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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 an 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 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. Fiber selection from a normative human connectome database, constructed using a global tractography approach, showed that F3op and STG are connected via the arcuate fasciculus, while F3tri and STG are connected via the extreme capsule. Like language, the anatomical framework characterizing conducting gestures is located in the left dorsal system centered on F3op. This system reflected the sensorimotor mapping for structuring gestures to musical tempo. The ventral system centered on F3Tri may reflect the art of conductors to set this musical tempo to the individual orchestra's voices in a global, holistic way.

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 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.

BACKGROUND AND PURPOSE: Focal cortical dysplasias are the most common resected epileptogenic lesions in children and the third most common lesion in adults, but they are often subtle and frequently overlooked on MR imaging. The purpose of this study was to evaluate whether MP2RAGE-based morphometric MR imaging analysis is superior to MPRAGE-based analysis in the detection of focal cortical dysplasia. MATERIALS AND METHODS: MPRAGE and MP2RAGE datasets were acquired in a consecutive series of 640 patients with epilepsy. Datasets were postprocessed using the Morphometric Analysis Program to generate morphometric z score maps such as junction, extension, and thickness images based on both MPRAGE and MP2RAGE images. Focal cortical dysplasia lesions were manually segmented in the junction images, and volumes and mean z scores of the lesions were measured. RESULTS: Of 21 focal cortical dysplasias discovered, all were clearly visible on MP2RAGE junction images, whereas 2 were not visible on MPRAGE junction images. In all except 4 patients, the volume of the focal cortical dysplasia was larger and mean lesion z scores were higher on MP2RAGE junction images compared with the MPRAGE-based images (P = .005, P = .013). CONCLUSIONS: In this study, MP2RAGE-based morphometric analysis created clearer output maps with larger lesion volumes and higher z scores than the MPRAGE-based analysis. This new approach may improve the detection of subtle, otherwise overlooked focal cortical dysplasia.

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.

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.

The purpose of this study is to relate hippocampal volume and FLAIR signal intensity to Wyler grading of hippocampal sclerosis (HS). Of 100 consecutive patients with temporal lobe epilepsy and HS as histopathological diagnosis, 32 had high-resolution 3 Tesla MRI and anatomically well-preserved hippocampi following amygdalo-hippocampectomy. Hippocampal volume on 3D T1-weighted gradient echo and signal intensity on coronal FLAIR sequences were determined using FreeSurfer and SPM tools and related to Wyler grading. Seizure outcome was determined after 1 year. Histopathology showed four Wyler II, 19 Wyler III, and 9 Wyler IV HS. Hippocampal volumes were 3.08 ml for Wyler II (Wyler II/contralateral side: p > 0.05), 2.19 ml for Wyler III (p

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.

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).

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 (dPMCright, dPMCleft, SMAleft and the right inferior parietal lobule, IPLright). The earliest time point at which a GM change was detected was 1 day 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.

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.

Situationally adaptive behavior relies on the identification of relevant target stimuli, the evaluation of these with respect to the current context and the selection of an appropriate action. We used functional magnetic resonance imaging (fMRI) to disentangle the neural networks underlying these processes within a single task. Our results show that activation of mid-ventrolateral prefrontal cortex (PFC) reflects the perceived presence of a target stimulus regardless of context, whereas context-appropriate evaluation is subserved by mid-dorsolateral PFC. Enhancing demands on response selection by means of response conflict activated a network of regions, all of which are directly connected to motor areas. On the midline, rostral anterior paracingulate cortex was found to link target detection and response selection by monitoring for the presence of behaviorally significant conditions. In summary, we provide new evidence for process-specific functional dissociations in the frontal lobes. In target-centered processing, target detection in the VLPFC is separable from contextual evaluation in the DLPFC. Response-centered processing in motor-associated regions occurs partly in parallel to these processes, which may enhance behavioral efficiency, but it may also lead to reaction time increases when an irrelevant response tendency is elicited.

Several studies have attempted to identify the neuronal basis of sex differences in cognition. However, group differences in cognitive ability rather than genuine neurocognitive differences between the sexes may account for their results. Here, we compare with functional magnetic resonance imaging the relation between gender, individual task performance, and planning-related brain activation. Men and women preselected to display identical performance scores showed a strong relation between individual task performance and activation of the right dorsolateral prefrontal and right inferior parietal cortex activation during a visuospatial planning task. No gender-specific activations were found. However, a different pattern emerged when subjects had to execute the motor responses to the problems. Better performance was associated with right dorsolateral prefrontal and right parahippocampal activations, and females exhibited a stronger right hippocampal activation than males. These findings underline that an individual's performance level rather than his or her sex largely determines the neuronal activation patterns during higher-level cognition.

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 patient9s 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 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.

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.

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 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.

Die Bestimmung der zerebralen Sprachreprasentation ist wesentlicher Bestandteil der prachirurgischen Diagnostik vor Operationen in potentiell sprachrelevanten Regionen, insbesondere vor elektiven epilepsiechirurgischen Eingriffen. Die etablierten Verfahren Wada-Test und kortikale Stimulation sind invasiv und belastend. Seit ca. 10 Jahren steht die funktionelle Magnetresonanztomographie (fMRT) als nichtinvasive Alternative zur Verfugung. Obwohl in zahlreichen Untersuchungen eine gute Ubereinstimmung der Ergebnisse von fMRT und Wada-Test gezeigt werden konnte, gibt es keine allgemein akzeptierten Empfehlungen, in welchen Fallen auf einen Wada-Test verzichtet werden kann. In der vorliegenden Zusammenstellung untersuchten die Autoren, wie sich das diagnostische Procedere seit der klinischen Einfuhrung der Sprach-fMRT an ihrer Institution verandert hat. Seit 1999 wurden in Freiburg 208 Sprach-fMRTs bei 198 Patienten durchgefuhrt. Im gleichen Zeitraum reduzierte sich der relative Anteil der Patienten der Sektion Prachirurgische Epilepsiediagnostik, bei denen ein Wada-Test durchgefuhrt wurde, um ca. 50%. Der Anteil der Sprach-fMRTs, der vorwiegend aufgrund mangelhafter Kooperationsfahigkeit der Patienten nicht verwertbar war, lag in den vergangenen 2 Jahren < 10%. Nach Ansicht der Autoren besteht lediglich noch in den Fallen eine zwingende Indikation fur einen Wada-Test, in denen keine Sprach-fMRT durchfuhrbar ist oder die fMRT therapeutisch entscheidende Fragen nicht beantworten kann.

The neuronal processes underlying correct and erroneous problem solving were studied in strong and weak problem-solvers using functional magnetic resonance imaging (fMRI). During planning, the right dorsolateral prefrontal cortex was activated, and showed a linear relationship with the participants' performance level. A similar pattern emerged in right inferior parietal regions for all trials, and in anterior cingulate cortex for erroneously solved trials only. In the performance phase, when the pre-planned moves had to be executed by means of an fMRI-compatible computer mouse, the right dorsolateral prefrontal cortex was again activated jointly with right parahippocampal cortex, and displayed a similar positive relationship with the participants' performance level. Incorrectly solved problems elicited stronger bilateral prefrontal and left inferior parietal activations than correctly solved trials. For both individual ability and trial-specific performance, our results thus demonstrate the crucial involvement of right prefrontal cortex in efficient visuospatial planning.

The protein rop, some of its mutants and the human complement component C9 were studied using steady state fluorescence spectroscopy and lifetime resolved fluorescence quenching experiments. —The rop molecule has a hairpin like structure and a tail consisting of 7 amino acids, which is not visible in the electron density map of X-ray crystallography. The lifetime resolved quenching experiments show that at low salt concentrations the tail is attached to the main body of the molecule, while it is removed at high salt concentrations. This difference can be explained by shielding of electrostatic interactions at high salt. —A comparision of C9 and its polymer with respect to their fluorescence quantum yields and fluorescence lifetimes shows that in the poly C9 three of the four tryptophanes are quenched by intramolecular processes. Furthermore the experiments reveal a discrepancy between exposure of tryptophan determined by the emission spectrum or determined by use of the surface quenchers I− and Cs+.

The fluorescence decay of the aromatic amino acid tyrosine, as well as of symmetric tripeptides is monoexponential, the fluorescence lifetimes can be understood on the basis of a simple empirical equation for first order rate constants of energy transfer from tyrosine to neighboring amino acids. Fluorescence energy transfer from tyrosine to DNA in protein-DNA complexes can be used to elucidate the role of Tyr-DNA interaction in the formation of inverted DNA, a postulated new type of DNA structure and gives information on differences of the role of the positively charged amino acids lysine and arginine in electrostatic protein-DNA interaction.

Using a new type of fluorescence lifetime spectrometer, the time resolution of single shot fluorescence detection is improved by two orders of magnitude. The spectrometer is based on a streak camera and an excimer laser pumped distributed feedback dye laser (DFDL) providing UV pulses of 50 μJ and 15 ps FWHM, corresponding to a peak power of ∼ 5 · 106 W in the ultraviolet. —This spectrometer is used to investigate the fluorescence decay of peptides containing a tyrosine as the single fluorophore. Peptides with tyrosine at the N-terminus reveal a biexponential decay, while peptides with C-terminal tyrosine are mainly monoexponential. This difference can be explained by the relative orientation of the fluorescing phenol ring and the quenching peptide bond. —The fluorescence decay of a number of peptides with tyrosine in a non terminal position can be described by two lifetimes, 2.3 · 0.1 ns and 380 ± 70 ps, where the percentage of the long lifetime increases to up to 100% when the rotational flexibility of the peptide chain decreases, either due to increasing weight of the chain or due to formation of an H-bridge. —Similar processes seem to be relevant for the fluorescence of the dye coumarin 120 coupled to nucleotides. The fluorescence lifetime of such molecules is significantly different, so that the four DNA nucleotides can be identified on the basis of the fluorescence decay of the attached dye.