Attentional influences on functional mapping of speech sounds in human auditory cortex

Background  

The speech signal contains both information about phonological features such as place of articulation and non-phonological features such as speaker identity. These are different aspects of the 'what'-processing stream (speaker vs. speech content), and here we show that they can be further segregated as they may occur in parallel but within different neural substrates. Subjects listened to two different vowels, each spoken by two different speakers. During one block, they were asked to identify a given vowel irrespectively of the speaker (phonological categorization), while during the other block the speaker had to be identified irrespectively of the vowel (speaker categorization). Auditory evoked fields were recorded using 148-channel magnetoencephalography (MEG), and magnetic source imaging was obtained for 17 subjects.     

Morphological correlates of injury-induced reorganization in primate somatosensory cortex

Background  

Topographic reorganization of central maps following peripheral nerve injury has been well characterized. Despite extensive documentation of these physiological changes, the underlying anatomical correlates have yet to be fully explored. In this study, we used Golgi impregnation and light microscopy to assess dendritic morphology following denervation of the glabrous hand surface in adult primates.     

Tomography of functional organization in protein-protein interaction network

In recent years, after high throughput PPI data was available, studies have focused on unraveling how proteins organize their functionality from architecture of the PPI network. We examine the functional organization of a PPI network by dividing the network into layered structure around a protein according to shortest path length. We proposed an index, functional correlation, to assess the functional closeness of a specific protein with its l layer neighbors, i.e. proteins having l shortest path length from the center protein. Our results showed that functional correlation decays exponentially with the number of layers within a characteristic length l_c, and it becomes uncorrelated outside such a characteristic length. A simple model based on functional unit structure was proposed to explain this exponential decay of functional correlation.     

Reproducibility and postprocessing of gradient-echo functional MRI to improve localization of brain activity in the human visual cortex

High reproducibility of human FMRI studies is imperative for potential clinical applications of this new method for mapping human brain functions. So far, published data are not comparable quantitatively (even at the same field strength) as differences in sequence design and parameters as well as statistical methods applied to enhance function related image contrast, in particular, to extract the size of the “activated areas,” are manifold. We present a study on reproducibility of gradient-echo FMRI in the human visual cortex using thee different threshold strategies for correlation analysis that shows that, (a) applying adaptive correlation thresholds results in higher reproducibility compared to a fixed (0.5) threshold; (b) highly reproducible data can be obtained on a clinical 1.5 T MRI system, at least for repeated single subject studies (i.e., standard deviation of 2–30% for signal enhancement in 72–94% of the studies and 5–50% for activated area size in 63–88% of the studies, respectively, depending on threshold strategies); however, depending also on subject cooperation; (c) reproducibility across groups (α = const.) is worse, i.e., standard deviations are within 33–45% for signal enhancement and 41–74% for activated area size, respectively; (d) SNR is maximum at about 30° flip angle, suggesting significant contributions from T₁-effects for larger flip angles. Various technical, methodological, and physiological factors are influencing variability of signal enhancement and apparently activated area size, which should be taken into account if interpreting FMRI data quantitatively.     

Hierarchical organization unveiled by functional connectivity in complex brain networks

How do diverse dynamical patterns arise from the topology of complex networks? We study synchronization dynamics in the cortical brain network of the cat, which displays a hierarchically clustered organization, by modeling each node (cortical area) with a subnetwork of interacting excitable neurons. We find that in the biologically plausible regime the dynamics exhibits a hierarchical modular organization, in particular, revealing functional clusters coinciding with the anatomical communities at different scales. Our results provide insights into the relationship between network topology and functional organization of complex brain networks.     

Universal scaling law in human behavioral organization

We describe the nature of human behavioral organization, specifically how resting and active periods are interwoven throughout daily life. Active period durations with physical activity count successively above a predefined threshold, when rescaled with individual means, follow a universal stretched exponential (gamma-type) cumulative distribution with characteristic time, both in healthy individuals and in patients with major depressive disorder. On the other hand, resting period durations below the threshold for both groups obey a scale-free power-law cumulative distribution over two decades, with significantly lower scaling exponents in the patients. We thus find universal distribution laws governing human behavioral organization, with a parameter altered in depression.     

Optimizing the mapping of finger areas in primary somatosensory cortex using functional MRI

Functional magnetic resonance imaging mapping of the finger somatotopy in the primary somatosensory cortex requires a reproducible and precise stimulation. The highly detailed functional architecture in this region of the brain also requires careful consideration in choice of spatial resolution and postprocessing parameters. The purpose of this study is therefore to investigate the impact of spatial resolution and level of smoothing during tactile stimulation using a precise stimuli system. Twenty-one volunteers were scanned using 2³ mm³ and 3³ mm³ voxel volume and subsequently evaluated using three different smoothing kernel widths. The overall activation reproducibility was also evaluated. Using a high spatial resolution proved advantageous for all fingers. At 2³ mm³ voxel volume, activation of the thumb, middle finger and little finger areas was seen in 89%, 67% and 50% of the volunteers, compared to 78%, 61% and 33% at 3³ mm³, respectively. The sensitivity was comparable for nonsmoothed and slightly smoothed (4 mm kernel width) data; however, increasing the smoothing kernel width from 4 to 8 mm resulted in a critical decrease (50%) in sensitivity. In repeated measurements of the same subject at six different days, the localization reproducibility of all fingers was within 4 mm (1 S.D. of the mean). The precise computer-controlled stimulus, together with data acquisition at high spatial resolution and with only minor smoothing during evaluation, could be a very useful strategy in studies of brain plasticity and rehabilitation strategies in hand and finger disorders and injuries.     

Fine-scale functional connectivity in somatosensory cortex revealed by high-resolution fMRI

High-resolution functional magnetic resonance imaging (fMRI) at high field (9.4 T) has been used to measure functional connectivity between subregions within the primary somatosensory (SI) cortex of the squirrel monkey brain. The hand-face region within the SI cortex of the squirrel monkey has been previously well mapped with functional imaging and electrophysiological and anatomical methods, and the orderly topographic map of the hand region is characterized by a lateral to medial representation of individual digits in four subregions of areas 3a, 3b, 1 and 2. With submillimeter resolution, we are able to detect not only the separate islands of activation corresponding to vibrotactile stimulations of single digits but also, in subsequent acquisitions, the degree of correlation between voxels within the SI cortex in the resting state. The results suggest that connectivity patterns are very similar to stimulus-driven distributions of activity and that connectivity varies on the scale of millimeters within the same primary region. Connectivity strength is not a reflection of global larger-scale changes in blood flow and is not directly dependent on distance between regions. Preliminary electrophysiological recordings agree well with the fMRI data. In human studies at 7 T, high-resolution fMRI may also be used to identify the same subregions and assess responses to sensory as well as painful stimuli, and to measure connectivity dynamically before and after such stimulations.     

Anatomical and functional MR imaging in the macaque monkey using a vertical large-bore 7 Tesla setup

Functional magnetic resonance imaging (MRI) in the nonhuman primate promises to provide a much desired link between brain research in humans and the large body of systems neuroscience work in animals. We present here a novel high field, large-bore, vertical MR system (7 T/60 cm, 300 MHz), which was optimized for neuroscientific research in macaque monkeys. A strong magnetic field was applied to increase sensitivity and spatial resolution for both MRI and spectroscopy. Anatomical imaging with voxel sizes as small as 75×150×300 μm³ and with high contrast-to-noise ratios permitted the visualization of the characteristic lamination of some neocortical areas, e.g., Baillarger lines. Relaxation times were determined for different structures: at 7 T, T1 was 2.01/1.84/1.54 s in GM/GM-V1/WM, T2 was 59.1/54.4 ms in GM/WM and T2* was 29 ms. At 4.7 T, T1 was 25% shorter, T2 and T2* 18% longer compared to 7T. Spatiotemporally resolved blood-oxygen-level-dependent (BOLD) signal changes yielded robust activations and deactivations (negative BOLD), with average amplitudes of 4.1% and −2.4%, respectively. Finally, the first high-resolution (500 μm in-plane) images of cerebral blood flow in the anesthetized monkey are presented. On functional activation we observed flow increases of up to 38% (59 to 81 ml/100 g/min) in the primary visual cortex, V1. Compared to BOLD maps, functional CBF maps were found to be localized entirely within the gray matter, providing unequivocal evidence for high spatial specificity. The exquisite sensitivity of the system and the increased specificity of the hemodynamic signals promise further insights into the relationship of the latter to the underlying physiological activity.     

Short range and long range coupling in stochastic functional self organization

A new stochastic model for the stochastic functional self-organization is proposed. Our model does not require any hierarchical decision maker or direct communication between the individuals in order to organize the environment. The environment is a two-dimensional rectangular lattice with a number of initially random distributed physical objects which have to be sorted by some individuals – random-walk like robots. The goal of the system's dynamics is to organize, i.e. to sort, the physical objects in order to form some well defined lattice structures (clusters or even more general texture).We present some theoretical arguments and numerical simulations to support the idea that our new algorithm represents a powerful tool in studying collective sorting.     

Depth-resolved imaging of functional activation in the rat cerebral cortex using optical coherence tomography

Co-registered optical coherence tomography (OCT) and video microscopy of the rat somatosensory cortex were acquired simultaneously through a thinned skull during forepaw electrical stimulation. Fractional signal change measured by OCT revealed a functional signal time course corresponding to the hemodynamic signal measurement made with video microscopy. OCT can provide high-resolution, cross-sectional images of functional neurovascular activation and may offer a new tool for basic neuroscience research in the important rat cerebral cortex model.     

Developmental trajectory of the endocannabinoid system in human dorsolateral prefrontal cortex

ABSTRACT: BACKGROUND: Endocannabinoids provide control over cortical neurotransmission. We investigated the developmental expression of key genes in the endocannabinoid system across human postnatal life and determined whether they correspond to the development of markers for inhibitory interneurons, which shape cortical development. We used microarray with qPCR validation and in situ hybridisation to quantify mRNA for the central endocannabinoid receptor CB1R, endocannabinoid synthetic enzymes (DAGLalpha for 2-arachidonylglycerol [2- AG] and NAPE-PLD for anandamide), and inactivating enzymes (MGL and ABHD6 for 2- AG and FAAH for anandamide) in human dorsolateral prefrontal cortex (39 days - 49 years). RESULTS: CB1R mRNA decreases until adulthood, particularly in layer II, after peaking between neonates and toddlers. DAGLalpha mRNA expression is lowest in early life and adulthood, peaking between school age and young adulthood. MGL expression declines after peaking in infancy, while ABHD6 increases from neonatal age. NAPE-PLD and FAAH expression increase steadily after infancy, peaking in adulthood. CONCLUSIONS: Stronger endocannabinoid regulation of presynaptic neurotransmission in both supragranular and infragranular cortical layers as indexed through higher CB1R mRNA may occur within the first few years of human life. After adolescence, higher mRNA levels of the anandamide synthetic and inactivating enzymes NAPE-PLD and FAAH suggest that a late developmental switch may occur where anandamide is more strongly regulated after adolescence than earlier in life. Thus, expression of key genes in the endocannabinoid system changes with maturation of cortical function.     

Psychological correlates of functional dysphonia:An investigation using the Minnesota multiphasic personality inventory

Abnormal psychological factors have been implicated in the development of functional dysphonia (FD). This investigation describes the personality and psychological characteristics of 25 female subjects who had received the diagnosis of FD. In all subjects symptoms were resolved after voice therapy. While vocally asymptomatic, these remitted subjects with FD completed the Minnesota Multiphasic Personality Inventory (MMPI), an objective personality questionnaire. When compared with a medical outpatient control group, the results showed that subjects with FD scored significantly higher on 7 of 10 clinical scales, suggesting an elevated degree of emotional maladjustment. A stepwise logistic discriminant analysis identified 2 clinical scales that provided valuable discriminatory power between the two groups. Scale I (Hs-hypochondriasis), which measures the number and type of reported somatic complaints, and scale 7 (Pt-psychasthenia), a measure of diffuse anxiety, discriminated the groups with 88% sensitivity and 89% specificity. The results suggested that in spite of symptom improvement after voice therapy, the subjects with FD continued to exhibit poor levels of adaptive functioning, which may represent trait-like vulnerability. The clinical implications of these results for voice practitioners are discussed.     

Complex tone processing in primary auditory cortex of the awake monkey. I. Neural ensemble correlates of roughness

Previous physiological studies [e.g., Bieser and Muller-Preuss, Exp. Brain Res. 108, 273-284 (1996); Schulze and Langner, J. Comp. Physiol. A 181, 651-663 (1997); Steinschneider et al., J. Acoust. Soc. Am. 104, 2935-2955 (1998)] have suggested that neural activity in primary auditory cortex (A1) phase-locked to the waveform envelope of complex sounds with low (<300 Hz) periodicities may represent a neural correlate of roughness perception. However, a correspondence between these temporal response patterns and human psychophysical boundaries of roughness has not yet been demonstrated. The present study examined whether the degree of synchronized phase-locked activity of neuronal ensembles in A1 of the awake monkey evoked by complex tones parallels human psychoacoustic data defining the existence region and frequency dependence of roughness. Stimuli consisted of three consecutive harmonics of fundamental frequencies (f(0)s) ranging from 25 to 4000 Hz. The center frequency of the complex tones was fixed at the best frequency (BF) of the cortical sites, which ranged from 0.3 to 10 kHz. Neural ensemble activity in the thalamorecipient zone (lower lamina III) and supragranular cortical laminae (upper lamina III and lamina II) was measured using multiunit activity and current source density techniques and the degree of phase-locking to the f0 was quantified by spectral analysis. In the thalamorecipient zone, the stimulus f0 at which phase-locking was maximal increased with BF and reached an upper limit between 75 and 150 Hz for BFs greater than about 3 kHz. Estimates of limiting phase-locking rates also increased with BF and approximated psychoacoustic values for the disappearance of roughness. These physiological relationships parallel human perceptual data and therefore support the relevance of phase-locked activity of neuronal ensembles in A1 for the physiological representation of roughness.     

The bilingual brain: Flexibility and control in the human cortex

The goal of the present review is to discuss recent cognitive neuroscientific findings concerning bilingualism. Three interrelated questions about the bilingual brain are addressed: How are multiple languages represented in the brain? how are languages controlled in the brain? and what are the real-world implications of experience with multiple languages? The review is based on neuroimaging research findings about the nature of bilingual processing, namely, how the brain adapts to accommodate multiple languages in the bilingual brain and to control which language should be used, and when. We also address how this adaptation results in differences observed in the general cognition of bilingual individuals. General implications for models of human learning, plasticity, and cognitive control are discussed.     

Assessing functional connectivity in the human brain by fMRI

Functional magnetic resonance imaging (fMRI) is widely used to detect and delineate regions of the brain that change their level of activation in response to specific stimuli and tasks. Simple activation maps depict only the average level of engagement of different regions within distributed systems. FMRI potentially can reveal additional information about the degree to which components of large-scale neural systems are functionally coupled together to achieve specific tasks. In order to better understand how brain regions contribute to functionally connected circuits, it is necessary to record activation maps either as a function of different conditions, at different times or in different subjects. Data obtained under different conditions may then be analyzed by a variety of techniques to infer correlations and couplings between nodes in networks. Several multivariate statistical methods have been adapted and applied to analyze variations within such data. An approach of particular interest that is suited to studies of connectivity within single subjects makes use of acquisitions of runs of MRI images obtained while the brain is in a so-called steady state, either at rest (i.e., without any specific stimulus or task) or in a condition of continuous activation. Interregional correlations between fluctuations of MRI signal potentially reveal functional connectivity. Recent studies have established that interregional correlations between different components of circuits in each of the visual, language, motor and working memory systems can be detected in the resting state. Correlations at baseline are changed during the performance of a continuous task. In this review, various methods available for assessing connectivity are described and evaluated.     

Apolipoprotein-E forms dimers in human frontal cortex and hippocampus

Background  

Apolipoprotein-E (apoE) plays important roles in neurobiology and the apoE4 isoform increases risk for Alzheimer's disease (AD). ApoE3 and apoE2 are known to form disulphide-linked dimers in plasma and cerebrospinal fluid whereas apoE4 cannot form these dimers as it lacks a cysteine residue. Previous in vitro research indicates dimerisation of apoE3 has a significant impact on its functions related to cholesterol homeostasis and amyloid-beta peptide degradation. The possible occurrence of apoE dimers in cortical tissues has not been examined and was therefore assessed. Human frontal cortex and hippocampus from control and AD post-mortem samples were homogenised and analysed for apoE by western blotting under both reducing and non-reducing conditions.     

The laminar pattern of resting state in human cerebral cortex

Resting state functional Magnetic Resonance Imaging (RS-fMRI) provides the means to measure neuronal activity. One of the most commonly used methods to explore the RS-fMRI signal is the Probabilistic Independent Component Analysis (PICA). PICA allows to depict brain functional connectivity (FC) networks. Yet most of the IC maps obtained with this method do not represent any particular FC network. Consequently, those IC maps are classified as artifacts or noise of an unknown source. We hypothesized that the unexplained RS-fMRI signal patterns that are picked up by the PICA can be related to the differences in oxygen metabolism and blood flow in cortical layers. This study aimed at (1) providing preliminary evidence to the effects of laminar organization of neocortex on the RS-fMRI signal, and (2) evaluating the application of laminar maps to aid the classification of IC maps. We created laminar maps 1–4 that depict relative cortical thickness of layers IV and VI. Our data show that the RS-fMRI signal is significantly related to the relative thickness of the cortical layer VI but not layer IV. Importantly, the laminar maps 1–4 overlap with four separate IC maps. Thus, the laminar maps 1–4 improve classification and interpretation of the IC maps. Moreover, the laminar maps 1–4 may be considered as FC networks that are the bridging piece between particular cognitive functions. Together, these data provide preliminary evidence to the fundamental questions about the role of cortical layering in the RS-fMRI signal and brain FC networks.     

Increasing mean airway pressure reduces functional MRI (fMRI) signal in the primary visual cortex

Changes in both blood flow and blood oxygenation determine the functional MRI (fMRI) signal. In the present study factors responsible for blood oxygenation (e.g., FiO(2)) were held constant so that changes in pixel count would above all reflect changes in regional cerebral blood flow (rCBF). Continuous positive airway pressure (CPAP) breathing at 12 cm H(2)O, which was previously shown to influence rCBF, was applied in human volunteers (n = 19) to investigate the sensitivity of fMRI for changes in rCBF caused by increased mean airway pressure. Increasing the mean airway pressure decreased the pixel count in the primary visual cortex (median (range)): baseline: 219 (58-425) pixels vs. CPAP (12 cm H(2)O): 92 (0-262) pixels). These findings indicate that fMRI is sensitive to detect a reduced rCBF-response in the primary visual cortex. The underlying mechanism is likely to be a reduced basal rCBF due to constriction and/or compression of postcapillary venoles during CPAP breathing. These findings are important for interpreting fMRI results in awake and in artificially respirated patients, in whom positive airway pressure is used to improve pulmonary function during the diagnostic procedure.