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On February 24, 2022, a war began within the Ukrainian borders. At least 3.0 million Ukrainian inhabitants have already fled the country. Critical infrastructure, including hospitals, has been damaged. Children with cancer were urgently transported to foreign countries, in an effort to minimize interruption of their life-saving treatments. Most adults did not have that option. War breeds cancer-delaying diagnosis, preventing treatment, and increasing risk. We project that a modest delay in care of only 4 months for five prevalent types of cancer will lead to an excess of over 3,600 cancer deaths in the subsequent years. It is critical that we establish plans to mitigate that risk as soon as possible.
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Neoplasias , Pesquisa , Adulto , Conflitos Armados , Criança , Humanos , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Neoplasias/terapia , Ucrânia/epidemiologiaRESUMO
This review aims to summarize information about the genetic etiology of attention deficit disorder with hyperactivity (ADHD), with particular reference to the contributions of our research group. We also discuss the genetic comorbidity estimated from genome-wide single nucleotide polymorphisms (SNP´s) between ADHD and major psychiatric disorders such as schizophrenia (E), major depressive disorder (MDD), bipolar disorder (BD) and autism spectrum disorders (ASD). A high genetic comorbidity was found between E and BD (46%), a moderate comorbidity between MDD and E, MDD and BD and MDD and ADHD (18%, 22% and 10% respectively) and a low comorbidity between E and ASD (2.5%). Furthermore, we show evidence concerning the genetic determination of psychiatric diseases, which is significantly lower when it is estimated from genome-wide SNP´s rather than using traditional quantitative genetic methodology (ADHD = E = 23%, BD = 25%, MDD = 21% and ASD = 17%). From an evolutionary perspective, we suggest that behavioral traits such as hyperactivity, inattention and impulsivity, which play a role in ADHD and perhaps also other hereditary traits which are part of major psychiatric disorders, could have had a high adaptive value during the early stages of the evolution of Homo sapiens. However, they became progressively less adaptive and definitively disadvantageous, to the extreme that they are involved in frequently diagnosed major psychiatric disorders.
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Humanos , Transtorno do Deficit de Atenção com Hiperatividade/genética , Característica Quantitativa Herdável , Predisposição Genética para Doença/genética , Esquizofrenia/genética , Transtorno Bipolar/genética , Comorbidade , Transtorno Depressivo Maior/genética , Transtorno do Espectro Autista/genéticaRESUMO
Schizophrenia is a severe psychiatric disorder that results in a significant disability for the patient. The disorder is characterized by impairment of the adaptive orchestration of actions, a cognitive function that is mainly dependent on the prefrontal cortex. This behavioral deficit, together with cellular and neurophysiological alterations in the prefrontal cortex, as well as reduced density of GABAergic cells and aberrant oscillatory activity, all indicate structural and functional deficits of the prefrontal cortex in schizophrenia. Among the several risk factors for the development of schizophrenia, stress during the prenatal period has been identified as crucial. Thus, it is proposed that prenatal stress induces neurodevelopmental alterations in the prefrontal cortex that are expressed as cognitive impairment observed in schizophrenia. However, the precise mechanisms that link prenatal stress with the impairment of prefrontal cortex function is largely unknown. Reelin is an extracellular matrix protein involved in the development of cortical neural connectivity at embryonic stages, and in synaptic plasticity at postnatal stages. Interestingly, down-regulation of reelin expression has been associated with epigenetic changes in the reelin gene of the prefrontal cortex of schizophrenic patients. We recently showed that, similar to schizophrenic patients, prenatal stress induces down-expression of reelin associated with the methylation of its promoter in the rodent prefrontal cortex. These alterations were paralleled with altered prefrontal cortex functional connectivity and impairment in prefrontal cortex-dependent behavioral tasks. Therefore, considering molecular, cellular, physiological and behavioral evidence, we propose a unifying framework that links prenatal stress and prefrontal malfunction through epigenetic alterations of the reelin gene.
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Humanos , Feminino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Esquizofrenia/etiologia , Esquizofrenia/fisiopatologia , Estresse Fisiológico/fisiologia , Encéfalo/embriologia , Serina Endopeptidases/genética , Moléculas de Adesão Celular Neuronais/genética , Proteínas da Matriz Extracelular/genética , Epigênese Genética/fisiologia , Proteínas do Tecido Nervoso/genética , Transtornos do Comportamento Social/fisiopatologia , Encéfalo/fisiopatologia , Expressão Gênica , Fatores de Risco , Transtornos Cognitivos/fisiopatologia , Metilação de DNARESUMO
Background: The assessment of Attentional Deficit Hyperactivity Disorder (ADHD) among ethnic groups may reveal environmental or cultural variables that influence the appearance of this disorder. Aim: To assess the presence and characteristics of ADHD in two communities of the inland Arica valleys (Azapa and Lluta), where the Aymara population predominates. Material and Methods: Startingfrom a screening based on the Conner's test, we evaluated 79 children aged 8 to 13 years. Sixty children were of Aymara origin and 19 children were of non-Aymara origin. Twenty Aymara and 9 non-Aymara children had ADHD. They were compared with a group of patients from Santiago, Chile (110 children) that were previously assessed. Results: Patientsfrom Azapa/Lluta displayed similar characteristics to those from Santiago. However the former had significantly less psychiatric comorbidities than the latter. On the other hand, the non-Aymara subgroup of Azapa/ Lluta displayed an increased rate of comorbidities and was exclusively of the combined subtype, although their sample size is too small to draw strong conclusions. Conclusions: Although we cannot dismiss biological variables, the importance of family values and the respect to authorities may be protective factors for ADHD, associated to Aymara culture. Our findings suggest that the clinical characteristics of ADHD are not uniform among ethnic groups and cultures. The relative contribution of environmental and genetic factors in this variability remain to be determined.
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Adolescente , Criança , Feminino , Humanos , Masculino , Transtorno do Deficit de Atenção com Hiperatividade/etnologia , Indígenas Sul-Americanos/etnologia , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Chile/epidemiologia , Comorbidade , Indígenas Sul-Americanos/psicologia , Transtornos Mentais/etnologia , Escalas de Graduação PsiquiátricaRESUMO
Background: Worldwide diversity of alleles of D4 receptor gene (DRD4), linked to attention deficit hyperactivity disorder (ADHD), is mostly the result of length and single nucleotide polymorphisms in a 48-bp tandem repeat (VNTR). Alleles containing from two (2R) to eleven (11R) repeats have been identified. The most common are 4R, 7R and 2R. Aim: To study the association of ADHD risk with DRD4 genotypes in Chilean students. Subjects and Methods: ADHD risk data were obtained through the abbreviated Conner's Scale for School Teachers in 66 Aymara children (11 cases and 55 controls), 91 Rapa-Nui children (60 cases ad 31 controls) and 96 children from a mixed urban population from Santiago (51 cases and 45 controls). DNA extracted from saliva was amplified by polymerase chain reaction (PCR) to genotype the DRD4 VNTR. Results: The distribution of DRD4 alleles reveals that, beneath the 4R allele, 7R exhibits the second highest frequencies in Aymara and Santiago children. In Polynesian children, 2R ranks after 4R. A statistically significant association between ADHD risk and 2R/4R genotype was identified in Polynesian children (p < 0.05; odds ratio = 3.7). Conclusions: Different DRD4 genotypes are associated with ADHDphenotype in Chilean populations, probably as a consequence of their initial colonization history.
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Criança , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/genética , Dopamina/genética , Indígenas Sul-Americanos/genética , /genética , Alelos , Estudos de Casos e Controles , Chile , Frequência do Gene , Genótipo , Fatores de RiscoRESUMO
Los niños con Trastorno por Déficit Atencional e Hiperactividad (TDAH) presentan dificultades en el terreno de las competencias sociales. Pese a que varios modelos han sido propuestos para explicar estas observaciones, ninguno de ellos ha podido dar cuenta a cabalidad de todos los aspectos observados en este tipo de disfuncionalidad. La investigación ha comenzado a evidenciar que alteraciones en el procesamiento de estímulos con contenido emocional estarían a la base de estas dificultades. A partir de esto, el estudio del procesamiento de caras y expresiones faciales se ha transformado en una herramienta de gran utilidad en este campo. La Neurociencia ha realizado importantes contribuciones a la comprensión de los procesos neurocognitivos del TDAH, sin embargo, hasta ahora se ha interesado menos en el estudio del procesamiento afectivo de estos niños. Se propone que mediante la investigación de las bases neurales del procesamiento de expresiones faciales en niños con TDAH, la rama Afectiva de la Neurociencia puede contribuir con importantes antecedentes que permitan comprender y abordar las dificultades que estos niños presentan a nivel de su desempeño social.
Children with Attention Deficit Hyperactivity Disorder (ADHD) have difficulties in the field of social competences. Although several models have been proposed to explain these observations, none of them has been able to fully account for all the aspects observed in this type of dysfunction. Research has begun to evidence that at the basis of these difficulties there are alterations in emotional processing. In this line, the study of face processing and facial expressions has become an important tool in this field. The field of Neuroscience has made significant contributions to the understanding of the neurocognitive processes of ADHD; however, it there has been less interest in the study of affective processing of these children. We propose that by investigating the neural basis of facial expression processing in children with ADHD, Affective Neuroscience could contribute with important evidence for understanding and addressing the difficulties these children have in their social performance.
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Humanos , Criança , Emoções , Expressão Facial , Comportamento Social , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Relações Interpessoais , Neurociências , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologiaRESUMO
The effect of prenatal malnutrition on the anatomy of the corpus callosum was assessed in adult rats (45-52 days old). In the prenatally malnourished animals we observed a significant reduction of the corpus callosum total area, partial areas, and perimeter, as compared with normal animals. In addition, the splenium of corpus callosum (posterior fifth) showed a significant decrease of fiber diameters in the myelinated fibers without changing density. There was also a significant decrease in diameter and a significant increase in density of unmyelinated fibers. Measurements of perimeter's fractal dimensions from sagittal sections of the brain and corpus callosum did not show significant differences between malnourished and control animals. These findings indicate that cortico-cortical connections are vulnerable to the prenatal malnutrition, and suggest this may affect interhemispheric conduction velocity, particulary in visual connections (splenium).
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Animais , Feminino , Masculino , Gravidez , Ratos , Corpo Caloso/anatomia & histologia , Desnutrição/patologia , Fibras Nervosas/ultraestrutura , Efeitos Tardios da Exposição Pré-Natal/patologia , Peso Corporal/fisiologia , Grupos Controle , Corpo Caloso/fisiologia , Desnutrição/fisiopatologia , Fibras Nervosas Mielinizadas/ultraestrutura , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Ratos Sprague-DawleyRESUMO
Background: Attention deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurobiological disorder of childhood onset, characterized by hyperactivity, impulsiveness or inattentiveness. Aim: To search for differences in risk for ADHD and its components among Chilean native and mixed populations and to look forpossible associations with dopamine receptor D4 (DRD4) and dopamine transporter 1 (DAT1) polymorphisms. Material and Methods: School teachers were requested to complete the Conners test, which uses DSM-IV criteria, to screen for ADHD risk among Aymara and Rapa-Nui students. Results: Rapa-Nui children from Easter Island had the highest risk of hyperactivity/impulsiveness. Aymara children from the Arica-Parinacota Region had lower scores. Although inattentiveness scores had lower differences between groups, overall ADHD score differences among studied populations were highly significant. DRD4 and DAT1 alleles had a heterogeneous distribution. Easter islanders had more divergent frequencies, mostprobably as a result of separate migration routes utilized at different timeperiods during the colonization of America and Polynesia. Conclusions: The comparison of ADHD risk parameters between Rapa-Nui and Aymara children showed marked differences. Allele distri-bution of dopamine polymorphisms in Easter Island was also significantly different from northern Chile, due probably to different colonization histories. These findings suggest that higher ADHD risk scores in Easter Island children may be linked to the presence of different DRD4 alleles.
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Criança , Feminino , Humanos , Masculino , Transtorno do Deficit de Atenção com Hiperatividade/genética , Proteínas da Membrana Plasmática de Transporte de Dopamina/genética , Polimorfismo Genético/genética , /genética , Transtorno do Deficit de Atenção com Hiperatividade/etnologia , Estudos de Casos e Controles , Chile/etnologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Fatores de RiscoRESUMO
The present study explores the neural correlates of voluntary modulations of attention in an auditory-visual matching task. Visual stimuli (a female or a male face) were preceded in close temporal proximity by auditory stimuli consisting of the Spanish word for "man" and "woman" ("hombre" or "mujer"). In 80 percent of the trials the gender of the two stimuli coincided. Participants were asked to mentally count the specific instances in which a female face appeared after hearing the word "man" (10 percent of the trials). Our results show attention-related amplitude modulation of the early visual ERP components NI and anterior P2, but also amplitude modulations of (i) the N270 potential usually associated with conflict detection, (ii) a P300 wave related to infrequency, and (iii) an N400 potential related to semantic incongruence. The elicitation of these latter components varied according to task manipulations, evidencing the role of voluntary allocation of attention in fine-tuning cognitive processing, which includes basic processes like detection of infrequency or semantic incongruity often considered to be volition-independent.
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Adolescente , Adulto , Feminino , Humanos , Masculino , Adulto Jovem , Atenção/fisiologia , Percepção Auditiva/fisiologia , Potenciais Evocados/fisiologia , Reconhecimento Visual de Modelos/fisiologia , Semântica , Eletroencefalografia , Estimulação Luminosa , Adulto JovemRESUMO
Background: Attention deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurobiological disorder of childhood onset, characterized by hyperactivity, impulsiveness, and/or inattentiveness. Aún: To search forpossible associations between dopamine receptor D4 (DRD4) and dopamine transponer 1 (DATl) polymorphisms and ADHD in Chilean families. Material and methods: We extended a previous family-based discordant sib pair analysis that included 26 cases diagnosed according to DSM-IV entena and 25 controls (healthy siblings of cases), adding 14 cases and 11 controls. Results: Both loci, individually classified as homozygotes or heterozygotes for the DRD4 7-repeat and DATl 10-repeat alleles, did not exhibit genotype frequency differences between affected children and their healthy siblings. However, the simultaneous presence of both DRD4 7-repeat heterozygosity and DATl 10 allele homozygosity was significantly higher (22.5 percent) in cases (40), compared with (2.8 percent) unaffected siblings (36), with an odds-ratio of 10.16. Conclusions: The genotype combination DRD4/7 heterozygotes and DAT1/10 homozygotes is a high risk factors in Chilean families for ADHD. Increased density of dopamine transporters in ADHD brains, along with abundance of 7-repeat D4 receptors in prefrontal cortex, which is impaired in ADHD patients, make the observed gene-gene interaction worthy of studies to understand the functional basis ofADHD.
Assuntos
Criança , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/genética , Proteínas da Membrana Plasmática de Transporte de Dopamina/genética , Família , Polimorfismo Genético/genética , /genética , Estudos de Casos e Controles , Manual Diagnóstico e Estatístico de Transtornos Mentais , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Repetições Minissatélites , Reação em Cadeia da Polimerase , Fatores de RiscoRESUMO
El síndrome de déficit atencional es uno de los problemas frecuentes en neuropsiquiatría. Es interesante para los pediatras conocer la evolución de los pacientes a futuro, es decir, cómo se desarrollan y desempeñan en la vida adulta los niños que han padecido este problema. En este artículo se realiza una revisión del déficit atencional del adulto.
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Humanos , Criança , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/diagnósticoRESUMO
Se presenta un resumen de la tesis realizada para optar al grado de Doctor en Ciencias Médicas del programa de Postgrado de la Pontificia Universidad Católica de Chile. Desde el año 1995este programa ha permitido la formación de Médicos que sean capaces de originar investigación independiente en el área biomédica, de constituir un puente entre la investigación básica y la práctica clínica, y que contribuyan al mejoramiento de la docencia académica. El resumen de la tesis que se presenta a continuación fue realizado en el laboratorio de Neurociencias cognitivas del Dr. Francisco Aboitiz, perteneciente al departamento de Psiquiatría de la Pontificia Universidad Católica de Chile en estrecha colaboración con dos centros de investigación internacionales: El F.C. Donders Center para el estudio de neuroimágenes cognitivas, de la universidad de Radboud en Holanda, y el Laboratorio de imagen cerebral y neurociencia cognitiva (LENA ) en Francia.
This work corresponds to a summary of doctoral thesis performed to apply to the doctoral degree in medical science the Pontifical Catholic University of Chile. Since 1995, this program has allowed the training of medical doctors able to produce independent research in the biomedical sciences, bridging the gap between basic research and clinical practice and improving academic teaching. The following summary was made in the Cognitive Neuroscience Laboratory of the psychiatry department of the Pontifical Catholic University of Chile led by Dr. Francisco Aboitiz. This work was performed in close collaboration with two international research centers: The F.C. Donders Center for cognitive neuroimaging (Radboud University, Netherlands) and the cognitive neuroscience and brain-imaging laboratory (LENA, France).
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Humanos , Masculino , Feminino , Esquizofrenia/complicações , Esquizofrenia/diagnóstico , Transtornos da Memória/etiologia , Transtornos da Memória/psicologia , Eletrofisiologia , Escalas de Graduação Psiquiátrica , Esquizofrenia/fisiopatologia , Estudos de Casos e Controles , Fatores Socioeconômicos , Testes NeuropsicológicosRESUMO
Este artículo es una breve actualización en cuanto a las bases cognitivas del Síndrome de Déficit Atencional e Hiperactividad (SDAH). Presentamos algunos resultados recientes en que analizamos estrategias cognitivas y el efecto neurofisiológico de psicoestimulantes en esta condición. Esbozamos un modelo basado en resultados nuestros y de otros grupos, en el cual la estrategia atencional de los sujetos con SDAH se caracteriza por un amplio marco espacial y una corta ventana temporal en comparación a los controles. Por último, proponemos líneas de investigación básico-clínica respecto de éste síndrome.
This article is a brief update on the cognitive bases of Attention Deficit and Hyperactivity Disorder (ADHD). We show some of our recent results in which we analyze cognitive strategies and neurophysiological effect of psychostimulants in this disorder. We summarize a model, based on our own results and those of other laboratories, in which the attention strategy of ADHD subjects is characterized by a wide spatial frame but a narrow time window compared to controls. Finally, we suggest lines of basic-clinical research for this syndrome.
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Humanos , Masculino , Feminino , Criança , Adolescente , Adulto , Dopamina/uso terapêutico , Metilfenidato/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Potenciais Evocados , Estimulantes do Sistema Nervoso Central/uso terapêutico , FenótipoRESUMO
Although there is extensive literature about the effects of stimulants on sustained attention tasks in attentional deficit/hyperactivity disorder (ADHD), little is known about the effect of these drugs on other attentional tasks involving different neural systems. In this study we measured the effect of stimulants on ADHD children, both in the electroencephalographic (EEG) activity during sustained attentional tasks and in psychometric performance during selective attentional tasks. These tasks are known to rely on different cortical networks. Our results in children medicated with 10 mg of d-amphetamine administered 60 min before the study indicate (i) a significant increase in amplitude but not latency of the P300 component of the event-related potential (ERP) during the sustained attentional task and (ii) a significant improvement in the reaction times and correct responses in the selective attentional task. In addition to supporting the use of stimulants in children with attentional deficit/hyperactivity disorder, these results show a multifocal activity improvement of cortical structures linked to dopamine, and interestingly, to attention. All these analyses are framed in a wider study of diverse attentional functions in this syndrome.
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Humanos , Masculino , Feminino , Criança , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Atenção/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/uso terapêutico , Dextroanfetamina/uso terapêutico , Eletroencefalografia , /efeitos dos fármacos , Potenciais Evocados/efeitos dos fármacos , Tempo de ReaçãoRESUMO
Francisco Varela dedicó su vida al trabajo de encontrar una conexión entre los fenomenos conscientes y los mecanismos neurales asociados a ellos. Una aproximación actual a este problema consiste en el análisis de la actividad sincrónica entre grupos de neuronas distribuidas en el cerebro. Varela hizo una contribución sobresaliente a las neurociencias al establecer una relación entre percepción consciente en los seres humanos y la generación de amplias redes de actividad neuronal sincrónica en la corteza cerebral. Sin embargo, en mi opinión, el problema más complejo de cómo se originan las sensaciones sensoriales subjetivas en nuestros cerebros, permanece sin una respuesta clara
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Humanos , Neurônios , Percepção/fisiologia , Sensação/fisiologia , Córtex Cerebral , Consciência , Visão OcularRESUMO
Three main lines of investigation are discussed in this paper: (1) the comparison between the anatomical arrangement of the language areas and the large-scale neurocognitive cortical networks partly involved in active or working memory; (2) the relations between hemispheric specialization and the development of interhemispheric communication; and (3) the analysis of individual differences in brain organization for language. The hypothesis and evidence presented stem from work being performed in our laboratories
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Feminino , Humanos , Córtex Cerebral/anatomia & histologia , Desenvolvimento da Linguagem , Córtex Cerebral/ultraestrutura , Corpo Caloso/anatomia & histologia , Lobo Frontal/anatomia & histologia , Caracteres SexuaisRESUMO
In vertebrates, brain size variability relates to two main parameters: body size and ecological factors (in particular diet and foraging strategy). It has been considered by many authors that evolutionary brain growth is a unitary phenomenon whose main effect is to increase processing capacity. Alternatively, in this paper it is considered that brain growth is significantly associated with higher processing capacity only when it occurs associated with ecological circumstances (selection of behavioral or perceptual skills). This process is referred to as ®active® growth. When the brain scales on body size, there is little change in processing capacity, and this will be referred to as ®passive® growth. I propose that these two modes of phylogenetic brain growthrelate to different developmental/evolutionary processes and aredistinguishable at the level of adult and developing structure. Shortly, growth due to selection of behavioral capacities is associated with more differentiated brains in terms of number of areas, connectional rearrangements and cell types. Growth due to scaling of body mass produces little brain rearrangements, and many of those that occur relate to the maintenance of functions in a larger brain. In addition, active selection of brain size is triggered by plastic, ontogenic rearrangements of connectivity in the organisms, while passive growth produces the minor rearrangements that take place. Finally, I propose a research program oriented to test this model by separating the effects of body size and ecological variables in brain organization across species
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Animais , Evolução Biológica , Encéfalo/anatomia & histologia , Vertebrados/anatomia & histologia , Adaptação Fisiológica , Encéfalo/fisiologia , Ecologia , Seleção GenéticaRESUMO
The present review summarizes some results of a research program oriented to determine the anatomical substrates of interhemispheric communication in humans, as seen in postmortem material. One main finding is a sensible pattern of histological differentiation along the corpus callosum, indicating specific properties of interhemispheric conduction for axonal fibers involved in different brain functions. Callosal regions that connect primary and secondary sensory and motor areas are characterized by a large proportion of fast-conducting, large-diameter fibers, while regions connecting the so-called association areas and prefrontal areas bear a high density of slow-conducting, lightly myelinated and thin fibers. These findings are interpreted in a functional context, suggesting that the fast-conducting fibers connecting sensory and motor areas contribute to fuse the two hemirepresentations in each hemisphere. It has also been determined that an increased callosal area indicates an increased number of callosal fibers, a finding that validates previous morphometric studies done in several laboratories. No sex differences in callosal size, shape, or in callosal fiber composition were found. Finally, an inverse relation was found between the anatomical asymmetries in the size of the Sylvian fissure and the size and number of fibers in specific segments of the corpus callosum. There were sex differences in terms of the particular callosal regions showing a significant correlation with asymmetries, and in terms of the fiber types that were correlated with asymmetries