies on muscle biopsy. Mutations in VCP, filamin C, desmin, alphaB-crystallin, ZASP and myosin heavy chains 2 and 7 as well as the genes for facioscapulohumeral muscular dystrophy, Myotonic Dystrophy I and II, and LGMD1A-G were excluded by a combination of linkage analysis and direct sequencing. The family presented here suggests that a yet-unknown genetic defect can give rise to an autosomal dominant myopathy with Paget's disease but without dementia.

Lateralization of hippocampal activation differs between left and right temporal lobe epilepsy patients and correlates with postsurgical verbal learning decrement.

We addressed the question whether lateralization of memory-related medial temporal lobe (MTL) activity in medial temporal lobe epilepsy (MTLE) patients is determined by pathology or sex, differentiating between two MTL subregions implicated in visuospatial memory as regions-of-interest (ROI) - the hippocampus (Hc) and the parahippocampal place area (PPA). We further assessed the relation between lateralization of hippocampal activation and postsurgical memory decline regarding performance in standardized neuropsychological tests of verbal and visuospatial learning. Functional magnetic resonance imaging (fMRI) data were acquired from unilateral MTLE patients performing an object location memory task in a virtual environment. Individual lateralization indices (LI) based on memory-related brain activation patterns were calculated for each subject and ROI. Correlational analyses were computed between pre- to postsurgical changes in learning and asymmetry in hippocampal activation. Results revealed that lateralization of hippocampal, memory-related activity in patients with MTLE was determined by the side of seizure focus, not sex. Laterality of activation in the PPA was neither influenced by side of pathology nor sex. Lateralization of hippocampal activation was significantly correlated with decline in verbal learning after surgery. We were able to demonstrate that asymmetry of hippocampal fMRI-activation in unilateral MTLE patients is determined by the side of seizure focus, thus indicating the relative functional integrity of the hippocampi. This is corroborated by the finding that greater activation of the to-be-resected hippocampus leads to stronger verbal memory decline after surgery.

Precuneus is involved in allocentric spatial location encoding and recognition.

Using a declarative memory paradigm, the anatomical correlates of spatial location encoding and retrieval in the healthy human brain as reflected by BOLD fMRI were investigated. During encoding, subjects were instructed to view and keep in mind different locations of an object on a platform seen from different viewpoints in virtual 3D. In retrieval trials, subjects had to recognize previously learned object locations. Comparing activation patterns associated with encoding and recognition on a voxel-by-voxel basis, we found regions in the precuneus bilaterally activated by both processes. To our knowledge, this is the first study that directly compared human brain activation patterns associated with allocentric encoding and retrieval of spatial locations in virtual 3D. Our results provide further information concerning the role of the precuneus in declarative memory processes, pointing to precuneus involvement in encoding and retrieval of spatial locations.

The reliability of fMRI activations in the medial temporal lobes in a verbal episodic memory task.

The test-retest reliability of activation patterns elicited by encoding and recognition of word-pair associates within the whole brain and a predefined medial temporal region of interest (ROI) was investigated. Twenty healthy right-handed subjects were studied within two sessions, either on the same day or 210-308 days later. Three quantitative measures of reliability were calculated for the contrasts encoding and recognition versus a control condition within the ROI and also for the whole brain: A group correlational analysis between the lateralization indices of the first and second session, correlations of the individual SPM(t) maps of the first and the second run, and overlap ratios between both sessions. For the ROI, correlational analysis of lateralization indices during both encoding trials was significant. Eighty percent of the individual positive correlation coefficients of SPM(t) maps during encoding, and 75% during recognition reached significance. The mean percentage of overlapping voxels was 18% during encoding and 19% during recognition. The reproducibility measures evaluated for the whole brain demonstrated significantly higher values compared to the ROI. For the group that stayed inside the scanner, better whole brain test-retest reliability was observed, and no influence of the memory process (encoding or recognition) on reproducibility was found.