An oscillopathic approach to developmental dyslexia: from genes to speech processing

AbstractDevelopmental dyslexia is a heterogeneous condition entailing problems with reading and spelling. Several genes have been linked or associated to the disease, many of which contribute to the development and function of brain areas that are important for auditory and phonological processing. Nonetheless, a clear link between genes, the brain, and the symptoms of dyslexia is still pending. The goal of this paper is contributing to bridge this gap. With this aim, we have focused on how the dyslexic brain fails to process speech sounds and reading cues. We have adopted an oscillatory perspective, according to which dyslexia results from a deficient integration of different brain rhythms during reading/spellings tasks. Moreover, we show that some candidates for this condition are related to brain rhythms. This approach should help gain a better understanding of the aetiology and the clinical presentation of developmental dyslexia, but also achieve an earlier and more accurate diagnosis of the disease.

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How does literacy affect speech processing? Not by enhancing cortical responses to speech, but by promoting connectivity of acoustic-phonetic and graphomotor cortices.

10.1101/2021.06.04.446930 ◽

2021 ◽

Author(s):

Alexis Hervais-Adelman ◽

Uttam Kumar ◽

Ramesh K Mishra ◽

Viveka N Tripathi ◽

Anupam Guleria ◽

...

Keyword(s):

Functional Connectivity ◽

Speech Processing ◽

Phonological Processing ◽

Longitudinal Analyses ◽

Brain Areas ◽

Cross Sectional ◽

Learning To Read ◽

Brain Responses ◽

Fmri Study ◽

Cortical Responses

Previous research suggest that literacy, specifically learning alphabetic letter-to-phoneme mappings, modifies online speech processing, and enhances brain responses to speech in auditory areas associated with phonological processing (Dehaene et al., 2010). However, alphabets are not the only orthographic systems in use in the world, and hundreds of millions of individuals speak languages that are not written using alphabets. In order to make claims that literacy per se has broad and general consequences for brain responses to speech, one must seek confirmatory evidence from non-alphabetic literacy. To this end, we conducted a longitudinal fMRI study in India probing the effect of literacy in Devanagari, an abubgida, on functional connectivity and cerebral responses to speech in 91 variously literate Hindi-speaking individuals. Twenty-two completely illiterate participants underwent six months of reading and writing training. Devanagari literacy increases functional connectivity between acoustic-phonetic and graphomotor brain areas, but we find no evidence that literacy changes the way speech is processed, either in cross-sectional or longitudinal analyses. These findings shows that a radical reconfiguration of the neurofunctional substrates of online speech processing is not a universal result of learning to read, and raise the possibility that writing, not only reading, may be instrumental in moulding literate speech perception.

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A Different Olfactory Perception in Anosmic Patients: Evidence from Functional MRI

10.20944/preprints202109.0356.v1 ◽

2021 ◽

Author(s):

Mohsen Kohan Pour ◽

Sobhan Aarabi ◽

Seyed Amir Hossein Batouli ◽

Soodeh Moallemian ◽

Mohammad Ali Oghabian

Keyword(s):

Brain Activity ◽

Sensory System ◽

Noninvasive Method ◽

Functional Magnetic Resonance ◽

Resonance Imaging ◽

Brain Areas ◽

Normal Individuals ◽

Bold Responses ◽

And Function ◽

The Brain

Olfactory system is a vital sensory system in mammals, giving them the ability to connect with their environment. Anosmia, or the complete loss of olfaction ability, which could be caused by injuries, is an interesting topic for inspectors with the aim of diagnosing patients. Sniffing test is currently utilized to examine if an individual is suffering from anosmia; however, functional Magnetic Resonance Imaging (fMRI) provides unique information about the structure and function of the different areas of the human brain, and therefore this noninvasive method could be used as a tool to locate the olfactory-related regions of the brain. In this study, by recruiting 31 healthy and anosmic individuals, we investigated the neural BOLD responses in the olfactory cortices following two odor stimuli, rose and eucalyptus, by using a 3T MR scanner. Comparing the two groups, we observed a network of brain areas being more active in the normal individuals when smelling the odors. In addition, a number of brain areas also showed an activation decline during the odor stimuli, which is hypothesized as a resource allocation deactivation. This study illustrated alterations in the brain activity between the normal individuals and anosmic patients when smelling odors, and could potentially help for a better anosmia diagnosis in the future.

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Ultrastructure of developing visual cortical synapses in the cat superior colliculus

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100085083 ◽

1991 ◽

Vol 49 ◽

pp. 156-157

Author(s):

Caroline A. Miller ◽

Laura L. Bruce

Keyword(s):

Superior Colliculus ◽

Phosphate Buffer ◽

Receptive Fields ◽

Visual Cortical Area ◽

Cortical Synapses ◽

Visual Cortical ◽

And Function ◽

Phosphate Buffered Saline ◽

The Brain ◽

Cat Superior Colliculus

The first visual cortical axons arrive in the cat superior colliculus by the time of birth. Adultlike receptive fields develop slowly over several weeks following birth. The developing cortical axons go through a sequence of changes before acquiring their adultlike morphology and function. To determine how these axons interact with neurons in the colliculus, cortico-collicular axons were labeled with biocytin (an anterograde neuronal tracer) and studied with electron microscopy.Deeply anesthetized animals received 200-500 nl injections of biocytin (Sigma; 5% in phosphate buffer) in the lateral suprasylvian visual cortical area. After a 24 hr survival time, the animals were deeply anesthetized and perfused with 0.9% phosphate buffered saline followed by fixation with a solution of 1.25% glutaraldehyde and 1.0% paraformaldehyde in 0.1M phosphate buffer. The brain was sectioned transversely on a vibratome at 50 μm. The tissue was processed immediately to visualize the biocytin.

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Aetiologies and anatomy of confabulation

10.1093/oso/9780198789680.003.0004 ◽

2017 ◽

Author(s):

Armin Schnider

Keyword(s):

Brain Damage ◽

Limbic Encephalitis ◽

Artery Aneurysm ◽

Anterior Communicating Artery ◽

Brain Areas ◽

Anatomical Basis ◽

Korsakoff Syndrome ◽

Hypoxic Brain ◽

Degenerative Dementia ◽

The Brain

What diseases cause confabulations and which are the brain areas whose damage is responsible? This chapter reviews the causes, both historic and present, of confabulations and deduces the anatomo-clinical relationships for the four forms of confabulation in the following disorders: alcoholic Korsakoff syndrome, traumatic brain injury, rupture of an anterior communicating artery aneurysm, posterior circulation stroke, herpes and limbic encephalitis, hypoxic brain damage, degenerative dementia, tumours, schizophrenia, and syphilis. Overall, clinically relevant confabulation is rare. Some aetiologies have become more important over time, others have virtually disappeared. While confabulations seem to be more frequent after anterior brain damage, only one form has a distinct anatomical basis.

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Revision Targeted Muscle Reinnervation Improves Secondary Pain Insult in an Upper Extremity Amputee: A Case Report

Hand ◽

10.1177/1558944721992467 ◽

2021 ◽

pp. 155894472199246

Author(s):

David D. Rivedal ◽

Meng Guo ◽

James Sanger ◽

Aaron Morgan

Keyword(s):

Neuropathic Pain ◽

Peripheral Nerves ◽

Nerve Biopsy ◽

Sensory Cortex ◽

Denervated Muscle ◽

Unique Case ◽

Targeted Muscle Reinnervation ◽

Muscle Reinnervation ◽

And Function ◽

The Brain

Targeted muscle reinnervation (TMR) has been shown to improve phantom and neuropathic pain in both the acute and chronic amputee population. Through rerouting of major peripheral nerves into a newly denervated muscle, TMR harnesses the plasticity of the brain, helping to revert the sensory cortex back toward the preinsult state, effectively reducing pain. We highlight a unique case of an above-elbow amputee for sarcoma who was initially treated with successful transhumeral TMR. Following inadvertent nerve biopsy of a TMR coaptation site, his pain returned, and he was unable to don his prosthetic. Revision of his TMR to a more proximal level was performed, providing improved pain and function of the amputated arm. This is the first report to highlight the concept of secondary neuroplasticity and successful proximal TMR revision in the setting of multiple insults to the same extremity.

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Mechanisms of Neurodegeneration in Various Forms of Parkinsonism—Similarities and Differences

Cells ◽

10.3390/cells10030656 ◽

2021 ◽

Vol 10 (3) ◽

pp. 656

Author(s):

Dariusz Koziorowski ◽

Monika Figura ◽

Łukasz M. Milanowski ◽

Stanisław Szlufik ◽

Piotr Alster ◽

...

Keyword(s):

Neurodegenerative Diseases ◽

Tau Protein ◽

Protein Gene ◽

Clinical Presentation ◽

Neuronal Loss ◽

Corticobasal Degeneration ◽

Inflammatory Factors ◽

Parkinsonian Disorders ◽

Genetic Features ◽

The Brain

Parkinson's disease (PD), dementia with Lewy body (DLB), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and multiple system atrophy (MSA) belong to a group of neurodegenerative diseases called parkinsonian syndromes. They share several clinical, neuropathological and genetic features. Neurodegenerative diseases are characterized by the progressive dysfunction of specific populations of neurons, determining clinical presentation. Neuronal loss is associated with extra- and intracellular accumulation of misfolded proteins. The parkinsonian diseases affect distinct areas of the brain. PD and MSA belong to a group of synucleinopathies that are characterized by the presence of fibrillary aggregates of α-synuclein protein in the cytoplasm of selected populations of neurons and glial cells. PSP is a tauopathy associated with the pathological aggregation of the microtubule associated tau protein. Although PD is common in the world's aging population and has been extensively studied, the exact mechanisms of the neurodegeneration are still not fully understood. Growing evidence indicates that parkinsonian disorders to some extent share a genetic background, with two key components identified so far: the microtubule associated tau protein gene (MAPT) and the α-synuclein gene (SNCA). The main pathways of parkinsonian neurodegeneration described in the literature are the protein and mitochondrial pathways. The factors that lead to neurodegeneration are primarily environmental toxins, inflammatory factors, oxidative stress and traumatic brain injury.

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The Ncoa7 locus regulates V-ATPase formation and function, neurodevelopment and behaviour

Cellular and Molecular Life Sciences ◽

10.1007/s00018-020-03721-6 ◽

2020 ◽

Author(s):

Enrico Castroflorio ◽

Joery den Hoed ◽

Daria Svistunova ◽

Mattéa J. Finelli ◽

Alberto Cebrian-Serrano ◽

...

Keyword(s):

Neurodevelopmental Disorders ◽

Regulatory Protein ◽

Molecular Function ◽

Neuronal Connectivity ◽

Nuclear Receptor Coactivator ◽

Lysm Domain ◽

Behavioural Assessment ◽

And Function ◽

The Brain

Abstract Members of the Tre2/Bub2/Cdc16 (TBC), lysin motif (LysM), domain catalytic (TLDc) protein family are associated with multiple neurodevelopmental disorders, although their exact roles in disease remain unclear. For example, nuclear receptor coactivator 7 (NCOA7) has been associated with autism, although almost nothing is known regarding the mode-of-action of this TLDc protein in the nervous system. Here we investigated the molecular function of NCOA7 in neurons and generated a novel mouse model to determine the consequences of deleting this locus in vivo. We show that NCOA7 interacts with the cytoplasmic domain of the vacuolar (V)-ATPase in the brain and demonstrate that this protein is required for normal assembly and activity of this critical proton pump. Neurons lacking Ncoa7 exhibit altered development alongside defective lysosomal formation and function; accordingly, Ncoa7 deletion animals exhibited abnormal neuronal patterning defects and a reduced expression of lysosomal markers. Furthermore, behavioural assessment revealed anxiety and social defects in mice lacking Ncoa7. In summary, we demonstrate that NCOA7 is an important V-ATPase regulatory protein in the brain, modulating lysosomal function, neuronal connectivity and behaviour; thus our study reveals a molecular mechanism controlling endolysosomal homeostasis that is essential for neurodevelopment. Graphic abstract

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Breeder Diet Strategies for Generating Ttpa-Null and Wild-Type Mice with Low Vitamin E Status to Assess Neurological Outcomes

Current Developments in Nutrition ◽

10.1093/cdn/nzaa155 ◽

2020 ◽

Vol 4 (11) ◽

Author(s):

Katherine M Ranard ◽

Matthew J Kuchan ◽

John W Erdman

Keyword(s):

Animal Model ◽

Vitamin E ◽

Mouse Model ◽

Wild Type ◽

Future Studies ◽

Neurological Outcomes ◽

Transfer Protein ◽

And Function ◽

The Brain ◽

Vitamin E Status

ABSTRACT Studying vitamin E [α-tocopherol (α-T)] metabolism and function in the brain and other tissues requires an animal model with low α-T status, such as the transgenic α-T transfer protein (Ttpa)–null (Ttpa−/−) mouse model. Ttpa+/− dams can be used to produce Ttpa−/− and Ttpa+/+mice for these studies. However, the α-T content in Ttpa+/− dams’ diet requires optimization; diets must provide sufficient α-T for reproduction, while minimizing the transfer of α-T to the offspring destined for future studies that require low baseline α-T status. The goal of this work was to assess the effectiveness and feasibility of 2 breeding diet strategies on reproduction outcomes and offspring brain α-T concentrations. These findings will help standardize the breeding methodology used to generate the Ttpa−/− mice for neurological studies.

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Limbic Expression of mRNA Coding for Chemoreceptors in Human Brain—Lessons from Brain Atlases

International Journal of Molecular Sciences ◽

10.3390/ijms22136858 ◽

2021 ◽

Vol 22 (13) ◽

pp. 6858

Author(s):

Fanny Gaudel ◽

Gaëlle Guiraudie-Capraz ◽

François Féron

Keyword(s):

G Proteins ◽

The Body ◽

Trace Amines ◽

Chemical Senses ◽

Brain Areas ◽

Genes Encoding ◽

The Central Nervous System ◽

Human Brains ◽

The Brain ◽

Brain Atlases

Animals strongly rely on chemical senses to uncover the outside world and adjust their behaviour. Chemical signals are perceived by facial sensitive chemosensors that can be clustered into three families, namely the gustatory (TASR), olfactory (OR, TAAR) and pheromonal (VNR, FPR) receptors. Over recent decades, chemoreceptors were identified in non-facial parts of the body, including the brain. In order to map chemoreceptors within the encephalon, we performed a study based on four brain atlases. The transcript expression of selected members of the three chemoreceptor families and their canonical partners was analysed in major areas of healthy and demented human brains. Genes encoding all studied chemoreceptors are transcribed in the central nervous system, particularly in the limbic system. RNA of their canonical transduction partners (G proteins, ion channels) are also observed in all studied brain areas, reinforcing the suggestion that cerebral chemoreceptors are functional. In addition, we noticed that: (i) bitterness-associated receptors display an enriched expression, (ii) the brain is equipped to sense trace amines and pheromonal cues and (iii) chemoreceptor RNA expression varies with age, but not dementia or brain trauma. Extensive studies are now required to further understand how the brain makes sense of endogenous chemicals.

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The role of GABAA receptor biogenesis, structure and function in epilepsy

Biochemical Society Transactions ◽

10.1042/bst0340863 ◽

2006 ◽

Vol 34 (5) ◽

pp. 863-867 ◽

Cited By ~ 14

Author(s):

S. Mizielinska ◽

S. Greenwood ◽

C.N. Connolly

Keyword(s):

Gabaa Receptor ◽

Structure And Function ◽

Inhibitory Synapses ◽

Normal Brain ◽

Synaptic Targeting ◽

Acid Type ◽

Normal Brain Function ◽

And Function ◽

The Brain

Maintaining the correct balance in neuronal activation is of paramount importance to normal brain function. Imbalances due to changes in excitation or inhibition can lead to a variety of disorders ranging from the clinically extreme (e.g. epilepsy) to the more subtle (e.g. anxiety). In the brain, the most common inhibitory synapses are regulated by GABAA (γ-aminobutyric acid type A) receptors, a role commensurate with their importance as therapeutic targets. Remarkably, we still know relatively little about GABAA receptor biogenesis. Receptors are constructed as pentameric ion channels, with α and β subunits being the minimal requirement, and the incorporation of a γ subunit being necessary for benzodiazepine modulation and synaptic targeting. Insights have been provided by the discovery of several specific assembly signals within different GABAA receptor subunits. Moreover, a number of recent studies on GABAA receptor mutations associated with epilepsy have further enhanced our understanding of GABAA receptor biogenesis, structure and function.

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