Theta and alpha oscillations may underlie improved attention and working memory in musically trained children.

INTRODUCTION: Attention and working memory are key cognitive functions that allow us to select and maintain information in our mind for a short time, being essential for our daily life and, in particular, for learning and academic performance. It has been shown that musical training can improve working memory performance, but it is still unclear if and how the neural mechanisms of working memory and particularly attention are implicated in this process. In this work, we aimed to identify the oscillatory signature of bimodal attention and working memory that contributes to improved working memory in musically trained children. MATERIALS AND METHODS: We recruited children with and without musical training and asked them to complete a bimodal (auditory/visual) attention and working memory task, whereas their brain activity was measured using electroencephalography. Behavioral, time-frequency, and source reconstruction analyses were made. RESULTS: Results showed that, overall, musically trained children performed better on the task than children without musical training. When comparing musically trained children with children without musical training, we found modulations in the alpha band pre-stimuli onset and the beginning of stimuli onset in the frontal and parietal regions. These correlated with correct responses to the attended modality. Moreover, during the end phase of stimuli presentation, we found modulations correlating with correct responses independent of attention condition in the theta and alpha bands, in the left frontal and right parietal regions. CONCLUSIONS: These results suggest that musically trained children have improved neuronal mechanisms for both attention allocation and memory encoding. Our results can be important for developing interventions for people with attention and working memory difficulties.

Pupil Size Tracks Attentional Performance In Attention-Deficit/Hyperactivity Disorder.

Attention-deficit/hyperactivity disorder (ADHD) diagnosis is based on reported symptoms, which carries the potential risk of over- or under-diagnosis. A biological marker that helps to objectively define the disorder, providing information about its pathophysiology, is needed. A promising marker of cognitive states in humans is pupil size, which reflects the activity of an 'arousal' network, related to the norepinephrine system. We monitored pupil size from ADHD and control subjects, during a visuo-spatial working memory task. A sub group of ADHD children performed the task twice, with and without methylphenidate, a norepinephrine-dopamine reuptake inhibitor. Off-medication patients showed a decreased pupil diameter during the task. This difference was no longer present when patients were on-medication. Pupil size correlated with the subjects' performance and reaction time variability, two vastly studied indicators of attention. Furthermore, this effect was modulated by medication. Through pupil size, we provide evidence of an involvement of the noradrenergic system during an attentional task. Our results suggest that pupil size could serve as a biomarker in ADHD.

Attention-deficit hyperactivity disorder involves differential cortical processing in a visual spatial attention paradigm.

OBJECTIVE: Inattention is undoubtedly one of the main characteristics of Attention-deficit hyperactivity disorder (ADHD). Nevertheless, a growing corpus of evidence shows that not all attentional processes are affected in this condition. This study aimed to explore the distribution of attentional resources in children with ADHD via a spatially shifted double-oddball visual task. METHODS: We recorded event-related potentials (ERPs) for all visual stimuli. Subjects were instructed to allocate attention in a specific area of visual space while ignoring all stimuli presented outside. Ten male children (age: 9-14; mean = 11.6 +/- 2.1) who met DSM-IV criteria for the ADHD combined subtype participated in the study, along with ten age- and sex-matched healthy controls (9-14; mean = 11.2 +/- 2.3). RESULTS: ADHD subjects showed late differential cortical responses to initially suppressed irrelevant stimuli. The amplitude of early N1-P1 components were mainly modulated by stimulus location and showed no significant differences between groups, but a late P300-like positivity was clearly evoked in the ADHD group by peripheral stimuli. CONCLUSIONS: These results suggest that ADHD may not compromise the early attentional spatial filter but rather entails a different distribution of attentional resources at later stages of cortical processing. Perhaps these differences may be attributable to individual differences in attentional mechanisms. SIGNIFICANCE: ADHD may not affect initial focusing of visual attention but rather the allocation of processing resources in later stages.

Chronic stress impairs acoustic conditioning more than visual conditioning in rats: morphological and behavioural evidence.

Chronic stress affects brain areas involved in learning and emotional responses. These alterations have been related with the development of cognitive deficits in major depression. The aim of this study was to determine the effect of chronic immobilization stress on the auditory and visual mesencephalic regions in the rat brain. We analyzed in Golgi preparations whether stress impairs the neuronal morphology of the inferior (auditory processing) and superior colliculi (visual processing). Afterward, we examined the effect of stress on acoustic and visual conditioning using an avoidance conditioning test. We found that stress induced dendritic atrophy in inferior colliculus neurons and did not affect neuronal morphology in the superior colliculus. Furthermore, stressed rats showed a stronger impairment in acoustic conditioning than in visual conditioning. Fifteen days post-stress the inferior colliculus neurons completely restored their dendritic structure, showing a high level of neural plasticity that is correlated with an improvement in acoustic learning. These results suggest that chronic stress has more deleterious effects in the subcortical auditory system than in the visual system and may affect the aversive system and fear-like behaviors. Our study opens a new approach to understand the pathophysiology of stress and stress-related disorders such as major depression.

Hemispheric differences in variability of fissural patterns in parasylvian and cingulate regions of human brains.

We have determined different patterns of fissurization in Broca's area, the gyrus of Heschl, the planum temporale, the inferior parietal lobe, and the cingulate sulcus. Such patterns were asymmetrically distributed, indicating increased folding on the left side in most cases. More folding can sometimes be related to a larger cortical area, resulting in increased processing capacities in the respective brain region. Furthermore, the brain regions associated with the asymmetrical sulci are involved in lateralized functions. Of special interest are the asymmetries observed in regions corresponding to the inferior parietal lobe (the accessory postcentral sulcus and the intraparietal sulcus), which, according to recent studies, is involved in linguistic working memory. We did not detect a tendency of distinct fissurization patterns in a given brain region to be associated with specific patterns in other fissures, indicating that the different fissure types develop independently in each brain region and can therefore be determined by local processes. These descriptions are of relevance to imaging studies that intend to establish correspondences between gross morphology and functional parameters such as behavior and brain activation.

Age-related changes in fibre composition of the human corpus callosum: sex differences.

We found positive correlations between the number of myelinated callosal fibres > 1 micron in diameter and age in humans. The relatively abundant axons with diameters between 1 and 3 microns correlated with age only in females, while the scarce fibres > 3 microns in diameter correlated significantly with age only in males. When analysing different callosal segments, it was found that in the midbody (but not in the splenium) of females the number of fibres > 3 microns also increased with age. In males, the relationship between these large diameter fibres and age disappeared after dividing the callosum into distinct segments. There may, therefore, be sex differences in the course of callosal fibre growth and myelination during the normal lifespan.

A sex difference in the postcentral sulcus of the human brain.

The postcentral sulcus has two fissurization patterns: (I) the sulcus extends continuously into the sylvian fissure; (II) the sulcus is interrupted in its trajectory. In the left but not in the right hemisphere, there was a sex difference in the distribution of these fissural patterns, type I being more frequent in men and type II being more frequent in women. No hemispheric asymmetry was found for these patterns in either sex.

Fiber composition of the human corpus callosum.

The densities of fibers of different sizes were calculated in ten regions of the corpus callosum of twenty human brains (ten females, ten males). Light microscopic examination revealed a consistent pattern of regional differentiation of fiber types in the corpus callosum. Thin fibers are most dense in the anterior corpus callosum (genu), and decrease in density posteriorly towards the posterior midbody, where they reach a minimum. Towards the posterior corpus callosum (splenium), the density of thin fibers increases again, but in the posterior pole of the callosum the density decreases locally. Large-diameter fibers show a pattern complementary to that of thin fibers, having a peak of density in the posterior midbody and a local increase of density in the posterior pole of the corpus callosum. Across subjects, the overall density of callosal fibers had no significant correlation with callosal area and an increased callosal area indicated an increased total number of fibers crossing through. Considering different fiber sizes, this was only true for small diameter fibers, whose large majority is believed to interconnect association cortex. No sex differences in fiber composition of the corpus callosum were found.

Individual differences in brain asymmetries and fiber composition in the human corpus callosum.

There have been several recent reports concerning individual differences in the gross morphometry of the human corpus callosum. However, no studies exist on individual differences in the fiber composition of the corpus callosum. Here we report for the first time the relation of fiber composition in specific callosal segments (as seen in light microscopy) to anatomical asymmetries in language-gifted cortex, as a function of sex. We found a significant negative correlation between Sylvian fissure asymmetries and the total numbers of fibers in the isthmus of males, and in the anterior splenium of females. In addition, a population of relatively large fibers (between 1 micron and 3 microns in diameter) in the isthmus showed a strong negative correlation with perisylvian asymmetries only in males. These findings suggest a sex-dependent, pathway-specific decrease in interhemispheric connectivity with increasing lateralization.

Dendritic structure of single hippocampal neurons according to sex and hemisphere of origin in middle-aged and elderly human subjects.

The organization of basilar dendritic patterns in the CA1 hippocampal region obtained from 13 middle-aged and elderly human subjects was assessed using the Golgi method. Neurons were classified according to hemisphere of origin and the sex of the respective subjects. Three parameters were measured: total dendritic length (TDL), number of dendritic segments (NDS) and average segment length (ASL, which is TDL divided by NDS). Dendritic segments were classified into proximal (first to third order) and distal (fourth order and above). Sex differences were found in distal TDL and in proximal and distal NDS, neurons belonging to males having larger values than those belonging to females. In addition, a hemispheric difference was detected in distal TDL, in which neurons of the left hemisphere had larger values than those of the right hemisphere.

Histological asymmetry in the primary visual cortex of the rat: implications for mechanisms of cerebral asymmetry.

The present study was designed to specify the contributions of various histological parameters to hemispheric asymmetry of architectonic areas. It was found that the primary visual cortex of the rat is asymmetrical in volume, and that the asymmetry reflects side differences in the number of neurons. The implications of this finding for the understanding of mechanisms involved in the production of brain asymmetries are discussed.

Behavioral effects of aminochrome and dopachrome injected in the rat substantia nigra.

The exact mechanism of cell death in neurodegenerative diseases remains obscure, although there is evidence that their pathogenesis may involve the formation of free radicals originating from the oxidative metabolism of catecholamines. The purpose of this study was to evaluate the degree of neurodegenerative changes and behavioral impairments induced by unilateral injection into the rat substantia nigra of cyclized o-quinones, aminochrome and dopachrome, derived from oxidizing dopamine and L-DOPA, respectively, with Mn(3+)-pyrophosphate complex. The behavioral changes were compared with those induced after selective lesions of dopaminergic neurons with 6-hydroxydopamine (6-OHDA). Intranigral injection of aminochrome and dopachrome produced impairment in motor and cognitive behaviors. The behavioral impairment was also revealed by apomorphine-induced rotational asymmetry. Apomorphine (0.5 mg/kg sc) significantly increased rotational behavior in rats injected with aminochrome and dopachrome. These rats presented a clear motor bias showing a significant contralateral rotation activity, similar but less vigorous that in rats injected with 6-OHDA. The avoidance conditioning was seriously impaired in rats injected with aminochrome and dopachrome although only dopachrome-injected rats showed a similar hypomotility to 6-OHDA-injected rats. The behavioral effects were correlated to the extent of striatal tyrosine hydroxylase (TH)-positive fiber loss. Rats receiving unilateral intranigral aminochrome and dopachrome injections exhibited a 47.9+/-5.1% and a 39.7+/-4.4% reduction in nigrostriatal TH-positive fiber density. In conclusion, this study provided evidence that oxidizing DA and L-DOPA to cytotoxic quinones, aminochrome and dopachrome appears to be an important mediator of oxidative damage in vivo.

One hundred million years of interhemispheric communication: the history of the corpus callosum.

Analysis of regional corpus callosum fiber composition reveals that callosal regions connecting primary and secondary sensory areas tend to have higher proportions of coarse-diameter, highly myelinated fibers than callosal regions connecting so-called higher-order areas. This suggests that in primary/secondary sensory areas there are strong timing constraints for interhemispheric communication, which may be related to the process of midline fusion of the two sensory hemifields across the hemispheres. We postulate that the evolutionary origin of the corpus callosum in placental mammals is related to the mechanism of midline fusion in the sensory cortices, which only in mammals receive a topographically organized representation of the sensory surfaces. The early corpus callosum may have also served as a substrate for growth of fibers connecting higher-order areas, which possibly participated in the propagation of neuronal ensembles of synchronized activity between the hemispheres. However, as brains became much larger, the increasingly longer interhemispheric distance may have worked as a constraint for efficient callosal transmission. Callosal fiber composition tends to be quite uniform across species with different brain sizes, suggesting that the delay in callosal transmission is longer in bigger brains. There is only a small subset of large-diameter callosal fibers whose size increases with increasing interhemispheric distance. These limitations in interhemispheric connectivity may have favored the development of brain lateralization in some species like humans.

Critical steps in the early evolution of the isocortex: insights from developmental biology.

This article proposes a comprehensive view of the origin of the mammalian brain. We discuss i) from which region in the brain of a reptilian-like ancestor did the isocortex originate, and ii) the origin of the multilayered structure of the isocortex from a simple-layered structure like that observed in the cortex of present-day reptiles. Regarding question i there have been two alternative hypotheses, one suggesting that most or all the isocortex originated from the dorsal pallium, and the other suggesting that part of the isocortex originated from a ventral pallial component. The latter implies that a massive tangential migration of cells from the ventral pallium to the dorsal pallium takes place in isocortical development, something that has not been shown. Question ii refers to the origin of the six-layered isocortex from a primitive three-layered cortex. It is argued that the superficial isocortical layers can be considered to be an evolutionary acquisition of the mammalian brain, since no equivalent structures can be found in the reptilian brain. Furthermore, a characteristic of the isocortex is that it develops according to an inside-out neurogenetic gradient, in which late-produced cells migrate past layers of early-produced cells. It is proposed that the inside-out neurogenetic gradient was partly achieved by the activation of a signaling pathway associated with the Cdk5 kinase and its activator p35, while an extracellular protein called reelin (secreted in the marginal zone during development) may have prevented migrating cells from penetrating into the developing marginal zone (future layer I).

Lineage selection and the capacity to evolve.

The capacity of genetic recombination is an unusual adaptive trait since it is based on the capacity to produce evolutionary change rather than on the capacity to produce better performing individuals. The evolution of this character has been considered to be a case of group or species selection. Alternatively, I introduce a new concept, lineage selection, to account for the evolution of this trait.

Epigenesis and the evolution of the human brain.

This article proposes an hypothesis for the evolution of the human brain. It is based on the concepts of (i) regulation of nerve cell proliferation, and (ii) selective stabilisation of synapses during development. The former process is supposed to be rigidly regulated by the genome, while the latter (selective stabilisation) is proposed as developing in a more plastic manner. It is suggested here that genetic alterations of the regulation of neuroblast proliferation led to epigenetic rearrangements in selective synapse stabilisation, thus producing significant changes in cerebral connectivity. This view is in agreement with the punctuationalist theory of human evolution, and differs from other approaches to human nature, such as structuralist grammar and sociobiology.

Further comments on the evolutionary origin of the mammalian brain.

This paper is an extension of a previous report on the origin of the mammalian neocortex. Two main aspects are elaborated. The first is the evolution of visual projections from the midbrain to the telencephalon, featuring the encephalization of visual functions. Associated to this, the progressive fusion of the two main visual systems (thalamofugal and tectofugal) in the mammalian telencephalon (striate and extrastriate cortex, respectively) is viewed in the context of increasing cortico-cortical connectivity in the evolution of the mammalian brain. In addition, the issue of a presumed homology between mammalian extrastriate cortex and reptilian anterior dorsal ventricular ridge (ADVR) is reviewed in some detail, and it is concluded that extrastriate cortex is a derived character of mammals while ADVR is a derived character of reptiles and birds. It is not likely that ADVR is ancestral to extrastriate cortex. The second aspect under analysis is the origin of the inverted (inside-out) lamination pattern of mammalian neocortex that differs from the outside-in pattern of reptilian cortex. Furthermore, mammals have developed a transient embryonic cell layer (the subplate zone) that serves as a waiting compartment for thalamic and cortico-cortical axons while their prospective target cells end their migration process to reach their final positions. It is postulated that both, inverted lamination and the subplate zone arose in evolution as successive and complementary strategies to maximize synaptic contacts between thalamic afferents and the new cortical cell types (belonging to prospective granular and supragranular layers) that were being originated at that moment.

The origin of the mammalian brain as a case of evolutionary irreversibility.

The origin of the mammalian neocortex is usually considered as an improvement in the design of the brain. I suggest that the mammalian neocortex arose as a consequence of contingent adaptations in which there was no specific selection for more elaborate cognitive abilities. This perspective differs from the current view of brain evolution as a progressive phenomenon towards increased intelligence.

Mechanisms of adaptive evolution. Darwinism and Lamarckism restated.

This article discusses the conceptual basis of the different mechanisms of adaptive evolution. It is argued that only two such mechanisms may conceivably exist, Lamarckism and Darwinism. Darwinism is the fundamental process generating the diversity of species. Some aspects of the gene-centered approach to Darwinism are questioned, since they do not account for the generation of biological diversity. Diversity in biological design must be explained in relation to the diversity of interactions of organisms (or other higher-level units) with their environment. This aspect is usually overlooked in gene-centered views of evolution. A variant of the gene-selectionist approach has been proposed to account for the spread of cultural traits in human societies. Alternatively, I argue that social evolution is rather driven by what I call pseudo-Lamarckian inheritance. Finally, I argue that Lamarckian and pseudo-Lamarckian inheritance are just special cases of faithful replication which are found in the development of some higher-order units, such as multicellular organisms and human societies.