Lateralization of gene expression in human language cortex

Karlebach, Guy; Francks, Clyde

doi:10.1016/j.cortex.2015.03.003

Cited by 64 publications

(80 citation statements)

References 29 publications

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“…Although MRS measurements of glutamate do not allow inference about a neural mechanism for increased excitability, MRS glutamate concentrations are positively correlated with cortical excitability [63]. More generally, leftlateralized expression of genes associated with glutamatergic function has been found within the STG and auditory cortex [64], suggestive of a relationship between glutamatergic signaling and lateralized auditory processing, which is thought to be significant in language processing [65]. Collectively, these studies suggest hyperexcitability in RD due to enhanced glutamatergic signaling as a source of deficits in rapid auditory processing and reading.…”

Section: Glutamatergic Signalingmentioning

confidence: 97%

Neural Noise Hypothesis of Developmental Dyslexia

Hancock¹,

Pugh²,

Hoeft³

2017

Trends in Cognitive Sciences

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Developmental dyslexia (decoding-based reading disorder; RD) is a complex trait with multifactorial origins at the genetic, neural, and cognitive levels. There is evidence that low-level sensory-processing deficits precede and underlie phonological problems, which are one of the best-documented aspects of RD. RD is also associated with impairments in integrating visual symbols with their corresponding speech sounds. Although causal relationships between sensory processing, print-speech integration, and fluent reading, and their neural bases are debated, these processes all require precise timing mechanisms across distributed brain networks. Neural excitability and neural noise are fundamental to these timing mechanisms. Here, we propose that neural noise stemming from increased neural excitability in cortical networks implicated in reading is one key distal contributor to RD. Premise of the Neural Noise HypothesisDevelopmental dyslexia (specific reading disabilities/disorders, or decoding-based RD) is a neurodevelopmental disorder contributed to by multiple genetic, neural, and cognitive factors [1], yet neurobiological models that account for the diversity of RD phenotypes remain elusive. An increasing number of studies have investigated the function of RD risk genes in animal models [2][3][4][5][6][7][8][9][10][11][12][13], and the neurobiological and behavioral consequences of genetic RD risk variants in humans [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31], motivating the need for a synthesis of these findings, especially because they relate to emerging avenues of human research on the role of neurochemistry [32] and neural oscillations [33][34][35][36] in RD. Here, we present a timely integration of diverse lines of current research linking some of the key neural and behavioral deficits associated with RD to basic neural processes.A variety of neurobiological contributors to RD have been proposed, ranging from disrupted structural and functional connectivity [37,38] to atypical neural migration [39]. Recent work has investigated the neural dynamics that support language and sensory processing [40][41][42] and how these dynamics may be altered in RD [36,43]. We integrate these emerging lines of research to propose that excess neural noise (Box 1) within cortical regions implicated in reading may be a distal contributor to RD. We suggest that multifactorial sources of neural noise, for example arising from neural hyperexcitability related to RD risk genes, disrupt two key processes important for reading [phonological awareness [44] (see Glossary) and multisensory integration of visual symbols with their corresponding speech sounds [45,46]] through the impact of excess noise on neural synchrony and sensory representations (Figure 1). The neural noise hypothesis of RD synthesizes a range of neurobiological findings, providing a mechanistic framework for understanding the deficits observed in RD and identifying targets for systems-level intervention. While the potential for noisy proce...

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Section: Glutamatergic Signalingmentioning

confidence: 97%

Neural Noise Hypothesis of Developmental Dyslexia

Hancock¹,

Pugh²,

Hoeft³

2017

Trends in Cognitive Sciences

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“…The lateralized gene sets included sets responsible for neuronal electrophysiology, synaptic transmission (especially the Gprotein coupled receptor signalling pathway), nervous system development, and glutamate receptor activity. The contrasting results compared to Hawrylycz et al (2012) and Pletikos et al (2014) may be explained by the different analysis methods performed by Karlebach and Francks (2015). Some of these methods provide significant improvement when compared to former studies and are worth being highlighted: As STS and HG are asymmetrical in function, anatomy and neurophysiology, it is methodically reasonable to focus on these anatomically defined regions.…”

mentioning

confidence: 88%

“…The more brain areas and life stages are lumped together, the more possibly hidden expression asymmetries are balanced out, and no statistical significant results are found. Moreover, whereas Hawrylycz et al (2012) and Pletikos et al (2014) aimed to detect expression rates on the level of individual genes, Karlebach and Francks (2015) proposed that lateralization could better be detected at the level of functional GO groups, which was indeed the case as small effects were increased. This approach might be particularly useful when investigating the role of genes determining general brain development and development of the relevant cognitive system for a specific form of lateralization, since it is difficult to understand the functional relevance of such genes in isolation.…”

mentioning

confidence: 97%

“…Thus, in our opinion, the paper of Karlebach and Francks (2015) constitutes a major stepping stone towards understanding the genetic determinants of functional lateralization. The asymmetrically expressed genes and gene groups identified by Karlebach and Francks (2015) provide an objective starting point for a multitude of possible candidate gene studies (Ocklenburg, Beste, & Gü ntü rkü n, 2013) which could link genetic variation in these genes to behavioural or anatomical asymmetries.…”

mentioning

confidence: 98%

“…In the study by Karlebach and Francks (2015), the authors performed a re-analysis of the two datasets of Hawrylycz et al (2012) and Pletikos et al (2014). Importantly, they focused on specific regions involved in speech production and perception, and could show lateralization of individual genes as well as gene ontology (GO) groups in two language-related areas, the superior temporal sulcus (STS) and Heschl's Gyrus (HG).…”

mentioning

confidence: 99%

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A commentary on Karlebach and Francks, (2015)

Schmitz

Lor

Klose

et al. 2016

Cortex

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Asymmetric development of the nervous system

Alqadah

Hsieh

Morrissey

et al. 2017

Developmental Dynamics

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The human nervous system consists of seemingly symmetric left and right halves. However, closer observation of the brain reveals anatomical and functional lateralization. Defects in brain asymmetry correlate with several neurological disorders, yet our understanding of the mechanisms used to establish lateralization in the human central nervous system is extremely limited. Here, we review left-right asymmetries within the nervous system of humans and several model organisms, including rodents, Zebrafish, chickens, Xenopus, Drosophila, and the nematode Caenorhabditis elegans. Comparing and contrasting mechanisms used to develop left-right asymmetry in the nervous system can provide insight into how the human brain is lateralized. Developmental Dynamics 247:124-137,

show abstract

Lateralization of gene expression in human language cortex

Cited by 64 publications

References 29 publications

Neural Noise Hypothesis of Developmental Dyslexia

Neural Noise Hypothesis of Developmental Dyslexia

A commentary on Karlebach and Francks, (2015)

Asymmetric development of the nervous system

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