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.     

Background and evoked activity and their interaction in the human brain

Most functional neuroimaging studies have investigated brain activity evoked by certain types of stimulation or tasks. In recent years, resting brain activity and its influence on evoked activity has become accessible for investigation. However, despite numerous studies on background and evoked activities, either observed with vascular (functional magnetic resonance imaging, positron emission tomography, optical) or electrophysiological (electroencephalography, magnetoencephalography) or a combination of both methods, so far, there is no generally accepted view concerning both the precise meaning of background activity and its relationship to evoked activity. In this article, we give an overview of the current knowledge on this issue and we review recent studies examining the influence of ongoing activity on behavioral responses and the relationship between ongoing and evoked activity.     

Imaging patients pre and post deep brain stimulation: Localization of the electrodes and their targets

PurposeDeep brain stimulation (DBS) has become a widely performed surgical procedure for patients with medically refractory movement disorders and mental disorders. It is clinically important to set up a MRI protocol to map the brain targets and electrodes of the patients before and after DBS and to understand the imaging artifacts caused by the electrodes.MethodsFive patients with DBS electrodes implanted in the habenula (Hb), fourteen patients with globus pallidus internus (GPi) targeted DBS, three pre-DBS patients and seven healthy controls were included in the study. The MRI protocol consisted of magnetization prepared rapid acquisition gradient echo T1 (MPRAGE T1W), 3D multi-echo gradient recalled echo (ME-GRE) and 2D fast spin echo T2 (FSE T2W) sequences to map the brain targets and electrodes of the patients. Phantom experiments were also run to determine both the artifacts and the susceptibility of the electrodes. Signal to noise ratio (SNR) on T1W, T2W and GRE datasets were measured. The visibility of the brain structures was scored according to the Rose criterion. A detailed analysis of the characteristics of the electrodes in all three sequence types was performed to confirm the reliability of the postoperative MRI approach. In order to understand the signal behavior, we also simulated the corresponding magnitude data using the same imaging parameters as in the phantom sequences.ResultsThe mean ± inter-subject variability of the SNRs, across the subjects for T1W, T2W, and GRE datasets were 20.1 ± 8.1, 14.9 ± 3.2, and 43.0 ± 7.6, respectively. High resolution MPRAGE T1W and FSE T2W data both showed excellent contrast for the habenula and were complementary to each other. The mean visibility of the habenula in the 25 cases for the MPRAGE T1W data was 5.28 ± 1.11; and the mean visibility in the 20 cases for the FSE T2W data was 5.78 ± 1.30. Quantitative susceptibility mapping (QSM), reconstructed from the ME-GRE sequence, provided sufficient contrast to distinguish the substructures of the globus pallidus. The susceptibilities of the GPi and globus pallidus externa (GPe) were 0.087 ± 0.013 ppm and 0.115 ± 0.015 ppm, respectively. FSE T2W sequences provided the best image quality with smallest image blooming of stimulator leads compared to MPRAGE T1W images and GRE sequence images, the measured diameters of electrodes were 1.91 ± 0.22, 2.77 ± 0.22, and 2.72 ± 0.20 mm, respectively. High resolution, high bandwidth and short TE (TE = 2.6 ms) GRE helped constrain the artifacts to the area of the electrodes and the dipole effect seen in the GRE filtered phase data provided an effective mean to locate the end of the DBS lead.ConclusionThe imaging protocol consisting of MPRAGE T1W, FSE T2W and ME-GRE sequences provided excellent pre- and post-operative visualization of the brain targets and electrodes for patients undergoing DBS treatment. Although the artifacts around the electrodes can be severe, sometimes these same artifacts can be useful in identifying their location.     

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.     

Modeling the binding of peptides on carbon nanotubes and their use as protein and DNA carriers

An in-depth study of a novel functionalization of carbon nanotubes for their application as protein and DNA carriers is presented. First, the optimum conditions for the dispersion of single-walled carbon nanotubes (SWCNTs) with amphiphilic polypeptides were obtained, and the SWCNT–polypeptide complexes were characterized by different techniques (UV–Vis-NIR, CD, and AFM). Based on the properties of the SWCNT–polypeptide complexes, a model that characterizes the adsorption of natural proteins onto SWCNT was described for the first time. This model predicts the adsorption of natural proteins on SWCNTs based on the protein structure and composition, and therefore, allows the design of methods for the preparation of SWCNT–protein complexes. Besides, the use of cationic-designed amphiphilic polypeptides to disperse SWCNTs is applied for subsequent and efficient binding of DNA to carbon nanotubes by a bilayer approach. Therefore, in this article, we develop procedures for the use of SWCNTs as protein and DNA carriers. The systems were delivered into cells showing that the efficiency of delivery is affected by the charge of the complexes, which has important implications in the use of SWCNT as platforms for protein and DNA binding and subsequent use as delivery systems.     

Gene expression in the rat brain: High similarity but unique differences between frontomedial-, temporal- and occipital cortex

Background  

The six-layered neocortex of the mammalian brain may appear largely homologous, but is in reality a modular structure of anatomically and functionally distinct areas. However, global gene expression seems to be almost identical across the cerebral cortex and only a few genes have so far been reported to show regional enrichment in specific cortical areas.     

Abnormalities of cell packing density and dendritic complexity in the MeCP2 A140V mouse model of Rett syndrome/X-linked mental retardation

Background  

Rett syndrome (RTT), a common cause of mental retardation in girls, is associated with mutations in the MECP2 gene. Most human cases of MECP2 mutation in girls result in classical or variant forms of RTT. When these same mutations occur in males, they often present as severe neonatal encephalopathy. However, some MECP2 mutations can also lead to diseases characterized as mental retardation syndromes, particularly in boys. One of these mutations, A140V, is a common, recurring missense mutation accounting for about 0.6% of all MeCP2 mutations and ranking 21^st by frequency. It has been described in familial X-linked mental retardation (XLMR), PPM- X syndrome (Parkinsonism, Pyramidal signs, Macroorchidism, X-linked mental retardation) and in other neuropsychiatric syndromes. Interestingly, this mutation has been reported to preserve the methyl-CpG binding function of the MeCP2 protein while compromising its ability to bind to the mental retardation associated protein ATRX.     

Improvements in the clinical utility of calculated T2 images of the human brain

Magnetic Resonance Imaging (MRI) affords a considerable improvement in image contrast over other methods by virtue of the intrinsic NMR parameters spin density, T1, and T2. However, the clinical utility of routine quantification of these parameters is currently unknown. Calculated T2 images might afford additional disease specific information provided the calculation algorithm generates accurate T2 values. In this study, calculated T2 images of a MnCl2 phantom (spanning a T2 range of interest of 45.7 ms to 346.6 ms at 6 MHz) were generated utilizing a variety of calculation algorithms based upon a data set of 32 sequential spin-echo (SE) images. In general, when utilizing only the earliest sequential SE after the 90 degree pulse for the T2 calculation, the greater the number of SE used in the calculation algorithm, regardless of how they were averaged, the more accurate and less noisy was the calculated image. When only limited numbers of SE were used in the calculation algorithm, accuracy and noise varied with the choice of TE suggesting that there may be optimal timings for TE for a particular T2 range of interest. Forty-two calculated T2 head images of normal subjects, based upon data sets of 16 sequential SE, were evaluated for the T2 values of normal brain. These were compared to T2 images calculated via 7 different algorithms based upon 16 SE data sets from two patients with CNS pathology. An optimal algorithm was identified in which 16 SE Carr-Purcell-Meiboom-Gill (CPMG) were averaged into two images for the T2 calculation. With this algorithm, calculated images could be generated efficiently which were accurate and relatively noise free. The availability of such images maximized whatever disease specificity, and thus clinical utility, T2 information affords.     

2H NMR studies for the examination of methyl group rotations between their classical and quantum mechanical limits

²H NMR spectra of copper acetate monohydrate [Cu(CD₃CO₂)₂]·H₂O, hexamethylbenzene-d₁₈ and acetone-d₆ were analyzed to characterize methyl group rotations between their classical and quantum mechanical limits. The temperature dependent spectra show the three different possible developments of the lineshapes. Hexamethylbenzene is typical of compounds with small but resolvable tunnelling frequencies. Characteristic splittings in the spectra of copper acetate monohydrate reveal the temperature dependence of tunnelling frequencies that are slightly larger than the quadrupole coupling constant. While the tunnelling frequency of acetone is already too large to be specified from²H NMR lineshape analysis at temperatures low enough that quantum effects influence the spectra, the temperature dependent spectra deviate characteristically from those found for classical rotation. Additionally to these experimental results, we outline how from an NMR point of view mixed classical and quantum rotations can be described by a single complex frequency.     

Blockade of stress-induced increase of glutamate release in the rat prefrontal/frontal cortex by agomelatine involves synergy between melatonergic and 5-HT2C receptor-dependent pathways

Background

Agomelatine is a melatonergic receptor agonist and a 5HT_2C receptor antagonist that has shown antidepressant efficacy. In order to analyze separately the effect of the two receptorial components, rats were chronically treated with agomelatine, melatonin (endogenous melatonergic agonist), or S32006 (5-HT_2C antagonist), and then subjected to acute footshock-stress.

Results

Only chronic agomelatine, but not melatonin or S32006, completely prevented the stress-induced increase of glutamate release in the rat prefrontal/frontal cortex.

Conclusions

These results suggest a potential synergy between melatonergic and serotonergic pathways in the action of agomelatine.     

Diffuse optical measurement of blood flow, blood oxygenation, and metabolism in a human brain during sensorimotor cortex activation

We combine diffuse optical and correlation spectroscopies to simultaneously measure the oxyhemoglobin and deoxyhemoglobin concentration and blood flow in an adult human brain during sensorimotor stimulation. The observations permit calculation of the relative cerebral metabolic rate of oxygen in the human brain, for the first time to our knowledge, by use of all-optical methods. The feasibility for noninvasive optical measurement of blood flow through the skull of an adult brain is thus demonstrated, and the clinical potential of this hybrid, all-optical noninvasive, methodology can now be explored.     

Ontogeny of ATP hydrolysis and isoform expression of the Plasma Membrane Ca2+-ATPase in mouse brain

Background  

Plasma membrane Ca²⁺-ATPases (PMCAs) are high affinity Ca²⁺ transporters actively involved in intracellular Ca²⁺ homeostasis. Considering the critical role of Ca²⁺ signalling in neuronal development and plasticity, we have analyzed PMCA-mediated Ca²⁺-ATPase activity and PMCA-isoform content in membranes from mouse cortex, hippocampus and cerebellum during postnatal development.     

A microarray study of gene and protein regulation in human and rat brain following middle cerebral artery occlusion

Background

Our goal was to examine the spatiotemporal integration of tactile information in the hand representation of human primary somatosensory cortex (anterior parietal somatosensory areas 3b and 1), secondary somatosensory cortex (S2), and the parietal ventral area (PV), using high-resolution whole-head magnetoencephalography (MEG). To examine representational overlap and adaptation in bilateral somatosensory cortices, we used an oddball paradigm to characterize the representation of the index finger (D2; deviant stimulus) as a function of the location of the standard stimulus in both right- and left-handed subjects.

Results

We found that responses to deviant stimuli presented in the context of standard stimuli with an interstimulus interval (ISI) of 0.33s were significantly and bilaterally attenuated compared to deviant stimulation alone in S2/PV, but not in anterior parietal cortex. This attenuation was dependent upon the distance between the deviant and standard stimuli: greater attenuation was found when the standard was immediately adjacent to the deviant (D3 and D2 respectively), with attenuation decreasing for non-adjacent fingers (D4 and opposite D2). We also found that cutaneous mechanical stimulation consistently elicited not only a strong early contralateral cortical response but also a weak ipsilateral response in anterior parietal cortex. This ipsilateral response appeared an average of 10.7 ± 6.1 ms later than the early contralateral response. In addition, no hemispheric differences either in response amplitude, response latencies or oddball responses were found, independent of handedness.

Conclusion

Our findings are consistent with the large receptive fields and long neuronal recovery cycles that have been described in S2/PV, and suggest that this expression of spatiotemporal integration underlies the complex functions associated with this region. The early ipsilateral response suggests that anterior parietal fields also receive tactile input from the ipsilateral hand. The lack of a hemispheric difference in responses to digit stimulation supports a lack of any functional asymmetry in human somatosensory cortex.     

GD3- and O-acetylated GD3-gangliosides in the GM2 synthase-deficient mouse brain and their immunohistochemical localization

Gangliosides in the brain of the knockout mouse deficient in the activity of β1,4 N-acetylgalactosaminyl transferase (β1,4 GalNAc-T)(GM2 synthase) consisted of nearly exclusively of GM3- and GD3-gangliosides as expected from the known substrate specificity of the enzyme and in confirmation of the initial reports from two laboratories that generated the mutant mouse experimentally. The total molar amount of gangliosides was approximately 30% higher in the mutant mouse brain than that in the wild-type brain. However, contrary to the initial reports, one-fourth of total GD3-ganglioside was O-acetylated. It reacted positively with an anti-O-acetylated GD3 monoclonal antibody and disappeared with a corresponding increase in GD3-ganglioside after mild alkaline treatment. The absence of O-acetylated GD3 in the initial reports can be explained by the saponification step included in their analytical procedures. Although quantitatively much less and identification tentative, we also detected GT3 and O-acetylated GT3. Anti-GD3 and anti-O-acetylated GD3 monoclonal antibodies gave positive reactions in the brain of mutant mouse as expected from the analytical results. Either antibody barely stained wild-type brain except for immunoreactivity of GD3 in the cerebellar Purkinje cells. The distributions of GD3 and O-acetylated GD3 in the brain of mutant mouse were similar but differential localization was noted in the cerebellar Purkinje cells and cerebral cortex.