Auditory resting-state network connectivity in tinnitus: a functional MRI study

The underlying functional neuroanatomy of tinnitus remains poorly understood. Few studies have focused on functional cerebral connectivity changes in tinnitus patients. The aim of this study was to test if functional MRI "resting-state" connectivity patterns in auditory network differ between tinnitus patients and normal controls. Thirteen chronic tinnitus subjects and fifteen age-matched healthy controls were studied on a 3 tesla MRI. Connectivity was investigated using independent component analysis and an automated component selection approach taking into account the spatial and temporal properties of each component. Connectivity in extra-auditory regions such as brainstem, basal ganglia/NAc, cerebellum, parahippocampal, right prefrontal, parietal, and sensorimotor areas was found to be increased in tinnitus subjects. The right primary auditory cortex, left prefrontal, left fusiform gyrus, and bilateral occipital regions showed a decreased connectivity in tinnitus. These results show that there is a modification of cortical and subcortical functional connectivity in tinnitus encompassing attentional, mnemonic, and emotional networks. Our data corroborate the hypothesized implication of non-auditory regions in tinnitus physiopathology and suggest that various regions of the brain seem involved in the persistent awareness of the phenomenon as well as in the development of the associated distress leading to disabling chronic tinnitus.     

Intracellular pH regulation and metabolic interactions in hepatic tissues.

Intracellular pH (pHi) regulation in the vertebrate liver relies heavily on ionic transport mechanisms. Liver, in common with many tissues, has plasma membrane Na(+)-H+ and Cl(-)-HCO3- electroneutral exchangers which work in opposition to tightly control pHi. Mammalian livers also possess electrogenic Na(+)-HCO3- exchangers, capable of base uptake, which, when coupled to pHi-mediated changes in membrane potential, probably confer an additional measure of pHi control, compared to fish livers, where the transporter appears to be functionally absent. It is suggested that this may be a fundamental difference between aquatic and aerial breathing. pHi regulation has barely been examined in invertebrate hepatic tissues, but already some interesting differences are apparent. Notably, an electrogenic 2Na(+)-1H+ acid-extrusion system is present in apical membranes of crustacean hepatopancreas. Despite these ionic control systems, complex acid-base disturbances (e.g., "metabolic" acidosis) have been known for some time to influence hepatic metabolism in vertebrates, but few studies have carefully examined the independent effects of the acid-base variables involved. Thus mechanistic explanations for the effects of acid-base disturbances are scarce. Ureogenesis in mammals has been well studied, and several pH-related mechanisms are evident. In contrast, the pH-insensitivity of ureogenesis in fish liver may represent a second difference between aquatic and terrestrial species. In summary, by virtue of its metabolic diversity, liver represents a potentially important organ in acid-base balance, and an interesting study tissue for interrelationships between metabolism and acid-base balance.     

What is the cerebral amygdaloid complex?

The amygdaloid complex (AC) is considered to be one the basal nuclei of the telencephalon. However, a combination of two principals of the grey substance organizations--nuclear and shielded--in its territory, distinguished AC from the group of the subcortical nuclei defines its specific position among other structures of the telencephalon. A peculiar structure of AC is a consequence of certain evolutionary rearrangements of the brain in the process of histological development of organisms; principally important among them is appearance of the ancient cortex formations (++semi-separated) from elements of the ganglionic tubercle. The latter explains existence of tight anatomical and functional connections between typical nuclei and the ancient cortex structures. The new notion of the AC substrate as a specific nucleolar-paleocortical integrative center of the telencephalon gives a clue for understanding a number of specific, still remaining enigmatic functional phenomena in this formation. They evidently reflect a close interaction of its nuclei and paleocortical structures, that makes the base of its activity.     

Review: Impact of food,gut–brain signals and metabolic status on brain activity in the pig model: 10 years of nutrition research using in vivo brain imaging

The purpose of this review is to offer a panorama on 10 years of nutrition research using in vivo brain imaging in the pig model. First, we will review some work describing the brain responses to food signals, including basic tastants such as sweet and bitter at both oral and visceral levels, as well as conditioned preferred and aversive flavours. Second, we will have a look at the impact of weight gain and obesity on brain metabolism and functional responses, drawing the parallel with obese human patients. Third, we will evoke the concept of the developmental origins of health and diseases, and how the pig model can shed light on the importance of maternal nutrition during gestation and lactation for the development of the gut–brain axis and adaptation abilities of the progeny to nutritional environments. Finally, three examples of preventive or therapeutic strategies will be introduced: the use of sensory food ingredients or pre-, pro-, and postbiotics to improve metabolic and cognitive functions; the implementation of chronic vagus nerve stimulation to prevent weight gain and glucose metabolism alterations; and the development of bariatric surgery in the pig model for the understanding of its complex mechanisms at the gut–brain level. A critical conclusion will brush the limitations of neurocognitive studies in the pig model and put in perspective the rationale and ethical concerns underlying the use of pig experimentation in nutrition and neurosciences.     

Role of astrocytes in the maintenance and modulation of glutamatergic and GABAergic neurotransmission

The functional activity in the brain is primarily composed of an interplay between excitation and inhibition. In any given region the output is based upon a complex processing of incoming signals that require both excitatory and inhibitory units. Moreover, these units must be regulated and balanced such that an integrated and finely tuned response is generated. In each of these units or synapses the activity depends on biosynthesis, release, receptor interaction, and inactivation of the neurotransmitter in question; thus, it is easily understood that each of these processes needs to be highly regulated and controlled. It is interesting to note that in case of the most prevailing neurotransmitters, glutamate and GABA, which mediate excitation and inhibition, respectively, the inactivation process is primarily maintained by highly efficient, high-affinity transport systems capable of maintaining transmembrane concentration gradients of these amino acids of 10⁴–10⁵-fold. The demonstration of the presence of transporters for glutamate and GABA in both neuronal and astrocytic elements naturally raises the question of the functional importance of the astrocytes in the regulation of the level of the neurotransmitters in the synaptic cleft and hence for the activity of excitatory and inhibitory neurotransmission. Obviously, this discussion has important implications for the understanding of the role of astrocytes in disease states in which imbalances between excitation and inhibition are a triggering factor, for example, epilepsy and neurodegeneration.     

Co-analysis of Brain Structure and Function using fMRI and Diffusion-weighted Imaging

The study of complex computational systems is facilitated by network maps, such as circuit diagrams. Such mapping is particularly informative when studying the brain, as the functional role that a brain area fulfills may be largely defined by its connections to other brain areas. In this report, we describe a novel, non-invasive approach for relating brain structure and function using magnetic resonance imaging (MRI). This approach, a combination of structural imaging of long-range fiber connections and functional imaging data, is illustrated in two distinct cognitive domains, visual attention and face perception. Structural imaging is performed with diffusion-weighted imaging (DWI) and fiber tractography, which track the diffusion of water molecules along white-matter fiber tracts in the brain (Figure 1). By visualizing these fiber tracts, we are able to investigate the long-range connective architecture of the brain. The results compare favorably with one of the most widely-used techniques in DWI, diffusion tensor imaging (DTI). DTI is unable to resolve complex configurations of fiber tracts, limiting its utility for constructing detailed, anatomically-informed models of brain function. In contrast, our analyses reproduce known neuroanatomy with precision and accuracy. This advantage is partly due to data acquisition procedures: while many DTI protocols measure diffusion in a small number of directions (e.g., 6 or 12), we employ a diffusion spectrum imaging (DSI)^{1, 2} protocol which assesses diffusion in 257 directions and at a range of magnetic gradient strengths. Moreover, DSI data allow us to use more sophisticated methods for reconstructing acquired data. In two experiments (visual attention and face perception), tractography reveals that co-active areas of the human brain are anatomically connected, supporting extant hypotheses that they form functional networks. DWI allows us to create a "circuit diagram" and reproduce it on an individual-subject basis, for the purpose of monitoring task-relevant brain activity in networks of interest.     

Neotropical savannas: Their flora and vegetation

Covering approximately three million km(2), the savannas, the second largest major plant formation in the American tropics, are gaining increasing importance for land planning and occupational strategies. There has been much recent research on the floristic and ecological characteristics of these herbaceous ecosystems, resulting in considerable progress in the understanding of their complex ecological interrelationships. Hitherto little-known savanna "islands" within the Amazon region are being intensively studied, offering interesting information on their origin and dynamic relationships with the surrounding forests. Important gaps remain to be filled, however, before a critical evaluation of the great variety of neotropical savanna ecosystems is achieved and the preservation of at least some of these unique plant formations is assured.     

Functional interrelation of the brain structures of the cat during the generation of rhythmic activity. I. The frequency characteristics of the electroencephalogram

The similarity of frequency parameters of electroencephalograms (EEG) recorded from visual, associative and sensorimotor cortical area, caudate nucleus and several thalamic nuclei have been analysed using the period analysis of EEG and cluster analysis of data obtained to clarify the functional interrelationships between these parts of the brain during generation of rhythmic activity of different types. Functional interrelationships between brain structures in freely moving cats during the states of drowsiness and slow-wave sleep have been shown to differ from "classical" thalamo-cortical pacemaker relations.     

Evolutionary rate and gene expression across different brain regions

Background

The evolutionary rate of a protein is a basic measure of evolution at the molecular level. Previous studies have shown that genes expressed in the brain have significantly lower evolutionary rates than those expressed in somatic tissues.

Results

We study the evolutionary rates of genes expressed in 21 different human brain regions. We find that genes highly expressed in the more recent cortical regions of the brain have lower evolutionary rates than genes highly expressed in subcortical regions. This may partially result from the observation that genes that are highly expressed in cortical regions tend to be highly expressed in subcortical regions, and thus their evolution faces a richer set of functional constraints. The frequency of mammal-specific and primate-specific genes is higher in the highly expressed gene sets of subcortical brain regions than in those of cortical brain regions. The basic inverse correlation between evolutionary rate and gene expression is significantly stronger in brain versus nonbrain tissues, and in cortical versus subcortical regions. Extending upon this cortical/subcortical trend, this inverse correlation is generally more marked for tissues that are located higher along the cranial vertical axis during development, giving rise to the possibility that these tissues are also more evolutionarily recent.

Conclusions

We find that cortically expressed genes are more conserved than subcortical ones, and that gene expression levels exert stronger constraints on sequence evolution in cortical versus subcortical regions. Taken together, these findings suggest that cortically expressed genes are under stronger selective pressure than subcortically expressed genes.     

Pathophysiology and functional consequences of human partial epilepsy: lessons from positron emission tomography studies

Positron emission tomography (PET) is a powerful clinical and research tool that, in the past two decades, has provided a great amount of novel data on the pathophysiology and functional consequences of human epilepsy. PET studies revealed cortical and subcortical brain dysfunction of a widespread brain circuitry, providing an unprecedented insight in the complex functional abnormalities of the epileptic brain. Correlation of metabolic and neuroreceptor PET abnormalities with electroclinical variables helped identify parts of this circuitry, some of which are directly related to primary epileptogenesis, while others, adjacent to or remote from the primary epileptic focus, may be secondary to longstanding epilepsy. PET studies have also provided detailed data on the functional anatomy of cognitive and behavioral abnormalities associated with epilepsy. PET, along with other neuroimaging modalities, can measure longitudinal changes in brain function attributed to chronic seizures as well as therapeutic interventions. This review demonstrates how development of more specific PET tracers and application of multimodality imaging by combining structural and functional neuroimaging with electrophysiological data can further improve our understanding of human partial epilepsy, and helps more effective application of PET in presurgical evaluation of patients with intractable seizures.     

Functional interrelations of brain structures in the cat during the generation of rhythmic activity. III. Cluster analysis of rhythmic indices

The functional interrelationships of the brain structures of freely moving cats in generation of rhythmic EEG activity during the states of drowsiness and light sleep were evaluated using the claster analysis of mean values indexes of rhythms in different structures as well as correlation coefficients between them in time. It was shown that according these parameters visual cortical areas and lateral geniculate body appeared in different clusters. Lateral geniculate body suggested not to be the only pacemaker of EEG rhythms in visual cortex. The wide convergence of subcortical inputs to the visual cortex and possibility of autonomic generation of EEG rhythms at the cortical level are discussed as putative mechanisms of dissociation of EEG activities in visual cortex and thalamus.     

Use of Anisotropy, 3D Segmented Atlas,and Computational Analysis to Identify Gray Matter Subcortical Lesions Common to Concussive Injury from Different Sites on the Cortex

Traumatic brain injury (TBI) can occur anywhere along the cortical mantel. While the cortical contusions may be random and disparate in their locations, the clinical outcomes are often similar and difficult to explain. Thus a question that arises is, do concussions at different sites on the cortex affect similar subcortical brain regions? To address this question we used a fluid percussion model to concuss the right caudal or rostral cortices in rats. Five days later, diffusion tensor MRI data were acquired for indices of anisotropy (IA) for use in a novel method of analysis to detect changes in gray matter microarchitecture. IA values from over 20,000 voxels were registered into a 3D segmented, annotated rat atlas covering 150 brain areas. Comparisons between left and right hemispheres revealed a small population of subcortical sites with altered IA values. Rostral and caudal concussions were of striking similarity in the impacted subcortical locations, particularly the central nucleus of the amygdala, laterodorsal thalamus, and hippocampal complex. Subsequent immunohistochemical analysis of these sites showed significant neuroinflammation. This study presents three significant findings that advance our understanding and evaluation of TBI: 1) the introduction of a new method to identify highly localized disturbances in discrete gray matter, subcortical brain nuclei without postmortem histology, 2) the use of this method to demonstrate that separate injuries to the rostral and caudal cortex produce the same subcortical, disturbances, and 3) the central nucleus of the amygdala, critical in the regulation of emotion, is vulnerable to concussion.     

Le sujet cérébral: une esquisse historique et conceptuelle

Since the middle of the 20th century, numerous discourses and practices, both within and outside scientific and philosophical disciplines, have manifested the development of the notion of the human being as acerebral subject. The brain appears to be the only organ of the body that we need, and that has to be exclusively ours, in order for each individual to be himself or herself. Sincepersonhood is the quality or condition of being an individual person,brainhood is thus the quality or condition of being a brain. This property defines the cerebral subject. The anthropology ofbrainhood may seem a natural consequence of progress in the neurosciences. However, it is rooted in 17th-century developments in the philosophies of matter and personal identity. The neurosciences confirm and reinforce this perspective. The author outlines the historical narrative concerning the development of the cerebral subject as well as some contemporary issues arising from the neurosciences.     

Comparative studies of brain evolution: a critical insight from the Chiroptera

Comparative studies of brain size have a long history and contributed much to our understanding of the evolution and function of the brain and its parts. Recently, bats have been used increasingly as model organisms for such studies because of their large number of species, high diversity of life-history strategies, and a comparatively detailed knowledge of their neuroanatomy. Here, we draw attention to inherent problems of comparative brain size studies, highlighting limitations but also suggesting alternative approaches. We argue that the complexity and diversity of neurological tasks that the brain and its functional regions (subdivisions) must solve cannot be explained by a single or few variables representing selective pressures. Using an example we show that by adding a single relevant variable, morphological adaptation to foraging strategy, to a previous analysis a correlation between brain and testes mass disappears completely and changes entirely the interpretation of the study. Future studies should not only look for novel determinants of brain size but also include known correlates in order to add to our current knowledge. We believe that comparisons at more detailed anatomical, taxonomic, and geographical levels will continue to contribute to our understanding of the function and evolution of mammalian brains.     

Light and electron-microscopic study of leucine enkephalin immunoreactivity in the cat claustrum

The claustrum is a complex telencephalic structure owing to its reciprocal connectivity with most—if not all—cortical areas. However, there is a paucity of data in the literature concerning its histochemical components, including opioid peptide neurotransmitters. The aim of the present study was to examine the morphology, distribution and ultrastructure of leucine-enkephalin-immunoreactive (Leu-enk-ir) neurons and fibers in the dorsal claustrum (DC) of the cat. Seven healthy, adult male and female cats were used in our study. All animals received humane care. They were irreversibly anesthetized and transcardially perfused with fixative. Brains were removed, postfixed, blocked and sectioned. Sections were incubated with polyclonal anti-Leu-enk antibodies using the Avidin–Biotin–Peroxidase Complex method. Leu-enk-ir neurons and fibers were distributed throughout the DC. Some of the neurons were lightly-stained, while others were darkly-stained. Light-microscopically, they varied in shape: oval, fusiform, multipolar and irregular. With regard to size, they were categorized as small (15?μm or less in diameter), medium (16–20?μm in diameter) and large (21?μm or more in diameter). No specific pattern of regional distribution was found. On the electron microscope level, immunoproduct was observed in neurons, dendrites and terminal boutons. Different types of Leu-enk-ir neurons differ in their ultrastructural features, including two types of synaptic boutons. No gender-specific features were observed. In conclusion, it is our hope that our study will serve to contribute to a better understanding of the functional neuroanatomy of the DC in the cat, and that it can be extrapolated and applied to other mammals, including humans.     

Towards a fourth spatial dimension of brain activity

Current advances in neurosciences deal with the functional architecture of the central nervous system, paving the way for general theories that improve our understanding of brain activity. From topology, a strong concept comes into play in understanding brain functions, namely, the 4D space of a “hypersphere’s torus”, undetectable by observers living in a 3D world. The torus may be compared with a video game with biplanes in aerial combat: when a biplane flies off one edge of gaming display, it does not crash but rather it comes back from the opposite edge of the screen. Our thoughts exhibit similar behaviour, i.e. the unique ability to connect past, present and future events in a single, coherent picture as if we were allowed to watch the three screens of past-present-future “glued” together in a mental kaleidoscope. Here we hypothesize that brain functions are embedded in a imperceptible fourth spatial dimension and propose a method to empirically assess its presence. Neuroimaging fMRI series can be evaluated, looking for the topological hallmark of the presence of a fourth dimension. Indeed, there is a typical feature which reveal the existence of a functional hypersphere: the simultaneous activation of areas opposite each other on the 3D cortical surface. Our suggestion—substantiated by recent findings—that brain activity takes place on a closed, donut-like trajectory helps to solve long-standing mysteries concerning our psychological activities, such as mind-wandering, memory retrieval, consciousness and dreaming state.     

Functional brain networks: great expectations,hard times and the big leap forward

Many physical and biological systems can be studied using complex network theory, a new statistical physics understanding of graph theory. The recent application of complex network theory to the study of functional brain networks has generated great enthusiasm as it allows addressing hitherto non-standard issues in the field, such as efficiency of brain functioning or vulnerability to damage. However, in spite of its high degree of generality, the theory was originally designed to describe systems profoundly different from the brain. We discuss some important caveats in the wholesale application of existing tools and concepts to a field they were not originally designed to describe. At the same time, we argue that complex network theory has not yet been taken full advantage of, as many of its important aspects are yet to make their appearance in the neuroscience literature. Finally, we propose that, rather than simply borrowing from an existing theory, functional neural networks can inspire a fundamental reformulation of complex network theory, to account for its exquisitely complex functioning mode.     

Orienting reaction, organizing for action, and emotional processes

In the first half of the sixties, general notions were formulated concerning the functional role of the orienting reaction (OR) in adaptive activity, its elicitation and habituation. These notions included the following: a) The OR is elicited only by significant changes in a situation. This implies that OR elicitation is preceded by brain processes (usually unconscious) pertaining to the evaluation of the significance of changes according to an existing hierarchy of motivations, attitudes, and goals. Therefore, the OR is of an active (vs. reactive) nature, i.e., is inevitably determined by internal factors of brain activity. b) The OR is not a unitary reaction, but a complex polyfunctional activity, different aspects of which are reflected in different OR components which can be modified rather independently. c) The OR represents the processes of organizing new (non-standard) actions: sensory, motor, or intellectual. OR habituation is a manifestation of attenuation of the active control of an action, and an increase in its automation. Thus, the emphasis in understanding the OR has shifted from a predominantly "sensualistic" platform to a predominantly "actualistic" one. In recent experiments, the role of emotional processes in the elicitation and habituation of components of the OR has been analyzed. Complex relations between the GSR and anxiety were found in a study of patients with acute alcohol withdrawal syndrome treated with different psychopharmacological agents. The study of auditory evoked potential habituation in depressive patients has shown the emotional state influence on sensory aspects of the OR with the participation of the OR brain mechanisms in perceptual defense.(ABSTRACT TRUNCATED AT 250 WORDS)     

Binding of the Rett syndrome protein, MeCP2, to methylated and unmethylated DNA and chromatin

Methylated CpG Binding Protein 2 (MeCP2) is a nuclear protein named for its ability to selectively recognize methylated DNA. Much attention has been focused on understanding MeCP2 structure and function in the context of its role in Rett syndrome, a severe neurodevelopmental disorder that afflicts one in 10,000-15,000 girls. Early studies suggested a connection between DNA methylation, MeCP2, and establishment of a repressive chromatin structure at specific gene promoters. However, it is now recognized that MeCP2 can both activate and repress specific genes depending on the context. Likewise, in the cell, MeCP2 is bound to unmethylated DNA and chromatin in addition to methylated DNA. Thus, to understand the molecular basis of MeCP2 functionality, it is necessary to unravel the complex interrelationships between MeCP2 binding to unmethylated and methylated regions of the genome. MeCP2 is unusual and interesting in that it is an intrinsically disordered protein, that is, much of its primary sequence fails to fold into secondary structure and yet is functional. The unique structure of MeCP2 is the subject of the first section of this article. We then discuss recent investigations of the in vitro binding of MeCP2 to unmethylated and methylated DNA, and the potential ramifications of this work for in vivo function. We close by focusing on mechanistic studies indicating that the binding of MeCP2 to chromatin results in compaction into local (secondary) and global (tertiary) higher order structures. MeCP2 also competes with histone H1 for nucleosomal binding sites. The recent finding that MeCP2 is found at near stoichiometric levels with nucleosomes in neuronal cells underscores the multiple modes of engagement of MeCP2 with the genome, which include the cooperative tracking of methylation density.     

Scaling of body weight and fat content in fungus-gardening ant queens: does this explain why leaf-cutting ants found claustrally?

Offspring traits are among the most important life history traits, yet we lack an adequate understanding of their role in social insect life history evolution. Colony founding in the fungus-gardening ants (Tribe Attini) is different from most other ant species because the queens forage during the founding phase. Queens of the most derived genus, Atta, are the only attines that exhibit the more typical claustral founding, where the queens seal themselves in a below-ground chamber and produce their first generation of workers with only body fat reserves. Here I report the dry weights, fat content and energetic value of newly mated queens of ten attine species. Published phylogenies were used to make inferences on the evolutionary transitions in this clade. It appears that the evolution of fungus-gardening was associated with the manufacture of smaller, leaner queens as basal taxa are characterized by small bodies that contain relatively less fat than derived taxa. Moreover, there appears to be an allometric function between fat, energetic content and dry weight, which means that for fatter and claustral queens to develop, they also must become larger.