Albert M Galaburda

Harvard Medical School | HMS · Department of Neurology

In this response paper, we start by addressing the main points made by the commentators on the target article's main theoretical conclusions: the existence and characteristics of the intermediate shape-centered representations (ISCRs) in the visual system, their emergence from edge detection mechanisms operating on different types of visual propert...

As some critics have stated, the term “developmental dyslexia” refers to a strictly human disorder, relating to a strictly human capacity – reading – so it cannot be modeled in experimental animals, much less so in lowly rodents. However, two endophenotypes associated with developmental dyslexia are eminently suitable for animal modeling: Cerebral...

Although a great deal is known about the early sensory and the later, perceptual, stages of visual processing, far less is known about the nature of intermediate representational units and reference frames. Progress in understanding intermediate levels of representations in vision is hindered by the complexity and interactions between multiple leve...

We report the study of a woman who perceives 2D bounded regions of space (“shapes”) defined by sharp edges of medium to high contrast as if they were rotated by 90, 180 degrees around their centre, mirrored across their own axes, or both. In contrast, her perception of 3D, strongly blurred or very low contrast shapes, and of stimuli emerging from a...

Exposure to an adverse prenatal environment can influence fetal development and result in long-lasting changes in the offspring. However, the association between maternal exposure to stressful events during pregnancy and the achievement of pre-reading skills in the offspring is unknown. Here we examined the association between prenatal exposure to...

Objective To show the possible occurrence of exosomal transport of neprilysin from masseter muscle to hippocampus via trigeminal nerve in the living mouse. Design Mouse C2C12 myotube-derived exosomes were labeled with near-infrared (NIR) dye and injected into the masseter muscle to track their fluorescence from masseter muscle to hippocampus via t...

The primary visual cortex represents the retinotopic orientation of visual primitives (edges, blobs, bars), but our conscious perception is of orientated objects (e.g., dogs, forks) in the environment. How this transformation operates remains unknown. We report here the study of a young woman presenting with an extraordinarily clear and informative...

Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) used to treat mood and anxiety disorders. Chronic treatment with this antidepressant drug is thought to favor functional recovery by promoting structural and molecular changes in several forebrain areas. At the synaptic level, chronic fluoxetine induces an increased size and density of d...

Although the effects of neprilysin (NEP), also called CD10, on the clearance of Alzheimer's disease (AD)-associated amyloid-β (Aβ) have been reported, NEP is not made in the brain, and the mechanism for the transport of NEP to the brain has not been investigated. Our hypothesis is that muscle packages NEP in exosomes in response to a neuromuscular...

Autism is a group of complex neurodevelopmental disorders characterized by impaired social interaction and restricted/repetitive behavior. We performed a large-scale retrospective analysis of 1,996 clinical neurological structural magnetic resonance imaging (MRI) examinations of 781 autistic and 988 control subjects (aged 0–32 years), and extracted...

Autism is a group of complex neurodevelopmental disorders characterized by impaired social interaction, restricted and repetitive behavior. We performed a large-scale retrospective analysis of 1,996 structural magnetic resonance imaging (MRI) examinations of the brain from 1,769 autistic and neurologically typically developing patients (aged 0 to 3...

Developmental dyslexia, a reading disorder that piggybacks on some of the highest human cognitive functions, can be studied in animal models. This is because dyslexia can be decomposed into endophenotypes, some of which are present in one form or another in non-human animals, and because dyslexia has a developmental trajectory beginning at a time w...

Fractional anisotropy (FA) threshold is commonly used to perform diffusion MRI tractography. However, FA threshold may be one aspect of tractography that needs additional scrutiny in accurately assessing pathways in immature, developing brains, as well as in adult brains. Using high-angular resolution diffusion MRI (HARDI) tractography without an F...

Individuals with dyslexia exhibit subtle impairments in speech processing. Informed by these findings, a large literature has attributed dyslexia to a phonological deficit. Phonology, however, is only one of many systems engaged in speech processing. Accordingly, the speech perception deficit is consistent with any of multiple loci, including both...

Background: Polymicrogyric cortex demonstrates interindividual variation with regard to both extent of dyslamination and functional capacity. Given the relationship between laminar structure and white matter fibers, we sought to define the relationship between polymicrogyria (PMG), intrahemispheric association pathways, and network function. Meth...

Significance All spoken languages express words by sound patterns, and certain sound patterns (e.g., blog ) are systematically preferred to others (e.g., lbog ). However, whether those preferences reflect abstract rules or the motor difficulties associated with speech production is unknown. We address this question using transcranial magnetic stimu...

In this study of eight rare atypical deletion cases with Williams-Beuren syndrome (WS; also known as 7q11.23 deletion syndrome) consisting of three different patterns of deletions, compared to typical WS and typically developing (TD) individuals, we show preliminary evidence of dissociable genetic contributions to brain structure and human cognitio...

Dyslexia is a complex neurodevelopmental disorder characterized by impaired reading ability despite normal intellect, and is associated with specific difficulties in phonological and rapid auditory processing, visual attention, and working memory. Genetic variants in DCDC2 have been associated with dyslexia, impairments in phonological processing,...

Among the various asymmetrical structures of the human brain, the planum temporale, an anatomical region associated with a variety of auditory and language-related processes, has received particular attention. While its surface area has been shown to be greater in the left hemisphere compared to the right in about two-thirds of the general populati...

Little is known about the emergence of structural asymmetry of white matter tracts during early brain development. We examined whether and when asymmetry in diffusion parameters of limbic and association white matter pathways emerged in humans in 23 brains ranging from 15 gestational weeks (GW) up to 3 years of age (11 ex vivo and 12 in vivo cases)...

In Williams Syndrome (WS), a known genetic deletion results in atypical brain function with strengths in face and language processing. We examined how genetic influences on brain activity change with development. In three studies, event-related potentials (ERPs) from large samples of children, adolescents, and adults with the full genetic deletion...

Developmental dyslexia, the most common childhood learning disorder, is highly heritable, and recent studies have identified KIAA0319-Like (KIAA0319L) as a candidate dyslexia susceptibility gene at the 1p36-34 (DYX8) locus. In this experiment, we investigated the anatomical effects of knocking down this gene during rat corticogenesis. Cortical prog...

Dyslexia is commonly attributed to a phonological deficit, but whether it effectively compromises the phonological grammar or lower level systems is rarely explored. To address this question, we gauge the sensitivity of dyslexics to grammatical phonological restrictions on spoken onset clusters (e.g., bl in block). Across languages, certain onsets...

Developmental dyslexia is a language learning disorder that affects approximately 4–10% of the population. A number of candidate dyslexia susceptibility genes have been identified, including DCDC2 and KIAA0319 on Chromosome (Chr) 6p22.2 and DYX1C1 on Chr 15q21. Embryonic knockdown of the function of homologs of these genes in rat neocortical projec...

Developmental dyslexia is a language learning disorder that affects approximately 4–10% of the population. A number of candidate dyslexia susceptibility genes have been identified, including DCDC2 and KIAA0319 on Chromosome (Chr) 6p22.2 and DYX1C1 on Chr 15q21. Embryonic knockdown of the function of homologs of these genes in rat neocortical projec...

Developmental dyslexia is a language learning disorder that affects approximately 4-10% of the population. A number of candidate dyslexia susceptibility genes have been identified, including DCDC2 and KIAA0319 on Chromosome (Chr) 6p22.2 and DYX1C1 on Chr 15q21. Embryonic knockdown of the function of homologs of these genes in rat neocortical projec...

Laminar markers FOXP2 (A) and CTIP2 (B) in the somatosensory cortex. FOXP2+ and CTIP2+ neurons are found predominantly in layer 6, although CTIP2 inconsistently labels layer 5 and layer 2 neurons as well. Bar = 500 µm. (TIF)

Dyslexia is associated with numerous deficits to speech processing. Accordingly, a large literature asserts that dyslexics manifest a phonological deficit. Few studies, however, have assessed the phonological grammar of dyslexics, and none has distinguished a phonological deficit from a phonetic impairment. Here, we show that these two sources can...

The effect of reading skill on the discrimination of words from nonwords (in Experiment 1). Note: Box plots mark one SE above and below the mean. Each whisker bar marks 2 SD. Individual data plots are indicated by triangles. (PDF)

The effect of reading skill on the discrimination of speech from nonspeech (in Experiment 2). Note: Box plots mark one SE above and below the mean. Each whisker bar marks two SD. Individual data plots are indicated by triangles. (PDF)

Response of type time to speech and nonspeech as a function of reading skill and stem type (in Experiment 2). Note: Box plots mark one SE above and below the mean. Each whisker bar marks two SD. Individual data plots are indicated by triangles. (PDF)

Identification of the ba-pa continuum by dyslexic and skilled readers. Regression lines were fit to each individual’s response data across step (treated as a continuous variable) using logistic regression. (PDF)

Identification of the a-e continuum by dyslexic and skilled readers. Regression lines were fit to each individual’s response data across step (treated as a continuous variable) using logistic regression. (PDF)

Discrimination in the da-ta continuum by dyslexic and skilled readers. Regression lines were fit to each individual’s accuracy data across step using logistic regression with a natural cubic spline (df = 2). (PDF)

Discrimination in the o-u continuum by dyslexic and skilled readers. Regression lines were fit to each individual’s accuracy data across step using logistic regression with a natural cubic spline (df = 2). (PDF)

Discrimination in the a-e continuum by dyslexic and skilled readers. Regression lines were fit to each individual’s accuracy data across step using logistic regression with a natural cubic spline (df = 2). (PDF)

Response time and response accuracy to nonwords as a function of reading skill and stem type (in Experiment 1). Note: Box plots mark two SE above and below the mean. Each whisker bar marks two SD. (PDF)

Identification of the da-ta continuum by dyslexic and skilled readers. Regression lines were fit to each individual’s response data across step (treated as a continuous variable) using logistic regression. (PDF)

Identification of the o-u continuum by dyslexic and skilled readers. Regression lines were fit to each individual’s response data across step (treated as a continuous variable) using logistic regression. (PDF)

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Discrimination in the ba-pa continuum by dyslexic and skilled readers. Regression lines were fit to each individual’s accuracy data across step using logistic regression with a natural cubic spline (df = 2). (PDF)

Polymicrogyria (PMG) is a malformation of cortical development characterized by an irregular gyral pattern and its diagnosis and severity have been qualitatively judged by visual inspection of imaging features. We aimed to provide a quantitative description of abnormal sulcal patterns for individual PMG brains using our sulcal graph-based analysis...

Within the last decade several genes have been identified as candidate risk genes for developmental dyslexia. Recent research using animal models and embryonic RNA interference (RNAi) has shown that a subset of the candidate dyslexia risk genes--DYX1C1, ROBO1, DCDC2, KIAA0319--regulate critical parameters of neocortical development, such as neurona...

Cerebral axonal connections begin to develop before birth during radial migration in each brain area. A number of theories are still actively debated regarding the link between neuronal migration, developing connectivity, and gyrification. Here, we used high angular resolution diffusion tractography on postmortem fetal human brains (postconception...

The dyslexia-associated gene DCDC2 is a member of the DCX family of genes known to play roles in neurogenesis, neuronal migration, and differentiation. Here we report the first phenotypic analysis of a Dcdc2 knockout mouse. Comparisons between Dcdc2 knockout mice and wild-type (wt) littermates revealed no significant differences in neuronal migrati...

The immature cortex (cortical plate [CP]) and underlying subplate (SP), a transient cell layer just below the CP, play critical roles in the formation of intracerebral connections. The purpose of this study was to examine the diffusion characteristics of the developing cortex and subcortical structures and compare to histology. We obtained high-res...

Developmental dyslexia is a language-based learning disability, and a number of candidate dyslexia susceptibility genes have been identified, including DYX1C1, KIAA0319, and DCDC2. Knockdown of function by embryonic transfection of small hairpin RNA (shRNA) of rat homologues of these genes dramatically disrupts neuronal migration to the cerebral co...

Individuals with Williams syndrome (WS) demonstrate an abnormally positive social bias. However, the neural substrates of this hypersociability, i.e., positive attribution bias and increased drive toward social interaction, have not fully been elucidated. METHODS: We performed an event-related functional magnetic resonance imaging study while indiv...

Williams syndrome (WS) is a genetic condition characterized by atypical brain structure, cognitive deficits, and a life-long fascination with faces. Face recognition is relatively spared in WS, despite abnormalities in aspects of face processing and structural alterations in the fusiform gyrus, part of the ventral visual stream. Thus, face recognit...

We investigated the postnatal effects of embryonic knockdown and overexpression of the candidate dyslexia gene homolog Kiaa0319. We used in utero electroporation to transfect cells in E15/16 rat neocortical ventricular zone with either 1) small hairpin RNA (shRNA) vectors targeting Kiaa0319, 2) a KIAA0319 expression construct, 3) Kiaa0319 shRNA alo...

Examination of the three-dimensional axonal pathways in the developing brain is key to understanding the formation of cerebral connectivity. By tracing fiber pathways throughout the entire brain, diffusion tractography provides information that cannot be achieved by conventional anatomical MR imaging or histology. However, standard diffusion tracto...

Functional imaging in humans and anatomical data in monkeys have implicated the insula as a multimodal sensory integrative brain region. The topography of insular connections is organized by its cytoarchitectonic regions. Previous attempts to measure the insula have utilized either indirect or automated methods. This study was designed to develop a...

In this paper, we propose an automated approach for the joint detection of major sulci on cortical surfaces. By representing sulci as nodes in a graphical model, we incorporate Markovian relations between sulci and formulate their detection as a maximum a posteriori (MAP) estimation problem over the joint space of major sulci. To make the inference...

William's syndrome (WS) features a spectrum of neurocognitive and behavioral abnormalities due to a rare 1.5 MB deletion that includes about 24-28 genes on chromosome band 7q11.23. Study of the expression of these genes from the single normal copy provides an opportunity to elucidate the genetic and epigenetic controls on these genes as well as the...

Williams syndrome (WS) is a neurogenetic disorder resulting from a hemizygous microdeletion at band 7q11.23. It is characterized by aberrant development of the brain and a unique profile of cognitive and behavioral features. We sought to identify the neuroanatomical abnormalities that are most strongly associated with WS employing signal detection...

Induced or genetically based cortical laminar malformations in somatosensory cortex have been associated with perceptual and acoustic processing deficits in mammals. Perinatal freeze-lesions of developing rat primary somatosensory (S1) cortex induce malformations resembling human microgyria. Induced microgyria located in parietal somatosensory cort...

Inborn Errors of Development is the definitive work on genetically caused abnormalities of human development. Despite the explosion in genetic advances, the causes of two-thirds of all birth defects remain unknown. However, we are on the brink of a revolution in this area, and this book is at the forefront. It is the first book to connect the disea...

Embryonic knockdown of candidate dyslexia susceptibility gene (CDSG) homologs in cerebral cortical progenitor cells in the rat results in acute disturbances of neocortical migration. In the current report we investigated the effects of embryonic knockdown and overexpression of the homolog of DCDC2, one of the CDSGs, on the postnatal organization of...

Research into phenotype-genotype correlations in neurodevelopmental disorders has greatly elucidated the contribution of genetic and neurobiological factors to variations in typical and atypical development. Etiologically relatively homogeneous disorders, such as Williams syndrome (WS), provide unique opportunities for elucidating gene-brain-behavi...

Résumé Le terme de « néo-associationnisme » se réfère, dans ce chapitre, à un mouvement conceptuel né au lendemain de la Seconde Guerre mondiale, dont l’objet fut de restaurer un dialogue entre structure cérébrale et fonction. Ce mouvement s’inspira des approches localisationnistes et associationnistes du XIX e siècle et posa les bases d’une nouvel...

Early postnatal freeze-lesions to the cortical plate result in malformations resembling human microgyria. Microgyria in primary somatosensory cortex (S1) of rats are associated with a reduced behavioral detection of rapid auditory transitions and the loss of large cells in the thalamic nucleus projecting to primary auditory cortex (A1). Detection o...

The brains of individuals with developmental dyslexia have neocortical neuronal migration abnormalities including molecular layer heterotopias, laminar dysplasias, and periventricular nodular heterotopias (PNH). RNA interference (RNAi) of Dyx1c1, a candidate dyslexia susceptibility gene, disrupts neuronal migration in developing embryonic neocortex...