Temporal hierarchy of cortical responses reflects core-belt-parabelt organization of auditory cortex in musicians.

Human auditory cortex (AC) organization resembles the core-belt-parabelt organization in nonhuman primates. Previous studies assessed mostly spatial characteristics; however, temporal aspects were little considered so far. We employed co-registration of functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) in musicians with and without absolute pitch (AP) to achieve spatial and temporal segregation of human auditory responses. First, individual fMRI activations induced by complex harmonic tones were consistently identified in four distinct regions-of-interest within AC, namely in medial Heschl's gyrus (HG), lateral HG, anterior superior temporal gyrus (STG), and planum temporale (PT). Second, we analyzed the temporal dynamics of individual MEG responses at the location of corresponding fMRI activations. In the AP group, the auditory evoked P2 onset occurred ~25 ms earlier in the right as compared with the left PT and ~15 ms earlier in the right as compared with the left anterior STG. This effect was consistent at the individual level and correlated with AP proficiency. Based on the combined application of MEG and fMRI measurements, we were able for the first time to demonstrate a characteristic temporal hierarchy ("chronotopy") of human auditory regions in relation to specific auditory abilities, reflecting the prediction for serial processing from nonhuman studies.

Reduced cortical thickness in Heschl's gyrus as an in vivo marker for human primary auditory cortex.

The primary auditory cortex (PAC) is located in the region of Heschl's gyrus (HG), as confirmed by histological, cytoarchitectonical, and neurofunctional studies. Applying cortical thickness (CTH) analysis based on high-resolution magnetic resonance imaging (MRI) and magnetoencephalography (MEG) in 60 primary school children and 60 adults, we investigated the CTH distribution of left and right auditory cortex (AC) and primary auditory source activity at the group and individual level. Both groups showed contoured regions of reduced auditory cortex (redAC) along the mediolateral extension of HG, illustrating large inter-individual variability with respect to shape, localization, and lateralization. In the right hemisphere, redAC localized more within the medial portion of HG, extending typically across HG duplications. In the left hemisphere, redAC was distributed significantly more laterally, reaching toward the anterolateral portion of HG. In both hemispheres, redAC was found to be significantly thinner (mean CTH of 2.34 mm) as compared to surrounding areas (2.99 mm). This effect was more dominant in the right hemisphere rather than in the left one. Moreover, localization of the primary component of auditory evoked activity (P1), as measured by MEG in response to complex harmonic sounds, strictly co-localized with redAC. This structure-function link was found consistently at the group and individual level, suggesting PAC to be represented by areas of reduced cortex in HG. Thus, we propose reduced CTH as an in vivo marker for identifying shape and localization of PAC in the individual brain.

Increased volume and function of right auditory cortex as a marker for absolute pitch.

Absolute pitch (AP) perception is the auditory ability to effortlessly recognize the pitch of any given tone without external reference. To study the neural substrates of this rare phenomenon, we developed a novel behavioral test, which excludes memory-based interval recognition and permits quantification of AP proficiency independently of relative pitch cues. AP- and non-AP-possessing musicians were studied with morphological and functional magnetic resonance imaging (fMRI) and magnetoencephalography. Gray matter volume of the right Heschl's gyrus (HG) was highly correlated with AP proficiency. Right-hemispheric auditory evoked fields were increased in the AP group. fMRI revealed an AP-dependent network of right planum temporale, secondary somatosensory, and premotor cortices, as well as left-hemispheric "Broca's" area. We propose the right HG as an anatomical marker of AP and suggest that a right-hemispheric network mediates AP "perception," whereas pitch "labeling" takes place in the left hemisphere.

The neurological syndrome in adults during the 2011 northern German E. coli serotype O104:H4 outbreak.

The aim of this study was to describe the neurological syndrome in the largest cohort of adult patients with a complicated Shiga toxin-producing Escherichia coli infection. The recent outbreak of Shiga toxin-producing E. coli serotype O104:H4 in northern Germany affected more than 3842 patients, 22% of whom developed haemolytic uraemic syndrome. The proportion of adult patients was unusually high, and neurological complications were frequent and severe. In three hospitals, population-based evaluation of 217 patients with complicated Shiga toxin-producing E. coli infection was carried out, including neurological, neuroradiological, neurophysiological, cerebrospinal fluid and neuropathological analyses. Of the 217 patients with complicated Shiga toxin-producing E. coli infection, 104 (48%) developed neurological symptoms. Neurological symptoms occurred 5.3 days (mean) after first diarrhoea and 4 days after onset of haemolytic uraemic syndrome. Of the infected patients with neurological symptoms, 67.3% presented with cognitive impairment or aphasia. During the course of the disease, 20% of the patients developed epileptic seizures. The onset of neurological symptoms was paralleled by increases in blood urea nitrogen and serum creatinine. In 70 patients with cerebral magnetic resonance imaging, the most common findings were symmetrical hyperintensities in the region of abducens nucleus and lateral thalamus. On follow-up scans, these abnormalities were resolved. Neuropathological analysis revealed regionally accentuated astrogliosis and microgliosis, more predominant in the thalamus and brainstem than in the cortex, and neuronal expression of globotriaosylceramide. There were no signs of microbleeds, thrombotic vessel occlusion or ischaemic infarction. The neurological syndrome in adult patients with complicated Shiga toxin-producing E. coli infection is a rapidly progressive and potentially life-threatening disease necessitating intensive care unit treatment and intubation in >30% of cases. The outcome of neurological patients in the 2011 northern German Shiga toxin-producing E. coli O104:H4 outbreak was surprisingly good. Magnetic resonance imaging and neuropathological findings point to a mixed toxic and inflammatory pathomechanism leading to largely reversible damage of neuronal function.

Clinical functional MRI of sensorimotor cortex using passive motor and sensory stimulation at 3 Tesla.

PURPOSE: To establish a passive motor paradigm for clinical functional MRI (fMRI) that could be beneficial for patients with motor or attention deficits who are not able to perform active motor tasks. MATERIALS AND METHODS: A novel standardized sensorimotor fMRI protocol was applied in 16 healthy volunteers at 3 Tesla (T) using active and passive motor tasks as well as sensory stimulation of hands and feet. Data analysis was carried out individually using a dynamic thresholding routine. RESULTS: Active motor tasks yielded time efficient and robust blood-oxygen-level-dependent (BOLD) signals in primary motor cortex. Noteworthy, it was possible to achieve equal activation levels within identical anatomical localization for passive and active motor tasks with these paradigms. CONCLUSION: Patients unable to perform active movements can benefit from paradigms with passive motor and sensory stimulation. Therefore, we recommend these paradigms for functional somatotopic mapping of the central region at 3T in clinical routine.

Diagnostic benefits of presurgical fMRI in patients with brain tumours in the primary sensorimotor cortex.

OBJECTIVES: Reliable imaging of eloquent tumour-adjacent brain areas is necessary for planning function-preserving neurosurgery. This study evaluates the potential diagnostic benefits of presurgical functional magnetic resonance imaging (fMRI) in comparison to a detailed analysis of morphological MRI data. METHODS: Standardised preoperative functional and structural neuroimaging was performed on 77 patients with rolandic mass lesions at 1.5 Tesla. The central region of both hemispheres was allocated using six morphological and three functional landmarks. RESULTS: fMRI enabled localisation of the motor hand area in 76/77 patients, which was significantly superior to analysis of structural MRI (confident localisation of motor hand area in 66/77 patients; p < 0.002). FMRI provided additional diagnostic information in 96% (tongue representation) and 97% (foot representation) of patients. FMRI-based presurgical risk assessment correlated in 88% with a positive postoperative clinical outcome. CONCLUSION: Routine presurgical FMRI allows for superior assessment of the spatial relationship between brain tumour and motor cortex compared with a very detailed analysis of structural 3D MRI, thus significantly facilitating the preoperative risk-benefit assessment and function-preserving surgery. The additional imaging time seems justified. FMRI has the potential to reduce postoperative morbidity and therefore hospitalisation time.

Diagnosis of mast cell activation syndrome: a global "consensus-2".

The concept that disease rooted principally in chronic aberrant constitutive and reactive activation of mast cells (MCs), without the gross MC neoplasia in mastocytosis, first emerged in the 1980s, but only in the last decade has recognition of "mast cell activation syndrome" (MCAS) grown significantly. Two principal proposals for diagnostic criteria have emerged. One, originally published in 2012, is labeled by its authors as a "consensus" (re-termed here as "consensus-1"). Another sizable contingent of investigators and practitioners favor a different approach (originally published in 2011, newly termed here as "consensus-2"), resembling "consensus-1" in some respects but differing in others, leading to substantial differences between these proposals in the numbers of patients qualifying for diagnosis (and thus treatment). Overdiagnosis by "consensus-2" criteria has potential to be problematic, but underdiagnosis by "consensus-1" criteria seems the far larger problem given (1) increasing appreciation that MCAS is prevalent (up to 17% of the general population), and (2) most MCAS patients, regardless of illness duration prior to diagnosis, can eventually identify treatment yielding sustained improvement. We analyze these proposals (and others) and suggest that, until careful research provides more definitive answers, diagnosis by either proposal is valid, reasonable, and helpful.

Reduced anisotropy in the middle cerebellar peduncle in Chiari-II malformation.

Besides supratentorial abnormalities, spina bifida menigomyelocele (SBM) is typically associated with Chiari-II malformation comprising a small cerebellum, which herniates downward due to a shallow posterior fossa. We used diffusion tensor imaging to probe additional microstructural alterations of the major cerebellar white matter tracts, the cerebellar peduncles. A region-of-interest approach was employed in six SBM patients and six matched controls to compare the fractional anisotropy (FA) within the superior, middle, and inferior cerebellar peduncle (SCP, MCP, and ICP, respectively). The FA in the MCP was significantly reduced in the SBM patients (0.44 vs. 0.65, p = 0.002), while there was no significant difference in the other cerebellar peduncles. In the context of numerous supratentorial white matter abnormalities in SBM such as callosal dysplasia, the most likely explanation of reduced FA in the MCP is a reduced fiber density.

Reduced volume of Heschl's gyrus in tinnitus.

The neural basis of tinnitus is unknown. Recent neuroimaging studies point towards involvement of several cortical and subcortical regions. Here we demonstrate that tinnitus may be associated with structural changes in the auditory cortex. Using individual morphological segmentation, the medial partition of Heschl's gyrus (mHG) was studied in individuals with and without chronic tinnitus using magnetic resonance imaging. Both the tinnitus and the non-tinnitus group included musicians and non-musicians. Patients exhibited significantly smaller mHG gray matter volumes than controls. In unilateral tinnitus, this effect was almost exclusively seen in the hemisphere ipsilateral to the affected ear. In bilateral tinnitus, mHG volume was substantially reduced in both hemispheres. The tinnitus-related volume reduction was found across the full extent of mHG, not only in the high-frequency part usually most affected by hearing loss-induced deafferentation. However, there was also evidence for a relationship between volume reduction and hearing loss. Correlations between volume and hearing level depended on the subject group as well as the asymmetry of the hearing loss. The volume changes observed may represent antecedents or consequences of tinnitus and tinnitus-associated hearing loss and also raise the possibility that small cortical volume constitutes a vulnerability factor.

Prevalence and function of Heschl's gyrus morphotypes in musicians.

Morphological variations of the first transverse Heschl's gyrus (HG) in the human auditory cortex (AC) are common, yet little is known about their functional implication. We investigated individual morphology and function of HG variations in the AC of 41 musicians, using structural and functional magnetic resonance imaging (fMRI) as well as magnetoencephalography (MEG). Four main morphotypes of HG were (i) single HG, (ii) common stem duplication (CSD), (iii) complete posterior duplication (CPD), and (iv) multiple duplications (MD). The vast majority of musicians (90%) exhibited HG multiplications (type ii-iv) in either one (39%) or both (51%) hemispheres. In 27% of musicians, MD with up to four gyri were found. To probe the functional contribution of HG multiplications to auditory processing we performed fMRI and MEG with auditory stimulation using analogous instrumental tone paradigms. Both methods pointed to the recruitment of all parts of HG during auditory stimulation, including multiplications if present. FMRI activations extended with the degree of HG gyrification. MEG source waveform patterns were distinct for the different types of HG: (i) hemispheres with single HG and (ii) CSD exhibited dominant N1 responses, whereas hemispheres with (iii) CPD and (iv) MD exhibited dominant P1 responses. N1 dipole amplitudes correlated with the localization of the first complete Heschl's sulcus (cHS), designating the most posterior anatomical border of HG. P2 amplitudes were significantly higher in professional as compared to amateur musicians. The results suggest that HG multiplications occur much more frequently in musicians than in the general population and constitute a functional unit with HG.

Neural Biomarkers for Dyslexia, ADHD, and ADD in the Auditory Cortex of Children.

Dyslexia, attention deficit hyperactivity disorder (ADHD), and attention deficit disorder (ADD) show distinct clinical profiles that may include auditory and language-related impairments. Currently, an objective brain-based diagnosis of these developmental disorders is still unavailable. We investigated the neuro-auditory systems of dyslexic, ADHD, ADD, and age-matched control children (N = 147) using neuroimaging, magnetencephalography and psychoacoustics. All disorder subgroups exhibited an oversized left planum temporale and an abnormal interhemispheric asynchrony (10-40 ms) of the primary auditory evoked P1-response. Considering right auditory cortex morphology, bilateral P1 source waveform shapes, and auditory performance, the three disorder subgroups could be reliably differentiated with outstanding accuracies of 89-98%. We therefore for the first time provide differential biomarkers for a brain-based diagnosis of dyslexia, ADHD, and ADD. The method allowed not only allowed for clear discrimination between two subtypes of attentional disorders (ADHD and ADD), a topic controversially discussed for decades in the scientific community, but also revealed the potential for objectively identifying comorbid cases. Noteworthy, in children playing a musical instrument, after three and a half years of training the observed interhemispheric asynchronies were reduced by about 2/3, thus suggesting a strong beneficial influence of music experience on brain development. These findings might have far-reaching implications for both research and practice and enable a profound understanding of the brain-related etiology, diagnosis, and musically based therapy of common auditory-related developmental disorders and learning disabilities.

Leftward lateralization of auditory cortex underlies holistic sound perception in Williams syndrome.

BACKGROUND: Individuals with the rare genetic disorder Williams-Beuren syndrome (WS) are known for their characteristic auditory phenotype including strong affinity to music and sounds. In this work we attempted to pinpoint a neural substrate for the characteristic musicality in WS individuals by studying the structure-function relationship of their auditory cortex. Since WS subjects had only minor musical training due to psychomotor constraints we hypothesized that any changes compared to the control group would reflect the contribution of genetic factors to auditory processing and musicality. METHODOLOGY/PRINCIPAL FINDINGS: Using psychoacoustics, magnetoencephalography and magnetic resonance imaging, we show that WS individuals exhibit extreme and almost exclusive holistic sound perception, which stands in marked contrast to the even distribution of this trait in the general population. Functionally, this was reflected by increased amplitudes of left auditory evoked fields. On the structural level, volume of the left auditory cortex was 2.2-fold increased in WS subjects as compared to control subjects. Equivalent volumes of the auditory cortex have been previously reported for professional musicians. CONCLUSIONS/SIGNIFICANCE: There has been an ongoing debate in the neuroscience community as to whether increased gray matter of the auditory cortex in musicians is attributable to the amount of training or innate disposition. In this study musical education of WS subjects was negligible and control subjects were carefully matched for this parameter. Therefore our results not only unravel the neural substrate for this particular auditory phenotype, but in addition propose WS as a unique genetic model for training-independent auditory system properties.

2-D DIGE analysis of liver and red blood cells provides further evidence for oxidative stress in schizophrenia.

The molecular disease mechanisms associated with schizophrenia remain largely unknown. Although primarily considered a disorder of the brain, there is evidence of a peripheral component to schizophrenia. In this study, we investigated liver tissue and red blood cells (RBC) from schizophrenia patients and controls using 2-D DIGE proteomic analysis. Fourteen proteins were significantly altered in liver samples from schizophrenia patients (n = 15) compared to healthy controls (n = 15). Analysis of the schizophrenia RBC proteome revealed 8 proteins significantly altered in samples from schizophrenia patients (13 antipsychotic-treated and 7 drug-naïve) compared to controls (n = 20). Six of the altered proteins in the liver and four of the altered RBC proteins are related to oxidative stress. These results corroborate our earlier findings obtained from post-mortem brain studies and substantiate our hypothesis that metabolic alterations leading to oxidative stress are linked to the schizophrenia disease process. Our results also suggest that at least some of the pathological processes associated with the schizophrenia disease process can be traced in peripheral tissue. If peripheral cells can be used as a disease surrogate, promising new investigative avenues could be explored.

Persistent left superior vena cava with absent right superior vena cava: morphological CT features and clinical implications.

Here we report a rare case of the persisting left superior vena cava with simultaneous absence of the right superior vena cava. This central venous variation has been identified during a routine chest CT scan as follow-up after colonic cancer in an asymptomatic patient with no previous history of heart diseases. Morphological features of this variation are illustrated on axial CT images and 3D image reconstructions. This anomaly occurs in 0.1% of the general population. In presence with the right superior vena cava it is the most common anatomical variation in the central venous system with a reported occurrence of 0.2-8%. Such condition can be associated with additional congenital cardiovascular malformations and heart diseases or rhythm abnormalities. Diagnosis can be difficult and is often achieved incidentally since hemodynamics in these patients can be normal and clinical symptoms are mostly absent. Important clinical implications include difficulties in central venous access or cardiac pacemaker placement as well as management consequences in cardiothoracic surgery. In conclusion clinicians should be aware of this anomaly and their clinical relevance to avoid possible complications.